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Xiu Wang,1,2 Qianqian Yu,3 Jun Zhu,4 Junlan Liu,2 Xuyuan Gao,2 Xiudie Wang,2 Lanlan Wang,2 Xia Xu2 1Department of Traditional Chinese Medicine, Shandong College of Traditional Chinese Medicine, Yantai City, Shandong Province, 264199, People’s Republic of China; 2College of Traditional Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei City, Anhui Province, 230012, People’s Republic of China; 3Department of Critical Care Medicine, Qingdao University Affiliated Hospital, Qingdao City, Shandong Province, 266035, People’s Republic of China; 4Department of Traditional Chinese Medicine, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui, 241005, People’s Republic of ChinaCorrespondence: Xia Xu, College of Traditional Chinese Medicine, Anhui University of Traditional Chinese Medicine, 1 Qianjiang Road, Yaohai District, Hefei City, Anhui Province, People’s Republic of China, Tel +86 15955170282, Email 907367552@qq.comObjective: This systematic review and meta-analysis aims to investigate the effectiveness and safety of acupuncture and moxibustion in managing perioperative anxiety during gynecological surgery.Methods: Relevant studies published from the establishment of the databases to March 20, 2023, were searched in PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM. Literature screening and data extraction were independently conducted by two investigators. The Cochrane risk-of-bias tool 2.0 was utilized to assess the risk of bias in the included studies. Data analysis was carried out using Stata 15.1 software.Results: The analysis included a total of 3254 patients from twenty studies. It was found that acupuncture and moxibustion therapy resulted in a reduction of postoperative State-Trait Anxiety Inventory (STAI-S) scores (mean difference [MD] = − 3.50, 95% confidence interval [CI] [− 6.93 to − 0.07], P = 0.046), as well as both preoperative and postoperative Visual Analogue Scale-Anxiety (VAS-anxiety) and Self-Rating Anxiety Scale (SAS) scores (pre-operation: SMD = − 1.04, 95% CI [− 1.73 to − 0.35], P = 0.003; post-operation: SMD = − 0.78, 95% CI [− 1.21 to − 0.35], P < 0.001) in comparison to the control group. Nonetheless, no significant variances were noted between the two groups with regards to preoperative and intraoperative STAI-S scores (pre-operation: MD = − 3.38, 95% CI [− 9.58 to 2.82], P = 0.286; intraoperative: MD = − 1.09, 95% CI [− 7.32 to 5.13], P = 0.730), and intraoperative VAS-anxiety and SAS scores (SMD = − 0.44, 95% CI [− 1.51 to 0.64], P = 0.427).Conclusion: During the perioperative period of gynecological surgery, acupuncture and moxibustion therapy show potential in alleviating anxiety in patients. It is noteworthy that the current level of evidence is limited by the small sample size. Therefore, further validation of these findings is necessary.Keywords: perioperative anxiety, gynecological surgery, acupuncture, systematic review, meta-analysis

Gui-Fu Li, Qin Yu, Chun-Xia Li Shanghai TCM-Integrated Hospital, Shanghai University of TCM, Shanghai, People’s Republic of ChinaCorrespondence: Chun-Xia Li, Shanghai TCM-Integrated Hospital, Shanghai University of TCM, No. 230 Baoding Road, Shanghai, People’s Republic of China, Tel +86-18101915248, Email cx_li1964@outlook.comObjective: To explore the research hotspots in acupuncture treatment for myopia from 2014 to 2023.Methods: A comprehensive search was conducted in the Science Citation Index-Expanded (SCI-E) within the Web of Science Core Collection (WOSCC). We used CiteSpace 6.2.R6 to perform an in-depth analysis of the annual publication trends, prolific authors, institutions, keyword co-occurrences, and citation bursts. The study followed the PICO framework: the population (P) includes studies on patients with myopia, the intervention (I) is acupuncture treatment, no direct comparison (C) is applied, and the primary outcome (O) focuses on the identification of research trends and hotspots. Major outcome assessments included the analysis of publication trends over time, author productivity, influential journals, and the detection of emerging research topics through citation burst analysis. This bibliometric analysis was conducted on November 15, 2023.Results: A total of 281 articles were included in the analysis. The trend line of annual publications over the past decade showed a modest increase, with a significant decline in 2019 and a surge in 2021. China and its affiliated academic institutions led globally in publication volume, with Ma Xiaopeng being the most prolific author and Fudan University the most influential institution. Ophthalmology emerged as the journal with the highest citation frequency. The most frequently occurring keywords were related to adolescent myopia and its complications. The developmental trajectory of the field is distinct, characterized by the integration of a single discipline.Conclusion: Acupuncture shows promise as a complementary and alternative therapy for treating myopia, with growing interest in its clinical efficacy and mechanisms of action. Future research is likely to focus on optimizing treatment protocols and understanding the underlying biological mechanisms of acupuncture in myopia management.Keywords: myopia, acupuncture, bibliometric analysis

Song-Xing Wang,1,2,&ast; Li-Yan Sun,3,&ast; Qiong Yu,2 Ran Li,4 Yun-Ping Xu,3 Jin-Feng Zeng4 1Clinical Laboratory, The Third People’s Hospital of Longgang District, Shenzhen, People’s Republic of China; 2Quality Control Department, Shenzhen Blood Center, Shenzhen, People’s Republic of China; 3Institution of Transfusion Medicine, Shenzhen Blood Center, Shenzhen, People’s Republic of China; 4Clinical Laboratory, Shenzhen Blood Center, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun-Ping Xu; Jin-Feng Zeng, Email yunpingxu1982@hotmail.com; zzengjf@163.comBackground: In Shenzhen of China, the continuous increase of syphilis infections threatens the safety of blood transfusion. In 2020, COVID-19 was discovered and spread rapidly around the world, and affected the prevalence of syphilis among blood donors.Methods: From 2013 to 2020, there were 839,161 blood samples collected in the Shenzhen Blood Center. Blood samples were screened by ELISA tests and confirmed by the TPPA (Treponema pallidum particle agglutination) tests and the TRUST (toluidine red unheated serum tests). All data was analyzed by the chi-square test.Results: From 2013 to 2020, the positive rate of syphilis among blood donors varied significantly among individuals in different ages, educational backgrounds, regions, and blood donation histories (P< 0.001). In 2020, It was the first time that there were more repeat blood donors than first-time blood donors and more blood donors with a higher education level than those with a lower education level, and the lowest reactive and positive rate of syphilis among blood donors was observed. Compared to 2019, the prevalence of syphilis among female and repeat blood donors decreased significantly in 2020 (P< 0.01).Conclusion: The prevalence of syphilis in blood donors is related to the characteristics of blood donors (in addition to gender) and the COVID-19 epidemic. COVID-19 can affect the prevalence of syphilis among blood donors by influencing the composition of blood donors and the number of syphile-positive donors in certain blood donors, including female and repeat blood donors.Keywords: syphilis, COVID-19, blood donors

Yueyao Jiang,1,* Chengran Wang,2,* Chuancheng Zu,3,* Xin’ao Rong,2 Qian Yu,1 Jinlan Jiang2 1Department of Pharmacy, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China; 2Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China; 3China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Yu, Department of Pharmacy, China–Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, Jilin Province, 130033, People’s Republic of China, Email yuqian@jlu.edu.cn Jinlan Jiang, Department of Scientific Research Center, China–Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun, Jilin Province, 130033, People’s Republic of China, Email jiangjinlan@jlu.edu.cnAbstract: Given the global prevalence of prostate cancer in men, it is crucial to explore more effective treatment strategies. Recently, immunotherapy has emerged as a promising cancer treatment due to its unique mechanism of action and potential long-term effectiveness. However, its limited efficacy in prostate cancer has prompted renewed interest in developing strategies to improve immunotherapy outcomes. Nanomedicine offers a novel perspective on cancer treatment with its unique size effects and surface properties. By employing targeted delivery, controlled release, and enhanced immunogenicity, nanoparticles can be synergized with nanomedicine platforms to amplify the effectiveness of immunotherapy in treating prostate cancer. Simultaneously, nanotechnology can address the limitations of immunotherapy and the challenges of immune escape and tumor microenvironment regulation. Additionally, the synergistic effects of combining nanomedicine with other therapies offer promising clinical outcomes. Innovative applications of nanomedicine include smart nanocarriers, stimulus-responsive systems, and precision medicine approaches to overcome translational obstacles in prostate cancer immunotherapy. This review highlights the transformative potential of nanomedicine in enhancing prostate cancer immunotherapy and emphasizes the need for interdisciplinary collaboration to drive research and clinical applications forward. Keywords: prostate cancer, nanomedicine, immunotherapy, TME

Qingyang Yu,1,2 Yuanyuan Cui,1 Shuwen Dong,1 Yanqing Ma,1 Yi Xiao,1 Li Fan,1 Shiyuan Liu1 1Department of Radiology, Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Neurosurgery, Changhai Hospital, Navy Military Medical University, Shanghai, 200433, People’s Republic of ChinaCorrespondence: Shiyuan Liu, Department of Radiology, Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Fax +86 2181886012, Email radiology_cz@163.comObjective: Hemifacial spasm (HFS) is a clinical neurosurgical disease, which brain structural alterations caused by HFS remain a topic of debate. We evaluated changes in brain microstructure associated with HFS and observed their relevance to clinical characteristics.Methods: We enrolled 72 participants. T1-weighted structural and diffusion tensor images were collected from all participants using 3.0T magnetic resonance equipment. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to identify changes in gray matter volume (GMV) and disruptions in white matter (WM) integrity. The severity of the spasms was graded using the Cohn scale.Results: VBM analysis revealed that the GMV was significantly reduced in the left Thalamus and increased GMV in the right Cerebellum IV-V of the HFS group. TBSS analysis showed that FA in the left superior longitudinal fasciculus (SLF) of the HFS group was significantly increased. GMV in the thalamus showed a negative correlation with disease duration and Cohn grade, while FA in the left SLF had a positive correlation with both the disease duration and Cohn grade.Conclusion: We identified regions with altered GMV in HFS patients. Additionally, we determined that FA in the left SLF might serve as a significant neural indicator of HFS.Keywords: hemifacial spasm, voxel-based morphometry, diffusion tensor imaging, tract-based spatial statistics, Cohn grading

Qingfei Yu, Qin Zhang Department of Nephrology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Qin Zhang, Department of Nephrology, Shandong Provincial Third Hospital, Shandong University, No. 11 Wuyingshan Middle Road, Tianqiao District, Jinan, Shandong, 250031, People’s Republic of China, Tel/Fax +8615628768081, Email jtyyzq@126.comPurpose: Pulmonary hypertension (PH) is a serious complication in hemodialysis patients, which is associated with a significantly increased risk of morbidity and mortality. The present study aims to investigate PH frequency and associated factors in patients undergoing maintenance hemodialysis.Patients and Methods: This cross-sectional study was conducted in the hemodialysis department of the Shandong Provincial Third Hospital, China, from January 2016 to December 2022. A total of 167 consecutive patients who underwent regular hemodialysis treatment for at least three months were included in the study. Patients with a systolic pulmonary artery pressure (sPAP) value > 35 mmHg at rest were considered to have PH. The relationship between PH and various demographic, laboratory, and echocardiographic parameters was evaluated.Results: A total of 93 patients (55.7%) were diagnosed with PH. Multivariate logistic regression analysis indicated that low serum levels of albumin (OR 0.89, 95% CI 0.82– 0.98, p = 0.017), low serum levels of triglycerides (OR 0.32, 95% CI 0.15– 0.69, p = 0.003), and high right atrial diameter (OR 1.19, 95% CI 1.04– 1.37, p = 0.011) were significantly associated with an increased risk of PH.Conclusion: PH is a common finding in hemodialysis patients and is independently associated with serum levels of albumin, serum levels of triglyceride, and right atrial diameter; this suggests that evaluating these non-invasive and relatively easily available parameters may be useful in identifying patients with a high risk of PH. However, further studies are required to confirm these findings.Keywords: pulmonary hypertension, triglycerides, pulmonary artery, renal dialysis, echocardiography, albumins

Xiaolong Wang,1,2,&ast; Guanyi Wang,2,&ast; Peibin Cen,1,&ast; Hongyu Lan,1 Linfa Guo,2 Zuhaer Yisha,2 Aodun Gu,2 Guiyong Liu,3 Zijian Wang,2 Tongzu Liu,2,4– 8 Qingfeng Yu1,9– 11 1Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Urology, Qianjiang Central Hospital of Hubei Province, Qianjiang, People’s Republic of China; 4Hubei Key Laboratory of Urological Diseases, Wuhan University, Wuhan, People’s Republic of China; 5Hubei Clinical Research Center for Laparoscopic/Endoscopic Urologic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Institute of Urology, Wuhan University, Wuhan, People’s Republic of China; 7Hubei Medical Quality Control Center for Laparoscopic/Endoscopic Urologic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Wuhan Clinical Research Center for Urogenital Tumors, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 9Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou Medical University, Guangzhou, People’s Republic of China; 10Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou Medical University, Guangzhou, People’s Republic of China; 11Guangzhou Institute of Urology, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongzu Liu, Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Email liutongzu@163.com Qingfeng Yu, Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Email sunriseyu@yeah.netIntroduction: Overactive bladder (OAB) is a highly prevalent condition with limited treatment options due to poor efficacy, side effects, and patient compliance. Novel drug delivery systems that can target the bladder wall may improve OAB therapy.Methods: We explored a polydopamine (PDA)-coated lactobacillus platform as a potential carrier for localized OAB treatment. Urinary microbiome profiling was performed to identify the presence of lactobacillus in healthy and OAB groups. Lactobacillus-PDA nanoparticles were synthesized and characterized by electron microscopy and spectrophotometry. A rat bladder perfusion model and human bladder smooth muscle cell spheroids were used to assess the distribution and penetration of the nanoparticles. The efficacy of the Lactobacillus-PDA system (LPS) for delivering the antimuscarinic drug solifenacin was evaluated in an OAB rat model.Results: Urinary microbiome profiling revealed lactobacillus as a dominant genus in both healthy and OAB groups. The synthesized Lactobacillus-PDA nanoparticles exhibited uniform size and optical properties. In the rat bladder perfusion model, the nanoparticles distributed throughout the bladder wall and smooth muscle without toxicity. The nanoparticles also penetrated human bladder smooth muscle cell spheroids. In the OAB rat model, LPS facilitated the delivery of solifenacin and improved treatment efficacy.Discussion: The results highlight LPS as a promising drug carrier for targeted OAB therapy via penetration into bladder tissues. This bacteriotherapy approach may overcome limitations of current systemic OAB medications. Lactobacillus, a probiotic bacterium present in the urinary tract microbiome, was hypothesized to adhere to and penetrate the bladder wall when coated with PDA nanoparticles, making it a suitable candidate for localized drug delivery. Keywords: polydopamine, lactobacillus, nano material, drug delivery, overactive bladder

