Search

Pengfeng Gong,1,&ast; Jie Shen,1 Yu Yang,2,&ast; Dong Xue,1 Hao Lu,1 Qianfeng Zhuang,1 Xiaogang Wang,1 Zinong Tian,1 Yiming Chen,1 Cheng Chen,1 Yunjie Cao1 1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213000, People’s Republic of China; 2Department of Hepato-Pancreato-Biliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunjie Cao, Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, 213000, People’s Republic of China, Tel +86-13775188220, Email caoyunjie1847@163.comObjective: To explore patients’ knowledge, attitude, and practice (KAP) toward varicocele in China and the relationship between treatment selection and KAP.Methods: This cross-sectional study enrolled varicocele patients at the Third Affiliated Hospital of Soochow University (September to October 2023). Structural equation modeling (SEM) was used to explore the relationship between clinical factors and KAP. A score >mean score for each dimension was defined as adequate knowledge, positive attitude, and proactive practice. The patients were grouped according to varicocelectomy vs no surgery. Univariable and multivariable logistic regression analyses were used to identify the factors independently associated with KAP. A structural equation modeling (SEM) analysis was performed to examine how the KAP dimensions influenced each other.Results: Among 502 patients, 44.02%, 35.86%, and 20.12% were ≤ 30, 31– 40, and > 40 years old, respectively. Those who underwent varicocelectomy (n=407) had significantly higher knowledge (20 (15– 22) vs 0 (0– 6), P< 0.001), attitude (26 (24– 26) vs 14 (10– 18), P< 0.001), and practice (20 (17– 24) vs 8 (6– 16), P< 0.001) than those who did not. A higher proportion of patients with varicocelectomy were < 40 years old, more educated, had higher income, and were unmarried compared with those without surgery (all P< 0.001). High school or higher education level and varicocelectomy (irrespective of type) were independently associated with adequate knowledge (all P< 0.001). Knowledge, college/bachelor’s degree education, and varicocelectomy type (irrespective of type) were associated with positive attitudes (all P< 0.05). In the SEM, knowledge directly influenced attitude, knowledge directly influenced practice, and attitude directly influenced practice (all P< 0.001). Having knowledge of the subject may direct varicocele patients to varicocelectomy.Conclusion: Chinese patients who underwent varicocelectomy exhibit appropriate KAP regarding varicocele, while non-surgery patients have poorer KAP. These results suggest that patients who did not undergo surgery should nevertheless be properly informed about their disease.Keywords: knowledge, attitude, practice, varicocele, varicocelectomy, cross-sectional study

Kun Li,1 Ahmad Alhaskawi,2 Haiyin Zhou,2 Yanzhao Dong,2 QingFang Zhao,3 Chenxi Wang,4 Hui Lu2 1Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Plastic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 4Medical Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Kun Li, Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, People’s Republic of China, Email Likicu@zju.edu.cn Hui Lu, Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang Province, People’s Republic of China, Email HuiLu@zju.edu.cnObjective: This retrospective study examines risk factors and electromyographic (EMG) characteristics associated with acquired weakness in critically ill patients and assesses their impact on patient prognosis.Methods: Ninety-seven critically ill patients, ventilated for over 48 hours, were included. Patient data, encompassing general condition, medical history, Medical Research Council (MRC) scores, serum markers (c-reactive protein, calcitonin gene, albumin, brain natriuretic peptide, urea nitrogen, creatinine), EMG characteristics, respiratory treatment modalities, and parameters, were recorded. Mechanical ventilation duration, ICU stay duration, hospitalization duration, and patient prognosis were documented. Based on MRC scores, patients were categorized into the ICU-acquired weakness (ICU-AW) group (MRC < 48 points) and the non-ICU-AW group (MRC ≥ 48 points).Results: The study comprised 47 ICU-AW and 50 non-ICU-AW patients. Significant differences (p < 0.05) were observed in age, MRC scores, albumin levels, c-reactive protein, calcitonin gene, brain natriuretic peptide, urea nitrogen, creatinine, mechanical ventilation duration, ICU stay duration, and hospitalization duration between groups. In the ICU-AW group, nerve conduction examinations revealed slow conduction velocity, reduced wave amplitude, and in severe cases, a complete loss of motor and sensory potentials. Multivariate logistic analysis identified low serum albumin levels and MRC scores as potential ICU-AW risk factors.Conclusion: This study suggests that low serum albumin levels and MRC scores may contribute to ICU-AW risk. The ICU-AW group exhibited varied peripheral nerve damage and slow conduction velocities on EMG. Additionally, severe systemic inflammatory responses, renal function, brain natriuretic peptide levels, prolonged mechanical ventilation, and peripheral nerve damage may be associated with ICU-AW. Follow-up studies are essential for further understanding these complex interactions.Keywords: ICU-acquired weakness, risk factor, critical care, therapy, respiratory failure, electromyography

Jingfang Chen,1,2 Linlin Liu,3 Junxiong Huang,1 Youli Jiang,4 Chengliang Yin,1 Lukun Zhang,5 Zhihuan Li,1 Hongzhou Lu1,5 1Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, People’s Republic of China; 2Department of Research and Teaching, The Third People’s Hospital of Shenzhen, Shenzhen, 518112, People’s Republic of China; 3Hengyang Medical School, School of Nursing, University of South China, Hengyang, 421001, People’s Republic of China; 4Department of Neurology, The People’s Hospital of Longhua, Shenzhen, 518109, People’s Republic of China; 5Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, Shenzhen, 518112, People’s Republic of ChinaCorrespondence: : Zhihuan Li; Hongzhou Lu, Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, People’s Republic of China, Email baopullon@163.com; luhongzhou@szsy.sustech.edu.cnBackground: Both HIV and TB are chronic infectious diseases requiring long-term treatment and follow-up, resulting in extensive electronic medical records. With the exponential growth of health and medical big data, effectively extracting and analyzing these data has become the research hotspot. As a fundamental aspect of artificial intelligence, machine learning has been extensively applied in medical research, encompassing diagnosis, treatment, patient monitoring, drug development, and epidemiological investigations. This significantly enhances medical information systems and facilitates the interoperability of medical data.Methods: In our study, we analyzed longitudinal data from the electronic health records of 4540 patients, gathered from the National Clinical Research Center for Infectious Diseases in Shenzhen, China, spanning from 2017 to 2021. Initially, we employed the fine-tuned ChatGLM to structure the electronic medical records. Subsequently, we utilized a multi-layer perceptron to classify each patient and determined the presence of tuberculosis in HIV patients. Using machine learning-based natural language processing, we structured these records to build a specialized database for HIV and TB co-infection. We studied the epidemiological characteristics, focusing on incidence patterns, patient characteristics, and influencing factors, to uncover the transmission characteristics of these diseases in Shenzhen. Additionally, we used Long Short-Term Memory to create a predictive model for TB co-infection among HIV patients, based on their medical records. This model predicted the risk of TB co-infection, providing scientific evidence for clinical decision-making and enabling early detection and precise intervention.Results: Based on the refined ChatGLM model tailored for structured electronic health records, the accuracy of symptom extraction consistently surpassed 0.95 precision. Key symptoms such as diarrhea and normal showed precision rates exceeding 0.90. High scores were also achieved in recall and F1 scores. Among 4540 HIV patients, 758 were diagnosed with concurrent tuberculosis, indicating a 16.7% co-infection rate, while syphilis co-infection affected 25.1%, underscoring the prevalence of concurrent infections among HIV patients. Utilizing electronic health records, a Multilayer Perceptron classifier was developed as a benchmark against Long Short-Term Memory to predict high-risk groups for HIV and tuberculosis co-infections. The Multilayer Perceptron classifier demonstrated predictive ability with AUROC values ranging from 0.616 to 0.682 on the test set, suggesting opportunities for further optimization and generalization despite its accuracy in identifying HIV-TB co-infections. In tuberculosis intelligent diagnosis based on laboratory results, the Long Short-Term Memory showed consistent performance across 5-fold cross-validation, with AUROC values ranging from 0.827 to 0.850, indicating reliability and consistency in tuberculosis prediction. Furthermore, by optimizing classification thresholds, the model achieved an overall accuracy of 81.18% in distinguishing HIV co-infected tuberculosis from simple HIV infection.Conclusion: Combining the Multilayer Perceptron classifier with Long Short-Term Memory represented an advanced approach for effectively extracting electronic health records and utilizing it for disease prediction. This underscored the superior performance of deep learning techniques in managing both structured and unstructured medical data. Models leveraging laboratory time-series data demonstrated notably better performance compared to those relying solely on electronic health records for predicting tuberculosis incidence. This emphasized the benefits of deep learning in handling intricate medical data and provided valuable insights for healthcare providers exploring the use of deep learning in disease prediction and management.Keywords: Prediction models, HIV, Tuberculosis, Machine Learning, Artificial Intelligence

Min Yang,1– 3,&ast; Wenfei Wang,3,&ast; Peize Zhang,4 Guizhen Liu,5 Hailin Lu,6 Mingjie He,5 Guofang Deng,2,3 Xiaoyou Chen1,7 1Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Second Department of Pulmonary Medicine and Tuberculosis, the Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 3National Clinical Research Center for Infectious Disease, the Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 4Fourth Department of Pulmonary Medicine and Tuberculosis, the Third People’s Hospital of Shenzhen, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 5The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, People’s Republic of China; 6Gannan Medical University, Ganzhou, Jiangxi, People’s Republic of China; 7Infectious Diseases Department, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyou Chen; Guofang Deng, Email chenxy1998@hotmail.com; jxxk1035@yeah.netObjective: We aimed to investigate dysregulated metabolic pathways and identify diagnostic and therapeutic targets in patients with tuberculosis-diabetes (TB-DM).Methods: In our prospective cohort study, plasma samples were collected from healthy individuals, diabetic (DM) patients, untreated TB-only (TB-0)/TB-DM patients (TB-DM-0), and cured TB (TB-6)/TB-DM patients (TB-DM-6) to measure the levels of amino acids, fatty acids, and other metabolites in plasma using high-throughput targeted quantification methods.Results: Significantly different biological processes and biomarkers were identified in DM, TB-DM-0, and TB-DM-6 patients. Moreover, quinolinic acid (QA) showed excellent predictive accuracy for distinguishing between DM patients and TB-DM-0 patients, with an AUC of 1 (95% CI 1– 1). When differentiating between TB-DM-0 patients and TB-DM-6 patients, the AUC was 0.9297 (95% CI 0.8460– 1). Compared to those in DM patients, the QA levels were significantly elevated in TB-DM-0 patients and decreased significantly after antituberculosis treatment. We simultaneously compared healthy controls and untreated tuberculosis patients and detected an increase in the level of QA in the plasma of tuberculosis patients, which decreased following treatment.Conclusion: These findings improve the current understanding of tuberculosis treatment in patients with diabetes. QA may serve as an ideal diagnostic biomarker for TB-DM patients and contribute to the development of more effective treatments.Keywords: pulmonary tuberculosis, diabetes, metabolomics, quinolinic acid, biomarker

Hong Lu,&ast; Yanmei Mao,&ast; Ying Zeng, Pengyu Li, Pan Yan, Qunzhi Shi, Lin Liu Department of Pharmacy, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China&ast;These authors have contributed equally to this workCorrespondence: Hong Lu, Department of Pharmacy, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, People’s Republic of China, Email 1430368@qq.comPurpose: Voriconazole, a first-line therapeutic agent for chronic pulmonary aspergillosis, is metabolized by the cytochrome 450 enzymes, specifically CYP2C19 and CYP3A4. Rifampicin and rifapentine act as inducers of the cytochrome P450 enzyme. The current study explored the potential drug interactions arising from the co-administration of voriconazole with either rifampicin or rifapentine, as well as the duration of this effect on serum voriconazole levels after discontinuation of rifampicin or rifapentine.Patients and Methods: A retrospective study was conducted in tuberculosis patients with chronic pulmonary aspergillosis. These patients underwent a combination therapy involving voriconazole and rifampicin or rifapentine, or they were treated with voriconazole after discontinuation of rifampicin or rifapentine. The serum concentrations of voriconazole at steady-state were monitored. Data on demographic characteristics and the serum voriconazole levels were used for statistical analyses.Results: A total of 124 serum voriconazole concentrations from 109 patients were included in the study. The average serum concentration of voriconazole fell below the effective therapeutic range in patients treated with both voriconazole and rifampicin or rifapentine. Notably the co-administration of rifapentine led to a substantial (> 70%) decrease in serum voriconazole levels in two patients. Moreover, this interfering effect persisted for at least 7 days following rifampicin discontinuation, while it endured for 5 days or more after discontinuation of rifapentine.Conclusion: Concomitant use of voriconazole and rifampicin or rifapentine should be avoided, and it is not recommended to initiate voriconazole therapy within 5 or 7 days after discontinuation of rifapentine or rifampicin. Therapeutic drug monitoring not only provides a basis for the adjustment of clinical dose, but also serves as a valuable tool for identifying drug interactions.Keywords: voriconazole, rifampicin, rifapentine, serum concentration, discontinuation

Xin Liu,1,&ast; Ruofan Xi,1,&ast; Xinran Du,1 Yi Wang,1 Linyan Cheng,1 Ge Yan,1 Hanzhi Lu,1 Te Liu,2 Fulun Li1 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Te Liu; Fulun Li, Email liute1979@shutcm.edu.cn; drlifulun@163.comBackground: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota.Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration.Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group.Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.Keywords: psoriasis, thymopentin, 16S rRNA sequencing, T-cell subsets

