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Na Li,1,* Xinyao Zhang,1,* Yi Zheng,1 Qingchuan Liu,2 Sifang Niu,3 Yan Qin,4 Ying Zhang,5 Yan Liu,6 Jianli Wang7 1School of Mental Health, Jining Medical University, Jining, 272013, People’s Republic of China; 2School of Communication, East China Normal University, Shanghai, 200241, People’s Republic of China; 3School of Public Health, Binzhou Medical University, Yantai, 264003, People’s Republic of China; 4School of Public Health, Shandong First Medical University, Jinan, 250117, People’s Republic of China; 5School of Public Health, University of Sydney, Sydney, NSW, 2006, Australia; 6School of Public Health, Jining Medical University, Jining, 272013, People’s Republic of China; 7Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, B2N 5E3, Canada*These authors contributed equally to this workCorrespondence: Jianli Wang, Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, B2N 5E3, Canada, Email jianli.wang@dal.ca Yan Liu, School of Public Health, Jining Medical University, Jining, 272013, People’s Republic of China, Email hakunaly@163.comBackground: Perfectionism is a pivotal factor in the etiology and prognosis of major depression. Nevertheless, there is a scarcity of longitudinal research examining the association between perfectionism and major depressive disorder (MDD). The objective of this study was to explore the impact of perfectionism on MDD among a cohort of first-year Chinese university students.Methods: This study employed a longitudinal design to investigate the relationship between perfectionism and MDD in a sample of first-year Chinese university students (n=8079). Socially prescribed perfectionism and almost perfectionism were measured using the Multidimensional Perfectionism Scale (MPS) and the Almost Perfect Scale-Revised (APS-R), while MDD was assessed using the Composite International Diagnostic Interview (CIDI-3.0). Random effects logistic regression modeling was utilized to estimate the associations between the variables.Results: The findings revealed that the incidence of MDD was 0.6%. Lifetime exposure to severe traumatic events (≥ 10) (OR=2.619, 95% CI: 1.502– 4.565) and almost perfectionism (OR=1.015, 95% CI: 1.004– 1.026) were identified as significant risk factors for MDD.Conclusion: It is evident that perfectionism is linked to an increased susceptibility to MDD. However, additional longitudinal studies focusing on university students are imperative to delve deeper into the influence of perfectionism on the initial manifestation of MDD.Keywords: freshmen, major depressive disorder, perfectionism, lifetime severe traumatic events

Qi Liu,1,2,* Nan Nan,1,2,* Wenfang Li,1,2 Mengwei Dong,1,2 Wei Pu,1,2 Yang Liu,1,2 Jie Zhao,3 Huiqin Hao1,2 1Basic Laboratory of Integrated Traditional Chinese and Western Medicine, Shanxi University of Chinese Medicine, Jinzhong, 030619, People’s Republic of China; 2Engineering Research Center of Cross Innovation for Chinese Traditional Medicine of Shanxi Province, Jinzhong, 03619, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Classical Prescription Strengthening Yang, Taiyuan, 030013, People’s Republic of China*These authors contributed equally to this workCorrespondence:Huiqin Hao, Email hhq@sxtcm.edu.cnBackground: Rheumatoid arthritis (RA) is a synovial inflammation-associated autoimmune disease with secondary osteoporosis. Pain is the most important symptom of RA, and some patients with well-controlled inflammation may still experience pain.Purpose: To explore the relationship and dynamic changes between synovial inflammation and pain and bone destruction in collagen-induced arthritis (CIA) model rats, and to choose a better time window for drug treatment.Methods: The CIA model rats were constructed for 1, 2, 3, and 4-week groups. The changes were observed by joint swelling and behavioral assessment. The paw mechanical withdrawal threshold (PWT) was used for pain assessment. The micro-CT was used to assess joint injury and bone destruction. The biomechanics were performed to evaluate tension and compression test. The histological staining was used to observe ankle joint pathology. The immunohistochemical staining and Western blot were used to estimate the expression of calcitonin gene-related peptide (CGRP) and c-fos.Results: The results showed that the degree of joint swelling, synovial hyperplasia, and inflammatory response were alleviated to varying extents over time. However, there were no significant changes in bone destruction, osteoclasts, or the maximum load of compression and tension. It showed secondary osteoporosis from the first week of the CIA model with no significant changes during the course of the experiment. There was no significant improvement in the PWT, and the expression of CGRP and c-fos was significantly increased over time, indicating hyperalgesia aggravation. Additionally, the result showed that repeated open-field tests might reduce the total distance of spontaneous movement.Conclusion: The results suggested that the pain and joint inflammation might not be synchronized, possibly related to post-inflammatory hyperalgesia. CIA model could be used for the study of pain, also relatively stable and suitable for the study of RA with secondary osteoporosis.Keywords: collagen-induced arthritis rats, temporal changes, inflammation, pain, secondary osteoporosis

Lidan Yi,1,* Qiao Liu,1,* Chongqing Tan,1 Xiaomin Wan,1 Xia Luo,1 Yinbo Li,2 Haiying Li,3 Xiaohui Zeng3 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Center for Drug Evaluation and Adverse Reaction Monitoring, Hunan Provincial Food and Drug Administration, Changsha, People’s Republic of China; 3Department of Nuclear Medicine/PET Image Center, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohui Zeng; Haiying Li, Email zengxiaohui2008@csu.edu.cn; lihaiying2013@csu.edu.cnObjective: To assess the cost-effectiveness of adding daratumumab to carfilzomib and dexamethasone (KdD) in patients with relapsed or refractory multiple myeloma (RRMM).Materials and Methods: A Markov model was established to estimate health and economic outcomes of carfilzomib and dexamethasone (Kd) with or without daratumumab for RRMM patients over a lifetime horizon. The patients and intervention of the two arms were modeled according to the CANDOR trial. Costs were collected from the Chinese health system perspective. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of our conclusions.Results: Compared with the Kd arm, KdD achieved an additional 0.537 quality-adjusted life-years (QALYs) at an incremental cost of $138,084, resulting in an incremental cost-utility ratios (ICURs) of $257,319 per QALY. Uncertainty analyses revealed that the model is robust to all the input parameters.Conclusion: From the Chinese healthcare system perspective, adding daratumumab to the Kd regimen for patients with RRMM appears to lack cost-effectiveness. Exploring alternative avenues such as negotiating for a more favorable price or introducing a financial assistance program dedicated to daratumumab and/or carfilzomib could prove to be an effective strategy in enhancing accessibility of this combination.Keywords: cost-effectiveness, daratumumab, multiple myeloma, Markov model, China

Jiajing Li,1 Qi Liu,2 Ting Zhang,2 Qian Du3 1The Diagnostics Laboratory, Affiliated Hospital to Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 2Affiliated Hospital to Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 3Department of Endoscopy and Digestive System, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, 550002, People’s Republic of ChinaCorrespondence: Qian Du, Email DuqianL5@163.comIntroduction: Hepatocellular carcinoma (HCC), a prevalent and aggressive form of cancer, poses significant challenges due to its limited therapeutic options. This study aims to leverage multi-omics data from liver cancer to identify potential therapeutic targets for HCC.Methods: We employed an integrative approach by analyzing various omics datasets related to liver cancer. Through comprehensive data mining and analysis, we identified key genes that are significantly associated with HCC. To gain insights into their biological roles and underlying mechanisms, we constructed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway networks. Specifically, we focused on genes that exhibited high expression levels in HCC and were correlated with poor patient prognosis. Among these, CDK1 and DLGAP5 emerged as promising candidates and were further investigated for their potential involvement in tumor immune cell infiltration and HCC progression.Results: Our analysis revealed that CDK1 and DLGAP5 are highly expressed in HCC tissues compared to normal liver tissues, and their elevated expression is associated with unfavorable clinical outcomes. Furthermore, through GO and KEGG pathway analyses, we found that these genes are implicated in critical biological processes and signaling pathways relevant to HCC pathogenesis. Notably, CDK1 and DLGAP5 were shown to be associated with tumor immune cell infiltration, suggesting their potential role in modulating the tumor microenvironment and promoting HCC progression.Discussion: These findings provide valuable insights into the development of novel therapeutic approaches for HCC.Keywords: Hepatocellular carcinoma, bioinformatics analysis, DLGAP5, CDK1, immune cell infiltration

Yang Xu,* Qiankun Liu,* Jiaxue Pang, Chunlu Zeng, Xiaoqing Ma, Pengyao Li, Li Ma, Juju Huang, Hui Xie College of Nursing, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Xie, Bengbu Medical University, Donghai Avenue, Longzihu District, Bengbu City, Anhui Province, People’s Republic of China, Email hui2122@sina.comPurpose: Exercise is a vital adjunct therapy for patients with hypertension comorbidities. However, medical personnel and patients face significant obstacles in implementing exercise prescription recommendations. AI has been developed as a beneficial tool in the healthcare field. The performance of intelligent tools such as ChatGPT 4.0 and Intelligent Health Promotion Systems (IHPS) in issuing exercise prescriptions for patients with hypertension comorbidities remains to be verified.Patients and Methods: After collecting patient information through IHPS hardware and questionnaire systems, the data were input into the software terminals of ChatGPT 4.0 and IHPS according to the five stages of the Transtheoretical Model, resulting in exercise prescriptions. Subsequently, experts from various fields scored the accuracy, comprehensiveness, and applicability of each prescription, along with providing professional recommendations based on their expertise. By comparing the performance of both systems, their capability to serve this specific group was evaluated.Results: In most cases, ChatGPT scored significantly higher than IHPS in terms of accuracy, comprehensiveness, and applicability. However, when patients exhibited certain functional movement disorders, GPT’s exercise prescriptions involved higher health risks, whereas the more conservative approach of IHPS was advantageous.Conclusion: The path of generating exercise prescriptions using artificial intelligence, whether via ChatGPT or IHPS, cannot achieve a completely satisfactory state.But can serve as a supplementary tool for professionals issuing exercise prescriptions to patients with hypertension comorbidities, especially in alleviating the financial burden of consulting costs. Future research could further explore the performance of AI in issuing exercise prescriptions, harmonize it with physiological indicators and phased feedback, and develop an interactive user experience.Keywords: artificial intelligence, exercise prescription, hypertension, intelligent health promotion systems, transtheoretical model