Shengling Hu,1– 4 Jinqiang Guo,5 Zhe Chen,6 Fengyun Gong,1– 4 Qi Yu1– 4 1Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China; 2Hubei Clinical Research Center for Infectious Diseases, Wuhan, 430023, People’s Republic of China; 3Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Wuhan, 430023, People’s Republic of China; 4Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of China; 5Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Department of Thoracic Surgery, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of ChinaCorrespondence: Qi Yu; Fengyun Gong, Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China, Email fishns123@163.com; 2020jy0008@hust.edu.cnBackground: Multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) with high mortality remains a public health crisis and health security threat. This study aimed to explore the predictive value of nutritional indices for all-cause mortality (ACM) in MDR/RR-TB patients.Methods: We retrospectively recruited MDR/RR-TB patients between January 2015 and December 2021, randomly assigning them to training and validation cohorts. Patients were divided into high nutritional risk groups (HNRGs) and low nutritional risk groups (LNRGs) based on the optimal cut-off value obtained from receiver operating characteristic (ROC) analyses of the hemoglobin-albumin-lymphocyte-platelet (HALP) score, prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score. In the training cohort, Kaplan-Meier survival curves and Log rank tests were used to compare overall survival (OS) between the groups. Cox risk proportion regression analyses were used to explore the risk factors of ACM in patients with MDR/RR-TB. The predictive performance of ACM was assessed using area under the curve (AUC), sensitivity and specificity of ROC analyses.Results: A total of 524 MDR/RR-TB patients, with 255 in the training cohort and 269 in the validation cohort, were included. Survival analyses in the training cohort revealed significantly lower OS in the HNRGs compared to the LNRGs. After adjusting for covariates, multivariate analysis identified low HALP score, low PNI and high CONUT score were independent risk factors for ACM in MDR/RR-TB patients. ROC analyses demonstrated good predictive performance for ACM with AUCs of 0.765, 0.783, 0.807, and 0.811 for HALP score, PNI, CONUT score, and their combination, respectively. Similar results were observed in the validation set.Conclusion: HALP score, PNI, and CONUT scores could effectively predict ACM in patients with MDR/RR-TB. Hence, routine screening for malnutrition should be given more attention in clinical practice to identify MDR/RR-TB patients at higher risk of mortality and provide them with nutritional support to reduce mortality.Keywords: multidrug- and rifampicin- resistant tuberculosis, all- cause mortality, nutrition

Bailong Hou,1,&ast; Ying Zhou,2,&ast; Wei Wang,1 Weifeng Shen,1 Qinlong Yu,1 Minjie Mao,1 Siheng Wang,1 Wenxiu Ai,3 Fangyou Yu,2,3 Pingyang Shao1 1Department of Clinical Laboratory Medicine, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of China; 2Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200000, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pingyang Shao, Department of Clinical Laboratory Medicine, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of China, Email spy202001@163.com Fangyou Yu, Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200000, People’s Republic of China, Email wzjxyfy@163.comIntroduction: This study aimed to investigate the emergence and characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains that demonstrate resistance to multiple antibiotics, including aminoglycosides and tigecycline, in a Chinese hospital.Methods: A group of ten CRKP strains were collected from the nine patients in a Chinese hospital. Antimicrobial Susceptibility Testing (AST) and phenotypic inhibition assays precisely assess bacterial antibiotic resistance. Real-time quantitative PCR (RT-qPCR) was used to analyze the mRNA levels of efflux pump genes (acrA/acrB and oqxA/oqxB) and the regulatory gene (ramA). The core-genome tree and PFGE patterns were analyzed to assess the clonal and horizontal transfer expansion of the strains. Whole-genome sequencing was performed on a clinical isolate of K. pneumoniae named Kpn20 to identify key resistance genes and antimicrobial resistance islands (ARI).Results: The CRKP strains showed high resistance to carbapenems, aminoglycosides (CLSI, 2024), and tigecycline (EUCAST, 2024). The mRNA expression levels of efflux pump genes and regulatory genes were detected by RT-qPCR. All 10 isolates had significant differences compared to the control group of ATCC13883. The core-genome tree and PFGE patterns revealed five clusters, indicating clonal and horizontal transfer expansion. Three key resistance genes (blaoxa-232, blaCTX-M-15, and rmtF) were observed in the K. pneumoniae clinical isolate Kpn20. Mobile antibiotic resistance islands were identified containing blaCTX-M-15 and rmtF, with multiple insertion sequences and transposons present. The coexistence of blaoxa-232 and rmtF in a high-risk K. pneumoniae strain was reported. Conjugation assay was utilized to investigate the transferability of blaoxa-232-encoding plasmids horizontally.Conclusion: The study highlights the emergence of ST15-KL112 high-risk CRKP strains with multidrug resistance, including to aminoglycosides and tigecycline. The presence of mobile ARI and clonal and horizontal transfer expansion of strains indicate the threat of transmission of these strains. Future research is needed to assess the prevalence of such isolates and develop effective control measures.Keywords: blaOXA-232, rmtF, Klebsiella pneumoniae, carbapenemase, plasmid

Shengling Hu, Qi Yu, Fenfang Liu, Fengyun Gong Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology; Hubei Clinical Research Center for Infectious Diseases; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of ChinaCorrespondence: Fengyun Gong, Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology; Hubei Clinical Research Center for Infectious Diseases; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of China, Email 2020jy0008@hust.edu.cnBackground: The development of chronic obstructive pulmonary disease (COPD) following tuberculosis (TB) is known as tuberculosis-associated obstructive pulmonary disease (TOPD). This study aimed to explore the predictive value of inflammatory indicators for TOPD in TB patients.Methods: Data for this cross-sectional study were collected between January 2014 and January 2022 at Wuhan Jinyintan Hospital. The ratio of inflammatory indicators, including Systemic Inflammatory Response Index (SIRI), C-reactive protein-to-lymphocyte ratio (CLR), eosinophil count-to-lymphocyte count ratio (ELR), were calculated. Univariate and multivariate logistic regression analyses were conducted to explore the association between the ratio of inflammatory indicators and TOPD. Furthermore, the relationship between the ratio of inflammatory indicators and TOPD was investigated using propensity score matching (PSM) and receiver operating characteristic (ROC) curve analysis was performed to evaluate their predictive value for TOPD.Results: The present study included a total of 737 patients, of whom 83 participants (11.26%) had TOPD. Sixty-nine TOPD patients and 69 non-TOPD (NTOPD) patients were successfully matched. Univariate and multivariable logistics regression analysis, conducted before and after PSM, revealed that SIRI was independently significantly associated with an increased risk of TOPD. The area under curve (AUC) of SIRI were 0.702 and 0.668 before and after PSM, respectively. Additionally, patients were stratified into four different groups based on SIRI quartiles for further analysis. The prevalence of TOPD in TB patients showed an increase with higher SIRI values, both before and after PSM.Conclusion: Levels of inflammatory indicators were higher in TOPD patients when compared to NTOPD patients. SIRI may be a simple and useful inflammatory index for assessing TOPD, and TB patients with higher values of SIRI are more likely to be high-risk group for TOPD.Keywords: tuberculosis-associated obstructive pulmonary disease, systemic inflammatory response index, ratio inflammatory indicator, propensity score matching

Qiwen Yu,1 Chaopeng Mei,1 Mengwei Cui,1 Qianqian He,1 Xudong Liu,2 Xiaoxiao Du2 1Department of Emergency Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of ChinaCorrespondence: Xiaoxiao Du, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Erqi, Zhengzhou, Henan, People’s Republic of China, Email xiaoxiao5811@126.comBackground: Nepetoidin B (NB) has been reported to possess anti-inflammatory, antibacterial, and antioxidant properties. However, its effects on liver ischemia/reperfusion (I/R) injury remain unclear.Methods: In this study, a mouse liver I/R injury model and a mouse AML12 cell hypoxia reoxygenation (H/R) injury model were used to investigate the potential role of NB. Serum transaminase levels, liver necrotic area, cell viability, oxidative stress, inflammatory response, and apoptosis were evaluated to assess the effects of NB on liver I/R and cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to measure mRNA and protein expression levels, respectively. Molecular docking was used to predict the binding capacity of NB and mitogen-activated protein kinase phosphatase 5 (MKP5).Results: The results showed that NB significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, liver necrosis, oxidative stress, reactive oxygen species (ROS) content, inflammatory cytokine content and expression, inflammatory cell infiltration, and apoptosis after liver I/R and AML12 cells H/R injury. Additionally, NB inhibited the JUN protein amino-terminal kinase (JNK)/P38 pathway. Molecular docking results showed good binding between NB and MKP5 proteins, and Western blotting results showed that NB increased the protein expression of MKP5. MKP5 knockout (KO) significantly diminished the protective effects of NB against liver injury and its inhibitory effects on the JNK/P38 pathway.Conclusion: NB exerts hepatoprotective effects against liver I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.Keywords: liver ischemia/reperfusion injury, nepetoidin B, MKP5, JNK/P38 pathway

Kai Guo,1,2 Yuqin Zhu,3 Qian Yu,4 Hong Chen,5 Wei Cheng,2 Xiaoyan Zhang,2 Xuelian Zhang,2 Biwen Liu,2 Zunhai Zhou,2 Xingya Kuang5 1School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2Department of Endocrinology, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China; 3Department of Emergency, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China; 4Department of Dermatology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of China; 5Department of Occupational Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of ChinaCorrespondence: Xingya Kuang, Department of Occupational Medicine, Yangpu Hospital, School of Medicine, Tongji University, No. 1015, Hejian Road, Shanghai, 200090, People’s Republic of China, Tel +86-15021904362, Email kuangxingya@163.com Zunhai Zhou, Department of Endocrinology, Yangpu Hospital, School of Medicine, Tongji University, No. 450, Tengyue Road, Shanghai, 200090, People’s Republic of China, Tel +86-18001779479, Email zhouzunhai5008@163.comPurpose: Elevated urine albumin-to-creatinine ratio (UACR) is an established risk factor for microvascular disease in the general population. However, it is unclear whether UACR is associated with arterial stiffness in diabetes. We aimed to assess the relationship between UACR levels and the risk of arterial stiffness in patients with diabetes.Methods: From July 2021 to February 2023, a total of 1039 participants were assessed for the risk of arterial stiffness, which was evaluated by brachial-ankle pulse wave velocity (baPWV). The value of UACR≥ 30 mg/g was defined as high UACR. The UACR level had an abnormal distribution and was log2-transformed for analyses to reduce skewness and volatility. High baPWV was evaluated as categorical variables divided by the highest quartile of the values by sex. The relationship between UACR and arterial stiffness was analyzed by linear curve fitting analyses. Multiple logistic regression models were used to analyze the crude and adjusted odds ratio (OR) of UACR for high baPWV with 95% confidence interval (CI). In addition to applying non-adjusted and multivariate-adjusted models, interaction and stratified analyses were also carried out.Results: The baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group (1861.84 ± 439.12 cm/s vs 1723.13 ± 399.63 cm/s, p< 0.001). Adjusted smoothed plots suggested that there are linear relationships between log2-transformed UACR and high baPWV, and Spearman correlation coefficient was 0.226 (0.176– 0.276, p< 0.001). The OR (95% CI) between log2-transformed UACR and high baPWV were 1.26 (1.19– 1.33, p< 0.001), and 1.16 (1.08– 1.25, p< 0.001) respectively in diabetic patients before and after adjusting for potential confounders.Conclusion: The elevated UACR was associated with arterial stiffness in Chinese patients with diabetes.Plain Language Summary: 1. The mean baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group.2. The sex-specific hierarchical analysis revealed that baPWV levels and the incidence of high baPWV were significantly elevated with increased UACR.3. Curvilinear relationships between log2-transformed UACR and the risk of high baPWV.4. Positive association between UACR and high baPWV in patients with diabetes.Keywords: diabetic kidney disease, cardiovascular diseases, albuminuria, pulse wave velocity, biomarker, prognosis