Jun Zhang,1,&ast; Yinyu Wu,1,&ast; Yuanlin Du,1,&ast; Yunxia Du,1 Daiqin Bao,1 Haibin Lu,2 Xiaoqiong Zhou,1 Rui Li,1 Haoyu Pei,1 Han She,1 Qingxiang Mao1 1Department of Anesthesiology, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Department of Intensive Care Unit, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Han She; Qingxiang Mao, Email mazuishehan@163.com; qxmao@tmmu.edu.cnBackground: This study aimed to discover diagnostic and prognostic biomarkers for sepsis immunotherapy through analyzing the novel cellular death process, cuproptosis.Methods: We used transcriptome data from sepsis patients to identify key cuproptosis-related genes (CuRGs). We created a predictive model and used the CIBERSORT algorithm to observe the link between these genes and the septic immune microenvironment. We segregated sepsis patients into three subgroups, comparing immune function, immune cell infiltration, and differential analysis. Single-cell sequencing and real-time quantitative PCR were used to view the regulatory effect of CuRGs on the immune microenvironment and compare the mRNA levels of these genes in sepsis patients and healthy controls. We established a sepsis forecast model adapted to heart rate, body temperature, white blood cell count, and cuproptosis key genes. This was followed by a drug sensitivity analysis of cuproptosis key genes.Results: Our results filtered three key genes (LIAS, PDHB, PDHA1) that impact sepsis prognosis. We noticed that the high-risk group had poorer immune cell function and lesser immune cell infiltration. We also discovered a significant connection between CuRGs and immune cell infiltration in sepsis. Through consensus clustering, sepsis patients were classified into three subgroups. The best immune functionality and prognosis was observed in subgroup B. Single-cell sequencing exposed that the key genes manage the immune microenvironment by affecting T cell activation. The qPCR results highlighted substantial mRNA level reduction of the three key genes in the SP compared to the HC. The prediction model, which combines CuRGs and traditional diagnostic indicators, performed better in accuracy than the other markers. The drug sensitivity analysis listed bisphenol A as highly sensitive to all the key genes.Conclusion: Our study suggests these CuRGs may offer substantial potential for sepsis prognosis prediction and personalized immunotherapy.Keywords: sepsis, cuproptosis, prognosis, immune cell infiltration, nomogram

Xiaojuan Ji,1,&ast; Wenjie Zhu,1,&ast; Hongfei Lu,2 Zhiwei Wu,1 Huaqing Chen,1 Chunli Lin,1 Zhaolin Zeng,1 Cong You,1 Longnian Li1 1Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology, Ganzhou, People’s Republic of China; 2Clinical Laboratory, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cong You; Longnian Li, Department of Dermatology, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China, Email youcong1987@tmu.edu.cn; li_longnian@foxmail.comObjective: To analyze the antibiotic resistance profile, virulence genes, and molecular typing of Staphylococcus aureus (S. aureus) strains isolated in skin and soft tissue infections at the First Affiliated Hospital, Gannan Medical University, to better understand the molecular epidemiological characteristics of S. aureus.Methods: In 2023, 65 S. aureus strains were isolated from patients with skin and soft tissue infections. Strain identification and susceptibility tests were performed using VITEK 2 and gram-positive bacteria identification cards. DNA was extracted using a DNA extraction kit, and all genes were amplified using polymerase chain reaction. Multilocus sequence typing (MLST) was used for molecular typing.Results: In this study, of the 65 S. aureus strains were tested for their susceptibility to 16 antibiotics, the highest resistance rate to penicillin G was 95.4%. None of the staphylococcal isolates showed resistance to ceftaroline, daptomycin, linezolid, tigecycline, teicoplanin, or vancomycin. fnbA was the most prevalent virulence gene (100%) in S. aureus strains isolated in skin and soft tissue infections, followed by arcA (98.5%). Statistical analyses showed that the resistance rates of methicillin-resistant S. aureus isolates to various antibiotics were significantly higher than those of methicillin-susceptible S. aureus isolates. Fifty sequence types (STs), including 44 new ones, were identified by MLST.Conclusion: In this study, the high resistance rate to penicillin G and the high carrying rate of virulence gene fnbA and arcA of S.aureus were determine, and 44 new STs were identified, which may be associated with the geographical location of southern Jiangxi and local trends in antibiotic use. The study of the clonal lineage and evolutionary relationships of S. aureus in these regions may help in understanding the molecular epidemiology and provide the experimental basis for pathogenic bacteria prevention and treatment.Keywords: Staphylococcus aureus, skin and soft tissue infections, antibiotic resistance, multilocus sequence typing, virulence gene

Yiliang Zhong,1,2,&ast; Jing Wang,3,4,&ast; Zhou Liang,5 Tingcheng Han,3,4 Hua Lu,3,4 Zhaomeng Hou3,4 1Graduate School, Guangxi University of Chinese Medicine, Nanning, People’s Republic of China; 2Department of Spinal Surgery, People’s Hospital of Ganxian District, Ganzhou, People’s Republic of China; 3Department of Orthopedics and Traumatology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, People’s Republic of China; 4Department of Orthopedics and Traumatology, Yancheng TCM Hospital, Yancheng, People’s Republic of China; 5Department of Minimally Invasive Spinal Surgery, Yulin Orthopedic Hospital of Integrated Traditional Chinese and Western Medicine, Yulin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaomeng Hou, Department of Orthopedics and Traumatology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, People’s Republic of China, Email houzhaomeng1992@163.comBackground: The increasing utilization of endoscopic lumbar discectomy (ELD) in spinal surgery has sparked widespread interest and research. This study utilizes bibliometric analysis to identify current research trends and advancements in this innovative surgical technique, with the goal of informing and improving surgical practices.Methods: We retrieved relevant literature on ELD from the Science Citation Index Expanded (SCI-Expanded) within the Web of Science Core Collection (WoSCC) database as research samples. Various visualization tools, such as VOSviewer, CiteSpace, Scimago Graphica, Pajek, and online bibliometric platform, were employed to generate scientific knowledge maps for the purpose of visual presentation and data analysis.Results: Over the past two decades, there has been significant progress in the research related to ELD, particularly since 2016. China has emerged as the most productive country, while South Korea and the United States have exerted greater academic influence. Tongji University has contributed the highest number of research output, while academic achievements published by Wooridul Spine Hospital are highly esteemed by scholars. Lee SH and Ruetten S are the most prolific author and the most highly cited author, respectively. World Neurosurg has published the highest number of publications, while Spine has become the most influential journal. Clinical Neurology and Surgery are the primary subject categories. Research in this field primarily revolves around improving ELD techniques, evaluating postoperative efficacy and prognosis prediction, studying complications and risk factors, as well as comparative research with other surgical techniques. Keywords such as risk factors, LDH, PETD, lumbar spinal stenosis, degeneration, recurrent herniation, laminectomy, local anesthesia, and foraminoplasty highlight the current research hotspots and future cutting-edge trends.Conclusion: This study employed bibliometric analysis to elucidate the research hotspots and frontiers in ELD. The findings have significant implications for advancing research and development in this field.Keywords: endoscopic lumbar discectomy, bibliometric, visualization analysis, VOSviewer, CiteSpace

Yihua Fan,1– 3,&ast; Wei Liu,1,2,&ast; Yue Jin,1,2,&ast; Hang Lu,1,2 Chunliu Liu,1,2 Aihua Wang,1,2 Qingxiang Gu,1,2 Yuxiu Ka1,2 1Department of Rheumatism and Immunity, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, People’s Republic of China; 3Department of Rheumatism and Immunity, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Liu, Email fengshiliuwei@163.comBackground: Acute gouty arthritis (AGA) is characterized by the accumulation of monosodium urate crystals within the joints, leading to inflammation and severe pain. Western medicine treatments have limitations in addressing this condition. Previous studies have shown the efficacy of Qinpi Tongfeng formula (QPTFF) in treating AGA, but further investigation is needed to understand its mechanism of action.Methods: We used ultra-high-performance liquid chromatography tandem Q-Exactive Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-MS) to identify compounds in QPTFF. Target proteins regulated by these compounds were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Chemistry Database, and Swiss Target Prediction Database. AGA-related targets were searched and screened from various databases, including Genecards, PharmGKB, Drugbank, etc. Intersection targets of QPTFF and AGA were analyzed for protein–protein interaction networks, GO function enrichment, and KEGG pathway enrichment. We then verified QPTFF’s mechanism of action using an AGA rat model, assessing pathological changes via H&E staining and target expression via ELISA, RT-qPCR, and Western blot.Results: UHPLC-Q-Orbitrap-MS identified 207 compounds in QPTFF, with 55 selected through network pharmacology. Of 589 compound-regulated targets and 1204 AGA-related targets, 183 potential targets were implicated in QPTFF’s treatment of AGA. Main target proteins included IL-1β, NFKBIA, IL-6, TNF, CXCL8, and MMP9, with the IL-17 signaling pathway primarily regulated by QPTFF. Experimental results showed that medium and high doses of QPTFF significantly reduced serum inflammatory factors and MMP-9 expression, and inhibited IL-17A, IL-6, IKK-β, and NF-κB p65 mRNA and protein expression in AGA rats compared to the model group.Conclusion: Key targets of QPTFF include IL-1β, NFKBIA, IL-6, TNF-α, CXCL8, and MMP9. QPTFF effectively alleviates joint inflammation in AGA rats, with high doses demonstrating no liver or kidney toxicity. Its anti-inflammatory mechanism in treating AGA involves the IL-17A/NF-κB p65 signaling pathway.Keywords: acute gouty arthritis, Qinpi Tongfeng formula, network pharmacology, UHPLC-Q-Orbitrap-MS, IL-17 signaling pathway

Wanying Wu,1,2,&ast; Congzhuo Jia,1,2,&ast; Xiayan Xu,1– 3 Yibo He,1,2 Yun Xie,1,2,4 Yang Zhou,1,2 Hongyu Lu,1,2 Jin Liu,1,2 Jiyan Chen,1,2 Yong Liu1,2 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 4School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiyan Chen; Yong Liu, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email chenjiyandr@126.com; liuyong@gdph.org.cnBackground: Inflammation contributes to the initiation and advancement of both coronary atherosclerosis and type 2 diabetes mellitus (T2DM). Recent evidence has underscored the platelet-to-HDL-cholesterol ratio (PHR) as a promising inflammatory biomarker closely linked to the severity of coronary artery disease (CAD). Nevertheless, the risk of adverse clinical outcomes remains unclear among CAD patients with varying PHR levels and glycemic status.Methods: A total of 56,316 CAD patients were enrolled, primarily focusing on mortality outcomes. Patients were categorized into four subgroups based on median baseline PHR values and glycemic status: lower PHR (PHR-L) and higher PHR (PHR-H) with or without T2DM. Cox proportional hazard model and subgroup analysis were employed to investigate the association between PHR and glycemic status with mortality.Results: Over a median 5.32-year follow-up, 8909 (15.8%) patients experienced all-cause mortality, with 3873 (6.9%) deaths attributed to cardiovascular causes. Compared to individuals in PHR-L/non-DM, those in PHR-H/non-DM, PHR-L/DM and PHR-H/DM groups exhibited a higher risk of all-cause death [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.06– 1.18; HR 1.21, 95% CI 1.14– 1.29; HR 1.43, 95% CI 1.34– 1.52, respectively], as well as cardiac mortality [HR 1.19, 95% CI 1.08– 1.30; HR 1.58, 95% CI 1.44– 1.74; HR 1.89, 95% CI 1.72– 2.07, respectively]. Cox proportional hazard model also revealed the highest mortality risk among patients in PHR-H/DM compared to other groups (P < 0.05). Restricted cubic spline regression analysis revealed a positive linear association between PHR and all-cause as well as cardiac mortality (P for non-linearity > 0.05) after adjustment. Additionally, subgroup analysis indicated consistent effects on cardiac mortality within diverse subsets.Conclusion: In this real-world observational cohort analysis, elevated PHR levels joint with T2DM were related to adverse long-term clinical outcomes in CAD patients. PHR levels may serve as a valuable tool for identifying high-risk individuals within this specific group.Trial Registration: The Cardiorenal ImprovemeNt II registry NCT05050877.Keywords: platelet-to-HDL-cholesterol ratio, coronary artery disease, diabetes, all-cause mortality, cardiovascular mortality

Ying Chen,1,2,&ast; Wen-Xia Li,1,2,&ast; Jia-Hua Wu,1,2 Geng-Hang Chen,2 Chun-Min Yang,1,2 Hai Lu,1,2 Xi Wang,3 Shu-Sen Wang,4 Heng Huang,5 Li Cai,6 Li Zhao,7 Rou-Jun Peng,8 Ying Lin,9 Jun Tang,3 Jian Zeng,10 Le-Hong Zhang,11 Yong-Li Ke,12 Xian-Ming Wang,13 Xin-Mei Liu,14 An-Qin Zhang,15 Fei Xu,4 Xi-Wen Bi,4 Jia-Jia Huang,4 Ji-Bin Li,16 Dan-Mei Pang,17 Cong Xue,4 Yan-Xia Shi,4 Zhen-Yu He,18 Huan-Xin Lin,18 Xin An,4 Wen Xia,4 Ye Cao,16 Ying Guo,16 Ruo-Xi Hong,4 Kui-Kui Jiang,4 Yong-Yi Zhong,4 Ge Zhang,19 Piyawan Tienchaiananda,20 Masahiro Oikawa,21 Zhong-Yu Yuan,4 Qian-Jun Chen22,23 1Department of Breast Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Breast Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 5Department of Breast Oncology, Lianjiang People’s Hospital, Lianjiang, People’s Republic of China; 6Department of Medical Oncology, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, People’s Republic of China; 7Department of Breast Oncology, Guangzhou First People Hospital, Guangzhou, People’s Republic of China; 8Department of Integrated Therapy in Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 9Department of Breast Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 10Department of Breast Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 11Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 12Department of Breast Oncology, General Hospital of PLA Guangzhou Military Area, Guangzhou, People’s Republic of China; 13Department of Breast Oncology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 14Department of Breast Oncology, Haikou People’s Hospital, Haikou, People’s Republic of China; 15Department of Breast Oncology, Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 16Department of Good Clinical Practice, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 17Department of Medical Oncology, Foshan First People’s Hospital, Foshan, People’s Republic of China; 18Department of Radiotherapy, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 19Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong; 20Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Rangsit University, Rajavithi Hospital, Bangkok, Thailand; 21The Department of Breast Surgery, New-wa-kai Oikawa Hospital, Fukuoka, Japan; 22State Key Laboratory of Traditional Chinese Medicine Syndrome/Departments of Gynecologic Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 23State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian-Jun Chen, 55N, Neihuanxi Road, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel +86 1868883505, Email cqj55@163.com Zhong-Yu Yuan, 651 Dongfeng Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86 13798027658, Email yuanzhy@sysucc.org.cnPurpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.Keywords: adjuvant chemotherapy, capecitabine, SYSUCC-001, triple-negative breast cancer, TNBC