Youni Lin, Min Yang, Qifeng Liu, Yufu Cai, Zhouhua Zhang, Chongfei Xu, Ming Luo Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Youni Lin, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email linyn2024@126.comBackground: Atherosclerosis is a systemic disease that can involve multiple vascular beds. The risk factors for atherosclerosis in multiple vascular beds remain unclear. Apolipoprotein E (APOE) is involved in inflammation and lipid deposition in the process of atherosclerosis. The objective of this study was to investigate whether APOE polymorphisms are associated with atherosclerosis in multiple vascular beds.Methods: A total of 416 patients with atherosclerosis in single vascular bed and 658 patients with atherosclerosis in multiple vascular beds were included. APOE genotypes were detected and the differences of APOE genotypes between the groups were compared. Logistic regression analysis was performed to analyze the relationship between APOE genotypes and atherosclerosis in multiple vascular beds.Results: APOE E3/E4 genotype frequency was lower in the patients with atherosclerosis in multiple vascular beds than that of patients with atherosclerosis in single vascular bed (11.4% vs 17.8%, P=0.004). There was no significant difference in age and gender distribution, proportion of history of smoking, alcohol consumption, hypertension, and diabetes mellitus between the two groups (all P> 0.05), and among patients with different APOE alleles (all P> 0.05). Logistic regression analysis indicated that APOE E3/E4 genotype (E3/E4 vs E3/E3: odds ratio (OR) 0.598, 95% confidence interval (CI): 0.419– 0.854, P=0.005), and APOE ϵ4 allele (ϵ4 vs ϵ3: OR 0.630, 95% CI: 0.444– 0.895, P=0.010) associated with atherosclerosis in multiple vascular beds.Conclusion: APOE ϵ4 allele is associated with atherosclerosis in multiple vascular beds.Keywords: APOE, polymorphism, atherosclerosis, multiple vascular beds

Zheng Wan,1 Tianyi Liu,1 Ning Xu,1 Wenhao Zhu,2 Xiaoyu Zhang,2 Qin Liu,1 Haifeng Wang,2 Honglei Wang1 1Department of Neurovascular Surgery, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Neurotrauma, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Haifeng Wang; Honglei Wang, Email hfwang@jlu.edu.cn; wanghongl@jlu.edu.cnIntroduction: Extracellular vesicles (EVs) are nanosized membrane vesicles that are naturally secreted by almost all cells and have gained considerable attention. Many studies have applied EVs to the treatment of brain diseases and validated their effectiveness. Although only a few EVs can penetrate the blood‒brain barrier (BBB) into the brain after administration, it has been proven that EVs and their cargos exert their effects by interacting with brain cells. PKH dyes are commonly used to stain EVs for distribution studies. However, systematic investigations of imaging characteristics of the PKH-labeled EVs distributed in the brain are still scarce.Methods: We stained EVs derived from mesenchymal stem cells with PKH26 or PKH67. PKH26-labeled EVs and PKH67-labeled EVs were administered at the same time into each mouse while PKH26-labeled EVs were given through tail veins and PKH67-labeled EVs were given through intraperitoneal injection. Confocal microscopy was used to explore the distribution difference of two types of EVs given via different routes in the brain.Results: The fluorescence of PKH26 and PKH67 had nearly identical distributions in brain slices after 1 h, 6 h, 12 h and 1 day of EV administration. Under the same confocal parameters, brain slices without EVs administration demonstrated the same result. However, liver slices from mice administered with labeled EVs showed obviously different distributions of two types PKH fluorescence.Discussion: These findings raise questions about the ability of PKH dyes as labels for EVs when explore the EV brain distribution observed via confocal microscopy.Keywords: extracellular vesicles, PKH dyes, brain distribution

Mengdie Chen,1 Ping Feng,1 Yao Liang,2 Xun Ye,3 Yiyun Wang,2 Qiao Liu,1 Chaoyin Lu,1 Qidong Zheng,2 Lijing Wu2 1Department of Endocrinology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China; 2Department of Internal Medicine, Yuhuan Second People’s Hospital, Yuhuan, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Lijing Wu, Department of Internal Medicine, Yuhuan Second People’s Hospital, No.77, Environmental Protection Middle Road, Chu Men Town, Yuhuan, Zhejiang, 317600, People’s Republic of China, Tel: +86-13777603508, Email 13777603508@163.comPurpose: This study was developed with the goal of clarifying whether there is any relationship between type 2 diabetes mellitus (T2DM) age of onset and clinical outcomes for patients in National Metabolic Management Centers (MMC).Patients and Methods: From September 2017 - June 2022, 864 total T2DM patients were recruited in MMC and assigned to those with early-onset and late-onset diabetes (EOD and LOD) based on whether their age at disease onset was ≤ 40 or > 40 years. All patients received standardized management. Baseline and 1-year follow-up data from these two groups of patients were assessed. Associations between onset age and other factors were evaluated with a multivariate linear regression approach, adjusting for appropriate covariates. Outcomes in particular subgroups were also assessed in stratified analyses.Results: Markers of dysregulated glucose metabolism and BMI values were significantly higher among EOD patients as compared to LOD patients. Subjects in both groups exhibited significant improvements in several disease-related parameters on 1-year follow-up after undergoing metabolic management. EOD patients exhibited significantly greater percentage reductions in HbA1c levels (− 28.49 (− 44.26, − 6.45)% vs − 13.70 (− 30.15,-1.60)%, P =0.017) relative to LOD patients following adjustment for confounders. Significant differences were also detected between these groups when focused on subgroups of patients who were male, exhibited a BMI ≥ 25, an HbA1c ≥ 9, or had a follow-up frequency < 2.Conclusion: Data from a 1-year follow-up time point suggest that a standardized metabolic disease management model can promote effective metabolic control in newly diagnosed T2DM patients, particularly among individuals with EOD.Keywords: age of onset, disease management, type 2 diabetes

Zhihong Liu,1,2,&ast; Xiaofang Liang,1,&ast; Yu Zhang,1 Wenbo Deng,1 Yulin Wang,3 Zhangping Lu,2 Qianqian Liu,2 Lianhua Wei2 1School of Public Health, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China; 2Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianhua Wei, Email 107306723@qq.comAbstract: The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.Keywords: antimicrobial resistance, multi-drug resistance, niclosamide, a derivative, drug repurposing

Puhua Wu,1,2 Zhicheng Zhang,1 Yan Zhou,2 Quan Liu,2 Kin-Yip Tam,2 Zhenhong Su1 1Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, School of Medicine, Hubei Polytechnic University, Huangshi, People’s Republic of China; 2Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, People’s Republic of ChinaCorrespondence: Puhua Wu, Email wph75000@hotmail.comBackground: Pyruvate dehydrogenase kinases (PDHKs), important metabolic and abnormally expressed enzymes in cancer cells, are promising targets for cancer therapy, especially for non-small-cell lung cancer (NSCLC).Methods: In this study, a new hit, dichloroacetophenone (DAP) analog 9, was postulated to bind to the PDHK1 allosteric pocket, guided by molecular modeling and kinase biochemical experiments. Based on this binding mode, novel DAP analogs were designed and synthesized to confirm the importance of Phe180, Tyr411, and the hydrophobic core at the bottom of the pocket.Results: This structure–activity relationship (SAR) study led to the discovery of a novel potent hybrid scaffold, dichloroacetophenone biphenylsulfone ether. Dichloroacetophenone biphenylsulfone ether 31 and 32 inhibited PDHK1 with IC50 values of 86 and 140 nM, respectively.Conclusion: Compound 32 with acceptable in vitro metabolic stability, predicted drug-likeness properties and ADME/T profiles, showed promising therapeutic efficacy in a lung cancer xenograft mouse model. Keywords: PDHK1, dichloroacetophenone, allosteric pocket, anti-NSCLC activity, tumor xenograft mouse model

Guangming Yang,1,&ast; Jian Zhang,2,&ast; Qian Liu,2 Erqing Chai2 1The First Clinical School of Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu Province, 730000, People’s Republic of China; 2Gansu Provincial Hospital, Lanzhou, Gansu Province, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Erqing Chai, Email 18809407241@163.comAbstract: Inflammation of the frontal sinus is a relatively common clinical condition among paranasal sinusitis and is curable through anti-infection treatments, with a rare progression to frontal sinus abscess. An even rarer complication is the development of intracranial epidural empyema secondary to frontal sinus abscess. In this report, we describe a case of a 14-year-old male with a frontal sinus abscess that led to intracranial infection and was complicated by an epidural abscess misdiagnosed as an epidural hematoma. The primary symptoms were headache, dizziness, and fever. Following combined antibiotic therapy and surgical intervention, including maxillary and frontal sinus window drainage, the patient was cured. A follow-up period of three months showed no recurrence, indicating a favorable outcome.Keywords: sinusitis, frontal sinus abscess, intracranial infection, epidural abscess

Juanzhi Yang,1 Huanxia Qu,2 Qi Liu,1 Yixing Wang,1 Jiaxin Cao,1 Feng Jiang,3 Qian Wang,4 Jin Shu1 1Department of Pediatrics, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of China; 2Department of Blood Transfusion, Zhenjiang First People’s Hospital, Zhenjiang, People’s Republic of China; 3Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 4Department of Pediatrics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Jin Shu, Department of Pediatrics, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, 212008, People’s Republic of China, Email zjshujin@163.com Feng Jiang, Department of Neonatology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China, Email dxyjiang@163.comBackground: Premature infants, defined as those born before 37 weeks of gestation, face numerous health challenges due to their underdeveloped systems. One critical aspect of their health is the gut microbiota, which plays a vital role in their immune function and overall development. This study provides a comprehensive bibliometric analysis of research trends, influential contributors, and evolving themes in the study of gut microbiota in premature infants over the past two decades.Methods: We conducted a bibliometric analysis using the Web of Science Core Collection database, covering publications from January 1, 2004, to June 17, 2024. We employed VOSviewer, the R package “bibliometrix”, and Citespace for data visualization and analysis, focusing on co-authorship, co-citation, and keyword co-occurrence networks.Results: The temporal analysis revealed a significant increase in research output on gut microbiota in premature infants, particularly in the last decade. Early research primarily focused on characterizing the gut microbiota of premature infants, identifying less diversity and a higher prevalence of pathogenic bacteria compared to full-term infants. Key research themes identified include probiotics, necrotizing enterocolitis (NEC), and breastfeeding. Probiotic studies highlighted the potential of strains like Bifidobacterium and Lactobacillus in reducing NEC and sepsis incidences. Breastfeeding research consistently showed the benefits of human milk in fostering a healthier gut microbiota profile. Co-authorship and co-citation analyses identified key contributors and influential studies, emphasizing strong international collaborations, particularly among researchers from the United States, China, and European countries.Conclusion: This bibliometric analysis underscores the growing recognition of the gut microbiota’s crucial role in the health of premature infants. The field has seen significant advancements, particularly in understanding how interventions like probiotics and breastfeeding can modulate gut microbiota to improve health outcomes. Continued research and international collaboration are essential to further unravel the complexities of gut microbiota in premature infants and develop effective therapeutic strategies.Keywords: premature infants, gut microbiota, web of science, bibliometric analysis