Ya Zheng,1 Qunli Yu,1 Ling Han,1 Xinyi Chen2 1College of Food Science and Engineering, Gansu Agricultural University, Lanzhou, Gansu, 730070, People’s Republic of China; 2School of Biotechnology, East China University of Science and Technology, Shanghai, 200237, People’s Republic of ChinaCorrespondence: Qunli Yu, Tel +86-931-7631201, Email yuqunlihh@163.comPurpose: The present study was designed to investigate the resistance determinants and virulence factors of 45 Trueperella pyogenes isolates from clinical bovine mastitis in Hexi Corridor of Gansu, China.Methods: Minimum inhibitory concentrations (MICs) was tested by E-test method. Gene of antimicrobial resistance, virulence integrase and integron gene cassettes were determined by PCR and DNA sequencing.Results: The T. pyogenes isolates exhibited high resistance to streptomycin (88.9%) and tetracycline (64.4%), followed by erythromycin (15.6%) and gentamicin (13.3%). Resistance to streptomycin was most commonly encoded by aadA9 (88.9%); and to tetracycline, by tetW (64.4%). Importantly, all streptomycin-resistant isolates carried aadA9 alone or in combination with aadA1, aadA11 and strA-strB. Similarly, all tetracycline-resistant isolates harbored tetW alone or in combination with tetA33. Meanwhile, ermX was detected in 13.3% isolates, only one erythromycin-resistant isolate was not identified for this gene. Moreover, all T. pyogenes isolates carried class 1 integrons, and 17.8% of them contained gene cassettes, including arrays aadA1-aadB (4.4%), aad A24-dfrA1-ORF1 (2.2%) and aadA1 (2.2%). Furthermore, all tested isolates harbored virulent genes plo and fimA, followed by fimC (88.9%), fimE (86.6%) nanP (75.6%), nanH (40.0%), cbpA (35.6%) and fimG (6.7%).Conclusion: To our knowledge, this is the first report of integron gene cassettes of T. pyogenes isolates from bovine mastitis cases in China. These findings are useful for developing the prevention and the virulence factors of T. pyogenes could be promising candidates for vaccine antigens for bovine mastitis caused by T. pyogenes in China.Keywords: Trueperella pyogenes, resistance, integrons, gene cassette, bovine mastitis

Jue Li,1,&ast; Lusha Zhang,2,&ast; Teng Ge,2 Jiping Liu,1 Chuan Wang,1 Qi Yu1,2 1Engineering Research Center of Brain Health Industry of Chinese Medicine, Key Laboratory of Pharmacodynamics and Material Basis of Chinese Medicine of Shaanxi Administration of Traditional Chinese Medicine, Pharmacology of Chinese medicine, Shaanxi University of Chinese Medicine, Xianyang, 712046, People’s Republic of China; 2Shaanxi Key Laboratory of Ischemic Cardiovascular Diseases and Institute of Basic and Translational Medicine, Xi’an Medical University, Xi’an, 710021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Yu; Chuan Wang, Email qiyu6028@hotmail.com; wangchuan@sntcm.edu.cnAbstract: Tyrosine kinase inhibitors (TKIs) have been recognized as crucial agents for treating various tumors, and one of their key targets is the intracellular site of the vascular endothelial growth factor receptor (VEGFR). While TKIs have demonstrated their effectiveness in solid tumor patients and increased life expectancy, they can also lead to adverse cardiovascular effects including hypertension, thromboembolism, cardiac ischemia, and left ventricular dysfunction. Among the TKIs, sorafenib was the first approved agent and it exerts anti-tumor effects on hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC) by inhibiting angiogenesis and tumor cell proliferation through targeting VEGFR and RAF. Unfortunately, the adverse cardiovascular effects caused by sorafenib not only affect solid tumor patients but also limit its application in curing other diseases. This review explores the mechanisms underlying sorafenib-induced cardiovascular adverse effects, including endothelial dysfunction, mitochondrial dysfunction, endoplasmic reticulum stress, dysregulated autophagy, and ferroptosis. It also discusses potential treatment strategies, such as antioxidants and renin-angiotensin system inhibitors, and highlights the association between sorafenib-induced hypertension and treatment efficacy in cancer patients. Furthermore, emerging research suggests a link between sorafenib-induced glycolysis, drug resistance, and cardiovascular toxicity, necessitating further investigation. Overall, understanding these mechanisms is crucial for optimizing sorafenib therapy and minimizing cardiovascular risks in cancer patients.Keywords: sorafenib, vascular endothelial growth factor receptor, hypertension, cardiovascular toxicity, cancer

Ronglin Ma,1,2,&ast; Chunya Ji,1,&ast; Mengdan Shen,2 Shujuan Xu,2 Guojia Fan,3 Chengcheng Wu,1 Qiang Yu,2 Linliang Yin1 1Center for Medical Ultrasound, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China; 3Center for Cytotoxicity Testing, Sanitation & Environment Technology Institute, Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Yu, Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Jiangsu, People’s Republic of China, Tel +86 512 62362045, Email yuqiang0102sz@163.com Linliang Yin, Center for Medical Ultrasound, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Jiangsu, People’s Republic of China, Tel +86 13382183478, Email yllsznthello@hotmail.comBackground: Radionuclides have important roles in clinical tumor radiotherapy as they are used to kill tumor cells or as imaging agents for drug tracing. The application of radionuclides has been developing as an increasing number of nanomaterials are used to deliver radionuclides to tumor areas to kill tumor cells. However, promoting the efficient combination of radionuclides and nanocarriers (NCs), enhancing radionuclide loading efficiency, and avoiding environmental pollution caused by radionuclide overuse are important challenges that hinder their further development.Methods: In the present study, a new small molecule compound (3-[[(2S)-2-hydroxy-3-(4-hydroxyphenyl)-1-carbonyl] amino]-alanine, abbreviation: HN, molecular formula: C12H16N2O5) was synthesized as a linker between radionuclide iodine-125 (125I) and NCs to enable a more efficient binding between NCs and radionuclides.Results: In vitro evidence indicated that the linker was able to bind 125I with higher efficiency (labeling efficiency > 80%) than that of tyrosine, as well as various NCs, such as cellulose nanofibers, metal oxide NCs, and graphene oxide. Single-photon emission computed tomography/computed tomography imaging demonstrated the biological distribution of 125I-labeled NCs in different organs/tissues after administration in mice.Conclusion: These results showed an improvement in radionuclide labeling efficiency for nanocarriers and provided an approach for nanocarrier image tracing.Keywords: nanocarriers, radionuclide labeling, radionuclide 125i, SPECT/CT imaging

Zhiyun Zhang, Hao Zheng, Qingquan Yu, Xianghong Jing Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Xianghong Jing, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China, Email jxhtjb@263.netAbstract: The spinal dorsal horn (SDH) transmits sensory information from the periphery to the brain. Wide dynamic range (WDR) neurons within this relay site play a critical role in modulating and integrating peripheral sensory inputs, as well as the process of central sensitization during pathological pain. This group of spinal multi-receptive neurons has attracted considerable attention in pain research due to their capabilities for encoding the location and intensity of nociception. Meanwhile, transmission, processing, and modulation of incoming afferent information in WDR neurons also establish the underlying basis for investigating the integration of acupuncture and pain signals. This review aims to provide a comprehensive examination of the distinctive features of WDR neurons and their involvement in pain. Specifically, we will examine the regulation of diverse supraspinal nuclei on these neurons and analyze their potential in elucidating the mechanisms of acupuncture analgesia.Keywords: WDR neurons, spinal dorsal horn, pain, central sensitization, receptive fields, DNIC, acupuncture analgesia

Ke Liu,1,&ast; Meng-Ying Zhang,2,&ast; Lu-Lu Sun,2 Qiao-Huo Liao,2 Yuan-Yuan Yi,3 Yi-Ling Ji,1 Dan Ye,1 Qiu Yu1 1Department of Emergency, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 2Department of Pediatrics, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China; 3Department of Transplantation, The Third People’s Hospital of Shenzhen, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu-Lu Sun, Department of pediatrics, The Third People’s Hospital of Shenzhen, No. 29 of Bulan Road, Longgang District, Shenzhen, 518000, People’s Republic of China, Tel +86-13510332310, Fax +86-755-61238983, Email sunlulurainbow@126.comObjective: The primary aim of this study was to examine the extent of nutritional awareness concerning dietary requisites within a cohort comprising pediatric recipients of liver and kidney transplants, along with their respective caregivers. The overarching goal was to establish a foundation for enhancing the dietary nutrition of this specific population.Methods: This was a qualitative research study, involving in-depth interviews and subsequent qualitative data analysis. Our sample included pediatric patients in a specific age range who had undergone a liver or kidney transplant, as well as their parents. The data analysis technique we used was content analysis.Results: The survey focused on knowledge of dietary requirements and restrictions, nutritional needs, and adherence to daily dietary requirements among pediatric patients and their respective caregivers. Approximately 30% of the parents lacked relevant nutritional awareness, 30% relied on a single source for acquiring nutritional knowledge, and 40% expressed a considerable need for nutritional guidance. Our findings revealed a deficiency in the understanding of nutritional and dietary requirements for children who have undergone a liver or kidney transplant. Their nutrient intake was unbalanced, and their dietary habits were irregular, highlighting the need for better nutritional guidance and monitoring.Conclusion: The nutritional awareness and knowledge of dietary requirements among pediatric liver and kidney transplant recipients and their care providers are inadequate. Medical professionals are urged to tackle this concern by imparting comprehensive education to parents regarding the nutritional prerequisites essential for their children post-transplant. This approach empowers parents to implement requisite dietary modifications effectively. Furthermore, healthcare institutions should augment the nutritional proficiency of their medical staff through meticulously structured training initiatives.Keywords: kidney transplant in children, liver transplant in children, nutritional awareness, nutritional support, qualitative study

Zicheng Guo,1,2,&ast; Qingli Yu,1,&ast; Wencheng Huang,1 Fengyu Huang,1 Xiurong Chen,1 Chuzhong Wei1,2 1Department of Orthopaedics, Huizhou First Hospital, Huizhou, People’s Republic of China; 2Department of Orthopaedics, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuzhong Wei, Department of Orthopaedics, Southern Medical University, Guangzhou, People’s Republic of China, Email chuzhongwei2023@gmail.comBackground: Keloid is a common condition characterized by abnormal scarring of the skin, affecting a significant number of individuals worldwide.Objective: The occurrence of keloids may be related to the reduction of cell death. Recently, a new cell death mode that relies on copper ions has been discovered. This study aimed to identify novel cuproptosis-related genes that are associated with keloid diagnosis.Methods: We utilized several gene expression datasets, including GSE44270 and GSE145725 as the training group, and GSE7890, GSE92566, and GSE121618 as the testing group. We integrated machine learning models (SVM, RF, GLM, and XGB) to identify 10 cuproptosis-related genes (CRGs) for keloid diagnosis in the training group. The diagnostic capability of the identified CRGs was validated using independent datasets, RT-qPCR, Western blotting, and IHC analysis.Results: Our study successfully categorized keloid samples into two clusters based on the expression of cuproptosis-related genes. Utilizing WGCNA analysis, we identified 110 candidate genes associated with cuproptosis. Subsequent functional enrichment analysis results revealed that these genes may play a regulatory role in cell growth within keloid tissue through the MAPK pathway. By integrating machine learning models, we identified CRGs that can be used for diagnosing keloid. The diagnostic efficacy of CRGs was confirmed using independent datasets, RT-qPCR, Western blotting, and IHC analysis. GSVA analysis indicated that high expression of CRGs influenced the gene set related to ECM receptor interaction.Conclusion: This study identified 10 cuproptosis-related genes that provide insights into the molecular mechanisms underlying keloid development and may have implications for the development of targeted therapies. Keywords: machine learning, cuproptosis, keloid, novel biomarker

Xinmiao Hu,1– 3,&ast; Qian Wu,1,2,&ast; Qunfeng Lu,4,5,&ast; Jiangao Zhang,6 Xiaowei Yang,7 Wenjian Chen,3 Ping Wang,3 Qinglin Yu,3 Jingan Dong,3 Yan Sang8 1School of Medicine, Tong University, Shanghai, People’s Republic of China; 2Department of Nursing, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 3Department of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Department of Nursing, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 5School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 6Nantong Visionland Eye Hospital, Jiangsu, People’s Republic of China; 7School of Medicine, Nantong University, Jiangsu, People’s Republic of China; 8Department of Nursing, Department of Computer Technology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Sang, Department of Computer Technology, Affiliated Hospital of Nantong University, No. 20 Xisi Road, Nantong, Jiangsu, 226001, People’s Republic of China, Tel +86 13862915051, Email sangyan_cn@126.comPurpose: To identify the difficulties and burdens related to the experience of caring for children.Methods: A phenomenological approach was used in this qualitative study. Semi-structured and adolescents with idiopathic nephrotic syndrome (INS) in mainland China. Interviews lasting 35– 90 minutes were conducted with 13 parental caregivers of youth with INS. The Colaizzi’s analysis was used in data analysis.Results: The mean age of parental caregivers was 40.3 ± 6.1 years, and the average caregiving year of 3.2 ± 3.3 years. Most INS patients were male (69.2%), had a mean age of 7.6 ± 4.2 years. Based on the analysis of the data, five major themes emerged. These were: persistent emotional burden; neglected physical burden; overwhelming financial burden; absence of social support system and burden related to loss of normal life.Conclusion: Health professionals must develop strategies to provide stage-by-stage, targeted health education and psychological support services to parental caregivers of INS youth in China. The government must subsidize routine medications and frequent hospitalizations to minimize the financial burden on parental caregivers of INS youth. Moreover, anti-discrimination policies must be established to protect caregivers from explicit discrimination in public places.Keywords: caregiver, burden, idiopathic nephrotic syndrome, youth