You Zhou,1,&ast; Jing Dong,1,&ast; Hao Lu2 1Department of Cardiology, Shanghai Geriatric Medical Center, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200032, People’s Republic of China; 2Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Lu, Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64041990 ext 2728, Email lu.hao@zs-hospital.sh.cnBackground: The elderly patients are at increased high risk of myocardial injury and mortality after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aims to investigate the prevalence, predictors and prognostic implications of myocardial injury in the elderly patients with SARS-CoV-2 infection.Methods: Patients aged over 65 years were consecutively recruited between April to May, 2022. Myocardial injury was assessed using the high-sensitivity cardiac troponin T (hs-cTnT) assay. The primary endpoint was in-hospital mortality.Results: A total of 347 patients were recruited with a median age of 81 years. 45.8% were male and 18 (5.2%) deceased before discharge. Myocardial injury (hs-cTnT over 99% upper reference limit [URL]) was detected in 202 (58.2%) of patients. Predictors of myocardial injury included age (per 5-year increase), hypertension, vaccination, creatine, and neutrophil-to-lymphocyte ratio. hs-cTnT over 3 × URL was independently correlated with in-hospital mortality (adjusted odds ratio [adOR], 13.21; 95% confidence interval [CI], 2.11– 87.1; p = 0.005) in comparison to hs-cTnT > URL (adOR, 0.66; 95% CI, 0.09– 5.92; p = 0.680).Conclusion: Myocardial injury was a common phenomenon and prognostic predictor in elder patients after SARS-CoV-2 infection. Higher threshold of myocardial injury may be considered to improve risk stratification.Keywords: COVID-19, SARS-CoV-2, myocardial injury, mortality

Yanxu Zhong,1,2 Huan Lu,3 Xiaodan Lu,4 Zhini He,4 Yuyan Jiang,1 Jie Chen,1 Tippawan Liabsuetrakul2 1Food Safety Monitoring and Evaluation Department, Guangxi Zhuang Autonomous Region Centre for Disease Control and Prevention, Nanning, Guangxi Region, 530000, People’s Republic of China; 2Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand; 3Infectious Diseases Department, the Fourth People’s Hospital of Nanning, Nanning, Guangxi Region, 530000, People’s Republic of China; 4Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of ChinaCorrespondence: Tippawan Liabsuetrakul, Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, 90110, Thailand, Tel +66 74 451165, Fax +66 74 281166, Email tippawan.l@psu.ac.thBackground: Cooking oil and dietary foods are easily contaminated by aflatoxins (AFs) in Guangxi, China where low birth weight and preterm birth were prevalent. However, there are no data on AF exposure in pregnant women or their impact on newborn birth outcomes. This study aims to measure the levels and correlations of AFs in cooking oil, estimated dietary intake (EDI) of AFs in dietary foods, and serum AFB1 albumin adducts (AFB1-alb) with newborn birthweight and gestational age at birth.Methods: A prospective study was conducted among 126 pregnant women in Guangxi, China. All recruited women were interviewed for demographic data and behavior and obstetric information and then followed up until giving birth. AF measurements were obtained from cooking oil, dietary foods, maternal serum, and cord blood and the correlations of AF levels with newborn birthweight and gestational age at birth were tested using correlation analysis.Results: The median EDI of AFs in cooking oil was 2.61 ng/kg.bw/day and in dietary foods 2.95 ng/kg.bw/day. High positive correlations among EDI of aflatoxin B1 (AFB1) from cooking oil and dietary foods were found (r > 0.7). Low positive correlations of AFB1-alb in maternal serum and cord blood and both EDI of AFB1 in both cooking oil and dietary foods were shown (r &ap;0.3). Significant correlations between AF levels in both cooking oil and dietary foods with birth weight were found, but very low negative correlations (r = - 0.244 ~ − 0.285). AFB1 levels in foods, maternal serum and cord blood levels were high in pregnant women with newborn low birth weight and preterm birth.Conclusion: The EDIs of AFB1 from both cooking oil and dietary foods were significantly correlated with AFB1-alb in maternal serum and cord blood. Negative correlations of AFs from cooking oils and foods with newborn birth weight should be paid more attention.Keywords: aflatoxins, EDI, birthweight, gestational age at birth, AFB1 albumin adducts

Kun Li,1 Dongsheng Han,2 Ahmad Alhaskawi,3 Tingting Liu,1 Xiaojuan Wang,4 Wu Yang,1 Hui Lu,3 Xueling Fang1 1Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Laboratory Medicine, the First Affiliated Hospital, Zhejiang University school of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Xueling Fang, Department of Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, People’s Republic of China, Fax +86 571-87236838, Email 1191012@zju.edu.cn Hui Lu, Department of Orthopaedics, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79, Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, People’s Republic of China, Fax +86 571-87236121, Email HuiLu@zju.edu.cnBackground: Chromobacterium violaceum (C. violaceum) is a Gram-negative bacterium capable of causing severe infections in both humans and specific animals. Despite its infrequency, C. violaceum infections exhibit a notably high mortality rate. The timely and precise detection of this pathogen stands as a critical factor in achieving effective diagnosis and treatment. Traditional diagnostic approaches possess limitations, particularly in terms of their time-consuming nature and the range of pathogens they can identify. Metagenomic next-generation sequencing (mNGS) testing has emerged as a highly promising diagnostic tool for infectious diseases.Methods: Within this case report, we present a patient who developed a C. violaceum infection subsequent to a lower limb infection, leading to the progression of sepsis, a liver abscess, septic shock, multi-organ dysfunction, and altered mental status. Samples of the patient’s blood and tissue from the lower limb skin are collected, and the infection is swiftly diagnosed through mNGS, allowing for the immediate initiation of suitable treatment.Results: The mNGS results revealed the patient’s infection with C. violaceum. Subsequent conventional bacterial culture results were concordant with the mNGS findings. Following comprehensive management measures, including prompt and effective anti-infective treatment, the patient achieved cure and was successfully discharged.Conclusion: This case underscores the significance of employing advanced diagnostic methodologies like mNGS for the early detection of uncommon pathogens such as C. violaceum. The expedited diagnosis and timely intervention hold the potential to substantially enhance patient outcomes in cases of severe infections instigated by this bacterium.Keywords: chromobacterium violaceum, sepsis, infection, hepatapostema, liver, liver abscess, metagenomic next-generation sequencing

Jun Zhang,1 Yu Wang,1 Wei Zhang,1 Linglong Cai,1 Jianglong Feng,2 Yiwei Zhu,1 Hongguang Lu1 1Department of Dermatology, the Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Pathology, the Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of ChinaCorrespondence: Hongguang Lu, Department of Dermatology, the Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, Guizhou, 550001, People’s Republic of China, Tel +86-13885144269, Fax +86-851-86820346, Email hongguanglu@hotmail.com; luhongguang@gmc.edu.cnPurpose: The rising incidence and mortality associated with cutaneous malignant tumours highlight the importance of early diagnosis of these tumors. In clinical practice, these tumors are often misdiagnosed as benign skin lesions such as melanocytic nevi (MN) and seborrheic keratosis (SK) because of their similar morphologic features. The incidence and clinicopathological subtypes of cutaneous malignancies in East Asia populations significantly differ from those in fair-skinned groups. However, studies on misdiagnoses in Eastern countries are lacking. Therefore, this study focused on the clinical and pathological features of cutaneous malignant tumors misdiagnosed as MN or SK in a Chinese population.Patients and Methods: A total of 4592 samples clinically diagnosed as MN (n = 3503) or SK (n = 1089) from July 2014 to June 2022 were collected and evaluated retrospectively. The clinical and pathological data were analyzed to identify associated factors.Results: Pathological assessments showed that 2.5% (86/3503) of the specimens clinically diagnosed as MN were malignancies, predominantly basal cell carcinoma (BCC, 84.9%, 73/86), followed by malignant melanoma (MM, 8.1%, 7/86) and squamous cell carcinoma (SCC, 7.0%, 6/86). Similarly, 5.7% (62/1089) of the specimens clinically diagnosed as SK were malignant tumors, of which BCC (50.0%, 31/62) was the most common, followed by SCC (41.9%, 26/62) and MM (8.1%, 5/62). In both types of specimens, advanced age and facial lesions were risk factors for malignancy misdiagnosis. The malignancy rate, mean age, and proportion of SCC in the specimens clinically diagnosed as SK were higher than those in the specimens clinically diagnosed as MN. Dermoscopy significantly reduced the rate of misdiagnosis of these tumors as MN or SK.Conclusion: In China, cutaneous malignant tumors misdiagnosed as MN or SK are not uncommon in clinical practice, and active introduction of noninvasive diagnostic techniques is essential to distinguish them.Keywords: malignant melanoma, squamous cell carcinoma, basal cell carcinoma, skin benign neoplasms, dermoscopy, China

Benjie Xu,&ast; Jiahao Zhu,&ast; Ren Wang, Xiangyi Pang, Xin Wang, Jie Lian, Haibo Lu Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Lian; Haibo Lu, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 451 85718309, Email lianjie@hrbmu.edu.cn; luhaibo@hrbmu.edu.cnPurpose: The Nutritional Prognostic Score (NPS) is a composite indicator that effectively reflects the preoperative nutritional and inflammation status of patients. Its prognostic value has been extensively confirmed in various types of tumors. Our study aims to investigate the clinical implications of the NPS in the postoperative patients with cholangiocarcinoma (CCA).Patients and Methods: Data on clinicopathological characteristics were collected from CCA patients who underwent radical surgery between 2014 and 2019 at Harbin Medical University Cancer Hospital. NPS was calculated using relevant indicators to categorize the patients, and association of NPS with clinicopathological characteristics and survival outcomes were analyzed. To assess differences in survival rates between different groups, we utilized the Kaplan-Meier method. Independent prognostic risk factors were identified by Cox regression analysis. A CONomogram was created, and its accuracy in survival prediction was evaluated using receiver operating characteristic (ROC) curves. Independent verification was conducted in the validation group.Results: For this study, a cohort of 232 patients was enlisted and subsequently divided into training group (N=162) and validation group (N=70). An evident correlation was detected between NPS and preoperative malnutrition. Patients with higher NPS exhibited a worse overall survival (OS), with 5-year OS rates of 79.1%, 33.1%, and 10.6%. Multivariate analysis revealed that NPS was an independent risk factor for OS in resected CCA patients (P< 0.001). The NPS-based Nomogram was developed to accurately assess the risk of patients.Conclusion: The NPS was identified as a significant risk factor that impacts the prognosis of patients with resected CCA. In order to improve prognosis management, the NPS-based Nomogram has been demonstrated to be a precise and efficient tool.Keywords: Naples prognostic score, cholangiocarcinoma, nomogram, overall survival, real-world experience

Baofeng Wang,1,2,&ast; Jiang Wang,2,&ast; Tongyu Sun,2 Yilin Ding,2 Shasha Li,3 Hengxiao Lu2 1School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China; 3Clinic, Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hengxiao Lu, Department of Thoracic Surgery, Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China, Email luhengxiao1000@126.comPurpose: Lu’s approach for video-assisted thoracoscopic surgery (LVATS), which derives from Uniportal Video-Assisted Thoracoscopic Surgery(UVATS), is a novel surgical approach for VATS and carries out micro-innovation for lung cancer resection. The objective of this study is to elucidate the safety, feasibility, and efficacy of this novel surgical approach.Patients and Methods: The clinical data of patients with non-small cell lung cancer (NSCLC) who underwent a curative thoracoscopic lobectomy between Mar. 2021 and Mar. 2022, were retrospectively collected and analyzed. Patients were divided into the LVATS group and the UVATS group. Propensity score matching (PSM) was used to reduce selection bias and create two comparable groups. Perioperative variables were compared, and a p-value < 0.05 was deemed statistically significant.Results: A total of 182 patients were identified, among whom 86 patients underwent LVATS and 96 UVATS. Propensity matching produced 62 pairs in this retrospective study. There were no deaths during perioperative period. Patients in the LVATS group experienced a shorter operation time (88 (75, 106) VS 122 (97, 144) min, P < 0.001), less intraoperative blood loss (20 (20, 30) VS 25 (20, 50) mL, P = 0.021), shorten incision length (2.50 (2.50, 2.50) VS 3.00 (3.00, 3.50) cm, P < 0.001), and more drainage volume (460 (310, 660) VS 345 (225, 600) mL, P = 0.041) than patients in the UVATS group. There was not significant difference in the lymph node stations dissected (5 (4, 5) VS 5 (4, 5), P = 0.436), drainage duration (3 (3, 4) VS 3 (3, 4) days, P =0.743), length of postoperative hospital stay (4 (4, 5) VS 4 (4, 6) days, P = 0.608), VAS on the POD1 (4 (4, 4) VS 4 (4, 4), P=0.058) and POD3 (3 (3, 4) VS 4 (3, 4), P=0.219), and incidence of postoperative complications (P=0.521) between the two groups.Conclusion: Lu’s approach for video-assisted thoracoscopic lobectomy is safe and feasible, potentially reducing surgery time, incision length, and intraoperative blood loss.Keywords: non-small cell lung cancer, uniportal video-assisted thoracoscopic surgery, Lu’s approach for VATS, lobectomy