Xianglian Bai,1 Aiwu Luo,2 Qin Liu,1 Xiaofeng Ma1 1The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Hengyang City, Hunan Province, 421001, People’s Republic of China; 2Department of Health Education, Hengyang Center for Disease Control and Prevention, Hengyang City, 421002, People’s Republic of ChinaCorrespondence: Xiaofeng Ma, The Affiliated Nanhua Hospital, Department of Cardiology, Hengyang Medical School, University of South China, Dongfeng Street, Zhuhui District, Hengyang City, Hunan Province, People’s Republic of China, Tel + 8613786437543, Email 1607251097@qq.comObjective: To explore the influencing factors of left ventricular thrombosis after percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction (STEMI) and construct a column chart model.Methods: A retrospective study was conducted on 331 STEMI patients who underwent PCI between July 2020 and January 2024. According to the principle of approximately 3:1, patients were randomly separated into 245 in the modeling group and 86 in the validation group, and clinical data of patients were collected. Multivariate logistic regression was applied to screen for risk factors. R software was applied to draw column charts. Bootstrap method was applied for internal validation. Hosmer-Lemeshow (H-L) was applied to test the fitting degree of the column chart model. Calibration curve and ROC curve were applied to verify calibration and discrimination, respectively. DCA curve was applied to analyze the clinical practicality of the column chart model.Results: A history of angina pectoris, ventricular aneurysm, alcohol abuse, postoperative TIMI grade ≤ 2, LVEF, and total ischemic time were influencing factors for left ventricular thrombosis in STEMI patients after PCI (P< 0.05). The predicted probabilities of the internal and external validation calibration curves were highly consistent with the actual probabilities, the concordance index of the ROC curve was 0.962 (95% CI: 0.931– 0.994) and 0.958 (95% CI: 0.926– 0.990), respectively, indicating high model calibration and discrimination; H-L inspection showed χ2=11.977, 9.757 (P=0.152, 0.282). DCA curve showed that when the probability range of the high-risk threshold was 0.02~0.99, the column chart model performed better and had a higher net return.Conclusion: The column chart model constructed by risk factors such as history of angina, ventricular aneurysm, history of alcohol abuse, postoperative TIMI ≤ grade 2, LVEF, and total ischemic time has high predictive value and can effectively predict left ventricular thrombosis in STEMI patients after PCI.Keywords: acute ST-segment elevation myocardial infarction, percutaneous coronary intervention, left ventricular thrombosis, influencing factors, column chart

Yaonan Hong,1,2,&ast; Qi Liu,1,2,&ast; Chuanao Xin,1,2,&ast; Huijin Hu,1,2 Zhenchao Zhuang,1– 3 Hangping Ge,1,2,4 Yingying Shen,1,2,4 Yuechao Zhao,1,2,4 Yuhong Zhou,1,2,4 Baodong Ye,1,2,4 Dijiong Wu1,2,4,5 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 5Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dijiong Wu, Department of Hematology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang, 310006, People’s Republic of China, Tel +86-571-86620325, Email wudijiong@zcmu.edu.cnBackground: Limited data were available to understand the significance of ferroptosis in leukemia prognosis, regardless of the genomic background.Methods: RNA-seq data from 151 AML patients were analyzed from The Cancer Genome Atlas (TCGA) database, along with 70 healthy samples from the Genotype-Tissue Expression (GTEx) database. Ferroptosis-related genes (FRGs) features were constructed by multivariate COX regression analysis and risk scores were calculated for each sample and a novel prediction model was identified. The validation was carried out using data from 35 AML patients and 13 healthy controls in our cohort. Drug sensitivity analysis was conducted on various chemotherapeutic drugs.Results: A signature of 10 FRGs was identified, as prognostic predictors for AML, and the risk scores were calculated to constructed the prognostic features of FRGs. Significantly lower overall survival was observed in the high-risk group. The predictive ability of these features for AML prognosis was confirmed using Cox regression analysis, ROC curves, and DCA. The prediction model performed well in our clinical practices, and had its potential superiority when comparing to classical NCCN risk stratification. Multiple chemotherapy drugs, including paclitaxel, dactinomycin, cisplatin, etc. had a lower IC50 in FRGs high-risk group than low-risk group.Conclusion: The AML prognosis model based on FRGs accurately predicts AML prognosis and drug sensitivity, and the drugs identified worthy further investigation.Keywords: ferroptosis, prediction model, TCGA, acute myeloid leukemia, drug sensitivity

Qianfeng Liu,&ast; Kangbi Wu, Xiaofang Lin, Kali Xiang,&ast; Jing Wang&ast; Department of Pulmonary and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi City, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kali Xiang; Jing Wang, Department of Pulmonary and Critical Care Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, No. 158 Wuyang Avenue, Enshi City, Hubei, 445000, People’s Republic of China, Email xkl18963926688@163.com; 366413620@qq.comBackGround: Considerable studies have demonstrated a significant association between red blood cell distribution width (RDW) and clinical adverse events in cardiovascular or respiratory diseases, infections, and pulmonary embolism. However, there are limited data on prognostic predictions for patients suffering from chronic obstructive pulmonary disease (COPD).Methods: This study conducted a retrospective cohort analysis using data gathered from patients who diagnosed with COPD in the respiratory department of The Central hospital of Enshi Tujia and Miao Autonomous Prefecture between 2018 and 2021. Specifically, the RDW was recorded on their first admission. Multivariate logistic regression analysis were employed to examine the correlation between RDW and deterioration of COPD within one-year period.Results: The cohort of 1799 patients in the study comprised 74.7% male and had an average age of 68.9 ± 9.9 years. The fully adjusted model revealed that, the RDW-middle group (≤ 13.7,> 12.8; OR 1.5, 95% CI 1.0– 2.3, p=0.055) and the RDW-high group (> 13.7; OR 1.7, 95% CI 1.1– 2.6, p=0.013) had a 50% and 70% increased risk of deterioration within 1 year, respectively, in comparison with the RDW-low group (≤ 12.8). Subgroup analysis indicated that this trend was more significant in patients with hypertension (p for interaction = 0.016), and the probability of deterioration within 1 year in the RDW-high group was 3.3 times higher compared to the RDW-low group (OR 3.3, 95% CI 1.4– 7.9, p=0.008).Conclusion: A significant association was observed between the increase in RDW and the heightened risk of deterioration within a year in patients diagnosed with COPD. Most importantly, our findings suggested the importance of RDW in enhancing the risk stratification and prevention of deterioration of COPD.Keywords: red blood cell distribution width, COPD, prognosis, deterioration, risk stratification

Pingping Xiang,1,2,&ast; Qi Liu,1,3,&ast; Wangwei Jing,1,4 Yaping Wang,1 Hong Yu1,5,6 1Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310009, People’s Republic of China; 2Key Laboratory of Multiple Organ Failure (Zhejiang University), Ministry of Education, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Cardiology, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, People’s Republic of China; 5State Key Laboratory of Transvascular Implantation Devices, Hangzhou, 310009, People’s Republic of China; 6Binjiang Institute of Zhejiang University, Hangzhou, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Yu; Yaping Wang, Tel +86-571-87783992, Fax +86-571-88002709, Email yuvascular@zju.edu.cn; yapingwang@zju.edu.cnBackground and Purpose: Growth hormone-releasing hormone (GHRH) agonist, a 29-amino acid peptide, shows significant potential in treating myocardial infarction (MI) by aiding the repair of injured heart tissue. The challenge lies in the effective on-site delivery of GHRH agonist. This study explores the use of a targetable delivery system employing ROS-responsive PEG-PPS-PEG polymers to encapsulate and deliver GHRH agonist MR409 for enhanced therapeutic efficacy.Methods: We synthesized a self-assembling poly (ethylene glycol)-poly (propylene sulfide)-poly (ethylene glycol) polymer (PEG-PPS-PEG) amphiphilic polymer responsive to reactive oxygen species (ROS). The hydrophilic peptide GHRH agonist MR409 was encapsulated within these polymers to form nano PEG-PPS-PEG@MR409 vesicles (NPs). Cardiomyocyte apoptosis was induced under hypoxia and serum-free culture condition for 24 hours, and their production of ROS was detected by fluorescence dye staining. The cellular uptake of PEG-PPS-PEG@MR409 NPs was observed using fluorescence-labeled MR409. Targeting ability and therapeutic efficacy were evaluated using a mouse MI model.Results: PEG-PPS-PEG@MR409 NPs were efficiently internalized by cardiomyocytes, reducing ROS levels and apoptosis. These NPs exhibited superior targeting to the infarcted heart compared to naked MR409 peptide. With a reduced injection frequency (once every three days), PEG-PPS-PEG@MR409 NPs significantly promoted cardiac function recovery post-MI, matching the efficacy of daily MR409 injections.Conclusion: ROS-responsive PEG-PPS-PEG polymers provide a novel and effective platform for the targeted delivery of GHRH agonist peptides, improving cardiac function and offering a new approach for peptide therapy in MI treatment. Keywords: myocardial infarction, targeted therapy, growth hormone-releasing hormone, reactive oxygen species

Qian Liu,1,&ast; Jun Zhang,2,&ast; Mingqin Wei,1 Xue Zhou,3 Hao Sun,4 Youhong Dong,1 Dongdong Zhang1 1Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 2Department of Neurology, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 3Department of Pathology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 4Department of Oncology, Baokang County People’s Hospital, Xiangyang, 441000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youhong Dong, Dongdong Zhang, Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Jiefang Road No. 15, Xiangyang, Hubei, 441000, People’s Republic of China, Tel +8615072278600, Email dongyouhong2005@163.com; zhangdongdong@whu.edu.cnBackground: Pulmonary spindle cell carcinoma (PSCC), a highly malignant tumor, often exhibits cell pleomorphism, a histopathological characteristic. Owing to its extremely low incidence, atypical imaging and clinical presentations, and insufficient awareness among clinicians, PSCC is often misdiagnosed, which results in delays in treatment. Herein, we reported a rare case of PSCC that was initially misdiagnosed as granulomatous inflammation.Case Presentation: A 66-year-old male visited a local hospital with symptoms such as cough and hemoptysis. A computed tomography (CT) scan of the chest revealed a mass in his right lung, and no mediastinal lymphadenopathy was observed. Bronchoscopy showed no major abnormalities, and the results of fine needle aspiration biopsy showed granulomatous inflammation. Even though the patient received anti-infection treatment, his symptoms did not improve markedly. After two months, a follow-up CT scan of the lung showed a noticeably enlarged mass accompanied by multiple instances of mediastinal lymphadenopathy in the upper lobe of the right lung. Consequently, he underwent a second CT-guided lung biopsy at our hospital. The pathology report indicated PSCC. Due to financial constraints, genetic testing was not performed. Given his poor overall physical condition, the patient was unable to undergo systemic chemotherapy and instead received palliative radiotherapy. The prescribed radiotherapy dose for the right upper lobe lung cancer and multiple metastatic lymph nodes was 60 Gy, administered in 30 fractions. Unfortunately, he failed to adhere to scheduled follow-ups and succumbed to the disease 6 months later, as confirmed during a telephone follow-up.Conclusion: PSCC is a rare but highly malignant lung cancer. Multiple pathological biopsies are necessary to accurately and promptly diagnose the disease, which is crucial for early treatment intervention as well as improving patient prognosis.Keywords: pulmonary spindle cell carcinoma, granulomatous inflammation, radiotherapy, multiple pathological biopsies