Ye Liang,1– 4,&ast; Bing Wang,1– 4,&ast; Qing Yu,1– 4 Weijia Wang,1– 4 Shaohua Ge,1– 4 Jinlong Shao1– 4 1Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 2Shandong Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, People’s Republic of China; 3Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, 250012, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Oral Diseases, School of Stomatology, Shandong University, Jinan, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Ge; Jinlong Shao, Tel +86 531 88382123 ; +86 531 88382597, Fax +86 531 88382923, Email shaohuage@sdu.edu.cn; jinlong.shao@sdu.edu.cnObjective: Silver nanoparticles (AgNPs) possess excellent antibacterial effects on periodontal pathogens, but their clinical application is limited mainly due to their cytotoxicity through inducing oxidative stress in human cells. Ebselen disrupts the reactive oxygen species (ROS) scavenging in bacteria and relieves oxidative stress in mammalian cells. This study aimed to assess the antibacterial and anti-inflammatory effects of AgNPs and ebselen as well as the protective effect of ebselen, to further provide the theoretical basis for their future application in periodontal treatment.Methods: The antibacterial and anti-biofilm effects of the synthesized AgNPs combined with ebselen were assessed on Porphyromonas gingivalis (P. gingivalis), Streptococcus gordonii (S. gordonii), and Fusobacterium nucleatum (F. nucleatum) in planktonic condition and as biofilms. In addition, the intracellular bactericidal efficiency of AgNPs and ebselen was evaluated in P. gingivalis-infected human gingival fibroblasts (HGFs). The cytotoxicity, intracellular ROS levels, and potential antioxidative enzymes were detected in HGFs treated with AgNPs and ebselen. Further, the anti-inflammatory effects were evaluated by in vitro and in vivo experiments.Results: The combination of AgNPs and ebselen showed excellent antibacterial effects against planktonic P. gingivalis and F. nucleatum and synergistic antibiofilm effects on all mono- and multi-species biofilms. In addition, ebselen significantly enhanced the intracellular bactericidal efficiency of AgNPs. Furthermore, ebselen combined with up to 20 μg/mL AgNPs showed no obvious cytotoxicity to HGFs. Evidently, ebselen alleviated the AgNPs-induced ROS by increasing the levels of glutathione and superoxide dismutase 2. Moreover, AgNPs and ebselen together declined the release of P. gingivalis-stimulated inflammatory cytokines both in vitro and in vivo, and reduced alveolar bone resorption effectively.Conclusion: AgNPs combined with ebselen would be an effective adjuvant for periodontal treatment owing to their synergistic antibacterial and anti-inflammatory effects. Keywords: periodontitis, antibacterial, oxidative stress, anti-inflammation

Li-Yan Sun,1 Qiong Yu,2 Cai-Ming He,2 Song-Xing Wang3 1Institution of Transfusion Medicine, Shenzhen Blood Center, Shenzhen, People’s Republic of China; 2Quality Control Department, Shenzhen Blood Center, Shenzhen, People’s Republic of China; 3Business Management Department, Shenzhen Blood Center, Shenzhen, People’s Republic of ChinaCorrespondence: Song-Xing Wang, Email wsxdxyx2003@163.comBackground: The adverse donor reaction (ADR) means the uncomfortable feeling felt by blood donors during the whole process of blood donation, which can affect the blood donation behavior of blood donors. So, it is very necessary for blood centers to monitor and prevent it.Methods: Data about ADRs in Shenzhen Blood Center from January 2018 to December 2022 were collected, and correlation analysis was conducted using SPSS 24.0 software.Results: From January 2018 to December 2022, a total of 1265 ADRs occurred in 642,767 blood donations in Shenzhen Blood Center, with an incidence of 0.20%. Most of the ADRs were mild and occurred during blood collections (> 90%). The ADR rate of young individuals aged 18– 29 years old was the highest (p< 0.0001). In addition, a higher ADR rate was observed in first-time blood donors, whole blood donors, and blood donors who donated in the mobile sites (p< 0.05).Conclusion: The occurrence of ADRs is related to the sociodemographic factors of blood donors, including age, donation type, donation history, and donation sites. Shenzhen Blood Centers should pay special attention to the process of blood donation among young blood donors aged 18– 29 years old, first-time blood donors, whole-blood donors, and blood donors who donate at mobile sites to further reduce the occurrence of ADRs.Keywords: blood donors, adverse donor reactions, sociodemographic factors

Zhaoyi Liu,1,&ast; Qing Yu,1,2,&ast; Hongxiao Liu2,&ast; 1Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Rheumatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongxiao Liu, Tel +86-15165152738, Email liuhongxiao_123@163.com; E3388942893@163.comBackground: Heterotopic ossification is a complication in the late stage of ankylosing spondylitis (AS), and involves abnormal osteogenesis by mesenchymal stem cells (MSC). Research activity in this area has been rapidly expanding, but there is a lack of bibliometric studies that summarize the progresses.Methods: We searched the Web of Science (WoS) for articles pertaining to the role of MSCs in heterotopic ossification in AS from the database inception to December 2022 and visualized the countries, authors, institutions, references, and keywords using CiteSpace 6.1.R6 and VOSViewer.Results: A total of 127 publications from 188 institutions were identified, with a trend for increasing number of articles per year. China published the largest number of literature, followed by the United States and France. There were 47 core authors. The most recent research in this area mainly focused on “osteogenic differentiation”, “gene expression”, “inflammation”, “TNF-α” and “bone formation”. Current research can be broadly summarized into two topics: abnormalities in the inflammatory microenvironment and abnormalities in the MSCs. Aberrant expression of a variety of surface proteins in MSCs predisposes these cells to undergo osteogenic differentiation, and pro-inflammatory cytokines in the inflammatory milieu stimulate osteogenic differentiation of MSCs.Conclusion: MSCs in heterotopic ossification in AS is a relatively new area of research. Research activities primarily consist abnormalities in the inflammatory microenvironment and abnormalities in the MSCs.Keywords: ankylosing spondylitis: mesenchymal stem cells, VOSViewer, CiteSpace, heterotopic ossification, visualization analysis

Jin Zhang,1 Mengyang He,2 Qiduo Yu,1 Fei Xiao,1 Yongming Zhang,3 Chaoyang Liang1 1Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital; National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of ChinaCorrespondence: Yongming Zhang; Chaoyang Liang, No. 2 Yinghua East Street, Chao Yang District, Beijing, 100029, People’s Republic of China, Tel/Fax +86-10-8420 6191, Email cacpzym@163.com; liangchaoyang@zryhyy.com.cnBackground: Asthma is a public health problem requiring focused attention. This study aimed to systematically evaluate the association between dietary structure and asthma or wheezing in children.Methods: The study protocol of this meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) with the registration code CRD42023390191. A total of 8397 articles were retrieved, searching PubMed, Medline, Embase, Web of Science, and Scopus databases as of November 21, 2022. Two independent authors were responsible for independently conducting the literature screening process. Effect-size estimates were expressed as odds ratio (OR) in cross-sectional studies and risk ratio (RR) in cohort studies with a 95% confidence interval (CI). Summary effect estimates were evaluated with random-effect models. Meanwhile, subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and the robustness of the pooled estimation.Results: A total of 65 studies, including 567,426 subjects had been analyzed. Overall analyses of cross-sectional studies revealed that a healthy diet was protective against asthma (adjusted OR=0.85, 95% CI: 0.80– 0.89, P < 0.001, I2=69.8%, Tau2=0.026) and wheezing (adjusted OR=0.85, 95% CI: 0.81– 0.89, P < 0.001, I2=66.8%, Tau2=0.015) in children and adolescents. Conversely, unhealthy diets can exacerbate asthma (adjusted OR=1.28, 95% CI: 1.20– 1.36, P < 0.001, I2=64.9%, Tau2=0.019) and wheeze (adjusted OR=1.09, 95% CI: 1.02– 1.16, P =0.006, I2=75.2%, Tau2=0.023) in children and adolescents. The same trend was found in cohort studies (adjusted RR=0.72, 95% CI: 0.58– 0.90, P =0.003, I2=83.5%, Tau2=0.105). A clear trend was observed between high-frequency healthy diets (OR=0.80; 95% CI: 0.71– 0.89; P < 0.001) is more protective against asthma than low-frequency healthy diets (OR=0.81; 95% CI: 0.70– 0.94; P =0.007).Conclusion: Our findings highlight the protective effects of a healthy diet on asthma and wheezing in children, including fruit, seafood, cereals, and the Mediterranean diet.Keywords: dietary habits, wheezing, asthma, children, meta-analysis

Xiaoqin Niu, Bolong Hou, Lunyun Yang, Wei Wang, Qinlong Yu, Minjie Mao, Weifeng Shen Department of Clinical Laboratory, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, People’s Republic of ChinaCorrespondence: Weifeng Shen, Department of Clinical Laboratory, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing, Zhejiang, 314000, People’s Republic of China, Tel +86-18868345828, Email jyzhy526@163.comBackground: Urinary tract infections (UTIs) and the antibiotic resistance of pathogenic bacteria pose severe threats to public health in the current healthcare environment.Objective: The purpose of this study was to assess the frequency distribution of bacterial pathogens causing UTIs as well as the characteristics of antibiotic susceptibility and resistance.Methods: The retrospective study was conducted on 32,391 samples of midstream urine culture from January 1, 2020, to December 31, 2022, in Jiaxing. Bacteria were cultivated on blood agar and identified using MALDI-TOF, and their susceptibility to different antibiotics was assessed using the Kirby-Bauer disk diffusion method and drug sensitivity reaction cards. The SPSS 22 software was used for data analysis. Bivariate logistic regression was used to analyze the risk factors for multidrug resistance.Results: The total number of positive growth samples was 5378 (16.6%), including 3206 females (59.6%) and 2172 males (40.4%). The four most common urinary pathogens were Escherichia coli (39.2%), Enterococcus faecalis (12.4%), Klebsiella pneumoniae (7.6%), and Enterococcus faecium (7.6%). As far as antibiotic resistance was concerned, Escherichia coli had a greater than 50% resistance rate to ampicillin (76.1%), ciprofloxacin (58.6%), and levofloxacin (51.2%). The multidrug resistance rate was high (41.8%). Low levels of resistance were seen to ertapenem (0.1%), imipenem (0.7%), meropenem (0.7%), piperacillin/tazobactam (0.7%), and nitrofurantoin (1.8%). Klebsiella pneumoniae was highly sensitive to ertapenem (100%). The resistance rates to nitrofurantoin, ceftriaxone, and ciprofloxacin were 37.4%, 37.1%, and 35.1%, respectively. Up to 41% of Escherichia coli strains and 26% of Klebsiella pneumoniae strains produced extended-spectrum lactamases (ESBL). Two species of enterococci were highly sensitive to tigecycline and linezolid (100%), and a small number of norvancomycin-resistant strains (0.2%/two strains) were found.Conclusion: Escherichia coli and Enterococcus faecium were the most common urinary pathogens in this study. The isolated pathogens showed different sensitivity patterns. Antibiotics should be selected reasonably according to the sensitivity mode of pathogenic bacteria to effectively treat and prevent urinary tract infections.Keywords: antibiotic resistance, urinary tract infections, pathogenic bacteria, urine culture

Qi Yu,1,&ast; Jinqiang Guo,2,&ast; Fengyun Gong1 1Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China; 2Department of Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Yu; Fengyun Gong, Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China, Email fishns123@163.com; 2020jy0008@hust.edu.cnIntroduction: Tuberculosis (TB) is a life-threatening single infectious disease, which remains a major global public health concern. This study was to establish and validate a clinically practical diagnostic scoring system for predicting active pulmonary tuberculosis (APTB) in patients with positive tuberculosis T cell spot test [T-SPOT] using indicators associated with coagulation and inflammation.Methods: A single-center retrospective cross-sectional study was performed to include patients with positive T-SOPT registered and hospitalized at Wuhan Jinyintan Hospital between January 2017 and December 2019. All patients were separated into the active pulmonary tuberculosis (APTB) group and the inactive pulmonary tuberculosis (IPTB) group, according to the diagnostic criteria from China’s Expert Consensus for APTB and IPTB. Subsequently, the patients were randomized into a training set and a validation set at a ratio of 2:1. Indicators associated with coagulation and inflammation, including prothrombin time activity (PTA), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration (Fbg-C), C-reactive protein/albumin ratio (CAR), C-reactive protein/prealbumin ratio (CPR), neutrophils count/lymphocyte count ratio (NLR), platelet count/lymphocyte count ratio (PLR), monocyte count/lymphocyte count ratio (MLR), and erythrocyte sedimentation rate (ESR) were obtained from electronic medical record system (EMRS). Stepwise logistic regression was performed in the training set to build a diagnostic model for predicting APTB, which was transformed into an easily applicable scoring system via nomogram. Receiver operating characteristic (ROC) analysis, calibration curve (CC), and decision curve analysis (DCA) were conducted to evaluate the predictive performance of the established diagnostic scoring system.Results: A total of 508 patients [training set (211 cases of APTB and 116 cases of IPTB) and validation set (103 cases of APTB and 78 cases of IPTB)] with positive T-SPOT were recruited in the study. Stepwise logistic regression showed that CPR, MLR, ESR, APTT and Fbg-C were independent predictors for APTB. The scoring system was subsequently formulated based on the abovementioned predictors, which correspond to scores of 10, 6, 7, 5, and 5, respectively. In addition, patients are more likely to be diagnosed as APTB when the cut-off score was ≥ 16 scores, while patients with < 16 scores are more likely to be diagnosed as IPTB. The scoring system showed good predictive efficacy in both the training set [area under the curve (AUC): 0.887] and the validation set (AUC: 0.898). Furthermore, both CC and DCA confirmed the clinical utility of the scoring system.Conclusion: The data suggest that the combination of indicators associated with coagulation and inflammation could serve as biomarkers to identify APTB in patients with positive T-SPOT. In addition, patients with positive T-SPOT were more prone to be diagnosed with APTB when having a combined total of scores ≥ 16 in the scoring system.Keywords: coagulation indices, inflammatory biomarkers, scoring system, active pulmonary tuberculosis