Xuejiao Liao,1,&ast; Yuan Guan,1,2,&ast; Zixun Lin,1 Qingrong Tang,3 Zhenghua Ma,1 Shuting Wu,1 Xiaobin Wang,1 Jingke Dong,1 Liping Zhang,1 Jiayu Deng,1 Zhonghui Liao,1,4 Sumei Yang,1,4 Cheng Wang,1,4 Shuo Song,1 Hongyang Yi,1 Song Wu,5 Tetsuya Asakawa,6 Hongzhou Lu1 1Institute for Hepatology, National Clinical Research Center for Infectious Disease, The Third People’s Hospital of Shenzhen, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 2Department of Epidemiology, School of Public Health Fudan University, Shanghai, People’s Republic of China; 3The First Hospital of Changsha, Infectious Diseases Department, Changsha, People’s Republic of China; 4School of Public Health, Bengbu Medical College, Bengbu, People’s Republic of China; 5Department of Central Laboratory, South China Hospital, Medical School, Shenzhen University, Shenzhen, People’s Republic of China; 6Institute of Neurology, National Clinical Research Center for Infectious Diseases, the Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongzhou Lu, Institute for Hepatology, National Clinical Research Center for Infectious Disease, The Third People’s Hospital of Shenzhen, The Second Hospital Affiliated with the School of Medicine, Southern University of Science and Technology, No. 29 Bulan Road, Long Gang District, Shenzhen, Guangdong, 518112, People’s Republic of China, Email luhongzhou@fudan.edu.cn Tetsuya Asakawa, Institute of Neurology, National Clinical Research Center for Infectious Diseases, the Third People’s Hospital of Shenzhen, No. 29 Buji Bulan Road, Shenzhen, Guangdong, 518112, People’s Republic of China, Email asakawat1971@gmail.comPurpose: The purpose was to review relevant clinical data and formulate recommendations supporting the use of saline as a simple rinse for an early reassuring intervention to reduce the occurrence of re-positive COVID-19 patients.Methods: We conducted a single-centre retrospective cohort study, which enrolled patients with confirmed re-testing positive COVID-19 during 7– 60 days after discharge from Third People’s Hospital of Shenzhen. By one-to-two propensity score matching for age and sex, the control group of those not re-testing positive during the same period served as matched control.Results: A total of 223 patients were included in our study, 94 in re-positive group and 129 in non-re-positive group. The result shows that the rates of nasal douche treatment in the non-re-positive group were considerably higher than that of the re-positive group. And the Ct value of nasal douche group increased faster than that of non-nasal douche group after the Ct value reaching ≥ 35. Further analysis revealed that the higher the Ct value at the time of readmission, the shorter the time of average Ct values to reach ≥ 35.Conclusion: These findings suggest that nasal douche is beneficial to shorten the time of virus nucleic acid turning negative, thereby reducing the incidence of re-positive. The prevention and control of epidemics focuses on re-positive patients with Ct values < 35.Keywords: COVID-19, nasal douche, re-positive, RT-PCR

Xiayan Xu,1– 3,&ast; Yun Xie,2– 4,&ast; Xia Gu,5– 7,&ast; Yang Zhou,2,3 Yu Kang,2,3,8 Jin Liu,2,3 Wenguang Lai,2– 4 Hongyu Lu,2,3 Shiqun Chen,2,3 Jun-yan Xu,2,3,9 Feng Lin,10 Yong Liu1– 3 1School of Medicine, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4School of Biology and Biological Engineering South China University of Technology, Guangzhou, 510006, People’s Republic of China; 5Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 6The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang, 150086, People’s Republic of China; 7Cardiovascular Imaging Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 8Shantou University Medical College, Shantou, 515041, People’s Republic of China; 9Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, People’s Republic of China; 10Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Lin, Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China, Email linfeng3085@163.com Yong Liu, South China University of Technology, No. 382, Waihuan East Road, University City, Panyu District, Guangzhou, Guangdong Province, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email liuyong@gdph.org.cnBackground: Blood glucose levels significantly affect the clinical prognosis of patients with coronary artery disease (CAD), and systemic immune inflammation is a common risk factor for both CAD and diabetes. However, the relationship between immune inflammation levels and poor prognosis in patients with CAD with different glucose metabolic statuses remains unclear.Methods: Between January 2007 and December 2020, we recruited 84,645 patients with CAD. The systemic immune inflammation index (SII) was used to comprehensively reflect the immune and inflammatory levels of patients and was calculated using the following formula: neutrophils × platelets/lymphocytes. The patients were classified into nine groups according to their glucose metabolism status (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]). Cox regression models and competing risk Fine and Gray models were used to investigate the association between SII and clinical outcomes.Results: During the follow-up period, 12,578 patients died, including 5857 cardiovascular-related and 1251 cancer-related deaths. The risk of all-cause and cause-specific mortality increased with increasing SII tertiles in CAD patients with NGR, pre-DM, and DM. When considering glucose metabolism status, the multivariate cox regression revealed that CAD patients with DM and SII-H levels had the highest risk of all-cause mortality (1.69 [1.56– 1.83]), cardiovascular mortality (2.29 [2.02– 2.59]), and cancer mortality (1.29 [1.01– 1.66]). Moreover, incorporating the SII into traditional risk factor models significantly improved the C-index for predicting all-cause and cardiovascular mortality.Conclusion: Systemic immune inflammation levels on admission were correlated with a higher risk of all-cause and cause-specific mortality in patients with CAD, particularly in those with DM.Keywords: systemic immune inflammation index, coronary artery disease, type 2 diabetes, prognosis, mortality

You Zhou,&ast; Lixiang Deng,&ast; Zhe Wang,&ast; Yiqing Hu, Zhangwei Chen, Hao Lu, Juying Qian, Junbo Ge Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Lu, Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64041990, Email lu.hao@zs-hospital.sh.cn Juying Qian, Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University; National Clinical Research Center for Interventional Medicine; Shanghai Clinical Research Center for Interventional Medicine, 1609 Xietu Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64041990 ext 2728, Email qian.juying@zs-hospital.sh.cnBackground: The tip-in technique, which involves advancing an antegrade microcatheter cross the lesion over a retrograde guidewire, is an elaborated maneuver in the recanalization of coronary chronic total occlusion (CTO). We seek to assess the efficiency of a guide extension catheter-facilitated tip-in technique in comparison to the traditional retrograde approach, which is accomplished by an externalization wire.Methods: Thirty-three CTO patients successfully revascularized using guide extension catheter-facilitated “tip-in” were included and matched with another 33 patients by J-CTO score and operators, whose CTO was recanalized using an externalized wire. The manipulation time from the first retrograde wire entering the antegrade guide to the first antegrade balloon inflation in the occlusion was calculated.Results: Compared with the wire-externalization group, the manipulation time in the tip-in group was significantly shortened [389s; interquartile range (IQR), 272– 478 vs 706s; IQR, 560– 914; p < 0.001]. There was a trend in decreasing total operation time and radiation dose, but it did not reach statistical significance.Conclusion: Guide extension catheter-facilitated tip-in is an efficient method to achieve the recanalization of CTO in a retrograde way, which would be pivotal when the retrograde microcatheter could not be advanced into the antegrade guide catheter.Keywords: chronic total occlusion, extension guide catheter, tip-in, retrograde

Xuanxia Wu,1,&ast; Mingming Zhou,2,&ast; Juan Bu,1 Yuwen Chang,2 Yeledan Mahan,1 Huanhuan Lu,2 Yanmin Zhang,3 Xiaoling Zhang,1 Zhaoxia Wang,1 Ling Zhou1 1Medical Research and Transformation Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Health Management Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 3Scientific Research and Education Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhou, Medical Research and Transformation Center, People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86-13609959575, Email zlrmyy@sina.comPurpose: In this study, the aim was to investigate the prevalence and risk factors of hyperuricemia (HUA) in the urban health checkup population in Urumqi, Xinjiang, and thus provide clues for the prevention of HUA.Methods: People who attended medical examinations from May 2021 to June 2022 at a hospital in Urumqi, Xinjiang, were selected for evaluation based on their general information, physical examination results, and laboratory test results. The chi-square test was used to determine whether there was a difference in the prevalence of HUA among participants with different characteristics. Using logistic regression analyses, risk factors for HUA were identified.Results: There were 8722 participants diagnosed with HUA, with an overall prevalence of 26.96%. The prevalence in men was 37.72%, significantly higher than in women (13.29%). Participants were characterized by a multiethnic composition, with Han (28.61%), Hui (27.88%) and Manchu (38.46%) being the three ethnicities with the highest prevalence. According to logistic regression analyses, HUA was associated with age, ethnicity, residence, marital status, body mass index (BMI), diastolic blood pressure (DBP), fasting blood glucose (FPG), triglyceride glucose (TyG) index, abdominal obesity, and dyslipidemia differently in males and females.Conclusion: The prevalence of HUA was high in the urban health checkup population in Urumqi, Xinjiang, particularly among men and youth. The early intervention for HUA should be enhanced to reduce the risk of cardiovascular disease and other related conditions.Keywords: hyperuricemia, ethnicity, prevalence, risk factors, epidemiology

Lu Hua,1,2,&ast; Kaiyuan Sha,1,2,&ast; HongCheng Lu,1,2 Ying Han,1,2 Cehua Ou,1,2 Jiang-Lin Wang,1 Yue Zhang1,2 1Department of Pain Management, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou Southwest Medical University, Luzhou, Sichuan Province 646000 People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiang-Lin Wang; Yue Zhang, Department of Pain Management, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China, Email jianglin523@swmu.edu.cn; zhangyue0518@swmu.edu.cnPurpose: To explore the therapeutic effect of C2 dorsal root ganglion pulsed radiofrequency (PRF) combined with stellate ganglion block (SGB) in patients with cervicogenic headache (CEH).Patients and Methods: We retrospectively reviewed 90 patients diagnosed with CEH who were admitted to our hospital between May 2019 and May 2022. All patients were divided into three groups (n = 30 each) according to the actual treatment method used: ultrasound-guided SGB, ultrasound-guided C2 dorsal root ganglion PRF treatment, and ultrasound-guided C2 dorsal root ganglion PRF combined with SGB treatment. Patients’ pain intensity, sleep, and mood changes were assessed by statistically analyzing their pain visual analog scale (VAS), Pittsburgh Sleep Quality Inventory (PSQI), and short-form McGill Pain Questionnaire affective item scores before and after treatment.Results: The post-treatment VAS, PSQI, and McGill scores were significantly decreased in all patients (P < 0.05), and all three scores in ultrasound-guided C2 dorsal root ganglion PRF combined with SGB were lower than those in ultrasound-guided SGB alone and ultrasound-guided C2 dorsal root ganglion PRF alone (P < 0.05).Conclusion: The use of ultrasound-guided C2 dorsal root ganglion PRF combined with SGB in patients with CHE is effective in alleviating pain and improving sleep, and deserves to be replicated in the clinic.Keywords: cervicogenic headache, C2 dorsal root ganglion, pulsed radiofrequency, stellate ganglion block

Songsong Shi,&ast; Rong Liu,&ast; Haiying Yu,&ast; Long Xiang, Hua Lu Department of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Lu, Department of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of China, Tel +86 18930830609, Email luhua@scmc.com.cnBackground: The omicron pandemic in Shanghai has created unprecedented challenges for pediatric medical institutions, and the work of pediatric nurses has changed rapidly due to the introduction of parent-child treatment. This study aimed to explore the experiences of pediatric nurses in the parent-child isolation unit of COVID-19-designated hospitals and provide a basis for developing feasible interventions as the next step.Methods: Using phenomenological research methods, 12 nurses working in the parent-child isolation unit of Shanghai Children’s Medical Center affiliated with Shanghai Jiao Tong University School of Medicine from April 1, 2022, to June 15, 2022, were selected by purposive sampling. Semi-structured interviews and data analysis were conducted using Colaizzi’s 7-step analysis.Results: Data analysis revealed three major themes and 11 subthemes. The main themes were “risk factors”, “protection factors”, and “resilience strategies”. The sub-themes were “challenge of caring for both adults and children simultaneously”, “lack of adult expertise leads to inadequate coping skills”, “change in the care population increased communication difficulties”, “physical and psychological distress”, “social support”, “social recognition”, “awareness of responsibilities and roles”, “team coming together”, “hunger for knowledge”, “health promotion”, and “psychological adjustment strategies”.Conclusion: Hospital managers should optimize hospital management strategies, pay attention to multi-departmental and multidisciplinary team cooperation, reduce the burden on pediatric nurses, improve the work and rest environment, mobilize the hospital support system, and maintain nurse’s physical and mental health, establish a warm parent-child isolation unit encourages nurses to listen to the patients’ voices and adopt diversified communication methods, and strengthen the publicity of the nursing profession, improve social support and recognition, and enhance the sense of self-worth and mission.Keywords: pediatric nurse, COVID-19, parent-child unit, qualitative study

Xin Deng,1,&ast; Xin Zhong,1,&ast; Bin Nie,2 Ruochen Wang,1 Hao Lu,1 Lei Ge,1 Juying Qian,1 Jianying Ma,1 Junbo Ge1 1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, National Clinical Research Center for Interventional Medicine, Shanghai, People’s Republic of China; 2The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junbo Ge; Jianying Ma, Email jbge@zs-hospital.sh.cn; ma.jianying@zs-hospital.sh.cnBackground: The septal collateral channel (CC) is the preferred channel in retrograde percutaneous coronary intervention (PCI) for chronic total occlusion (CTO). However, reports on the utilization of the ipsilateral septal CC are limited.Objective: To evaluate the feasibility and safety of the ipsilateral septal CC in retrograde CTO PCI.Methods: Twenty-five patients with successful wire CC tracking via the ipsilateral septal CC in retrograde CTO PCI were retrospectively analyzed. All procedures were performed by experienced CTO operators. Procedures were divided into the left descending coronary artery (LAD)-septal-LAD group and the LAD-septal-left circumflex coronary artery (LCX) group. Procedural complications and in-hospital outcomes were ascertained.Results: Both groups were similar with respect to risk factors and angiographic characteristics of the CTO, except for the collateral tortuosity (86.7% vs 20%, p=0.002). The success rate of microcatheter CC tracking was 96%. Both technical success and procedural success rates were 92%. Procedural complications were found in one case (septal perforation, 4%), which happened in the LAD-septal-LAD group (p=0.250). One postoperative adverse event (Q-wave myocardial infarction, 4%) was observed before discharge.Conclusion: The retrograde approach via the ipsilateral septal CC was feasible, with high success rates and acceptable complications, in the hands of experienced operators.Keywords: percutaneous coronary interventions, chronic total occlusions, ipsilateral septal collateral, left coronary artery