Yingying Jiang,1,&ast; Siqi Ge,2,&ast; Chunyang Wang,1 Chen Jin,1 Yumei Zhao,1 Qingying Liu3 1Department of Neuropharmacology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neuroepidemiology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pain Medicine, the First Affiliated Hospital of Zhengzhou University, Henan, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingying Liu, Email liuqy1679@163.comBackground: Sleep played an important part in human health, and COVID-19 led to a continuous deterioration of sleep. However, the causal relationship between micronutrient and sleep disorder was not yet fully understood.Methods: In this research, the genetic causal relationship between micronutrient and sleep disorder was analyzed utilizing a two-sample Mendelian randomization (MR). Single nucleotide polymorphisms (SNPs) were used as instrumental variables. The analyses were conducted using the MR-Egger, inverse variance weighted, weighted mode, weighted median, simple mode, Cochran’s Q test and leave-one-out.Results: Our results suggested that 8 genetically predicted micronutrients participated in sleep disorders, including liver iron (L-iron) and iron in sleeping too much, spleen iron (S-iron) in sleeplessness/insomnia, trouble falling or staying asleep, sleep duration (undersleepers) and nonorganic sleeping disorders, iron metabolism disorder (IMD) and vitamin B12 deficiency anaemia (VB12DA) in narcolepsy, urine sodium (uNa) in narcolepsy, sleep apnea syndrome and sleep disorder, vitamin D (VD) in sleep duration (oversleepers), 25-Hydroxyvitamin D (25(OH)D) in trouble falling or staying asleep.Conclusion: Our study used Mendelian randomization methods at the SNP level to explore the potential causal relationship among L-iron, iron, S-iron, IMD, uNa, 25(OH)D, VD, VB12DA with certain sleep disorder subtypes. Our results uncovered a micronutrient-based strategy for alleviating sleep disorder symptoms.Keywords: Mendelian randomization, micronutrient, sleep disorder, causality, vitamin

Huizhen Yue,1– 3 Xiaolong Xu,1– 3 Bing Peng,1– 3 Xuanyu Wang,1 Shengnan Zhang,1 Jinhao Tian,4 Shuo Wang,1 Maifen Song,1 Qingquan Liu1– 3 1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Chinese Medicine, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Basic Research with Traditional Chinese Medicine on Infectious Diseases, Beijing, People’s Republic of China; 4Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Qingquan Liu, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23 Gallery Backstreet, Dongcheng District, Beijing, People’s Republic of China, Email liuqingquan_2003@126.comPurpose: CaoHuangGuiXiang (CHGX) formula is a traditional Chinese medicine for the treatment of Candida-related infection. However, its antifungal mechanisms against the emerging fungal pathogen Candida auris remain unclear. This study aimed to evaluate the antifungal activity of the dichloromethane extract of CHGX (CHGX-DME) and clarified its antifungal mechanims against C. auris.Methods: The major components of CHGX-DME were identified by ultra-performance liquid chromatography tandem mass spectrometry. Then, the minimal inhibitory concentration (MIC) assay and the time-kill kinetic assay were performed to investigate the in vitro antifungal activity of CHGX-DME against C. auris, including 8 isolates of 4 discrete clades and 2 special phenotypes (filamentous and aggregative). Furthermore, the effect of CHGX-DME on biofilm development was examined. In addition, the in vivo toxicity and efficacy of CHGX-DME were evaluated in a Galleria mellonella infection model.Results: First, 20 major compounds in CHGX-DME were detected and characterized. The MIC50% and MIC90% of CHGX-DME against C. auris isolates ranged from 50– 200 mg/L and 100– 400 mg/L, respectively. At 400 mg/L, CHGX-DME was able to efficiently kill more than 70% and 90% of C. auris cells after 3 hours and 6 hours of treatment, respectively. This notable antifungal activity exhibited a dosage- and time-dependent manner. Moreover, CHGX-DME not only played a critical role in inhibiting the proliferation of filamentous and aggregative cells, but also showed restricting effect on biofilm development in C. auris. Importantly, it significantly improved the survival rate and reduced the fungal burden in G. mellonella infection models, suggesting a remarkable treatment effect against C. auris infection.Conclusion: CHGX-DME exhibited potent antifungal activity against C. auris and significantly ameliorated this fungal infection in the G. mellonella model, confirming that it would be a promising antifungal drug for the troublesome and emerging fungal pathogen C. auris.Keywords: Candida auris, multidrug resistance, CaoHuangGuiXiang formula, aggregative form, biofilm formation, antifungal efficiency

Na Li,1,&ast; Yue-xiang Ren,2,&ast; Heng-ming Ye,1,3 Ying Lin,4 Qiang Liu,5 Jiao Wang,1 Ze-fang Ren,1 Lin Xu1,6,7 1The School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Public Health Service Center of Bao’an District, Shenzhen, People’s Republic of China; 4The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6School of Public Health, the University of Hong Kong, Hong Kong; 7Institute of Applied Health Research, University of Birmingham, Birmingham, UK&ast;These authors contributed equally to this workCorrespondence: Ze-fang Ren; Lin Xu, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel +0086-20-87332577 ; Tel +0086-20- 87335523, Fax +011-86-20-87332577, Email renzef@mail.sysu.edu.cn; xulin27@mail.sysu.edu.cnPurpose: Chlamydia trachomatis (C. trachomatis) is associated with several gynecological tumors; yet its prognostic role in breast cancer remains unclear. Thus, we investigated the prognostic role of anti-C. trachomatis immunoglobulin G (IgG) in breast cancer patients and the modification effects of pro-inflammatory cytokines.Methods: The serum levels of C. trachomatis IgG and four pro-inflammatory cytokines were measured. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), including product terms to assess the modification effects of pro-inflammatory cytokines on the association between C. trachomatis IgG and breast cancer prognosis.Results: From 2008 to 2018, 1121 breast cancer patients were recruited and followed up until December 31, 2021, with a median follow-up time of 63.91 months (interquartile range: 39.16– 90.08 months). Patients positive for C. trachomatis IgG showed HRs of 1.09 (95% CI, 0.67– 1.78) for overall survival (OS) and 1.24 (0.87– 1.78) for progression-free survival (PFS), compared to those who were negative. These associations became statistically significant in women aged 50 years or younger (HR=1.43, 95% CI=0.79– 2.58 for OS; HR=1.79, 95% CI=1.16– 2.77 for PFS). Positive C. trachomatis IgG serology was associated with adverse prognostic effects among patients with higher levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1β), but with favorable prognostic effects for those with low levels. These interactions were particularly significant in those aged 50 years or younger.Conclusion: In breast cancer patients younger than 50 years of age or with higher levels of pro-inflammatory cytokines, C. trachomatis infection appeared to have a negative prognostic impact. These findings highlight the significance of C. trachomatis in predicting prognosis and personalized therapy for breast cancer patients.Keywords: Chlamydia trachomatis, breast cancer, prognosis, pro-inflammatory cytokines

Linghong Guo,1,2 Xu Liu,1,2 Qingfeng Liu,1,2 Xiaoqin Xie,1,2 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-028-85423315, Fax +86-028-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comObjective: This randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy of tranexamic acid essence combined with iontophoresis in treating melasma.Methods: Thirty participants were recruited and randomly assigned to the experimental (Group A) or control group (Group B). Group A received tranexamic acid essence iontophoresis treatment twice weekly for three months, while Group B received placebo treatment. Melasma Area and Severity Index (MASI) scores and skin luminance (L) values were assessed at baseline and weeks 4, 8, and 12.Results: No significant differences in baseline characteristics were observed between the groups. The mean MASI score reduction rate was significantly higher in Group A (− 0.10± 0.12%) compared to Group B (− 0.02± 0.09%) (p< 0.05). Skin L values significantly increased in Group A from 61.32± 3.53 to 63.32± 1.78, while slightly decreasing in Group B (p=0.037).Conclusion: Tranexamic acid essence combined with iontophoresis significantly improved MASI scores and skin luminance compared to placebo, demonstrating its effectiveness in treating melasma. Further research with larger sample sizes and longer follow-up is warranted to validate long-term effects and recurrence rates.Keywords: tranexamic acid, iontophoresis, melasma, clinical trial

Yue He,1,&ast; Qianhan Liu,1,&ast; Yurong Zheng,1 Shengdan Liu,1 Mingling Yu,1 Changhe Ren,2 Guangxiang Chen1 1Department of Radiology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Department of Pain, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changhe Ren, Department of Pain, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982784626, Email riverrch@163.com Guangxiang Chen, Department of Radiology, Affiliated Hospital of Southwest Medical University, No. 23 Tai Ping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Tel +86 18982409881, Email cgx23ly2002@163.comPurpose: Zoster-associated pain (ZAP) is frequently concomitant with psychiatric comorbidities. However, the underlying neuropathological mechanisms of ZAP with psychiatric comorbidities remain poorly understood.Patients and Methods: Rest-stating functional MRI (rs-fMRI) data from 41 ZAP patients without anxiety or depression (noA/D-ZAP), 11 ZAP patients with anxiety or depression (A/D-ZAP) and 29 healthy controls (HCs) were acquired. Degree centrality (DC) based on rs-fMRI was used to explore the node changes in the brain functional network in these subjects. Moreover, correlations and receiver operating characteristic curve analysis were performed.Results: One-way analysis of variance revealed abnormal DC values in the right middle frontal gyrus (MFG) and bilateral precuneus among the three groups. Compared with HCs, A/D-ZAP showed increased DC values in the bilateral pons, while noA/D-ZAP showed increased DC values in the right pons, left brainstem and rectal gyrus and decreased DC values in the right cingulate gyrus and bilateral precuneus. A/D-ZAP showed increased DC values in the left MFG and precentral gyrus (PG) compared with noA/D-ZAP. The DC value of the left pons in A/D-ZAP was positively correlated with the self-rating anxiety scale score. Areas under the curve of DC values in the left PG and MFG for distinguishing A/D-ZAP from the noA/D-ZAP group were 0.907 and 1.000, respectively.Conclusion: This study revealed the node differences in the brain functional network of ZAP patients with or without psychiatric comorbidities. In particular, abnormal DC values of the left MFG and PG may play an important role in the neuropathologic mechanism of the disease.Keywords: functional MRI, degree centrality, zoster-associated pain, anxiety, depression