Dan He,1,&ast; Qiao Yu,2,&ast; Xiaona Zeng,2,&ast; Jihua Feng,2 Ruiqi Yang,2 Huan Wan,2 Ying Zhong,2 Yanli Yang,2 Ruzhi Zhao,2 Junyu Lu,3,4 Jianfeng Zhang1,2,4 1Department of General Practice, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 2Department of Emergency Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 3Intensive Care Unit, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, People’s Republic of China; 4Guangxi Health Commission Key Laboratory of Emergency and Critical Medicine, Nanning, 530007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Zhang, Junyu Lu, The Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxuedong Road, Nanning, Guangxi, 530007, People’s Republic of China, Tel +86 7713277166, Fax +86 7713277285, Email zhangjianfeng@gxmu.edu.cn; junyulu@gxmu.edu.cnBackground: Acute respiratory distress syndrome (ARDS) is caused by severe pulmonary inflammation and the leading cause of death in the intensive care unit.Methods: We used single-cell RNA sequencing to compare peripheral blood mononuclear cells from sepsis-induced ARDS (SEP-ARDS) and pneumonic ARDS (PNE-ARDS) patient. Then, we used the GSE152978 and GSE152979 datasets to identify molecular dysregulation mechanisms at the transcriptional level in ARDS.Results: Markedly increased CD14 cells were the predominant immune cell type observed in SEP-ARDS and PNE-ARDS patients. Cytotoxic cells and natural killer (NK) T cells were exclusively identified in patients with PNE-ARDS. An enrichment analysis of differentially expressed genes (DEGs) suggested that Th1 cell differentiation and Th2 cell differentiation were enriched in cytotoxic cells, and that the IL-17 signaling pathway, NOD receptor signaling pathway, and complement and coagulation cascades were enriched in CD14 cells. Furthermore, according to GSE152978 and GSE152979, 1939 DEGs were identified in patients with ARDS and controls; they were mainly enriched in the Kyoto Encyclopedia of Genes and Genomes pathways. RBP7 had the highest area under the curve values among the 12 hub genes and was mainly expressed in CD14 cells. Additionally, hub genes were negatively correlated with NK cells and positively correlated with neutrophils, cytotoxic cells, B cells, and macrophages.Conclusion: A severe imbalance in the proportion of immune cells and immune dysfunction were observed in SEP-ARDS and PNE-ARDS patients. RBP7 may be immunologically associated with CD14 cells and serve as a potential marker of ARDS.Keywords: acute respiratory distress syndrome, single-cell RNA sequencing, biomarker, immune disorders, differentially expressed genes

Jipeng Shi,1 Zhen-Qi Lu,1 Qing-Mei Lin,2 Wang Zeng,1 Ping-Jiao Gu,1 Qing Yu,3 Jing Long,1 Da-Gui Huang,1 Yi-Heng Dai1 1Department of Neonatal, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of China; 2Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of ChinaCorrespondence: Yi-Heng Dai, Email daiyiheng@163.comBackground: There are many difficulties and uncertainties in the early diagnosis of neonatal sepsis. The aim of this study was to determine whether albumin (ALB) is useful for the early diagnosis of neonatal sepsis using ALB, C-reactive protein (CRP) and procalcitonin (PCT) together.Methods: ALB, CRP, PCT and white blood cell (WBC) data from 732 patients with neonatal sepsis and 1317 neonatal infection patients hospitalized in Foshan Maternal and Child Health Hospital from 2011 to 2022 were collected. Receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the diagnostic value of ALB, CRP, PCT and the WBC count for neonatal sepsis. The roles of ALB, CRP, PCT and the WBC count in the diagnosis of neonatal sepsis were analysed by using subject working characteristics (ROC) and areas under the curve (AUCs), and the variables were combined to determine which combination had the best diagnostic efficacy.Results: In the sepsis group, the ALB, CRP, and PCT levels and the WBC count were significantly higher than those in the infection group (P< 0.001). In all infants, the sensitivities and specificities of ALB, CRP, PCT, and WBC count were 0.411, 0.596, 0.483 and 0.411, respectively, and 0.833, 0.846, 0.901 and 0.796, respectively. With a sensitivity of 0.646, a specificity of 0.929, and an AUC of 0.834, the best combination was that of ALB, CRP, and PCT, which was better than that of CRP + PCT, CRP + ALB and PCT + ALB.Conclusion: In neonatal sepsis, in the absence of blood culture results, the combination of ALB, CRP, and PCT is more reliable than CRP, PCT, or CRP+PCT alone. These results suggest that ALB is a useful inflammatory biomarker for the early diagnosis of neonatal sepsis, and can improve the diagnostic efficiency.Keywords: albumin, C-reactive protein, procalcitonin, diagnosis, neonatal sepsis

Yunxia Huang,1,&ast; Yi Guo,2,&ast; Qin Xiao,3,&ast; Shuyu Liang,2 Qiang Yu,4 Lang Qian,1 Jin Zhou,1 Jian Le,1 Yuchen Pei,5 Lei Wang,4 Cai Chang,1 Sheng Chen,4 Shichong Zhou1 1Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 3Department of Electronic Engineering, Fudan University and Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Shanghai, People’s Republic of China; 4Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 5Precision Cancer Medical Center Affiliated to Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shichong Zhou, Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 21-64175590, Email sczhou@hotmail.com Sheng Chen, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86 21-64175590, Email 0456177@fudan.edu.cnPurpose: The emergence of genomic targeted therapy has improved the prospects of treatment for breast cancer (BC). However, genetic testing relies on invasive and sophisticated procedures.Patients and Methods: Here, we performed ultrasound (US) and target sequencing to unravel the possible association between US radiomics features and somatic mutations in TNBC (n=83) and non-TNBC (n=83) patients. Least absolute shrinkage and selection operator (Lasso) were utilized to perform radiomic feature selection. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was utilized to identify the signaling pathways associated with radiomic features.Results: Thirteen differently represented radiomic features were identified in TNBC and non-TNBC, including tumor shape, textual, and intensity features. The US radiomic–gene pairs were differently exhibited between TNBC and non-TNBC. Further investigation with KEGG verified radiomic–pathway (ie, JAK-STAT, MAPK, Ras, Wnt, microRNAs in cancer, PI3K-Akt) associations in TNBC and non-TNBC.Conclusion: The pivotal network provided the connections of US radiogenomic signature and target sequencing for non-invasive genetic assessment of precise BC treatment.Keywords: triple-negative breast cancer, radiomics, somatic mutation, signaling pathway

Qiaochu Zhou,1 Wei Wang,2 Qi Yu,1 Jinhui Wang,1 Wenzheng Zhu1 1Department of Dermatology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Gynecology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai University, Wenzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Wei Wang, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine of Shanghai University, 75Jinxiu, Wenzhou, 325000, People’s Republic of China, Tel +8613968900070, Fax +8657788980818, Email w2wangwei@126.comObjective: Hairline vitiligo is a special area. Hairy areas within the hairline often require repigmentation and regrowing hair shafts. The face and forehead outside the hairline do not require regrowing hair shafts, only repigmentation. To tackle this issue, we modified the conventional mini-punch grafting with a combined application of mini-punch grafting and follicular hair transplant.Methods: Five patients with localized hairline stable vitiligo aged 26– 32 years old had a history of nonsurgical treatments for at least 3 months and without progress. The grafts were transversely sectioned. The intact half follicles were preserved below the cross-section. Sectioned grafts were placed into the chambers for transplanting with forceps.Results: The treatment using transversely sectioned mini-punch grafting with the patient was performed for all five patients, and the results were satisfactory. In the area of the forehead outside the hairline with the sectioned mini-punch grafting above the cross-section, hair loss and repigmentation were observed. In the area of the hairy areas within the hairline, growing hair shafts and repigmentation were observed, without hair loss.Conclusion: Our report can help to manage hairline vitiligo or hairy areas vitiligo. This method can be considered a potential method for the treatment of hairline vitiligo, thus providing a simple solution to complex problems.Keywords: vitiligo, punch grafting, mini-punch grafting, skin punch

Rui Wang,1,&ast; Yijing Yao,1,2,&ast; Yihui Gao,1 Mengyao Liu,1 Qian Yu,3 Xuejiao Song,4 Xiao Han,5 Dechao Niu,6 Lixin Jiang1,2 1Department of Ultrasound, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, People’s Republic of China; 2Shanghai Institute of Ultrasound in Medicine, Shanghai, 200233, People’s Republic of China; 3Department of Ultrasonography, Shanghai Jiao Tong University Affiliated No. 6 Hospital, Shanghai, 200233, People’s Republic of China; 4School of Physical and Mathematical Sciences, Nanjing Tech University (NanjingTech), Nanjing, 211800, People’s Republic of China; 5Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu, 215123, People’s Republic of China; 6Lab of Low-Dimensional Materials Chemistry, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixin Jiang; Dechao Niu, Email jinger_28@sina.com; dcniu@ecust.edu.cnBackground: Pancreatic cancer is regarded as one of the most lethal types of tumor in the world, and optional way to treat the tumor are urgently needed. Cancer stem cells (CSCs) play a key role in the occurrence and development of pancreatic tumors. CD133 is a specific antigen for targeting the pancreatic CSCs subpopulation. Previous studies have shown that CSC-targeted therapy is effective in inhibiting tumorigenesis and transmission. However, CD133 targeted therapy combined with HIFU for pancreatic cancer is absent.Purpose: To improve therapeutic efficiency and minimize side effects, we carry a potent combination of CSCs antibody with synergist by an effective and visualized delivery nanocarrier to pancreatic cancer.Materials and Methods: Multifunctional CD133-targeted nanovesicles (CD133-grafted Cy5.5/PFOB@P-HVs) with encapsulated perfluorooctyl bromide (PFOB) in a 3-mercaptopropyltrimethoxysilane (MPTMS) shell modified with poly ethylene glycol (PEG) and superficially modified with CD133 and Cy 5.5 were constructed following the prescribed order. The nanovesicles were characterized for the biological and chemical characteristics feature. We explored the specific targeting capacity in vitro and the therapeutic effect in vivo.Results: The in vitro targeting experiment and in vivo FL and ultrasonic experiments showed the aggregation of CD133-grafted Cy5.5/PFOB@P-HVs around CSCs. In vivo FL imaging experiments demonstrated that the nanovesicles assemble for the highest concentration in the tumor at 24 h after administration. Under HIFU irradiation, the synergistic efficacy of the combination of the CD133-targeting carrier and HIFU for tumor treatment was obvious.Conclusion: CD133-grafted Cy5.5/PFOB@P-HVs combined with HIFU irradiation could enhance the tumor treatment effect not only by improving the delivery of nanovesicles but also by enhancing the HIFU thermal and mechanical effects in the tumor microenvironment, which is a highly effective targeted therapy for treating pancreatic cancer.Keywords: multifunctional nanovesicles, cancer stem cells, high-intensity focused ultrasound, in vivo fluorescent imaging, ultrasonic imaging

Liangjie Lu,1 Haiming Fang,1 Mengchao Gu,1 Huihan Wang,2 Qiuxia Yu,3 Aqiong Chen,3 Kai-feng Gan1 1Department of Orthopaedics, Li Huili Hospital Affiliated to Ningbo University, Ningbo, 315040, People’s Republic of China; 2Department of Orthopaedics, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, People’s Republic of China; 3Department of Rheumatology, Li Huili Hospital Affiliated to Ningbo University, Ningbo, 315040, People’s Republic of ChinaCorrespondence: Kai-feng Gan, Tel +86-15724288924, Email gankaifeng1982@163.comPurpose: This study aimed to compare the changes in the expression of microRNA Let-7i in peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and the correlation between Let-7i and innate pro-inflammatory factors. It is necessary to search for a new biomarker to guide the prognosis of AS.Methods: A total of 10 patients with AS and 10 healthy volunteers were selected as AS and control groups, respectively. The expression levels of Let-7i, Toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and interferon-gamma (IFN-γ) in PBMCs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting (WB) to explore the relationship between Let-7i and pro-inflammatory factors. Furthermore, the relationship between Let-7i and TLR4 was determined by the luciferase reporter technology.Results: The expression level of Let-7i in PBMCs of patients with AS was significantly lower than that of healthy control. The expression levels of TLR4, NF-κB, and IFN-γ in PBMCs derived from patients with AS were significantly higher than those of healthy control. The results show that Let-7i manipulation can regulate lipopolysaccharide (LPS)-induced TLR4 and IFN-γ expression in CD4+ T cells of patients with AS. The overexpression of Let-7i in T cells of patients with AS can suppress TLR4 and IFN-γ LPS-induced expression levels of cellular mRNA and protein. Let-7i can directly interfere TLR4-3’untranslated region (UTR) sequence and regulate the expression of the TLR4 gene in Jurkat T cells.Conclusion: Let-7i may be involved in the pathogenesis of AS, and Let-7i expression in PBMCs may be helpful for the diagnosis and treatment of AS in the future.Keywords: ankylosing spondylitis, Let-7i, TLR4, innate inflammatory