Limin Tang,1 Min Sha,2 Ting Guo,2 Huimin Lu,2 Jingyu Qian,2 Qixiang Shao,1 Jun Ye2 1Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 2Department of Central Laboratory, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, People’s Republic of ChinaCorrespondence: Jun Ye, Department of Central Laboratory, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, 399 Hailing Road, Taizhou, Jiangsu, 225300, People’s Republic of China, Tel +86-13625171902, Email m13625171902@163.comPurpose: The roles of T cell immunoreceptor with Ig and ITIM domains (TIGIT) in the diagnosis of primary breast cancer (PBC) are still unclear. This study was designed to investigate the expression of TIGIT in PBC patients, with an aim to analyze its diagnostic value in PBC.Patients and Methods: We first explore the expression of TIGIT in cancer patients based on TCGA database, and then we analyzed its correlation with clinicopathological features. Afterwards, we compared the protein and mRNA expressions of TIGIT in two BC cell lines (MCF-7 and MDA-MB-231) and normal breast epithelial cell line (MCF-10A). Subsequently, 56 PBC female patients admitted to the Taizhou People’s Hospital from October 2018 to June 2021 were included in this study. Flow cytometry was used to detect TIGIT level on peripheral blood CD3+ T cells of PBC patients and healthy controls. TIGIT expression in PBC tissues was detected by immunohistochemistry (IHC) and immunofluorescence staining.Results: TCGA database showed that compared with adjacent tissues, TIGIT was significantly upregulated in tumor tissues. High TIGIT expression was positively correlated with tumor stage and negatively correlated with recurrence free survival (RFS) and overall survival (OS). TIGIT level in BC cell lines, peripheral blood and tumor tissues of PBC patients was significantly higher than that of control (P < 0.05). TIGIT level was correlated with age (P < 0.05), rather than tumor size, pathological type, lymph node metastasis, ER, PR, HER-2, and P53. ROC curve showed that the optimal critical value of peripheral blood TIGIT for BC screening was 23.38%. Postoperative TIGIT level in peripheral blood was significantly decreased compared to the preoperative TIGIT level (P < 0.05).Conclusion: TIGIT was upregulated in PBC and was correlated with age. It may be a potential target for the diagnosis and immunotherapy of PBC.Keywords: TIGIT, primary breast cancer, immune checkpoint, tumor immunity, bioinformatics analysis

Hongyu Lu,1,2,&ast; Yun Xie,1,3,&ast; Ziyou Zhou,1,4,&ast; Peijian Hong,5,&ast; Jiyan Chen1,2 1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 4School of medicine, South China University of Technology, Guangzhou, People’s Republic of China; 5Department of Histology and Embryology School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiyan Chen, Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China, Tel + (86)02083827812-10528, Fax + (86)02083851483, Email chen-jiyan@163.comPurpose: This study aimed to investigate the role of ferroptosis in dilated cardiomyopathy (DCM) and to identify new targets for treatment and diagnosis of DCM.Methods: GSE116250 and GSE145154 were downloaded from the Gene Expression Omnibus database. Unsupervised consensus clustering of DCM patients was used to confirm the impact of ferroptosis. Ferroptosis-related hub genes were identified by WGCNA and single cell sequencing analyses. Finally, we established a DCM mouse model via injection of Doxorubicin to verify the expression level of OTUD1 and colocalization between cell markers and OTUD1 in DCM mouse heart.Results: A total of 13 ferroptosis-related differentially expressed genes (DEGs) were identified. The DCM patients were divided into two clusters according to the expression of 13 DEGs. The DCM patients in different clusters showed discrepancies in immune infiltration. Four hub genes were further identified by WGCNA analysis. Single cell data analysis revealed that OTUD1 may regulate B cells and DC cells and then participate in immune infiltration discrepancy. The upregulation of OTUD1 and the colocalization of OTUD1 with CD19 (B cell maker) and CD11c (DCs markers) markers were confirmed in DCM mouse hearts.Conclusion: Ferroptosis and the immune microenvironment are closely associated with DCM, and OTUD1 may play an important role through B cells and DCs.Keywords: dilated cardiomyopathy, ferroptosis, immune infiltrations, single cell sequencing

Yayun Qian,1 Yuexing Gu,2 Jialin Deng,3 Zhaoying Cai,3 Yang Wang,3 Ruoyu Zhou,3 Dongxu Zhu,3 Hongmei Lu,4 Zheng Wang1 1Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, People’s Republic of China; 2Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, People’s Republic of China; 3Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, People’s Republic of China; 4Department of Pathology, Yangzhou Maternal and Child Health Hospital, Yangzhou, People’s Republic of ChinaCorrespondence: Zheng Wang; Yayun Qian, Email yzdxfsyywz@163.com; yyqian@yzu.edu.cnIntroduction: As the most common malignant tumor in the world, the prognosis of patients with advanced lung cancer remains poor even after treatment. There are many prognostic marker assays available, but there is still more room for the development of high-throughput and sensitive detection of circulating tumor DNA (ctDNA). Surface-enhanced Raman spectroscopy (SERS), a spectroscopic detection method that has received wide attention in recent years, can achieve exponential amplification of Raman signals by using different metallic nanomaterials. Integrating SERS with signal amplification strategy into the microfluidic chip and applying it to ctDNA detection is expected to be an effective tool for the prognosis of lung cancer treatment effect in the future.Methods: To construct a high-throughput SERS microfluidic chip integrated with enzyme-assisted signal amplification (EASA) and catalytic hairpin self-assembly (CHA) signal amplification strategies, using hpDNA-functionalized Au nanocone arrays (AuNCAs) as capture substrates and cisplatin-treated lung cancer mice to simulate the detection environment for sensitive detection of ctDNA in serum of lung cancer patients after treatment.Results: The SERS microfluidic chip constructed by this scheme, with two reaction zones, can simultaneously and sensitively detect the concentrations of four prognostic ctDNAs in the serum of three lung cancer patients with a limit of detection (LOD) as low as the aM level. The results of the ELISA assay are consistent with this scheme, and its accuracy is guaranteed.Conclusion: This high-throughput SERS microfluidic chip has high sensitivity and specificity in the detection of ctDNA. This could be a potential tool for prognostic assessment of lung cancer treatment efficacy in future clinical applications.Keywords: circulating tumor DNA, surface-enhanced Raman scattering, lung cancer, AuNCAs, prognostic assessment

Pingyi Wang,1– 3 Hongyan Lu,1– 3 Hao Rong,1– 3 Yuhe Wang,1– 4 Li Wang,1– 3 Xue He,1– 3 Dongya Yuan,1– 3 Yongjun He,1– 3 Tianbo Jin1– 3 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 2Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 3School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 4Department of Clinical Laboratory, the Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of ChinaCorrespondence: Tianbo Jin; Yongjun He, Tel +86-18681940990 ; +86-18691008772, Email jintb@xzmu.edu.cn; 545139647@qq.comBackground: High altitude pulmonary edema (HAPE) is still the most common fatal disease at high altitudes. DNA methylation proceeds with an important role in HAPE progression. This study was designed to investigate the association between CYP39A1 methylation and HAPE.Methods: Peripheral blood samples were enrolled from 106 participants (53 HAPE patients and 53 healthy subjects) to study the association of CYP39A1 methylation with HAPE. DNA methylation site in the promoter region of CYP39A1 was detected by Sequenom MassARRAY EpiTYPER platform.Results: Probability analysis showed that the methylation probabilities of CYP39A1_1_CpG_5 and CYP39A1_3_CpG_21 are significant differences between the cases and controls (p< 0.05). The methylation level analysis indicated that CYP39A1_1_CpG_2.3.4, CYP39A1_5_CpG_6.7, and CYP39A1_5_CpG_9.10 were higher methylation in HAPE compared to the controls (p< 0.05). CYP39A1_3_CpG_21 and CYP39A1_4_CpG_3 exhibited a lower methylation level in HAPE than that in the controls (p< 0.05). The association analysis given that CYP39A1_1_CpG_2.3.4 (OR 2.56, p= 0.035), CYP39A1_5_CpG_6.7 (OR 3.99, p= 0.003), CYP39A1_5_CpG_9.10 (OR 3.99, p= 0.003), CYP39A1_5_CpG_16.17.18 (OR 2.53, p= 0.033), and CYP39A1_5_CpG_20 (OR 3.05, p= 0.031) are associated with an increased risk of HAPE. Whereas CYP39A1_1_CpG_5 (OR 0.33, p= 0.016) and CYP39A1_3_CpG_21 (OR 0.18, p= 0.005) have a protective role in HAPE. Besides, age-stratification analysis showed that CYP39A1_1_CpG_5 (OR 0.16, p= 0.014) and CYP39A1_3_CpG_21 (OR 0.08, p= 0.023) had a protective impact on HAPE in people aged ≤ 32 years. CYP39A1_5_CpG_6.7 (OR 6.70, p= 0.008) and CYP39A1_5_CpG_9.10 (OR 6.70, p= 0.008) were related to an increased susceptibility to HAPE aged > 32 years. Moreover, the diagnostic value of CYP39A1_3_CpG_21 (AUC = 0.712, p< 0.001) was significantly better than other CpG sites.Conclusion: The methylation level of CYP39A1 was associated with a risk of HAPE in the Chinese population, which provided new perspective for preventing and diagnosing of HAPE.Keywords: HAPE, DNA methylation, CYP39A1, CpG, the Chinese population

Yuqi Zhou,1,&ast; Yuanmeng Yang,2,&ast; Rongpu Liu,1,&ast; Qin Zhou,3 Haixia Lu,2 Wenjie Zhang1 1Department of Prosthodontics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Preventive Dentistry, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjie Zhang, Department of Prosthodontics, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People’s Republic of China, Email zhangwenjie586@126.com Haixia Lu, Department of Preventive Dentistry, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People’s Republic of China, Email ritalu0225@hotmail.comAbstract: Oral diseases represent one of the most prevalent diseases globally and are associated with serious health and economic burdens, greatly altering the quality of life of affected individuals. Various biomaterials play important roles in the treatment of oral diseases. To some extent, the development of biomaterials has promoted progress in clinically available oral medicines. Hydrogels have unique tunable advantages that make them useful in the next generation of regenerative strategies and have been widely applied in both oral soft and hard tissues repair. However, most hydrogels lack self-adhesive properties, which may result in low repair efficacy. Polydopamine (PDA), the primary adhesive component, has attracted increasing attention in recent years. PDA-modified hydrogels exhibit reliable and suitable adherence to tissues and easily integrate into tissues to promote repair efficiency. This paper reviews the latest research progress on PDA hydrogels and elaborates on the mechanism of the reaction between PDA functional groups and hydrogels, and summarizes the biological properties and the applications of PDA hydrogels in the prevention and treatment of the field of oral diseases. It is also proposed that in future research we should simulate the complex microenvironment of the oral cavity as much as possible, coordinate and plan various biological events rationally, and realize the translation from scientific research to clinical practice.Graphical Abstract: Keywords: polydopamine, hydrogel, catechol groups, adhesive properties, prevention and treatment, oral diseases

Haoran Lu,1,&ast; Rou Zhao,2,&ast; Qianqian Qin,3 Liyong Tang,1 Guodong Ma,1 Baoyu He,2 Jing Liang,2 Li Wei,2 Xutong Wang,2 Qingli Bie,2 Xuning Wang,4 Bin Zhang2,5 1Department of Hepatobiliary Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 3Department of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, People’s Republic of China; 4Department of General Surgery, The Air Force Hospital of Northern Theater PLA, Liaoning, People’s Republic of China; 5Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Zhang, Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People’s Republic of China, Tel +86 186 0647 3594, Fax +86 537 2213030, Email zhb861109@163.comBackground: Hepatocellular carcinoma (HCC) is one of the most common type of cancers, but there is still a lack of known biomarkers for the effective diagnosis or prognosis of HCC. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a substrate of protein kinase C, which was located in the cell plasma membrane. The purpose of our study was to evaluate the role of MARCKS in HCC.Methods: The role of MARCKS in HCC was explored by bioinformatics and experiment.Results: We demonstrated that MARCKS expression was significantly elevated in HCC datasets of TCGA. MARCKS was up-regulated in tumor sample in HCC. Functional enrichment indicated that MARCKS-related differentially expressed genes (DEGs) were mainly enriched in cell junction tissue, response to growth factors and cell population proliferation. Tumor and ECM-receptor interactions related pathways were enriched by the KEGG. MARCKS expression in HCC patients was higher in females, younger individuals, and those at worse clinical stages. Cox regression analysis showed that MARCKS expression was a risk factor for overall survival and disease-specific survival of patients.Conclusion: MARCKS was up-regulated in HCC, may play a crucial role in HCCs, and has prognostic value for clinical outcomes.Keywords: myristoylated alanine-rich C-kinase substrate, HCC, TCGA, prognostic value

Yiqun Liao,1 Junjie Gong,1 Xiaoliang Yuan,2 Hongfei Lu,1 Lixia Jiang1 1Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Respiratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzho, People’s Republic of ChinaCorrespondence: Yiqun Liao, Department of Laboratory Medicine, First Affiliated Hospital of Gannan Medical University, 23 Qingnian Road, Zhanggong District, Ganzhou, 341000, Jiangxi Province, People’s Republic of China, Tel +86-15979704263, Email joanna_qun@163.comBackground: The global prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a serious challenge for nosocomial infection and attracted worldwide attention. This study explored the drug resistance genes and molecular characteristics for CRKP, providing a reference for nosocomial prevention and control.Methods: A total of 42 CRKP isolates were collected from the First Affiliated Hospital of Gannan Medical University (Ganzhou, China) from January 2018 to February 2021. The drug resistance of CRKP was tested by the VitekII Compact system. Drug resistance gene expression was detected by poly-merase chain reaction (PCR), and molecular typing was performed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing (MLST).Results: All the 42 CRKP isolates were multi-drug resistant. Among them, 35 isolates (83.3%) produced blaKPC-2 and 12 isolates (28.6%) produced blaNDM-1. The detection rate of blaIMP-4 and blaOXA-48 was 2.4% (1/42), respectively. Twelve isolates (28.6%) carried both blaKPC-2 and blaNDM-1, one isolate (2.4%) carried both blaKPC-2 and blaIMP-4, and one isolate (2.4%) carried blaKPC-2, blaNDM-1 and blaOXA-48. A variety of other extended-spectrum beta-lactamases (ESBLs) were also detected. All 42 isolates carried blaSHV and blaCTX-M-1, 27 isolates (64.3%) carried blaTEM and 12 isolates (28.6%) carried blaCTX-M-9. The MLST data classified the 42 CRKP isolates into 11 sequence types, mainly ST11, accounting for 61.9% (26/42), of which 92.3% of isolates (24/26) carrying blaKPC-2. The PFGE results demonstrated that the 42 CRKP isolates could be divided into 20 clusters A-T, with cluster A (26.2%, 11/42) and cluster H (21.4%, 9/42) dominating, which were all ST11.Conclusion: The CRKP isolates were severely multi-drug resistant, and the main resistant gene was blaKPC-2 production, carrying multiple ESBLs genes simultaneously. The MLST and PFGE revealed that the ST11-blaKPC-2 Klebsiella pneumoniae was the main clonotype. Our findings may offer help to antibiotics selection and nosocomial infection prevention and control.Keywords: carbapenem-resistant Klebsiella pneumoniae, drug resistance genes, homology, molecular epidemiological characteristics