Qingyang Liu,1,&ast; Jian Wang,2,&ast; Chunhui Ding,3 Ying Chu,1 Fengying Jiang,1 Yunxia Hu,4 Haifeng Li,2 Qiubo Wang1 1Department of Clinical Laboratory, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Department of Orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 3Department of Pharmacy, Wuxi Ninth People’s Hospital Affiliated to Soochow University, Wuxi, Jiangsu, 214000, People’s Republic of China; 4Department of Rheumatology and Immunology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiubo Wang, Department of Clinical Laboratory, Wuxi Ninth People’s Hospital Affiliated to Soochow University, No. 999 Liang Xi Road, Binhu District, Wuxi, Jiangsu, 214000, People’s Republic of China, Email wangqiubo2020@suda.edu.cn Haifeng Li, Department of orthopedics, Wuxi Ninth People’s Hospital Affiliated to Soochow University, No. 999 Liang Xi Road, Binhu District, Wuxi, Jiangsu, 214000, People’s Republic of China, Email lihaifeng2008@suda.edu.cnPurpose: Sinomenine (SIN) is commonly used in Traditional Chinese Medicine (TCM) as a respected remedy for rheumatoid arthritis (RA). Nevertheless, the therapeutic mechanism of SIN in RA remains incompletely understood. This study aimed to delve into the molecular mechanism of SIN in the treatment of RA.Methods: The potential targets of SIN were predicted using the TCMSP server, STITCH database, and SwissTarget Prediction. Differentially expressed genes (DEGs) in RA were obtained from the GEO database. Enrichment analyses and molecular docking were conducted to explore the potential mechanism of SIN in the treatment of RA. In vitro and in vivo studies were conducted to validate the intervention effects of SIN on rheumatoid arthritis, as determined through network pharmacology analyses.Results: A total of 39 potential targets associated with the therapeutic effects of SIN in RA were identified. Enrichment analysis revealed that these potential targets are primarily enriched in PI3K-Akt signaling pathway, and the molecular docking suggests that SIN may act on specific proteins in the pathway. Experimental results have shown that exposure to SIN inhibits cytokine secretion, promotes apoptosis, reduces metastasis and invasion, and blocks the activation of the PI3K-Akt signaling pathway in RA fibroblast-like synoviocytes (RA-FLS). Moreover, SIN treatment alleviated arthritis-related symptoms and regulated the differentiation of CD4+ T cells in the spleen of collagen-induced arthritis (CIA) mice.Conclusion: By utilizing network pharmacology, molecular modeling, and in vitro/in vivo validation, this study demonstrates that SIN can alleviate RA by inhibiting the PI3K-Akt signaling pathway. These findings enhance the understanding of the therapeutic mechanisms of SIN in RA, offering a stronger theoretical foundation for its future clinical application. Keywords: sinomenine, rheumatoid arthritis, network pharmacology, PI3K-Akt signaling pathway

Wenguang Deng, Zhiming Zeng, Qingyan Liu, Jingjing Deng, Liyu Wang, Hui Li, Yuenong Zhang The Anesthesiology Surgery Center of The Third Affiliated Hospital of Sun Yat-sen University-Yuedong Hospital, Guangdong, People’s Republic of ChinaCorrespondence: Yuenong Zhang, Email 36856665@qq.comBackground: This study explored the effects of different doses of remimazolam tosilate (RT) and propofol combined with remifentanil anesthesia on hemodynamic and inflammatory responses in patients undergoing laparoscopic surgery.Subjects and Methods: Ninety patients with a BMI of less than 35 kg/m², classified as ASA II–III and scheduled for laparoscopic surgery, were enrolled in this study. Patients were divided into three groups: low-dose RT group (A), high-dose RT group (B), and propofol group (C). The changes in hemodynamic indices such as SBP, DBP, HR, MAP, and inflammatory response indices such as IL-6, SAA, CRP, and PCT, along with extubation time and doses of sufentanil, remifentanil, urapidil, and phenylephrine, were compared among the three groups.Results: There were no statistically significant differences in extubation time, doses of sufentanil and remifentanil, or the usage rates and average doses of urapidil and phenylephrine between the three groups. The average dose of phenylephrine in group A was lower than in group B and group C, with a statistically significant difference. There were no statistically significant differences among the groups in SBP, DBP, HR, and MAP from T0 to T2, nor in IL-6, SAA, CRP, or PCT levels.Conclusion: Using RT for induction and maintenance of anesthesia in laparoscopic surgery ensures stable hemodynamic and inflammatory responses in patients. Low-dose RT may reduce the usage rate and dose of vasopressors such as phenylephrine during surgery.Keywords: remimazolam tosilate, propofol, remifentanil, hemodynamic, inflammatory, laparoscopic surgery

Qiming Gan,1,&ast; Quanzhen Liu,1,2,&ast; Yanjuan Wu,1,&ast; Xiaofeng Zhu,1,2 Jingcun Wang,1 Xiaofen Su,1 Dongxing Zhao,1 Nuofu Zhang,1 Kang Wu1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Disease, Department of Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2Nanshan School, Guangzhou Medical University, Guangzhou, Guangdong, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kang Wu; Nuofu Zhang, Department of Pulmonary and Critical Care Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, No. 28 Qiaozhong Mid Road, Guangzhou, Guangdong, 510160, People’s Republic of China, Email d102_wk@126.com; nfzhanggird@163.comPurpose: Obstructive sleep apnea (OSA) had been associated with asthma in observational studies, but the effect of OSA on the onset of asthma in childhood or adulthood remains unclear, and the causal inferences have not been confirmed. This study aims to investigate the potential causal association between OSA with asthma, including different age-of-onset subtypes, providing reliable basis for the clinical treatment of OSA and asthma.Patients and Methods: Causality between OSA and asthma was assessed using a two-sample bi-directional Mendelian randomization (MR) analysis. OSA data were obtained from the FinnGen consortium R9, while asthma and its subtypes (adult-onset asthma, child-onset asthma, and moderate-to-severe asthma) were sourced from the IEU OpenGWAS project. The inverse-variance weighted (IVW) method was chosen as the primary analysis and was complemented by various sensitivity analyses. The MR-PRESSO outlier test was employed to systematically identify and remove outlier variants, mitigating heterogeneity and potential effects of horizontal pleiotropy.Results: The MR analyses provided evidence of genetically predicted OSA having a promoting effect on child-onset asthma (OR,1.49; 95% CI, 1.05– 2.11; P=0.025) and moderate-to-severe asthma (OR,1.03; 95% CI, 1.00– 1.06; P=0.046). However, no causal association between OSA with asthma and adult-onset asthma was observed.Conclusion: Our study revealed a causal association between OSA and child asthma, but not in adults. Moderate-to-severe asthma may have a potential promoting effect on OSA. These findings underscore the importance of age-specific considerations in managing asthma and suggests the need for personalized approaches in clinical practice.Keywords: asthma, obstructive sleep apnea, Mendelian randomization, genetic

Ente Li,1,2,&ast; Qingfeng Zhu,3,&ast; Ziman Lv,1,2,&ast; Songsong Xie,3 Chunju Zhang,4 Wei Li,5 Ligu Mi,1,2 Quan Liu,6 Yuanzhi Wang,1,2 Xiaobo Lu2 1Department of Basic Medicine, School of Medicine, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 2Key Laboratory for Prevention and Control of Emerging Infectious Diseases and Public Health Security, the Xinjiang Production and Construction Corps, Shihezi University, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 3The First Affiliated Hospital of Shihezi University Medical College, Shihezi City, Xinjiang Uygur Autonomous Region, 832002, People’s Republic of China; 4Tumxuk Center for Disease Prevention and Control, Tumxuk City, Xinjiang Uygur Autonomous Region, 843806, People’s Republic of China; 5Department of Basic Medicine, School of Medicine, Tarim University, Alaer City, Xinjiang Uygur Autonomous Region, 843300, People’s Republic of China; 6Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, Key Laboratory of Zoonotic Diseases, The First Hospital of Jilin University, Changchun City, Jilin Province, 30061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanzhi Wang; Xiaobo Lu, Email wangyuanzhi621@126.com; xjykdluxiaobo@126.comAbstract: Visceral leishmaniasis (VL), also known as kala-azar. It is characterized by prolonged intermittent fever, anemia, splenomegaly, hepatomegaly, and skin darkening. VL is primarily endemic in regions, such as Brazil, East Africa, and India. However, Northern Xinjiang, which is located in northwestern China, is considered a low-incidence area for VL, contributing to its status as a neglected infectious disease. In this report, we present a case of VL caused by Leishmania donovani that was diagnosed using metagenomic next-generation sequencing (mNGS). This case underscores the diagnostic value of mNGS, particularly in regions with low incidence of VL. Keywords: Visceral leishmaniasis, Leishmania donovani, metagenomic next-generation sequencing, northwestern China

Qiqi Cheng,1 Xiaolin Zhou,1 Peng Wang,2 Rong Liu,3 Qiang Liu1 1Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 2Department of Clinical Laboratory, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 3Department of Ultrasound, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaCorrespondence: Qiang Liu, Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China, Tel +86 13720181669, Email liuqiang@ctgu.edu.cnAbstract: We report a rare case of mechanical aortic valve infective endocarditis caused by Neisseria sicca. A 44-year-old man, with a history of aortic valve replacement, presented to the hospital with a 10-day history of fever. Investigations revealed that the blood cultures grew Neisseria sicca. Although the transthoracic echocardiogram (TTE) was negative, a transesophageal echocardiogram showed a 0.5 cm × 0.3 cm piece of vegetation attached to the aortic valve. After eight weeks of therapy, according to the antibiotic susceptibility test, the patient’s blood cultures were negative, and repeat TTE showed no vegetation. This report can offer valuable insights for clinical diagnosis and treatment of Neisseria sicca endocarditis, particularly when selecting sensitive antibiotics.Keywords: infective endocarditis, Neisseria sicca, aortic valve, bacteremia

Qing Liu,1,2,&ast; Xiao-Jiao Tang,1,2,&ast; Xin-Ke Chen,1,2 Lin Chen1,2 1Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Chen, Children’s Hospital of Chongqing Medical University, 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Tel +8618623041022, Fax +86-23-63651759, Email chenlin1220@126.comObjective: To investigate the effectiveness of flipped classrooms (FC) based on outcomes-based education (OBE) on clinical ophthalmology clerkships.Methods: Ninety-nine undergraduates were non-randomly assigned to the FC based on the OBE (FC-OBE) group or traditional lecture (TL) group in the ophthalmology clerkship. Pre- and post-tests were performed to assess student learning outcomes. Anonymous questionnaires were collected to compare students’ attitudes and classroom engagements between the two groups.Results: More participants agreed FC-OBE was helpful in developing teamwork ability and knowing the work standard. Teaching staff in the FC-OBE classroom received higher evaluations. More participants in the FC-OBE group had higher classroom engagement in skills and emotions than in the TL group. The post-class test scores, mainly case analysis scores were higher in the FC-OBE group than in the TL group.Conclusion: FC-OBE classroom improves student engagement and clinical analysis competence in undergraduate ophthalmology clerkship.Keywords: ophthalmology education, OBE, flipped classroom, clinical clerkship, undergraduate