Qingquan Yu, Wanying Cao, Xiaoyu Wang, Wei He, Xiaoyue Sun, Lizhen Chen, Yangshuai Su, Zhiyun Zhang, Xianghong Jing Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Zhiyun Zhang; Xianghong Jing, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, 16th Nanxiaojie of Dongzhimennei, Beijing, 100700, People’s Republic of China, Email zhangzhyun@yeah.net; jxhtjb@263.netPurpose: Spinal wide dynamic range (WDR) neurons are well studied in pain models and they play critical roles in regulating nociception. Evidence has started to accumulate that acupuncture produces a good analgesic effect via activating different primary fibers with distinct intensities. The purpose of the present study was to compare the distinct intensities of pre-electroacupuncture (pre-EA) at local muscular receptive fields (RFs), adjacent or contralateral non-RFs regulating the nociceptive discharges of spinal WDR neurons evoked by hypertonic saline (HS).Materials and Methods: Spinal segments of electrophysiological recording were identified by neural tracers applied at the left gastrocnemius muscle. The thresholds of Aβ (TAβ), Aδ (TAδ) and C (TC) components of WDR neurons were measured to determine the intensity of pre-EA by extracellular recording. The discharges of WDR neurons induced by distinct intensities of pre-EA and 200 μL HS (6%) injection in left gastrocnemius muscle of rats were observed by extracellular recording.Results: The spinal segments of WDR neurons were confirmed in lumbar (L)5– 6 area according to the projective segments of dorsal root ganglion. TAβ, TAδ and TC of WDR neurons was determined to be 0.5, 1, and 2 mA, respectively. The pre-EA with intensities of TAβ (P < 0.05), TAδ (P < 0.05), TC (P < 0.05) or 2TC (P < 0.01) at ipsilateral adjacent non-RFs significantly reduced the discharges of WDR neurons, while at local RFs only pre-EA of TAδ (P < 0.05), TC (P < 0.05) and 2TC (P < 0.01) could inhibit the nociceptive discharges. In addition, intensity of pre-EA at contralateral non-RFs should reach at least TC to effectively inhibit the firing rates of WDR neurons (P < 0.01).Conclusion: Pre-EA could suppress nociceptive discharges of WDR neurons and the inhibitory effects were dependent on the distinct intensities and locations of stimulation.Keywords: pre-electroacupuncture, wide dynamic range neurons, muscular receptive fields, intensity, hypertonic saline

Song-Xing Wang,&ast; Li-Yan Sun,&ast; Qiong Yu, Tong Li, Ran Li, Yun-Ping Xu, Jin-Feng Zeng Shenzhen Blood Center, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yun-Ping Xu; Jin-Feng Zeng, Email yunpingxu1982@qq.com; zzengjf@163.comBackground: New HIV (Human immune deficiency virus) infections are continuously increasing in China and it remains a huge challenge to blood donation. As access to health services has affected by COVID-19 (Corona virus disease 2019) pandemic, a drop in new diagnoses (especially HIV) was observed worldwide.Methods: During 2013– 2021, 735,247 specimens from unpaid blood donors collected by Shenzhen Blood Center underwent ELISA (Enzyme -linked immunosorbent assay) and NAT (Nucleic acid test). Samples with reactivity results were sent to the Shenzhen Center for Disease Control and Prevention for WB (Western blot). All data were statistically analyzed by the Chi-Square test.Results: From 2013 to 2021, the prevalence of HIV among male blood donors was higher than in females (P < 0.01). During the COVID-19 pandemic, the prevalence of HIV among repeat blood donors decreased significantly compared to 2019 (P < 0.05), and the characteristics of blood donors changed in 2020 compared to 2019 and 2021.Conclusion: The high proportion of female blood donors would help prevent HIV from getting into the blood supply. The COVID-19 pandemic affected the demographics of blood donors as well as the prevalence of HIV among repeat blood donors. An increased number of repeat blood donors can help decrease the risk of HIV transfusion transmission during the epidemic.Keywords: COVID-19, Shenzhen, blood donors, HIV

Qian Yu,1,&ast; Chentao Shen,2,3,&ast; Xiangsheng Wang,4 Zhenxing Wang,5,6 Lu Liu,2,3 Jufang Zhang4 1Research Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100144, People’s Republic of China; 2Department of Gastrointestinal Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Cancer Research Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 4Department of Plastic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 5Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 6Wuhan Clinical Research Center for Superficial Organ Reconstruction, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jufang Zhang; Lu Liu, Tel +86-18800293916 ; +86-13476226821, Fax +86-571-87914773 ; +86-27-83662640, Email doctorzjf@zju.edu.cn; halesan@163.comPurpose: We aimed to develop an antioxidant dressing material with pro-angiogenic potential that could promote wound healing. Gelatin (Gel) was selected to improve the biocompatibility of the scaffolds, while graphene oxide (GO) was added to enhance their mechanical property. The loaded N-Acetyl cysteine (NAC) was performing the effect of scavenging reactive oxygen species (ROS) at the wound site.Materials and Methods: The physicochemical and mechanical properties, NAC releases, and biocompatibility of the NAC-GO-Gel scaffolds were evaluated in vitro. The regeneration capability of the scaffolds was systemically investigated in vivo using the excisional wound-splinting model in mice.Results: The NAC-GO-Gel scaffold had a stronger mechanical property and sustainer NAC release ability than the single Gel scaffold, which resulted in a better capacity for cell proliferation and migration. Mice wound-splinting models revealed that the NAC-GO-Gel scaffold effectively accelerated wound healing, promoted re-epithelialization, enhanced neovascularization, and reduced scar formation.Conclusion: The NAC-GO-Gel scaffold not only promotes wound healing but also reduces scar formation, showing a great potential application for the repair of skin defects.Keywords: gelatin, graphene oxide, electrospinning, NAC, wound healing

Jisong Yan,1 Hong Luo,1 Qi Nie,1 Shengling Hu,2 Qi Yu,2 Xianguang Wang1 1Department of Respiratory and Critical Care Medicine, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China; 2Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of ChinaCorrespondence: Qi Yu, Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China, Email fishns123@163.com Xianguang Wang, Department of Respiratory and Critical Care Medicine, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China, Email 907395635@qq.comBackground: The growth of antibiotic resistance to Mycobacterium TB represents a major barrier to the goal of “Ending the global TB epidemics”. This study aimed to develop and validate a simple clinical scoring system to predict the unfavorable treatment outcomes (UTO) in multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) patients.Methods: A total of 333 MDR/RR-TB patients were recruited retrospectively. The clinical, radiological and laboratory features were gathered and selected by lasso regression. These variables with area under the receiver operating characteristic curve (AUC)> 0.6 were subsequently submitted to multivariate logistic analysis. The binomial logistic model was used for establishing a scoring system based on the nomogram at the training set (N = 241). Then, another independent set was used to validate the scoring system (N = 92).Results: The new scoring system consists of age (8 points), education level (10 points), bronchiectasis (4 points), red blood cell distribution width-coefficient of variation (RDW-CV) (7 points), international normalized ratio (INR) (7 points), albumin to globulin ratio (AGR) (5 points), and C-reactive protein to prealbumin ratio (CPR) (6 points). The scoring system identifying UTO has a discriminatory power of 0.887 (95% CI=0.835– 0.939) in the training set, and 0.805 (95% CI=0.714– 0.896) in the validation set. In addition, the scoring system is used exclusively to predict the death of MDR/RR-TB and has shown excellent performance in both training and validation sets, with AUC of 0.930 (95% CI=0.872– 0.989) and 0.872 (95% CI=0.778– 0.967), respectively.Conclusion: This novel scoring system based on seven accessible predictors has exhibited good predictive performance in predicting UTO, especially in predicting death risk.Keywords: multidrug- and rifampicin-resistant tuberculosis, treatment outcome, laboratory parameters, scoring system

Minhua Li,1,&ast; Zehui Qin,1,&ast; Qiuxia Yu,2 Ziwei Huang,3 Juanjuan Cheng,1 Linjiang Zhong,1 Yuhong Liu,1 Jianhui Xie,4– 6 Yucui Li,1 Jiannan Chen,1 Ruoting Zhan,1 Ziren Su1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 2The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 3The First Affiliated Hospital of Chinese Medicine Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 4The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 5State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China; 6Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruoting Zhan; Ziren Su, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, no. 232, Waihuandong Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, People’s Republic of China, Email zhanrt@gzucm.edu.cn; suziren@gzucm.edu.cnBackground: Berberine (BBR) is the primary active component of Phellodendri Chinensis Cortex (PCC), which has been traditionally used to treat inflammatory diseases. However, the discrepancy between its low bioavailability and significant therapeutic effect remains obscure. The purpose of this study was to explore the previously unsolved enigma of the low bioavailability of BBR and its appreciable anti-inflammatory effect to reveal the action mechanism of BBR and PCC.Methods: The quantitative analysis of BBR and its metabolite oxyberberine (OBB) in blood and tissues was performed using high-performance liquid chromatography to investigate the conversion and distribution of BBR/OBB mediated by erythrocytes. Routine blood tests and immunohistochemical staining were used to explore the potential relationship between the amounts of monocyte/macrophage and the drug concentration in erythrocytes and tissues (liver, heart, spleen, lung, kidney, intestine, muscle, brain and pancreas). To comparatively explore the anti-inflammatory effects of BBR and OBB, the acetic acid-induced vascular permeability mice model and lipopolysaccharide-induced RAW 264.7 macrophages were employed.Results: Nearly 92% of BBR existed in the erythrocytes in rats. The partition coefficient of BBR between plasma and erythrocytes (Kp/b) decreased with time. OBB was found to be the oxidative metabolite of BBR in erythrocytes. Proportion of BBR/OBB in erythrocytes changed from 9.38% to 16.30% and from 13.50% to 46.24%, respectively. There was a significant relationship between the BBR/OBB concentration in blood and monocyte depletion after a single administration of BBR. BBR/OBB was transported via erythrocytes to various tissues (liver, kidney, spleen, lung, and heart, etc), with the liver achieving the highest concentration. OBB exhibited similar anti-inflammatory effect in vitro and in vivo as BBR with much smaller dosage.Conclusion: BBR was prodominantly found in erythrocytes, which was critically participated in the biodistribution, pharmacokinetics, metabolism and target delivery of BBR and its metabolite. The anti-inflammatory activity of BBR and PCC was intimately associated with the metabolism into the active congener OBB and the targeted delivery to monocytes/macrophages mediated by the erythrocytes.Graphical Abstract: Keywords: erythrocytes, Phellodendri Chinensis Cortex, transformation, berberine, anti-inflammation

Wenqi Shen, Qifeng Yu, Yuwei Pu, Chungen Xing Department of General Surgery, Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Chungen Xing; Yuwei Pu, Email xingcg@suda.edu.cn; puyuwei2017@163.comBackground: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a conserved transcript with 8000 nt, is highly associated with malignancy of numerous cancer types. However, the function of MALAT1 plays in regulating the response to radiotherapy in colorectal cancer (CRC) remains unclear. Thus, the object of this study is to investigate the functions of MALAT1 in CRC radioresistance.Methods: First, the expression of MALAT1 in colon adenocarcinoma (COAD) was analyzed through the Cancer Genome Atlas (TCGA) database. Then, we detected the expression level of MALAT1 in tumor tissues and CRC cell lines and analyzed the relevance of MALAT1 and clinicopathological parameters. In the end, the effect of silencing MALAT1 on the radiosensitivity of CRC cells was investigated, and its potential mechanism was preliminarily illustrated.Results: The analysis of TCGA data showed that MALAT1 was closely related to the type of tumor, and high expression of MALAT1 was remarkably relevant to poor outcome. MALAT1 was highly expressed in CRC tissues and cell lines and related to tumor stages. Knockdown of MALAT1 could significantly suppress colony survival, proliferation, and migration and increase apoptosis, G2/M phase arrest, and formation of gamma-H2AX foci in HCT116, whether in combination with X-rays or not. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that the regulated proteins were principally enriched in the glycosaminoglycan degradation pathway after silencing MALAT1.Conclusion: Our results implied that MALAT1 was highly expressed in CRC and associated with tumor stage and prognosis. Silencing MALAT1 can increase HCT116 cell radiosensitivity, which may be potentially influenced by glycosaminoglycan degradation pathway.Keywords: lnc RNA MALAT1, radiation sensitivity, aggressive phenotypes, colorectal cancer, prognosis

Zhe Chen,1– 5,&ast; Jiefeng Luo,1– 5,&ast; Siyu Li,1– 4,6 Peipei Xu,1– 4,6 Linan Zeng,1– 4 Qin Yu,4,7 Lingli Zhang1– 4 1Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China; 3NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation, Chengdu, People’s Republic of China; 4Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, People’s Republic of China; 5West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China; 6West China School of Medicine, Sichuan University, Chengdu, People’s Republic of China; 7National Drug Clinical Trial Institute, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingli Zhang, Email zhanglingli@scu.edu.cn Qin Yu, Email 908929936@qq.comPurpose: The systematic review aims to analyze and summarize the characteristics of living systematic review (LSR) for coronavirus disease 2019 (COVID-19).Methods: Six databases including Medline, Excerpta Medica (Embase), Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database and China Science, and Technology Journal Database (VIP), were searched as the source of basic information and methodology of LSR. Descriptive analytical methods were used to analyze the included COVID-19 LSRs, and the study characteristics of COVID-19 LSRs were further assessed.Results: Sixty-four COVID-19 LSRs were included. Eighty-nine point one percent of LSRs were published on Science Citation Index (SCI) journals, and 64.1% publication with an impact factor (IF) > 5 and 17.2% with an IF > 15 among SCI journals. The first unit of the published LSRs for COVID-19 came from 19 countries, with the largest contribution from the UK (17.2%, 11/64). Forty point six percent of LSRs for COVID-19 were related to therapeutics topic which was considered the most concerned perspective for LSRs for COVID-19. Seventy-six point six percent of LSRs focused on the general population, with less attention to children, pregnant women and the elderly. However, the LSR for COVID-19 was reported incomplete on “living” process, including 40.6% of studies without search frequency, 79.7% of studies without screening frequency, 20.3% of studies without update frequency, and 65.6% of studies without the timing or criteria of transitioning LSR out of living mode.Conclusion: Although researchers in many countries have applied LSRs to COVID-19, most of the LSRs for COVID-19 were incomplete in reporting on the “living” process and less focused on special populations. This could reduce the confidence of health-care providers and policy makers in the results of COVID-19 LSR, thereby hindering the translation of evidence on COVID-19 LSR into clinical practice. It was necessary to explicitly enact preferred reporting items for systematic reviews and meta-analyses (PRISMA) to improve the reporting quality of LSR and support ongoing efforts of therapeutics research for special patients with COVID-19.Keywords: living systematic review, coronavirus disease 2019, systematic review, reporting quality