Yuqi Liang,1,2,&ast; Guosong Wu,3,&ast; Tianyu Luo,1,2,&ast; Haimei Xie,2 Qian Zuo,2 Ping Huang,2 Huachao Li,2 Liushan Chen,2 Hai Lu,4,&ast; Qianjun Chen1,2,&ast; 1The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, People’s Republic of China; 2Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Nanfang Hospital Baiyun Branch, Guangzhou, Guangdong, 510000, People’s Republic of China; 4The First People’s Hospital of Shaoguan, Shaoguan, Guangdong, 512099, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianjun Chen, Department of Breast, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Yuexiu District, Guangzhou, 510102, People’s Republic of China, Email cqj55@163.com Hai Lu, The First People’s Hospital of Shaoguan, No. 3, South Dongdi Road, Shaoguan, 512099, People’s Republic of China, Tel +86 15622187291, Email hysa1985@163.comPurpose: Although paclitaxel is widely used in cancer treatment, severe side effects and drug resistance limit its clinical use. 10-gingerol (10-G) is a natural compound isolated from ginger, which displays anti-inflammatory, antioxidant, and antiproliferative properties. However, the chemotherapy-sensitization effect of 10-G on triple-negative breast cancer (TNBC) has not been fully clarified. This study is aimed at investigating the effect of 10-G on the paclitaxel sensitivity in TNBC, and its underlying mechanism.Methods: The study was determined through in vitro and in vivo experiments. Cell viability and proliferation were detected by cell counting kit 8 (CCK-8) and colony formation. To detect cell apoptosis, flow cytometry and TUNEL were used. The expression of proteins was detected by Western blotting and immunohistochemistry. The molecular docking and gene knockout were corroborated by interactions between 10-G and adrenoceptor Beta 2 (ADRB2). The body weight of mice, histopathology and organs (kidney and spleen) coefficients were used to monitor the drug toxicities.Results: In vitro, 10-G increased the sensitivity of TNBC cells to paclitaxel, and could synergistically promote the apoptosis of TNBC cells induced by paclitaxel. In combination with molecular docking and lentivirus knockdown studies, ADRB2 was identified as a 10-G binding protein. 10-G inhibited ADRB2 by binding to the active site of ADRB2. Knockdown of ADRB2 reduces the proliferation activity of TNBC cells but also attenuates the sensitizing effects of 10-G to paclitaxel. Western blotting and immunohistochemistry showed that 10-G played an anti-proliferation and chemotherapy-sensitizing role by inhibiting the ADRB2/ERK signal. Toxicity evaluation showed that 10-G would not increase hepatorenal toxicity with paclitaxel.Conclusion: This data suggests that 10-G may be used as a new chemotherapeutic synergist in combination with paclitaxel to enhance anticancer activity. The potential value of ADRB2 as a target for improving chemotherapy sensitivity was also emphasized.Keywords: triple-negative breast cancer, combined therapies, 10-gingerol, paclitaxel, adrenoceptor Beta 2

Zihui Yan,1 Mengjie Cai,1 Xu Han,2 Qingguang Chen,2 Hao Lu1,2 1Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Diabetes Research Institute, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Qingguang Chen; Hao Lu, Email ruiqi3721@163.com; tangniaobing107@163.comObjective: This study aimed to investigate the interaction between age groups and risk factors for diabetes and prediabetes in Shanghai communities and to identify the effect of age on other risk factors for diabetes and prediabetes.Methods: This study recruited 3540 participants with undiagnosed diabetes or prediabetes in 14 communities in Shanghai from February to August 2019. All participants underwent a comprehensive examination, including filling out a detailed questionnaire, physical examination, 75 g oral glucose tolerance test, and blood sample collection. In addition, logistic regression was used to analyze the interaction between age and risk factors for prediabetes and diabetes.Results: The statistical analysis included 2776 people. In this study, the prevalence of diabetes and prediabetes were 15.1% and 52.3%, respectively. The prevalence of diabetes and prediabetes is higher in the elderly than in the middle-aged group. Among the risk factors for diabetes, overweight was associated with higher age (P-interaction 0.028). In addition, among the risk factors for prediabetes, a high level of education was associated with higher age (P-interaction 0.039) and elevated serum cholesterol level was associated with lower age (P-interaction 0.019).Conclusion: This study confirmed an interaction between age and other influencing factors, which may be important in explaining differences in risk factors for diabetes and prediabetes in the middle-aged and elderly populations. Community health facilities can provide health guidance to people of different age groups to prevent and control prediabetes and diabetes.Keywords: diabetes, prediabetes, risk factors, age, interaction

Xinxin Zhu,1,* Shiyun Huang,1,* Yuxuan Tang,1,* Zhonglan Wu,2,* Yue Sun,1 Huiyan Ren,1 Hongmei Lu,1 Tingting Yin,1 Qing Zuo,1,* Zhiping Ge,1,* Ziyan Jiang1,* 1Department of Obstetrics and Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ziyan Jiang, Department of Obstetrics, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-13512534017, Email zyjiangchm@163.comBackground: Grade III meconium stained amniotic fluid (MSAF) is a common obstetric disease, and has the greatest impact on poor maternal and neonatal outcomes.Question or Hypothesis or Aim: There is no consensus on treatment, especially on the timing of delivery.Methods: We collected the medical records of 345 women who gave birth with grade III MSAF and analyzed the difference in baseline characteristics and maternal and neonatal outcomes relative to different labor stage, observation times in the first stage of labor, and the presence or absence of abnormal fetal heart rate (FHR) or thick amniotic fluid.Findings: Higher rate of cesarean section was observed when grade III MSAF was found in active labor. Intervention occurred at an observation time of 90– 120 min, but there were no significant differences in maternal or neonatal outcomes shown when the observation time was greater than 3 or 4 hours. However, a higher rate of admission to the neonatal intensive care unit was demonstrated in cases with grade III MSAF with abnormal FHR either in the first or second stage of labor or in cases with thick MSAF in the second stage of labor.Discussion: Higher rate of composite adverse neonatal outcomes was found when secondary MSAF (a transition from clear AF to MSAF) was diagnosed > 3 h before delivery.Conclusion: In the first stage of labor, an observation time of greater than 4 hours might be possible after grade III MSAF is found if the labor has progressed and is without abnormal FHR.Keywords: MSAF, grade III MSAF, observation time, abnormal FHR, thick AF

Xuhua Duan,&ast; Wenze Xu,&ast; Hao Li, Manzhou Wang, Wenhui Wang, Huibin Lu, Yancang Zhang, Xinwei Han Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yancang Zhang; Xinwei Han, Department of Interventional Radiology, The First Affiliated Hospital, Zhengzhou University, No. 1, East Jian She Road, People’s Republic of China, 450052, Tel +86-371-66278081, Email zhangyancang2016@126.com; zzudxh@yeah.netPurpose: Chemoresistance is a major factor contributing to the failure of cancer treatment. The conventional chemotherapy agent 5-fluorouracil (5-FU) has been used for cancer treatment for decades. However, its use is limited in the treatment of hepatocellular carcinoma (HCC) due to acquired resistance. Nrf2 (NF-E2-related factor 2) is known to be associated with drug resistance across a wide range of cancer types. Also, since arsenic trioxide (As2O3) showed antitumor effects on HCC, the purpose of this study was to determine whether As2O3 and Nrf2-siRNA could inhibit HCC synergistically.Methods: We generated two separate 5-FU-resistant HCC cell lines (SNU-387/5-FU and Hep3B/5-FU). Western blotting was used to determine protein levels. An efficient lentiviral delivery system was used to establish stable knockdown or overexpression of Nrf2 and HIF-1α. In vitro and in vivo analyses of the effects of Nrf2 gene knockdown and As2O3 on 5-FU-resistant HCC cells were conducted.Results: The expression of Nrf2 was higher in the 5-FU-resistant HCC cell lines than in the parental cell lines. When coupled with Nrf2 knockdown, As2O3 treatment significantly decreased 5-FU-resistant SNU-387 and Hep3B cell viability, migration, and invasion, inactivated HIF-1α/HSP70 signaling, inhibited anti-apoptotic B-cell lymphoma (Bcl-2) activity, and increased the expression of pro-apoptotic Bcl-2-associated X protein (BAX) along with caspase-3. The synergistic effect was also confirmed using a 5-FU-resistant Hep3B mouse xenograft model in vivo.Conclusion: Nrf2 knockdown could improve the effect of As2O3 on reversing drug resistance in 5-FU-resistant HCC cells.Keywords: arsenic trioxide, 5-fluorouracil, chemoresistance, hepatocellular carcinoma, Nrf2, HIF-1&#x03B1

Haibin Lu,1,2,* Lei Wan,2,* Xiaoling Li,2 Mu Zhang,2 Adnan Shakoor,3 Wenqiang Li,4 Xueyang Zhang1,2 1Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, 528308, People’s Republic of China; 2Stomatological Hospital, Southern Medical University, Guangzhou, 510280, People’s Republic of China; 3Department of Control and Instrumentation Engineering, King Fahd University of Petroleum & Minerals, Dhahran, Kingdom of Saudi Arabia; 4Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, 510000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenqiang Li, Engineering Technology Research Center for Sports Assistive Devices of Guangdong, Guangzhou Sport University, Guangzhou, 510000, People’s Republic of China, Tel +8602038025086, Fax +02038025086, Email liwq@gzsport.edu.cn Xueyang Zhang, Email zhangxueyang666@126.comIntroduction: Kochiae Fructus has been widely used in Chinese Herbal medicine to treat various diseases. We report a rapid and eco-friendly approach for cerium oxide (CeO2) nanoparticles (NPs) synthesis using the extract of medicinally important plant “Kochiae Fructus”, and the synthesized NPs were named KF-CeO2 NPs.Methods: Various spectroscopic approaches such as transmission electron microscope (TEM), powder X-ray diffraction (XRD), and energy-dispersive X-Ray (EDX) were used to characterize the KF-CeO2 NPs effectively. The antibacterial and biofilm inhibition activity of KF-CeO2 NPs against Gram-positive and Gram-negative multi-drug resistant (MDR) bacteria was determined using the serial dilution method and XTT assay. KF-CeO2 NPs were assessed for anticancer activity against HeLa cancer cells using an MTT assay. Cytobiocompatibility was determined in two normal cell lines (3T3 and hMSC).Results and Discussion: The average size of the KF-CeO2 NPs was 11.3 ± 3.9 nm with spherical morphology. KF-CeO2 NPs demonstrated a greater than 95% bactericidal efficacy against MDR microorganisms. In addition, KF-CeO2 NPs strongly suppressed (more than 79%) the biofilms of MDR bacteria, indicating their potential for addressing antibiotic resistance issues. Compared to Kochiae Fructus extract and CH-CeO2 NPs, they exhibited significant cytotoxic effects (35.60% cell viability) on HeLa cancer cells. In addition, the KF-CeO2 NPs were shown to be highly biocompatible with hMSC and 3T3 cell lines (85.13% and 81.17% cell viability, respectively), suggesting that they may be employed in biological systems.Conclusion: These data indicate that KF-CeO2 NPs synthesized using Kochiae Fructus extract are promising alternative treatments for MDR. In addition, this study will give the potential for the sustained development of biocompatible NPs with enhanced biological capabilities derived from vital pharmaceutical plants.Graphical Abstract: Keywords: green synthesis, CeO2 NPs, Kochiae Fructus, antimicrobial, cytobiocompatibility

Licui Li,1,2 Huixiu Lu,1,3 Yanli Zhang,4 Qian Li,4 Shaomin Shi,4 Yaling Liu1,4 1Department of Dermatology and Venereology, Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Dermatology, Shijiazhuang Gaocheng People’s Hospital, Shijiazhuang, People’s Republic of China; 3Department of Dermatology, Shijiazhuang People’s Hospital, Shijiazhuang, People’s Republic of China; 4Department of Dermatology, The Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yaling Liu, Department of Dermatology and Venereology, Hebei Medical University, Shijiazhuang, People’s Republic of China, Email yzling_liu1214@126.comObjective: To probe into the effect of azelaic acid on psoriasis based on the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.Methods: Psoriasis gene expression data were downloaded from the GEO database for differential expression analysis to identify differentially expressed genes (DEGs). KEGG and GSEA analyses were performed to identify important signaling pathways that may be involved in psoriasis progression for subsequent validation. Thirty-six C57BL/6 mice aged 8 weeks old were randomly assigned into the blank control group (n = 9), negative control group (n = 9), psoriasis model group (n = 9), and azelaic acid treat group (n = 9). Mice models of psoriasis were prepared with imiquimod (IMQ) in the latter two groups, and azelaic acid ointment was applied in azelaic acid treat group. Then, hematoxylin-eosin (HE) staining was carried out to detect the effect of azelaic acid on the pathological damage of mice models of psoriasis in each group. HaCaT cells cultured in vitro were divided into blank control group, negative control group (addition of azelaic acid), IL-17 group (20 ng/mL) and IL-17+azelaic acid group, with 3 replicates for each group. Immunofluorescence assay and Western blotting were used to detect the protein expression of PI3K/AKT signaling pathway related molecules.Results: KEGG analysis showed that DEGs were significantly enriched in PI3K-AKT signaling pathway. GSEA analysis showed that PI3K and MTOR signaling pathways were up-regulated in psoriasis, while AUTOPHAGY signaling pathway was down-regulated. HE staining showed that azelaic acid could significantly inhibit the local skin injury in mice caused by IMQ-induced psoriasis. Moreover, azelaic acid can inhibit the expression of PI3K/AKT signaling pathway related proteins phosphorylated (p)-PI3K, p-AKT, p-mammalian target of rapamycin (mTOR), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), angiogenin-1 and hypoxia-inducible factor-1α (HIF-1α). These results imply that azelaic acid may inhibit the activation of PI3K/AKT signaling pathway and angiogenesis, thereby improving the symptoms of psoriasis.Conclusion: Azelaic acid may inhibit the activation of PI3K/AKT signaling pathway and angiogenesis, thereby improving the symptoms of psoriasis.Keywords: psoriasis, azelaic acid, PI3K/AKT signaling pathway, angiogenesis