Xiao-Jiao Tang,1– 4 Jia-Tong He,5 Qing Liu,1– 4 Enmei Liu,2– 4,6 Lin Chen1– 4 1Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2National Clinical Research Center for Child Health and Disorders, Chongqing, People’s Republic of China; 3Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 4Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing, People’s Republic of China; 5Department of Health Management, Chongqing General Hospital, Chongqing, People’s Republic of China; 6Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Enmei Liu, Department of Respiratory Medicine, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Chongqing, Yuzhong District, 400014, People’s Republic of China, Tel +8613368070773, Email emliu186@126.com Lin Chen, Department of Ophthalmology, Children’s Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Chongqing, Yuzhong District, 400014, People’s Republic of China, Tel +8618623041022, Email chenlin1220@126.comPurpose: To investigate the patterns of allergens in allergic conjunctivitis (AC) and the association with allergic comorbidity.Methods: This retrospective cross-sectional study enrolled 2972 children with AC. Clinical data, including sex, age, allergic comorbidities (allergic asthma, allergic rhinitis, and atopic dermatitis), and serum allergen-specific immunoglobulin E (sIgE), were collected from the electronic medical record (EMR). The categorical variables were compared with the chi-square test. The characteristics of allergens in children of different ages and comorbidities were analyzed by trend chi-square. The sensitivity level of HDM associated with AC and comorbidities was assessed by odds ratios (ORs) with 95% confidence intervals of logistic regression analysis.Results: A total of 2972 children (2015 boys and 957 girls) with AC were included in the study. The mean age was 3.78 (0.5~12) years. The most common allergen was house dust mite(HDM) (43.41%). With age, the positive rate for inhaled allergens gradually increased, and the positive rate for ingested allergens decreased. With the number of comorbidities increasing, the positive rates of sensitization were 38.33%, 74.51%, 80.72%, and 89.05%, and the incidence of polysensitization was 44.66%, 56.48%, 59.54%, and 74.59%, respectively. With the increase of HDM-sIgE level, the number of comorbidities and the risk increased gradually.Conclusion: HDM is the most common allergen in AC children of different ages. High levels of HDM-sIgE may be a predictor for allergic comorbidities. Children with polysensitization and high levels of HDM sIgE will be an important target population for future intervention in other allergy-related disease prevention.Keywords: allergic conjunctivitis, specific IgE, allergic comorbidity, house dust mite, children

Qingyi Liu,1,2 Qiongdan Zhang,1,2 Zhijian Yao,1,2 Gangqiang Yi,2 Yeonseok Kang,3 Yixing Qiu,1,2 Yupei Yang,1,2 Hanwen Yuan,1,2 Ronggeng Fu,2 Wenbing Sheng,1,2 Lidong Cheng,4 Wei Wang,1,2 Huizhen Wang,1,2 Caiyun Peng1,5 1TCM and Ethnomedicine Innovation & Development International Laboratory, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 2School of Pharmacy, Hunan University of Chinese Medicine, Changsha, People’s Republic of China; 3College of Korean Medicine, Wonkwang University, Jeonbuk, Korea; 4Hunan Yirentang Chinese Herbal Pieces Co., Ltd, Changde, People’s Republic of China; 5Institute of Innovation and Applied Research in Chinese Medicine Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Huizhen Wang; Caiyun Peng, Tel +86-151-1648-1295 ; +86-138-7480-7689, Email whuiz0086@163.com; caiyunpeng@hnucm.edu.cnAbstract: Extracellular vesicles (EVs) are microparticles released from cells in both physiological and pathological conditions and could be used to monitor the progression of various pathological states, including neoplastic diseases. In various EVs, tumor-derived extracellular vesicles (TEVs) are secreted by different tumor cells and are abundant in many molecular components, such as proteins, nucleic acids, lipids, and carbohydrates. TEVs play a crucial role in forming and advancing various cancer processes. Therefore, TEVs are regarded as promising biomarkers for the early detection of cancer in liquid biopsy. However, the currently developed TEV detection methods still face several key scientific problems that need to be solved, such as low sensitivity, poor specificity, and poor accuracy. To overcome these limitations, DNA walkers have emerged as one of the most popular nanodevices that exhibit better signal amplification capability and enable highly sensitive and specific detection of the analytes. Due to their unique properties of high directionality, flexibility, and efficiency, DNA walkers hold great potential for detecting TEVs. This paper provides an introduction to EVs and DNA walker, additionally, it summarizes recent advances in DNA walker-based detection of TEVs (2018– 2024). The review highlights the close relationship between TEVs and DNA walkers, aims to offer valuable insights into TEV detection and to inspire the development of reliable, efficient, simple, and innovative methods for detecting TEVs based on DNA walker in the future. Keywords: EVs, TEVs, DNA walker, detection

Xiaojuan Wu,1,2,&ast; Daoyan Wu,1,2,&ast; Guzhen Cui,1 Khui Hung Lee,3 Tingxiu Yang,1,2 Zhengrong Zhang,1,2 Qi Liu,4 Jinbao Zhang,1 Eng Guan Chua,3 Zhenghong Chen1,2 1Key Laboratory of Microbiology and Parasitology of Education Department of Guizhou & Joint Laboratory of Helicobacter Pylori and Intestinal Microecology of Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, People’s Republic of China; 2Key Laboratory of Endemic and Ethnic Diseases of Ministry of Education, Guizhou Medical University, Guiyang, People’s Republic of China; 3Helicobacter Research Laboratory, the Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia; 4Department of Gastroenterology, Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghong Chen, Department of Microbiology, School of Basic Medical Science, Guizhou Medical University, Guiyang, People’s Republic of China, Tel + 86-13985006815, Email chenzhenghong@gmc.edu.cnBackground: Persistent infections caused by Helicobacter pylori (H. pylori), which are resistant to antibiotic treatment, pose a growing global public health concern. Biofilm formation is known to be associated with persistent infections due to its role in enhancing antimicrobial resistance and the tolerance of many pathogenic bacteria.Objective: This study aims to evaluate the biofilm formation of clinical isolates of H. pylori and its impact on antibiotic eradication.Methods: The thickness, morphology, and structure of biofilms derived from nine H. pylori strains were examined using confocal laser scanning microscopy, scanning electron microscopy, and transmission electron microscopy. Subsequently, the susceptibility of both planktonic and biofilm bacteria was assessed through the determination of minimum inhibitory concentration and minimum biofilm eradication concentration for amoxicillin, clarithromycin, levofloxacin, and tetracycline.Results: The results revealed varying biofilm thicknesses and densities among the strains, characterised by the presence of numerous filaments intertwining and connecting bacterial cells. Additionally, several cases exhibited susceptibility based on MIC measurements but resistance according to MBEC measurements, with MBEC indicating a higher resistance rate. Pearson Correlation analysis demonstrated a positive correlation between biofilm thickness and MBEC results (0 < r < 1), notably significant for amoxicillin (r = 0.801, P = 0.009) and tetracycline (r = 0.696, P = 0.037).Conclusion: Different strains of H. pylori exhibit variations in their capacity to release outer membrane vesicles (OMVs) and form biofilms. Biofilm formation can influence the effectiveness of amoxicillin and tetracycline in eradicating susceptible bacterial strains.Keywords: Helicobacter pylori, antibiotic resistance, biofilm formation, biofilm-specific resistance

Fengyao Liu,1,2,&ast; Haochen Wang,2,3,&ast; Bingqing Bai,2,4 Han Yin,5 Yuting Liu,2 Yu Wang,2 Quanjun Liu,2 Shuxia Wang,6 Huan Ma,3 Qingshan Geng1,2,5 1School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 2Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 5Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, People’s Republic of China; 6Department of Nuclear Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huan Ma, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106 Zhongshan Er Road, Guangzhou, People’s Republic of China, Fax +8620-83827812, Email mahuandoctor@163.com Qingshan Geng, Department of Cardiology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), 1080 Cuizhu Road, Luohu District, Shenzhen, Guangdong, Fax +0755-25533018, Email gengqsh@163.netPurpose: Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited.Patients and Methods: We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI.Results: There is higher REI (7.8 vs 2.6, P=0.019), ODI (4.7 vs 9.2, P=0.028) and percentage of OSA (67.74% vs 33.33%, P=0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, P = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (β=1.226, OR = 3.408 (1.200– 9.681), P = 0.021).Conclusion: Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.Keywords: obstructive sleep apnea, mental stress induced myocardial ischemia, angina with no obstructive coronary artery disease, myocardial perfusion imaging

Yidong Cui,1 Qingming Liu,2 Qiqiang Zhang,3 Xuemei Di,3 Hai Zhang3 1Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of China; 2Department of Neurology, Shandong Second Provincial General Hospital, Jinan, 250012, People’s Republic of China; 3Department of Pharmacy, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Hai Zhang, Department of Pharmacy, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No. 2699 West Gaoke Road, Shanghai, 200092, People’s Republic of China, Tel/Fax +8621-20261401, Email zhxdks2005@126.comBackground: Aconitum carmichaelii (Fuzi) has been conventionally used to cure a variety of ailments, such as pain, cold sensations, and numbness of limb muscles (Bi Zheng) in China. Our prior investigations identified Benzoylaconine (BAC) as a bioactive alkaloid derived from Aconitum carmichaelii, with other studies also demonstrating its significant pharmacological potential.Purpose: This study aimed to explore the potential of BAC as a protective agent against skeletal muscle ischemia-reperfusion (I/R) injury and to elucidate the underlying mechanisms.Methods: In vivo models involved subjecting Sprague-Dawley rats to I/R through femoral artery ligation followed by reperfusion, while in vitro models utilized C2C12 cells subjected to hypoxia/reoxygenation (H/R). CCK-8 assay was used to assess cell viability. TUNEL staining and flow cytometric analysis were used to measure cell apoptosis. Biochemical assay was used to assess skeletal muscle injury and oxidative stress. Immunofluorescence and Western blot were performed to determine protein levels.Results: BAC effectively protected muscle tissue from I/R injury, enhancing cell viability (p< 0.01), elevating SOD levels (p< 0.05), and reducing CK (p< 0.01), LDH (p< 0.01), ROS (p< 0.01), MDA (p< 0.01), and apoptosis-related molecules in vivo and in vitro (p< 0.05, p< 0.01). Mechanistically, BAC increased the expression of IF1, phosphorylated AMPK, facilitated the translocation of nuclear Nrf2, and induced the expression of HO-1 (p< 0.01). Notably, AMPK inhibitor Compound C significantly hindered the ability of BAC to ameliorate H/R-induced cell injury (p< 0.05), oxidative stress(p< 0.01), and apoptosis (p< 0.05), as well as promote Nrf2 nuclear translocation (p< 0.01). Moreover, silencing of IF1 with siRNA abolished BAC-induced activation of AMPK/Nrf2 axis (p< 0.01).Conclusion: Our study provides novel evidence supporting the potential of BAC as a myocyte-protective agent against I/R injury, and we establish a previously unknown mechanism involving the activation of the IF1-dependent AMPK/Nrf2 axis in mediating the protective effects of BAC. Keywords: Benzoylaconine, ischemia-reperfusion injury, oxidative stress, AMPK, IF1