Qi Yu,1 Wujin Weng,2 Hong Luo,3 Jisong Yan,3 Xin Zhao4 1Department of Infectious Diseases, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology; Hubei Clinical Research Center for Infectious Diseases; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of China; 2Department of Oncology, Quzhou Hospital of Traditional Chinese Medicine, Zhejiang University of Chinese Medicine, Quzhou, 310053, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology; Hubei Clinical Research Center for Infectious Diseases; Wuhan Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences; Joint Laboratory of Infectious Diseases and Health, Wuhan Institute of Virology and Wuhan Jinyintan Hospital, Chinese Academy of Sciences, Wuhan, 430023, People’s Republic of China; 4Department of Pediatrics, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, People’s Republic of ChinaCorrespondence: Jisong Yan, Department of Respiratory and Critical Care Medicine, Wuhan Jinyintan Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430023, People’s Republic of China, Email Jisongyan163@163.com Xin Zhao, Department of Pediatrics, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, People’s Republic of China, Email 443608693@qq.comPurpose: This study was to explore the predictive value of monocyte to high-density lipoprotein cholesterol ratio (MHR), neutrophils to high-density lipoprotein cholesterol ratio (NHR), C-reactive protein-to-lymphocyte ratio (CLR), and C-reactive protein-to-albumin ratio (CAR) for type 2 diabetes mellitus (T2DM) in patients with active pulmonary tuberculosis (APTB).Patients and Methods: A total of 991 active pulmonary tuberculosis (APTB) patients (201 with T2DM) were hospitalized in the Department of Tuberculosis, Wuhan Jinyintan Hospital, Tongji Medical College, Huazhong University of Science and Technology were included. The routine blood examination indicators and biochemical parameters were collected to calculate MHR, NHR, CLR, and CAR. The Pearson correlation analysis, Univariate Logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were performed to assess the predictive value of MHR, NHR, CLR, and CAR for APTB-T2DM patients.Results: The levels of MHR, NHR, CLR, and CAR in the APTB-T2DM patients were significantly higher than in the APTB-no T2DM patients (P < 0.05). Additionally, the MHR, NHR, CLR, and CAR have a positive correlation with fasting blood glucose in the whole study population. However, in the APTB-T2DM patients, MHR, NHR, and CAR were not correlated with fasting blood glucose, and only CLR was positively correlated with fasting blood glucose. The area under curve (AUC) predicting APTB-T2DM patients of the MHR, NHR, CLR, and CAR was 0.632, 0.72, 0.715, and 0.713, respectively. Further, univariate logistic regression analyses showed that the higher MHR, NHR, CLR, and CAR were independent risk factors for APTB-T2DM (P < 0.01). The MHR, NHR, CLR, and CAR quartiles were used to divide the APTB patients into four groups for further analysis. The prevalence of T2DM was significantly higher in APTB individuals as MHR, NHR, CLR, and CAR values increased (P < 0.05).Conclusion: MHR, NHR, CLR, and CAR are simple and practicable inflammatory parameters that could be used for assessing T2DM in APTB. APTB patients have a greater possibility to be diagnosed with T2DM with the higher MHR, NHR CLR, and CAR values. Therefore, more attention should be given to the indicator in the examination of APTB.Keywords: active pulmonary tuberculosis, type 2 diabetes mellitus, MHR, NHR, CLR, CAR

Yueyao Jiang,1 Yichuan Jiang,1 Zhiying Ding,2 Qian Yu1 1Department of Pharmacy, China-Japan Union Hospital, Jilin University, Changchun, 130033, People’s Republic of China; 2Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Qian Yu, Department of Pharmacy, China-Japan Union Hospital, Jilin University, Changchun, 130033, People’s Republic of China, Tel +86 13664419002, Email yuqian@jlu.edu.cnPurpose: While developing huperzine A (HupA) to explore new approaches to treating Alzheimer’s disease (AD), intranasal administration was proposed as an alternative route to deliver drugs into the brain. This study aimed to prepare nanoemulsions (NEs) of HupA to investigate their potential “nose-to-brain” pathways and to evaluate their pharmacokinetic and brain-targeting parameters.Methods: HupA-NE and Lf-HupA-NE that underwent surface modification with lactoferrin (Lf) were characterized to determine various physicochemical properties, such as their size, PDI, zeta potential, pH, and loading efficiency; in addition, transmission electron microscopy and stability assessments were performed. We utilized an aggregation-caused quenching (ACQ) probe to monitor intact NEs in the brains of olfactory nerve transection model and normal rats. Immunohistochemistry, pharmacokinetic and targeting index analyses were performed to investigate the in vivo effects of HupA-NE and Lf-HupA-NE.Results: Based on the live imaging results, HupA-NE and Lf-HupA-NE could be transported into the brain via nerve and blood circulation pathways. Immunohistochemical staining tests demonstrated that the efflux proteins P-gp, MRP1, and BCRP were expressed in brain tissue. NEs can inhibit efflux pumps to improve drug concentrations in the brain. The findings of this study showed that NEs (especially Lf-HupA-NE) had better pharmacokinetic profiles and a better nose-to-brain drug transport efficiency than free HupA.Conclusion: The newly designed formulations might contribute to the transport and accumulation of HupA to achieve therapeutic results. The delivery system may be a promising strategy for the brain-targeted delivery of HupA.Graphical Abstract: Keywords: intranasal administration, nanoemulsions, “nose-to-brain” pathway, pharmacokinetics

Hongxin Shen,1– 3 Yuzhi Fu,1– 3 Ying Chen,1– 3 Wenxing Xia,1– 3 Zhi-Jun Jia,1– 4 Qin Yu,3,5 Lingli Zhang,1– 3 Lu Han1– 3 1Department of Pharmacy, West China Second University Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Evidence-Based Pharmacy Center, West China Second University Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of China; 4West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China; 5Institute of Drug Clinical Trial GCP, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Lu Han, West China Second University Hospital, Sichuan University, No. 20, Third Section, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email luhan830301@sina.comObjective: Pediatric electrolyte supplements injection is mainly used to supplement heat and body fluid, and commonly used in pediatrics. Its compatibility and stability with common clinical drugs such as antibiotics was rarely reported to ensure the children’s safety and the rational use of drugs. The aim of the present study was to investigate physical and chemical stability of pediatric electrolyte supplements injection mixed with ten commonly used clinical drugs.Methods: According to clinical drug concentration, we mix the pediatric electrolyte supplements injection mixed with ten drugs. The compatible solutions were withdrawn at certain time intervals (0, 0.5, 1, 2, 4, 6 hours) after mixing and tested by description, insoluble particles detection, pH determination and high performance liquid chromatography (HPLC) assay of active ingredient as measures of physicochemical compatibility.Results: No obvious appearance changes were observed when mixing. Furthermore, over the 6 hours post-preparation period the pH values were within the requirements of each drug quality standard and the number of insoluble particles (≥ 10 and ≥ 25μm) met requirements of Chinese Pharmacopeia (Edition 2020) except for mezlocillin sodium for injection. The percentages of the initial concentrations maintained at a minimum of 97% in the mixtures within 6 hours.Conclusions: Nine commonly used clinical drugs remained stable in the pediatric electrolyte supplements injection for 6 hours at 25°C and avoiding from light. Mezlocillin sodium for injection was not recommended to be combined with electrolyte supplement injection for children because its insoluble particles exceed the standard.Keywords: compatibility, stability, pediatric electrolyte supplements injection

Qiuxia Yu,* Gaoxiang Wang,* Jue Wang, Wei Zhang, Li Meng, Yang Cao Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang Cao, Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People’s Republic of China, Tel +86 2783662680, Fax +86 2783662680, Email caoyangemma@163.comAbstract: Philadelphia chromosome positive B cell lymphoblastic lymphoma (Ph+ B-LBL) is an extremely rare disease. We report a 27-year-old patient diagnosed with primary testicular and cutaneous Ph+ B-LBL without bone marrow involvement. The CCCG-LBL-2016 regimen (https://clinicaltrials.gov/ct2/show/NCT02845882) was initially administered due to the fast pathological diagnosis as B-LBL that was first obtained. To identify potential therapeutic targets, RNA sequencing (RNAseq) was also performed on lymph node specimens as a part of the routine diagnostic workup in our center. Unexpectedly, IKZF1 deletions and BCR-ABL1 fusion transcripts were detected. Based on these results, we retrospectively performed fluorescence in situ hybridization (FISH) for BCR/ABL1 rearrangements in the same lymph node specimen, and a 70% positive signal was detected. The patient subsequently received the CCCG-LBL-2016 protocol combined with the BCR-ABL tyrosine kinase inhibitor (TKI) dasatinib, along with prophylactic intrathecal infusion. Then, the patient underwent TBI-based haploidentical (haplo) allogeneic hematopoietic stem cell transplantation (haplo-allo-HSCT) as consolidation following the achievement of remission and continued taking dasatinib as maintenance therapy. The patient was still in complete remission 1 year after diagnosis. This case indicates that the detection of potential molecular targets, especially those targets that can be pharmacologically treated, such as BCR/ABL1 fusion transcripts, is of important value to both LBL diagnosis and therapeutic strategy choices. FISH, reverse transcriptase polymerase chain reaction (RT-PCR) and/or RNAseq should be routinely carried out in lymphoma specimens to depict its genetic landscape for the further execution of a precise therapy strategy.Keywords: B-cell lymphoblastic lymphoma, Philadelphia chromosome, tyrosine kinase inhibitor, hematopoietic stem cell transplantation

Junnan Peng,* Rui Tang,* Di Qi, Qian Yu, Hao Hu, Wen Tang, Jing He, Daoxin Wang Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Daoxin Wang; Jing He, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing, 400010, People’s Republic of China, Email wangdaoxin0163@163.com; miss_hejing@126.comBackground: Eosinophils play an essential role in the pathogenesis of acute respiratory distress syndrome (ARDS). We aimed to assess the association between the baseline blood eosinophils, eosinophil changes during the first week in the intensive care unit (ICU) and short-term patient outcomes.Methods: All patients meeting the Berlin definition of ARDS from the Medical Information Mart for Intensive Care IV database were retrospectively analyzed. We used logistic regression, Kaplan–Meier survival and random forest analysis to determine the association between the baseline eosinophils and short-term mortality. Then the trends in eosinophils over time were compared between the survivors and non-survivors using a generalized additive mixed model (GAMM), which is a common approach used for analysis of repeated measurement data. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the predictive value.Results: A total of 1685 patients were included, and the 30-day mortality was 25.1%. Kaplan–Meier analysis showed that patients with high baseline eosinophils (> 0.3%) had lower 30-day mortality (p < 0.001). Random forest model selected the baseline eosinophils as an important factor associated with 30-day mortality. Multivariable logistic regression analysis identified high baseline eosinophils as an independent factor for 30-day mortality (OR 0.743, 95% CI 0.568– 0.970). The GAMM result showed that the levels of eosinophils were increased in both survival and non-survival groups, and the between-group differences increased over time, with an average of 0.154 daily after adjusting for confounders. The AUC of changes in eosinophils within the first week was significantly higher than that of baseline eosinophils.Conclusion: There is a negative association between the baseline eosinophils and short-term mortality in ARDS patients, and the differences in eosinophils increased over time between the survivors and non-survivors. Higher increase in eosinophils is associated with decreased short-term mortality, and dynamic monitoring of eosinophils could better predict the survival of ARDS patients.Keywords: ARDS, eosinophils, 30-day mortality, generalized additive mixed model, change

Qingsong Yu,1 Hongfan Yu,1 Wei Xu,1 Yang Pu,1 Yuxian Nie,2 Wei Dai,3 Xing Wei,3 Xin Shelley Wang,4 Charles S Cleeland,4 Qiang Li,3 Qiuling Shi1,2,5 1School of Public Health and Management, Chongqing Medical University, Chongqing, People’s Republic of China; 2State Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 4Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5Center for Cancer Prevention Research, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Qiuling Shi, School of Public Health and Management, Chongqing Medical University, No. 1, Medical School Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-18290585397, Fax +86-28-85420116, Email qshi@cqmu.edu.cnPurpose: Patient-reported outcome (PRO)-based symptom assessment with a threshold can facilitate the early alert of adverse events. The purpose of this study was to determine whether shortness of breath (SOB) on postoperative day 1 (POD1) can inform postoperative pulmonary complications (PPCs) for patients after lung cancer (LC) surgery.Methods: Data were extracted from a prospective cohort study of patients with LC surgery. Symptoms were assessed by the MD Anderson Symptom Inventory-lung cancer module (MDASI-LC) before and daily after surgery. Types and grades of complications during hospitalization were recorded. SOB and other symptoms were tested for a possible association with PPCs by logistic regression models. Optimal cutpoints of SOB were derived, using the presence of PPCs as an anchor.Results: Among 401 patients with complete POD1 MDASI-LC and records on postoperative complications, 46 (11.5%) patients reported Clavien–Dindo grade II-IV PPCs. Logistic regression revealed that higher SOB score on POD1 (odds ratio [OR]=1.13, 95% CI=1.01– 1.27), male (OR=2.86, 95% CI=1.32– 6.23), open surgery (OR=3.03, 95% CI=1.49– 6.14), and lower forced expiratory volume in one second (OR=1.78, 95% CI=1.66– 2.96) were significantly associated with PPCs. The optimal cutpoint was 6 (on a 0– 10 scale) for SOB. Patients reporting SOB < 6 on POD1 had shorter postoperative length of stay than those reporting 6 or greater SOB (median, 6 vs 7, P =0.007).Conclusion: SOB on POD1 can inform the onset of PPCs in patients after lung cancer surgery. PRO-based symptom assessment with a clinically meaningful threshold could alert clinicians for the early management of PPCs.Keywords: lung cancer, surgery, postoperative pulmonary complications, patient-reported outcomes, shortness of breath