Hui-Shan Huang,1 Ming-Hsien Tsai,2– 4 Hui-Ching Chuang,2,3 Yu-Tsai Lin,2– 4 Kun-Lin Yang,2,3 Hui Lu,2 Chih-Yen Chien2,3,5 1Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 4College of Pharmacy and Health Care, Tajen University, Pingtung County, Taiwan; 5Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, TaiwanCorrespondence: Chih-Yen Chien, Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 833, Taiwan, Tel +886-7-7317123 ext. 2533, Fax +886-7-7313855, Email cychien3965@adm.cgmh.org.twBackground: It is well known that p16 negative oropharyngeal squamous cell carcinoma (OPSCC) has a high probability of spreading to the ipsilateral neck. However, no consensus exists as to whether to perform elective treatment for clinical nodal negative in contralateral neck.Methods: A total of 85 patients with p16 negative OPSCC who underwent primary tumor excision and bilateral neck dissections between 2005 and 2018 were analyzed retrospectively. Clinicopathologic variables were used to identify factors predicting occult contralateral nodal metastasis (OCNM). A nomogram was developed to assess the risk of OCNM and the model was validated internally by using bootstrap resampling.Results: The overall prevalence of pathologically positive contralateral nodes was 30.6% (26/85) in our cohort, and the rate of OCNM was 18.3% (11/60). The presence of ipsilateral clinical extranodal extension (cENE) was significantly associated with contralateral neck metastasis (odds ratio, 5.662; 95% CI, 2.079– 15.415) with increased risk of OCNM (odds ratio, 4.271; 95% CI, 1.045– 17.458). Moreover, the concordance index of the proposed nomogram model without ipsilateral cENE was 0.623 and could increase to 0.717 with the inclusion of ipsilateral cENE in the calculation.Conclusion: The risk of OCNM in p16 negative OPSCC with ipsilateral cENE is notable. Ipsilateral cENE-based nomogram might assist in individual decision-making regarding contralateral nodal negative neck management and help avoid the over- and under-treatment of p16 negative OPSCC.Keywords: p16, oropharyngeal cancer, occult contralateral neck metastasis, extranodal extension, nomogram

Hongzhi Lu,1 Li Ma,1 Hong Zhang,1 Li Feng,1 Ying Yu,1 Yihan Zhao,1 Li Li,1 Yujiao Zhou,1 Li Song,2,3 Wushuang Li,2,3 Jiangman Zhao,2,3 Lanxiang Liu4 1Department of Infectious Diseases, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of China; 2Shanghai Biotecan Pharmaceuticals Co., Ltd, Shanghai, 201204, People’s Republic of China; 3Shanghai Zhangjiang Institute of Medical Innovation, Shanghai, 201204, People’s Republic of China; 4Medical Imaging Center, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Lanxiang Liu, Department of Medical Imaging Center, First Hospital of Qinhuangdao, 258 Wenhua Road, Qinhuangdao, 066000, Hebei, People’s Republic of China, Email 155354189@qq.comBackground: Metagenomic next-generation sequencing (mNGS) has been widely studied, due to its ability of detecting all the microbial genetic information unbiasedly in a sample at one time and not relying on traditional culture. However, the application of mNGS in the diagnosis of clinical pathogens remains challenging.Methods: From December 2019 to March 2021, 134 specimens including Broncho alveolar lavage fluid (BAFL), blood, sputum, cerebrospinal fluid (CSF), bile, pleural fluid, pus, were continuously collected in The First Hospital of Qinhuangdao, and their retrospective diagnoses were classified into infectious disease (128, 95.5%) and noninfectious disease (6, 4.5%). The pathogen-detection performance of mNGS was compared with conventional microbiological tests (CMT) and culture method. In addition, the antibiotic resistance genes (ARGs) and evolutionary relationship of common drug-resistant A. baumannii were also analyzed.Results: Compared with CMT and culture methods, mNGS showed higher sensitivity in pathogen detection (74.2% vs 57.8%; P < 0.001 and 66.3% vs 31.7%; P < 0.001, respectively). Importantly, for cases that mNGS-positive only, 18 (35%) cases result in diagnosis modification, and 7 (23%) cases confirmed the clinical diagnosis. In 17 cases that A. baumannii were both detected in mNGS and culture, ade genes were the most frequently detected ARGs (from 13 cases), followed by sul2 and APH(3”)-Ib (both from 12 cases). High consistency was observed among these ARGs and the related phenotype (100% for ade genes, 91.6% for sul2 and APH(3”)-Ib). A. baumannii strains were classified into three groups, and most were well-clustered. It suggested those strains may be the epidemic strains.Conclusion: In our study, mNGS had a higher sensitivity than CMT and culture method. And the result of ARGs frequency and cluster analysis of A. baumannii was of great significance to the anti-infective therapy.Keywords: metagenomic next-generation sequencing, sensitivity, antibiotic resistance genes, infection, conventional microbiological tests

Jinyan Lin,&ast; Yu Zhang,&ast; Chongxi Bao, Huasong Lu, Yun Zhong, Chuanfeng Huang, Qiuping Huang, Dezhen Wang, Jing Luo, Ke Wang, Jinliang Kong Pulmonary and Critical Care Medicine Ward, Guangxi Medical University First Affiliated Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinliang Kong; Ke Wang, Pulmonary and Critical Care Medicine Ward, Guangxi Medical University First Affiliated Hospital, No. 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Email kjl071@126.com; 497256113@qq.comBackground: Streptococcus constellatus, a commensal, plays an important role in purulent infections. It has been reported as aggressive pathogen causing pleural empyema. But the role of S. constellatus in empyema has not been taken seriously. There are no studies about clinical characteristics of empyema caused by S. constellatus domestically and abroad. This study aimed to explore the clinical features and management of empyema caused by S. constellatus.Methods: A retrospective review of 9 patients diagnosed with empyema caused by S. constellatus in a hospital between January 2010 and August 2021 was performed.Results: S. constellatus empyema were mostly seen in old males (66.7%) with comorbid diseases. The high-risk factors include diabetes mellitus, oral infection, and oral surgery. All were unilateral encapsulated empyema (right-side, 55.6%), diagnosed with pneumonia (bilateral pneumonia, 88.9%; ipsilateral lung abscess, 44.4%). 33.3% of patients had S. constellatus and anaerobes co-isolated. S. constellatus were sensitive to penicillin G, linezolid, levofloxacin, vancomycin, ceftriaxone, and chloramphenicol, resistant to erythromycin, tetracycline, and clindamycin. 33.3% of the patients needed ventilator support. The primary treatment to S. constellatus empyema was timely pus drainage, intravenous antibiotics, and enough nutrition support, intrapleural fibrinolytics and surgery (VAST recommended first) in necessity.Conclusion: S. constellatus may cause pneumonia and lung abscess first and then spread to cause empyema mainly in old males with comorbid diseases. S. constellatus often co-isolated with anaerobes in empyema. Antibiotics should cover simultaneously both S. constellatus and anaerobes.Keywords: S. constellatus, empyema, clinical features, anaerobes

Xuecheng Tong,1,2 Zeyu Huang,1 Xiujun Zhang,1,2 Guocan Si,2 Huifen Lu,2 Wei Zhang,2 Yuan Xue,1,2 Weibin Xie3 1Institute of Hepatology, the Third People’s Hospital of Changzhou, Changzhou, People’s Republic of China; 2Department of Infectious Diseases, the Third People’s Hospital of Changzhou, Changzhou, People’s Republic of China; 3Department of Anesthesiology, the Third People’s Hospital of Changzhou, Changzhou, People’s Republic of ChinaCorrespondence: Yuan Xue; Weibin Xie, Institute of Hepatology, the Third People’s Hospital of Changzhou, No. 300 Lanling North Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 519 82009059, Email xueyuan80908@163.com; Xiewb2022@163.comObjective: Analyzing the risk factors for pneumonia development in breakthrough cases with a history of inactivated vaccine injection is important. The present study aimed to investigate the risk factors for pneumonia development during Omicron variant infection.Design and Methods: The clinical data were retrospectively collected from 187 patients who previously received inactivated vaccine and were infected by the Omicron variant.Results: Among the 187 patients, 73 had 2 doses of inactivated vaccine injection and the remaining 114 had 3 doses; 19 patients had pneumonia at admission. The univariate logistic analysis showed that age, baseline platelet count, D-dimer level, and CD8+ T lymphocyte count were associated with pneumonia development at admission. The multivariate analysis showed that only age was the independent risk factor for pneumonia development (odds ratio = 1.046, 95% confidence interval: 1.003– 1.091, P = 0.04). With an optimal cutoff value of 46, 4.4% (4/91) patients in the age < 46 years group and 15.63% (15/96) patients in the age ≥ 46 years group had pneumonia (χ2 = 6.454, P = 0.01). Moreover, age negatively correlated with CD8+ T cell count, B cell count, and albumin and uric acid levels (all P < 0.01), while age positively correlated with the glucose level (P < 0.01).Conclusion: Old age was the only independent risk factor for pneumonia development in patients with Omicron variant infection and a history of inactivated vaccine injection.Keywords: COVID-19, glucose, Omicron, pneumonia, SARS-CoV-2

Wei Yang,1– 3 Xue He,1,2 Yuying Yao,2 Hongyan Lu,2 Yuliang Wang,2 Zhanhao Zhang,2 Yuhe Wang,1,2,4 Li Wang,1,2 Yongjun He,1,2 Dongya Yuan,1,2 Tianbo Jin1,2 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 2School of Basic Medical Sciences, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 3Department of Emergency, The Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 4Department of Clinical Laboratory, The Affiliated Hospital of Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Tianbo Jin, Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, #6 East Wenhui Road, Xianyang, Shaanxi, 712082, People’s Republic of China, Tel/Fax +86-29-88895902, Email tianbo__jin@163.comBackground: Hematological characteristics have positive reference value as clinical indicators in the evaluation of various diseases. The purpose of this study was to determine the gene loci associated with 20 hematological phenotypes in the Han population from northwest China.Methods: A genome-wide association study (GWAS) was conducted on hematological indicators of 1005 Han people from northwest China. Genotyping was performed with a GeneTitan multichannel instrument and Axiom Analysis Suite 6.0. Using the 1000 Genomes Project (phase 3) as a reference, haplotype imputation was performed with IMPUTE2. SNVs (single nucleotide variants) significantly associated with hematological phenotypes were identified. The top SNV (p < 5E-7) was then selected for replication detection.Results: Ninety genetic variations identified in the GWAS were significantly associated with hematological indicators. Among them, only rs35289401 (CCDC157) was significantly associated (genome-wide) with red blood cell distribution width (RDW) (p = 4.21E-08). The fourteen top SNVs were selected for replication verification and were significantly associated with hematological phenotypes. However, only HBS1 L-MYB rs1331309 was significantly associated with the mean hemoglobin content (p = 6.42E-07). We also found that the mean corpuscular hemoglobin (MCH) level in the rs1331309 GG/GT genotype was significantly higher than that in the TT genotype (p = 0.023).Conclusion: The GWAS identified a total of 90 genetic variants significantly associated with hematological phenotypic indicators. In particular, rs1331309 (HBS1 L-MYB) is expected to be a biomarker for monitoring the dynamics of MCH levels. This study provides a reference for related studies on the genetic structure of hematological characteristics. It provides a valuable reference for the clinical diagnosis or prediction of a variety of diseases.Keywords: hematological, GWAS, hematological phenotype, MCH, Han population from northwest China

Guoding Huang, Hongquan Lu, Qizhu Chen, Xinting Huang Department of Oncology, The Central Hospital of Western Area of Hainan, Danzhou, Hainan, People’s Republic of ChinaCorrespondence: Guoding Huang, Department of Oncology, The Central Hospital of Western Area of Hainan, Danzhou, Hainan, People’s Republic of China, Tel +86-898-23836851, Fax +86-898-23836853, Email huangguoding123@gmail.comObjective: We aimed to evaluate the prevalence of BRCA1 and BRCA2 mutations in Chinese populations with breast cancer. Factors associated with BRCA1 and BRCA2 mutations are also evaluated.Methods: This was a cross-sectional study, and patients with breast cancer were included. Data on clinical characteristics, information of breast cancer, and BRCA1 and BRCA2 mutations were extracted. Patients were divided into the carrier and noncarrier groups.Results: A total of 368 patients were included. Compared to the noncarrier group (n = 240), patients in the carrier group (n = 128) were younger and more likely to have breast cancer at age < 40 years. Of the overall 128 patients in the carrier groups, 58 had BRCA1 mutation and 70 had BRCA2 mutation. Among patients with early onset breast cancer, there was no difference in the prevalence of BRCA1 and BRCA2 (20.7% vs 17.1%, P = 0.35). While among patients with a family history of breast/ovarian cancer, BRCA2 mutation was more prevalent than BRCA1 mutation (54.3% vs 44.8%, P = 0.01); and among patients with triple-negative breast cancer, BRCA1 mutation was more prevalent than BRCA2 mutation (34.5% vs 28.6%, P = 0.04). After adjusting for covariates, factors associated with BRCA1 mutation included breast cancer diagnosed < 40 years, tumor size > 2 cm, and lymph node metastasis; and after adjusting for covariates, factors associated with BRCA2 mutation included age, tumor size > 2 cm, and triple-negative breast cancer.Conclusion: The prevalence of BRCA1 and BRCA2 mutations varied according to three specific subgroups. Factors associated with BRCA1 and BRCA2 mutations were differential.Keywords: breast cancer, prevalence, predictors, breast cancer-associated gene