Jingyi Lao,1,&ast; Yijie Zeng,1,&ast; Zhangying Wu,1 Gaohong Lin,1 Qiang Wang,1 Mingfeng Yang,1 Si Zhang,1 Danyan Xu,1 Min Zhang,1 Kexin Yao,1 Shuang Liang,1 Qin Liu,1 Jiafu Li,1 Xiaomei Zhong,1 Yuping Ning1– 4 1Geriatric Neuroscience Center, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 3Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, People’s Republic of China; 4Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuping Ning; Xiaomei Zhong, The Affiliated Brain Hospital of Guangzhou Medical University, No. 36, Mingxin Road, Liwan District, Guangzhou, Guangdong, People’s Republic of China, Email ningjeny@126.com; lovlaugh@163.comBackground: Late-life depression (LLD) is characterized by disrupted brain networks. Resting-state networks in the brain are composed of both stable and transient topological structures known as microstates, which reflect the dynamics of the neural activities. However, the specific pattern of EEG microstate in LLD remains unclear.Methods: Resting-state EEG were recorded for 31 patients with episodic LLD (eLLD), 20 patients with remitted LLD (rLLD) and 32 healthy controls (HCs) using a 64-channel cap. The clinical data of the patients were collected and the 17-Item Hamilton Rating Scale for Depression (HAMD) was used for symptom assessment. Duration, occurrence, time coverage and syntax of the four microstate classes (A-D) were calculated. Group differences in EEG microstates and the relationship between microstates parameters and clinical features were analyzed.Results: Compared with NC and patients with rLLD, patients with eLLD showed increased duration and time coverage of microstate class D. Besides, a decrease in occurrence of microstate C and transition probability between microstate B and C was observed. In addition, the time coverage of microstate D was positively correlated with the total score of HAMD, core symptoms, and miscellaneous items.Conclusion: These findings suggest that disrupted EEG microstates may be associated with the pathophysiology of LLD and may serve as potential state markers for the monitoring of the disease.Keywords: late-life depression, microstate, electroencephalogram, resting-state networks

Chuang Qin,1 Xiaofei Ye,1 Hongliang Luo,1 Hu Jin,1 Qiang Liu,1 Jiangfa Li2 1Hepatobiliary Surgery, Liuzhou People’s Hospital Affiliated to Guangxi Medical University, Liuzhou City, Guangxi, People’s Republic of China; 2Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical University, Guilin City, Guangxi, People’s Republic of ChinaCorrespondence: Jiangfa Li, Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical University, No. 15, Lequn Road,Xiufeng District, Guilin City, Guangxi, 541001, People’s Republic of China, Email ljf.126@qq.comPurpose: This study contributes to the evolving understanding of the pivotal involvement of Sirtuins (SIRTs) in various human cancers, with a particular focus on elucidating their expression patterns and clinical relevance within the context of hepatocellular carcinoma (HCC). The investigation involves a comprehensive analysis of mRNA expression and prognostic implications associated with distinct SIRTs in HCC.Patients and Methods: Initial data pertaining to SIRT expression in HCC patients were collated from publicly accessible databases. Subsequently, the expression levels of select members of the SIRT family were validated using clinicopathological specimens from HCC patients. Additionally, HCC tissue microarray was employed to scrutinize the correlation between SIRT7 expression and HCC prognosis.Results: The findings indicated a substantial upregulation of SIRT2, SIRT3, SIRT4, SIRT6, and SIRT7 in HCC tissues. Survival analysis underscored a pronounced association between elevated mRNA levels of SIRT3, SIRT6, and SIRT7 and an adverse prognosis for HCC patients. Particularly, SIRT7 emerged as a potential independent risk factor for poor prognosis in HCC patients. Examination of the HCC tissue microarray revealed heightened expression of SIRT7 in 68 cases (54.8%) of HCC tissues. Multivariate analysis established high SIRT7 expression as an independent risk factor for diminished Disease-Free Survival (DFS) and Overall Survival (OS) in HCC patients.Conclusion: The aberrant expression of SIRT7 presents itself may be as a novel biomarker for predicting the prognosis of HCC patients.Keywords: HCC, microarray, prognosis, SIRT7, survivor

Tingting Wang,1 Yang Wang,2 Qingyue Liu,1 Wenbin Guo,1 Hongliang Zhang,1 Liangliang Dong,3 Jiajun Sun1 1Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 2Department of Laboratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 3Department of Respiratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of ChinaCorrespondence: Jiajun Sun, Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, No. 306 Jiankang Road, Linqing, Shandong, People’s Republic of China, Tel +86-13793092818, Email 13793092818@126.comBackground: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population.Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (> 98), mild malnutrition (92– 98), moderate malnutrition (82– 91), and severe malnutrition (≤ 81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect.Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 > 98), the adjusted HR values for GNRI in Q3 (92– 98), Q2 (82– 91), and Q1 (≤ 81) were 1.81 (95% CI: 1.27– 2.58, p=0.001), 1.23 (95% CI: 0.84– 1.79, p=0.296), 2.27 (95% CI: 1.57– 3.29, p< 0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5.Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients.Keywords: geriatric nutritional risk index, 90-day mortality, older adults, chronic obstructive pulmonary disease, MIMIC-IV

Xu Liu,1,&ast; Qingfeng Liu,1,&ast; Linghong Guo,1 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-28-85423315, Fax +86-28-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comAbstract: The increasing popularity of tattoo art, including facial cosmetic tattoos, has led to a growing societal acceptance of tattoos. However, complications such as lip inflammation following cosmetic lip tattoos remain a concern. This article presents the case of a 47-year-old Asian woman who experienced recurrent lip swelling, purulent discharge, and scarring after receiving lip tattoos. Despite previous treatment with corticosteroid injections yielding unsatisfactory results, the patient showed significant improvement with topical application of 2% Crisaborole, a phosphodiesterase-4 inhibitor. Crisaborole modulates intracellular cyclic adenosine monophosphate levels, thereby reducing tissue inflammation and swelling associated with chronic cheilitis. Additionally, pulse laser therapy was effective in addressing residual tattoo pigment and scar tissue. This case highlights the therapeutic challenges of managing chronic inflammatory diseases of the lips secondary to cosmetic tattoos and introduces Crisaborole as a promising treatment option, offering insights for managing similar conditions in the future.Keywords: lip tattoo, chronic cheilitis, Crisaborole, phosphodiesterase-4 inhibitor, laser therapy

Qingxiang Liu,1,&ast; Haitao Liu,2,&ast; Zihan Hu,1 Xing Zhou,1 Kai Jin,1 Yingzi Huang,1 Wei Huang,1 Yi Yang1 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Life Science, Fudan University, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang; Yi Yang, Email whuang@seu.edu.cn; yiyiyang2004@163.comBackground: Sepsis is a life-threatening clinical syndrome caused by dysregulated host response to infection. The mechanism underlying sepsis-induced immune dysfunction remains poorly understood. Natural killer T (NKT) cells are cytotoxic lymphocytes that bridge the innate and adaptive immune systems, the role of NKT cells in sepsis is not entirely understood, and NKT cell cluster differences in sepsis remain unexplored.Methods: Mendelian randomization (MR) analyses were first conducted to investigate the causal relationship between side scatter area (SSC-A) on NKT cells and 28-day mortality of septic patients. A prospective and observational study was conducted to validate the relationship between the percentage of NKT cells and 28-day mortality of sepsis. Then, the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from healthy controls and septic patients were profiled.Results: MR analyses first revealed the protective roles of NKT cells in the 28-day mortality of sepsis. Then, 115 septic patients were enrolled. NKT percentage was significantly higher in survivors (n = 84) compared to non-survivors (n = 31) (%, 5.00 ± 3.46 vs 2.18 ± 1.93, P < 0.0001). Patients with lower levels of NKT cells exhibited a significantly increased risk of 28-day mortality. According to scRNA-seq analysis, NKT cell clusters exhibited multiple distinctive characteristics, including a distinguishing cluster defined as FOS+NKT cells, which showed a significant decrease in sepsis. Pseudo-time analysis showed that FOS+NKT cells were characterized by upregulated expression of crucial functional genes such as GZMA and CCL4. CellChat revealed that interactions between FOS+NKT cells and adaptive immune cells including B cells and T cells were decreased in sepsis compared to healthy controls.Conclusion: Our findings indicate that NKT cells may protect against sepsis, and their percentage can predict 28-day mortality. Additionally, we discovered a unique FOS+NKT subtype crucial in sepsis immune response, offering novel insights into its immunopathogenesis.Keywords: natural killer T cells, sepsis, outcome, Mendelian randomization

Qingxiang Liu,1,&ast; Fei Peng,1,&ast; Haitao Liu,2,&ast; Qin Sun,1 Hui Chen,1 Xinyi Xu,1 Zihan Hu,1 Xing Zhou,1 Kai Jin,1 Jianfeng Xie,1 Yingzi Huang,1 Wei Huang,1 Yi Yang1 1Jiangsu Provincial Key Laboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of China; 2School of Life Science, Fudan University, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang; Yi Yang, Email whuang@seu.edu.cn; yiyiyang2004@163.comBackground: Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood.Methods: A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration.Results: A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46± 4.40 vs 11.65± 6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand–receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS.Conclusion: MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.Keywords: ARDS, inflammation, natural killer cells, sepsis

Tianle Chen, Qi Liu, Jie Yang College of Biomedical Engineering, Sichuan University, Chengdu, 610065, People’s Republic of ChinaCorrespondence: Qi Liu, College of Biomedical Engineering, Sichuan University, Chengdu, 610065, People’s Republic of China, Email liuqi@scu.edu.cnIntroduction: Skin disease is one of the most common diseases and can affect people of all ages and races. However, the diagnosis of skin diseases via observation is a highly challenging task for both doctors and patients, and would benefit from the use of an intelligent system. Building a large benchmark with professional dermatologists is resource-intensive, and we believe that few-shot learning (FSL) methods would be helpful in solving the problem of annotated data scarcity. In this paper, we propose CDD-Net (Context Feature Fusion and Dual Attention Dermatology Net), a plug-in module for FSL clinical skin disease classification.Methods: Current FSL methods used in skin disease classification are limited to nonuniversal approaches and few disease classes. Our CDD-Net has a flexible structure, including a context feature–fusion module and dual-attention module to extract discriminating texture feature and emphasize contributive regions and channels. The context feature–fusion module localizes discriminatory texture details of skin lesions by integrating features from different layers, while the dual-attention module highlights discriminative regions via channel-wise and pixel-wise depictions based on weight vectors and restrains the contributions of irrelevant areas. We also present Derm104, a new clinical skin disease data benchmark that has significant coverage of rare diseases and reliable annotation between primary species and subspecies for better validation of our approach.Results: Our experiments validated the versatility of CDD-Net for different FSL methods and achieved an improvement in accuracy of up to 9.14 percentage points compared with the vanilla network, which can be considered state of the art. The ablation study also showed that the dual-attention module and context feature–fusion module worked efficiently in CDD-Net. Keywords: clinical skin image, computer-aided diagnosis, few-shot learning, feature fusion, attention mechanism