Tingting Wang,1 Qian Yu,2 Wei Zhang,1 Li Gao1 1Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Ji’nan, 250014, People’s Republic of China; 2Department of Nuclear Medicine, The Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of ChinaCorrespondence: Tingting Wang, Email wtt64@163.comBackground: Papillary thyroid carcinoma (PTC) is a malignant tumor of the endocrine system, and distant metastasis leads to poor prognosis for patients with PTC. The competitive endogenous RNA (ceRNA) network and tumor-infiltrating immune cells might participate in tumor prognosis and distant metastasis. However, few studies have focused on ceRNAs and immune cells in PTC.Methods: We identified differentially expressed lncRNAs (DELs) using the GEO2R tool of the GEO database. Through comprehensive analysis, we selected lncRNA PROSER2-AS1 and constructed a PROSER2-AS1-mediated ceRNA network. Survival was analyzed with a Kaplan-Meier (KM) curve. Gene set enrichment analysis (GSEA) was performed to determine the function of PROSER2-AS1 in the ceRNA network using TCGA database. Moreover, the relationship between PROSER2-AS1 and immune cell infiltration was analyzed with ssGSEA using the “GSVA” package in R.Results: Comprehensive analysis of the GSE66783 dataset revealed 105 significantly differentially expressed lncRNAs. Univariate and multivariate Cox regression analyses were performed to assess the prognostic significance of the DELs, and we identified lncRNA PROSER2-AS1 as an independent factor for prognosis in PTC (p < 0.05). Considering the online tools LncRNASNP2 and miRWalk3.0, we constructed a PROSER2-AS1-related ceRNA network. Furthermore, the GSEA results suggested that PROSER2-AS1 may be involved in immune cell infiltration and that PROSER2-AS1 was correlated with 14 types of tumor-infiltrating immune cells. PROSER2-AS1 might function through TGFBR3.Conclusion: lncRNA PROSER2-AS1 and related mRNAs (TGFBR3) may be potential prognostic biomarkers in PTC and may correlate with immune infiltrates.Keywords: PROSER2-AS1, papillary thyroid carcinoma, immune cells, prognosis

Ye Han,1 Qingsong Yu,2 Xiaoqing Dong,3 Jianxia Hou,1,* Jianmin Han4,* 1Department of Periodontology, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, People’s Republic of China; 2Department of Mechanical and Aerospace Engineering, University of Missouri, Columbia, MO, USA; 3Marketing Department, PlasmaDent Inc., Columbia, MO, USA; 4Department of Dental Materials, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materials, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianmin Han; Jianxia Hou, Tel +86-10-82195746; +86-13683696349, Fax +86-10-62164691; +86-10-82195496Email hanjianmin@bjmu.edu.cn; jxhou@163.comPurpose: To evaluate the antibacterial and anti-inflammatory properties of SiOx:H nanocoatings using a plasma-deposition technique.Materials and Methods: Four groups of SiOx:H nanocoatings were prepared by plasma nanocoating technique using different deposition gases and durations, specifically trimethylsilane (TMS) for groups A1 and A2 and a mixture of TMS and oxygen for groups B1 and B2. Changes in surface chemistry and physical properties were measured. Staphylococcus aureus and Streptococcus mutans were cultured on plasma SiOx:H nanocoatings to evaluate antibacterial and antibiofilm formation activities. Human gingival fibroblasts (HGFs) and HaCaT human keratinocytes were cultured and stimulated with tumor necrosis factor-α (TNF-α). Cell viability was measured using a Cell Counting Kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to evaluate anti-inflammatory properties, including the mRNA and protein levels of inflammatory mediators and proinflammatory cytokines.Results: The carbon content was dominant in group A nanocoatings and the oxygen and silicon elements were dominant in group B nanocoatings. Groups A2 and B2 were approximately threefold thicker than groups A1 and B1. The plasma SiOx:H nanocoatings decreased bacterial growth and biofilm formation by 30– 70% (p < 0.05). Scanning electron microscopy (SEM) revealed damaged biofilm structures. Moreover, the antibacterial properties of group B were greater than group A, and the antibacterial properties of groups A2 and B2 were more effective than A1 and B1, respectively. CCK-8 assays revealed the plasma SiOx:H nanocoatings had good biocompatibility. Furthermore, under TNF-α-induced inflammation, the mRNA and protein levels of interleukin-6, interleukin-8, cyclooxygenase-2, and monocyte chemoattractant protein-1 were downregulated in the plasma SiOx:H nanocoating groups (p < 0.05).Conclusion: Plasma SiOx:H nanocoatings exerted antibacterial and anti-inflammatory effects with excellent biocompatibility. Therefore, the plasma SiOx:H nanocoating technique has potential for implant materials and other medical devices.Keywords: plasma SiOx:H nanocoating technique, biomaterial-related infection, bacterial adhesion, biofilm formation, anti-inflammation

Ying Cao,1,&ast; Yibei Dai,1,&ast; Lingyu Zhang,1 Danhua Wang,1 Wen Hu,2 Qiao Yu,3 Xuchu Wang,1 Pan Yu,1 Weiwei Liu,1 Ying Ping,1 Tao Sun,1 Yiwen Sang,1 Zhenping Liu,4 Yan Chen,3 Zhihua Tao1 1Department of Laboratory Medicine, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 2National Clinical Research Center for Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, People’s Republic of China; 3Center for Inflammatory Bowel Diseases, Department of Gastroenterology, Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 4Department of Laboratory Medicine, the First People’s Hospital of Yuhang District, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Chen; Zhihua Tao Tel +86 571 8778 3752Fax +86 571 8689 8730Email chenyan72_72@zju.edu.cn; zrtzh@zju.edu.cnBackground: Fecal biomarkers have emerged as one of the most useful tools for clinical management of inflammatory bowel disease (IBD). Oncostatin M (OSM), like fecal calprotectin (FC), is highly expressed in the inflamed intestinal mucosa which may have potential usefulness. We aimed to evaluate the additional utility of these two fecal biomarkers for IBD diagnosis, activity, and prediction of infliximab response over FC alone.Methods: In group 1, 236 IBD patients (145 Crohn’s disease, 91 ulcerative colitis), 50 disease controls, and 32 healthy controls were recruited for IBD diagnosis and activity. In group 2, baseline stool samples were collected from 62 patients to predict infliximab response at week 28 and 52. The performance of fecal biomarkers for IBD management was assessed by the area under the receiver operating characteristic curve (AUC).Results: Fecal OSM and FC levels were increased in IBD patients and were positively correlated with clinical and endoscopic activity. Their combination showed a better ability for disease diagnosis (AUC = 0.93) and slightly improved the capability to identify mucosal healing (AUC = 0.923). Baseline OSM and FC levels were elevated in non-responders at week 28 and 52. The AUCs of OSM, FC, and their combination to predict therapeutic response were 0.763, 0.834, and 0.859 at week 28, 0.638, 0.661, and 0.704 at week 52, respectively. Combined use of fecal and blood biomarkers improved predictive accuracy with an AUC of 0.919 at week 28 and 0.887 at week 52.Conclusion: In addition to FC, OSM is a novel fecal biomarker, and their combination is more beneficial for disease diagnosis and prediction of infliximab response but not for disease activity in IBD patients. Further larger-scale studies are required to confirm our findings.Keywords: inflammatory bowel disease, fecal biomarkers, oncostatin M, calprotectin, diagnosis, activity, infliximab response

Qiongjie Yu,&ast; Xuedan Du,&ast; Zhen Fang, Xiaolu Mao, Jinting Wu, Bin Wang, Wenfeng Li Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenfeng LiDepartment of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of ChinaEmail lwf720325@126.comPurpose: Inflammatory biomarkers and clinical pathological factors have been reported to predict survival of patients with non-small cell lung cancer (NSCLC). The goal of this study was to identify risk factors for early recurrence in patients with pIIIA-N2 NSCLC who had undergone radial resection.Methods: A retrospective analysis was conducted on 238 patients with pIIIA-N2 NSCLC who underwent surgical treatment at the First Affiliated Hospital of Wenzhou Medical University between December 2006 and August 2018. The early recurrence (ER) group included patients who recurred within one year of curative resection, while the non-early recurrence (NER) group included patients who did not recurrence or recurrence beyond one year. The univariate and multivariate Cox proportional risk analyses were used to identify prognostic factors associated with early recurrence, while the chi-square test was used for categorical data. Overall survival and recurrence-free survival were assessed by Kaplan–Meier estimates.Results: A total of 69 patients experienced an early recurrence, while the remaining 169 patients did not relapse within one year. ER patients had a much worse prognosis than NER patients, with median survival times of 20.6 and 83.1 months, respectively. Multivariate analysis showed that smoking status, tumor size, metastatic lymph node ratio (LNR) and platelet-to-lymphocyte ratio (PLR) were independent risk factor of early recurrence. Patients with early recurrence were more likely to develop bone metastases.Conclusion: Smoking history, large tumour size, and elevated LNR and PLR values in pIIIA-N2 NSCLC patients after complete resection may have a significant risk of early recurrence. Based on these independent risk indicators, this prediction model may successfully predict early recurrence and advise individual treatment.Keywords: non-small cell lung cancer, early recurrence, risk factors, inflammatory biomarkers, prognosis

Mengjie Tu,1 Yafei Guo,2 Xincai Zhang,3 Quanlei Yu1,4 1School of Psychology, Central China Normal University, Wuhan, Hubei, People’s Republic of China; 2Department of Business Administration, University of Illinois at Urbana-Champaign, Champaign, IL, USA; 3Fuyang City No.11 Middle School, Anhui, People’s Republic of China; 4School of Psychology, Beijing Normal University, Beijing, People’s Republic of ChinaCorrespondence: Quanlei Yu Email yulei19881987@mail.ccnu.edu.cnBackground: Parent-child facial resemblance, as an important cue of paternal uncertainty, may impact fathers’ parenting behaviors and further affect children’s academic performance. However, mothers are almost 100% confident of the blood relationship with their child and care less about the facial resemblance cues.Methods: To test these hypotheses, the present study recruited 122 junior high school students and measured the perceived facial resemblance with their parents, the parents’ parenting style, academic performance, and demographic variables.Results: The results showed that the perceived father-child facial resemblance rather than the mother-child facial resemblance significantly influenced adolescents’ academic performance. Further, fathers’ caring parenting style mediated the relationship between the perceived father-child facial resemblance and academic performance.Conclusion: These findings not only supported the paternal uncertainty hypothesis but also extended the parental investment theory.Keywords: perceived father–child facial resemblance, academic performance, caring parenting, paternal uncertainty

Xiang Jiang,1,&ast; Rongzhou Zhong,1,&ast; Weifan Dai,2,&ast; Hui Huang,1 Qinyuan Yu,1 Jiji Alexander Zhang,3 Yanrong Cai3 1Department of Orthopaedics and Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, 201619, People’s Republic of China; 2Department of Digital Hub, Decathlon International, Shanghai, 200131, People’s Republic of China; 3Department of Medicine, Heidelberg University Hospital, University of Heidelberg, Heidelberg, 69120, Germany&ast;These authors contributed equally to this workCorrespondence: Yanrong CaiDepartment of Medicine, Heidelberg University Hospital, University of Heidelberg, Heidelberg, 69120, GermanyEmail yanrongcai5@gmail.comBackground: Metabolic syndrome (MS) has grown in recognition to contribute to the pathogenesis of osteoarthritis (OA), which is the most prevalent arthritis characterized by joint dysfunction. However, the specific mechanism between OA and MS remains unclear.Methods: The gene expression profiles and clinical information data of OA and MS were retrieved from the Gene Expression Omnibus (GEO) database. The genes in the key module of MS were identified by weighted gene co-expression network analysis (WGCNA), which intersected with the differentially expressed genes (DEGs) between control and MS samples to obtain hub genes for MS. The potential functions and pathways of hub genes were detected through the Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses. The genes involved in the different KEGG pathways between the control and OA samples overlapped with the DEGs between the two groups via the Venn analysis to gain the hub genes for OA affected by MS (MOHGs). Additionally, the least absolute shrinkage and selection operator (LASSO) was performed on the MOHGs to establish a diagnostic model for each disease.Results: A total of 61 hub genes for MS were identified that significantly enriched in platelet activation, complement and coagulation cascades, and hematopoietic cell lineage. Besides, 4 candidate genes (ELOVL7, F2RL3, GP9, and ITGA2B) were screened among the 6 MOHGs to construct a diagnostic model, showing good performance for distinguishing controls from patients with MS and OA. GSEA suggested that these diagnostic genes were closely associated with immune response, adipocytokine signaling, fatty acid metabolism, cell cycle, and platelet activation.Conclusion: Taken together, we identified 4 potential gene biomarkers for diagnosing MS and OA patients, providing a theoretical basis and reference for the diagnostics and treatment targets of MS and OA.Keywords: osteoarthritis, OA, metabolic syndrome, MS, diagnostic biomarkers, pathogenesis, bioinformatics