Xiaorui Guo,1,2 Huiying Lu,3 Chunxiang Liu,3 Yi Zhang,3 Liangjia Bi1 1Department of Stomatology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, 150001, People’s Republic of China; 2State Key Laboratory of Military Stomatology and National Clinical Research Center for Oral Diseases and Shaanxi Key Laboratory of Oral Diseases, Department of Operative Dentistry and Endodontics, School of Stomatology, The Fourth Military Medical University, Xi’an, People’s Republic of China; 3National and Local Joint Stem Cell Research & Engineering Center for Aging Diseases, Tian Qing Stem Cell Co., Ltd, Harbin, 150028, People’s Republic of ChinaCorrespondence: Liangjia Bi, Department of Stomatology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, 150001, People’s Republic of China, Tel/Fax +86 451 82576565, Email biliangjia1963@163.comPurpose: To evaluate the effect of super-activated platelet lysate (sPL) on wound healing of tooth extraction sockets in rats.Methods: Rat models of the tooth extraction socket were established. Thirty-six rats were divided into control and sPL groups and sacrificed on days 7, 14, and 28 after tooth extraction. Bone formation in tooth extraction sockets were observed by microscopic computed tomography (micro-CT) and hematoxylin and eosin (HE) staining; osteoprotegerin (OPG), receptor activator of nuclear factor kappa-&Bgr; ligand (RANKL), interleukin 6(IL-6), and tumor necrosis factor-alpha (TNF-α) proteins were detected by immunohistochemistry; and chemokine and osteogenic gene expressions were detected by polymerase chain reaction (PCR).Results: sPL accelerated soft tissue wound healing in the extraction socket of rats. Micro-CT showed that the amount of bone formation and bone volume fraction were higher in the sPL group than the control 14 days after extraction. HE staining showed promotion of the formation of bony trabeculae by sPL in the apical third of the extraction socket 7 days after extraction and more mature and organized bony trabeculae in the sPL group than the control 14 days after extraction; mature bony trabeculae filling most of the fossa with lesser bone porosity in the socket in the sPL group than the control 28 days after extraction. Immunohistochemistry showed that sPL induced OPG expressions 7 and 14 days after tooth extraction but did not affect the RANKL expression while transiently promoting the IL-6 expression 7 days after extraction. PCR showed that sPL promoted chemokine expressions 7 and 14 days after extraction. The expressions of osteogenesis-related factors were higher in the sPL group than the control 7 and 28 days after extraction, while the opposite trend was observed 14 days after extraction.Conclusion: sPL has a transient pro-inflammatory effect and promotes soft tissue healing and bone formation during early wound healing of extraction sockets in rats.Keywords: sPL, blood product, wound healing, bone formation, cytokines

Zhongfang Yang,1– 3,&ast; Xiaoning Liu,4,5,&ast; Zheng Zhu,1,3,6 Lin Zhang,7 Shuyu Han,8 Yanfen Fu,9 Hongzhou Lu4 1School of Nursing, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China; 3Fudan University Centre for Evidence-Based Nursing: A Joanna Briggs Institute Centre of Excellence, Shanghai, People’s Republic of China; 4Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, People’s Republic of China; 5National Heart & Lung Institute, Faculty of Medicine, Imperial College London, London, UK; 6NYU Rory Meyers College of Nursing, New York University, New York, NY, USA; 7Shanghai Public Health Clinical Center, Shanghai, People’s Republic of China; 8School of Nursing, Peking University, Beijing, People’s Republic of China; 9School of Nursing, Dali University, Dali, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zheng Zhu, School of Nursing, Fudan University, 305 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 21-6443 0093, Email zhengzhu@fudan.edu.cn Hongzhou Lu, Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, 518112, Guangdong Province, People’s Republic of China, Email luhongzhou@szsy.sustech.edu.cnAbstract: With Western Pacific Region reporting more imported cases, the World Health Organization (WHO) declared monkeypox a public health emergency of international concern in July. Currently, we are now at the beginning of forming stigmatization toward monkeypox. Based on the experience of combating HIV stigmatization for over 30 years, in this comment, we proposed measures based on the three stages of the stigma formation process. We believe the paper may be of particular interest to the readers of your journal as it offered implications for both healthcare professionals and researchers in Western Pacific Region.Keywords: infectious disease, stigmatization, global public health, measures

Wenguang Lai,1,2,&ast; Xiaoli Zhao,3,&ast; Zhidong Huang,1,&ast; Yun Xie,1,2,&ast; Sijia Yu,1,4 Jiabin Tu,5 Dachuan Guo,6 Jiaming Xiu,5 Ziling Mai,1,2 Qiang Li,1 Haozhang Huang,1,4 Huanqiang Li,1 Jun-Yan Xu,1,7 Hongyu Lu,1 Guanzhong Chen,1 Shiqun Chen,1 Jin Liu,1 Yong Liu1 1Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 3Department of Cardiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Cardiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, 364000, People’s Republic of China; 6Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 7Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Liu; Jin Liu, Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China, Email liuyong@gdph.org.cn; ljaw397017568@163.comBackground: Inflammation and immune responses play an important role in the pathophysiology of contrast-associated acute kidney injury (CA-AKI), and systemic immune inflammation index (SII) has recently emerged as a new parameter for immune and inflammatory response evaluation. However, limited research has been undertaken to explore the relationship between SII and CA-AKI following coronary angiography (CAG).Patients and Methods: From January 2007 to December 2020, 46,333 patients undergoing CAG were included from 5 Chinese tertiary hospitals. SII was calculated as total peripheral platelets count × neutrophil-to-lymphocyte ratio. Patients were categorized by preprocedural SII quartiles: Q1 ≤ 404.5, Q2 > 404.5 and ≤ 631.7, Q3 > 631.7 and ≤ 1082.8, Q4 > 1082.8. Univariable and multivariable logistic regression were used to reveal the link between preprocedural SII and CA-AKI.Results: A total of the 46,333 patients (62.9 ± 11.5 years, female 28.1%) were included in the study. The incidence of CA-AKI was 8.4% in Q1 group, 8.7% in Q2 group, 9.4% in Q3 group, 15.1% in Q4 group. In the multivariable model, comparing the highest (Q4 group) to lowest (Q1 group) SII level categories, preprocedural SII was related to a higher risk of CA-AKI after fully adjusting for well-known confounders, and there was no statistically difference in the other two SII level categories (Q2 and Q3 groups) compared with Q1 group (adjusted model 3: Q2 group: OR: 0.98, 95% CI: 0.87– 1.11, P = 0.771; Q3 group: OR: 1.04, 95% CI: 0.92– 1.18, P = 0.553; Q4: OR: 1.65, 95% CI: 1.45– 1.88, p < 0.001; P for trend < 0.001). Similar results were found for all the subgroups analysis except for patients undergoing PCI, and the interaction analyses for age, PCI and AMI were significant. In addition, Kaplan–Meier curves demonstrated that the lowest quartile group showed the worst all-cause mortality in a significant SII level-dependent manner among the four groups (Log rank test; p < 0.0001).Conclusion: Elevated preprocedural SII level was a significant and independent risk factor for CA-AKI following CAG. Higher-quality prospective studies are needed to validate the predictive value of SII for CA-AKI.Keywords: systemic immune inflammation index, contrast-associated acute kidney injury, coronary angiography, preprocedural

Jiezuan Yang,1 Yongtao Li,1 Jing Ye,2 Ju Wang,1 Haifeng Lu,1 Xinsheng Yao3 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Infectious Diseases, Hangzhou, People’s Republic of China; 2Department of Surgical ICU, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 3Department of Immunology, Research Center for Medicine & Biology, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi, People’s Republic of ChinaCorrespondence: Jiezuan Yang, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Infectious Diseases, 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel +86 571 87236756, Email yangyan@zju.edu.cnBackground: Hepatitis B (HepB) vaccination can effectively prevent the prevalence of hepatitis B virus (HBV) infection. However, the incidence of vaccination failure is about 5∼ 10% and the underlying molecular mechanisms are poorly understood. T cells have an essential role in the recipient’s immune response to vaccine, which could be elucidated by high-throughput sequencing (HTS) and bioinformatics analysis.Methods: We conducted HTS of the T cell receptor β chain (TRB) complementarity-determining region 3 (CDR3) repertoires in eighteen positive responders (responders) and 10 negative responders (non-responders) who all had HepB vaccination, the repertoire features of BV, BJ and V-J genes and their diversity, respectively, were compared between the positive and negative responders using the Mann–Whitney test. Moreover, the relatively conserved motifs in CDR3 were revealed and compared to those in the other group’s report.Results: The diversity of TRB CDR3 and the frequencies of BV27 and BV7-9 are significantly increased for HepB vaccine responders compared to those in non-responders. The motifs of CDR3s in BV27/J1-1, BV27/J2-5, and BV7-9/J2-5, respectively, were most expressed as “NTE”, “QETQ”, and “GG-Q (E)-ETQ”. Moreover, the motif “KLNSPL” was determined in nearly 80% CDR3s in BV27/J1-6 from HepB vaccine responders for the first time.Conclusion: Our results present the comprehensive profiles of TRB CDR3 in the HepB vaccine responders and non-responders after standard vaccination protocol and determine the relatively conservative motifs of CDR3s that may respond to the HepB vaccine. Further results suggest that the profile of TRB repertoire could distinguish the HepB vaccine responders from non-responders and provide a new target for optimizing and improving the efficiency of the HepB vaccine.Keywords: hepatitis B vaccination, hepatitis B surface antibody, complementarity-determining region 3, immune repertoire, high-throughput sequencing

Miao Jia,1,2 Huiqi Lu,1,2 Femi Olutoye,1,2 Jinjun Li,1,2 Simin Huang,1,2 Hongzhen Zhou1,2 1Department of Nursing, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Nursing, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Hongzhen ZhouDepartment of Nursing, Nanfang Hospital, Southern Medical University, No. 1838 Guangzhou Avenue North, Guangzhou, 510515, People’s Republic of ChinaTel +86 13710310948Fax +86 20-61641186Email zhouhz_smu@126.comPurpose: This study aimed to translate the Post-stroke Checklist into Mandarin, validate its content, and cross-culturally adapt the Mandarin version of the Post-stroke Checklist (M-PSC) in line with expert review and cognitive interviewing.Patients and Methods: After translating into Mandarin, the M-PSC was modified and content validated using expert review, which resulted in a pilot version for cognitive interviewing among stroke survivors inclusive of subjects from an outpatient unit (n = 7), a rehabilitation department using traditional Chinese medicine (n = 10), and a community (n = 10). The interviews were transcribed and analyzed according to the four-stage cognitive model. A set of nine practice rounds where the number of rounds of iteration was determined based on the saturation of information was conducted. Data analysis was performed concurrently with data collection. Recommendations for changes to the M-PSC were made based on the analyses in the iteration.Results: We successfully developed an initial M-PSC, back-translated it into English, reviewed the discrepancies and performed a three-step expert review to modify the M-PSC and validate its excellent content. Twenty-seven interviews were carried out, and a wide range of sources of error primarily related to the comprehension, retrieval of information, and judgment was reported, and each item of the M-PSC was rectified accordingly.Conclusion: The Post-stroke Checklist was translated into Mandarin and cross-culturally adapted based on expert review and cognitive interviewing. Adaptations were made to support that the Mandarin version can be implemented in clinical practice for long-term post-stroke care.Keywords: stroke, stroke rehabilitation, long-term care, quality of life

Yuliang Wang,1– 3 Linna Peng,1– 3 Hongyan Lu,1– 3 Zhanhao Zhang,1– 3 Shishi Xing,1– 3 Dandan Li,1– 3 Chunjuan He,1– 3 Tianbo Jin,1– 3 Li Wang1– 3 1Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, 712082, Shaanxi, People’s Republic of China; 2Engineering Research Center of Tibetan Medicine Detection Technology, Ministry of Education, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of China; 3Key Laboratory of High Altitude Hypoxia Environment and Life Health, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, 712082, People’s Republic of ChinaCorrespondence: Li Wang Tel +86-15706028826Email wangli_xzmd@163.comBackground: We aimed to enrich the pharmacogenomic information of a Blang population (BP) from Yunnan Province in China.Methods: We genotyped 55 very important pharmacogene (VIP) variants from the PharmGKB database and compared their genotype distribution (GD) in a BP with that of 26 populations by the χ2 test. The minor allele frequency (MAF) distribution of seven significantly different single-nucleotide polymorphisms (SNPs) was conducted to compare the difference between the BP and 26 other populations.Results: Compared with the GD of 55 loci in the BP, among 26 studied populations, GWD, YRI, GIH, ESN, MSL, TSI, PJL, ACB, FIN and IBS were the top-10 populations, which showed a significantly different GD > 35 loci. CHB, JPT, CDX, CHS, and KHV populations had a significantly different GD < 20 loci. A GD difference of 27– 34 loci was found between the BP and 11 populations (LWK, CEU, ITU, STU, PUR, CLM, GBR, ASW, BEB, MXL and PEL). The GD of five loci (rs750155 (SULT1A1), rs4291 (ACE), rs1051298 (SLC19A1), rs1131596 (SLC19A1) and rs1051296 (SLC19A1)) were the most significantly different in the BP as compared with that of the other 26 populations. The genotype frequency of rs1800764 (ACE) and rs1065852 (CYP2D6) was different in all populations except for PEL and LWK, respectively. MAFs of rs1065852 (CYP2D6) and rs750155 (SULT1A1) showed the largest fluctuation between the BP and SAS, EUR, AFR and AMR populations.Conclusion: Our data can provide theoretical guidance for safe and efficacious personalized drug use in the Blang population.Keywords: Blang population, single-nucleotide polymorphism, SNP, very important pharmacogene, genotype distribution, pharmacogenomics, personalized drug use