Qinghao Liu,&ast; Weiwen Zhao,&ast; Hao Yin Department of Orthopedic, The First Affiliated Hospital of Hunan Normal University Hunan Provincial People’s Hospital, Changsha, China Mainland (PRC)&ast;These authors contributed equally to this workCorrespondence: Hao Yin, Email ehour@hunnu.edu.cnBackground: Spontaneous spinal epidural hematoma (SSEH) presenting in the context of JAK2 V617F-positive myeloproliferative neoplasms is a rare condition, characterized by the compression of the spinal cord leading to various symptoms. The etiology, pathogenesis, and optimal treatment strategies for this condition remain undetermined. The occurrence of spontaneous spinal epidural hematoma (SSEH) in the context of JAK2 V617F-positive myeloproliferative neoplasms (MPNs) represents a rare manifestation. Magnetic Resonance Imaging (MRI) plays a crucial role in the definitive diagnosis of this condition. With a good understanding of the pathogenic characteristics and clinical presentations of this disease, a diagnosis can be reasonably made, even in the absence of MRI, based on physical examinations indicating the affected area. Once diagnosed, immediate surgery is recommended to attempt the restoration of spinal cord function. Postoperatively, the use of hydroxyurea has proven effective in disease control.Case Presentation: We report a case of a 65-year-old male patient who presented with progressive lumbar back pain and bilateral lower limb paralysis lasting for 36 hours. CT imaging revealed an intraspinal lesion at the L1-3 level, and genetic testing confirmed the presence of the JAK2V617F mutation. Following surgery, there was a significant recovery of sensory and motor function in the lower limbs. At one-year follow-up, the patient demonstrated good functional status, and blood tests indicated a platelet count within the normal range.Conclusion: The presented case adds to the existing literature on SSEH by highlighting the association with myeloproliferative neoplasms (MPNs), as evidenced by the JAK2V617F mutation. MPNs constitute a group of hematologic malignancies, and the association with SSEH is a rare occurrence. The exact interplay between MPNs and SSEH warrants further investigation, as the underlying mechanisms linking these conditions remain elusive. The case also underscores the importance of a multidisciplinary approach, involving hematologists and neurosurgeons, in the comprehensive management of such complex cases.Keywords: myeloproliferative neoplasms, spinal epidural hematoma, JAK2V617F

Shuo Tian,1,2,&ast; Haitao Zhong,3,4,&ast; Mengyue Yin,5 Pei Jiang,3 Qiao Liu1 1Department of Pharmacy, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Clinical Pharmacy, Jining First People’s Hospital, Shandong First Medical University, Jining, Shandong, People’s Republic of China; 3Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Shandong First Medical University, Jining, Shandong, People’s Republic of China; 4Institute of Translational Pharmacy, Jining Medical Research Academy, Jining, Shandong, People’s Republic of China; 5The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital of Central South University, Central South University, Changsha, Hunan, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: This study aims to conduct a comprehensive cost-effectiveness comparison between novel oral anticoagulants (NOACs) and warfarin in Chinese patients with left ventricular thrombosis (LVT). By incorporating the impact of volume-based procurement (VBP) policy for pharmaceuticals in China, this analysis intends to provide crucial insights for informed healthcare decision-making.Patients and Methods: A Markov model was employed to simulate the disease progression of LVT over a 54-week time horizon, using weekly cycles and six mutually exclusive health states. The model incorporated transition probabilities between health states calculated based on clinical trial data and literature sources. Various cost and utility parameters were also included. Additionally, a series of sensitivity analyses were conducted to address parameter variations and associated uncertainties.Results: The study finding suggest that from the perspective of Chinese healthcare, the majority of brand-name drug (BND) NOACs generally lack cost-effectiveness when compared to warfarin. However, when considered the VBP policy, NOACs, particularly rivaroxaban, prove to be more cost-effective than warfarin. Rivaroxaban provided an additional 0.0304 quality-adjusted life years (QALYs) per patient and reduced overall medical costs by 9095.73 CNY, resulting in an incremental cost-effectiveness ratio (ICER) of − 298,786.20 CNY/QALY. Sensitivity analysis indicated a 78.4% probability of any NOACs being more cost-effective compared to warfarin. However, specifically considering NOACs under the VBP policy, the likelihood of them being more cost-effective approached 90%.Conclusion: Taking into account Chinese pharmaceutical procurement policies, the findings highlight the superior efficacy of NOACs, especially rivaroxaban, in enhancing both the quality of life and economic benefits for Chinese LVT patients. NOACs present a more cost-effective treatment option, improving patient quality of life and healthcare cost efficiency compared to warfarin.Keywords: cost-effectiveness, novel oral anticoagulants, left ventricular thrombosis, thrombus resolution

Yuanyuan Ding,&ast; Linjiang Chen,&ast; Jing Xu, Yuhan Feng, Qiong Liu Department of Ophthalmology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiong Liu, Department of Ophthalmology, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Baiyun District, Guangzhou, Guangdong Province, 510515, People’s Republic of China, Tel +86-13922442109, Email nanfanglq2023@163.comObjective: Diabetic retinopathy (DR) can cause permanent blindness with unstated pathogenesis. We aim to find novel biomarkers and explore the mechanism of apoptotic protease activating factor 1 (APAF1) in DR.Methods: Differential expression genes (DEGs) were screened based on GSE60436 dataset to find hub genes involved in pyroptosis after comprehensive bioinformatics analysis. DR mice model was constructed by streptozotocin injection. The pathological structure of retina was observed using hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was applied to assess inflammatory factors, vascular endothelial growth factor (VEGF), and oxidative stress. The mRNA and protein expression levels were detected using quantitative real-time polymerase-chain reaction and Western blot. Cell counting kit and flow cytometry were employed to detect proliferation and apoptosis in high glucose-induced ARPE-19 cells.Results: Total 71 pyroptosis-related DEGs were screened. BIRC2, CXCL8, APAF1, PPARG, TP53, and CYCS were identified as hub genes of DR. APAF1 was selected as a potential regulator of DR, which was up-regulated in DR mice. APAF1 silencing alleviated retinopathy and inhibited pyroptosis in DR mice with decreased levels of inflammatory factors, VEGF, and oxidative stress. Moreover, APAF1 silencing promoted proliferation while inhibiting apoptosis and caspase-3/GSDME-dependent pyroptosis with a decrease in TNF-α, IL-1β, IL-18, and lactate dehydrogenase in high glucose-induced ARPE-19 cells. Additionally, caspase-3 activator reversed the promotion effect on proliferation and inhibitory effect on apoptosis and pyroptosis after APAF1 silencing in high glucose-induced ARPE-19 cells.Conclusion: APAF1 is a novel biomarker for DR and APAF1 silencing inhibits the development of DR by suppressing caspase-3/GSDME-dependent pyroptosis.Keywords: diabetic retinopathy, APAF1, caspase-3, GSDME, pyroptosis

Qiang Liu,1,&ast; FeiFei Su,1,&ast; Aruhan Mu,1 Xiang Wu1,2 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Yunnan Key Laboratory of Service Computing, Yunnan University of Finance and Economics, Kunming, 650221, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aruhan Mu, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science &Technology, Wuhan, 430030, People’s Republic of China, Tel +86 15872374100, Email aruhan@hust.edu.cnPurpose: How individuals engage with social media can significantly impact their psychological well-being. This study examines the impact of social media interactions on mental health, grounded in the frameworks of the Elaboration Likelihood Model and Schema Activation Theory. It aims to uncover behavioral differences in information sharing between the general population and individuals with depression, while also elucidating the psychological mechanisms underlying these disparities.Methods: A pre-experiment (N=30) and three experiments (Experiment 1a N=200, Experiment 1b N=180, Experiment 2 N=128) were executed online. These experiments investigated the joint effects of information quality, content valence, self-referential processing, and depression level on the intention to share information. The research design incorporated within-subject and between-subject methods, utilizing SPSS and SPSS Process to conduct independent sample t-tests, two-factor ANOVA analyses, mediation analyses, and moderated mediation analyses to test our hypotheses.Results: Information quality and content valence significantly influence sharing intention. In scenarios involving low-quality information, individuals with depression are more inclined to share negative emotional content compared to the general population, and this tendency intensifies with the severity of depression. Moreover, self-referential processing acts as a mediator between emotional content and intention to share, yet this mediation effect weakens as the severity of depression rises.Conclusion: Our study highlights the importance of promoting viewpoint diversity and breaking the echo chamber effect in social media to improve the mental health of individuals with depression. To achieve this goal, tailoring emotional content on social media could be a practical starting point for practice.Keywords: depression, information-sharing behavior, cognitive schema, self-referential processing, information quality, content valence, social media

Lan-Fang Li,1 Ran Qi,1 Tian-Tian Wei,1 Lei Feng,1 Xin Zhang,1 Qiao Liu2 1Department of Clinical Pharmacy, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272029, People’s Republic of China; 2Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of ChinaCorrespondence: Qiao Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Email liuqiao6767@csu.edu.cnPurpose: The IPSOS study provided evidence supporting the efficacy and tolerability of first-line atezolizumab compared to single-agent chemotherapy for non-small-cell lung cancer (NSCLC) patients ineligible for treatment with a platinum-containing regimen. This study aimed to assess the cost-effectiveness of atezolizumab specifically in this population, considering the perspective of the Chinese healthcare system.Patients and Methods: In this analysis, a three-state Markov model was utilized. The survival data were derived from the IPSOS clinical trial. Direct medical costs and utility values were collected from national authoritative database and published literature. The primary outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). To ensure the robustness of our model, both one-way and probabilistic sensitivity analyses were conducted.Results: Atezolizumab monotherapy led to an increase in costs of &dollar;4139.23 compared to single-agent chemotherapy. Additionally, it resulted in a gain of 0.14 QALYs, leading to an ICER of &dollar;29,365.79 per QALY, which was below the willingness-to-pay threshold of &dollar;36,066 per QALY used in the model. One-way sensitivity analyses revealed cost of atezolizumab and utility of progressive disease (PD) as major influencing factors for ICER. Furthermore, probabilistic sensitivity analyses confirmed our base-case results.Conclusion: From the perspective of the Chinese healthcare system, atezolizumab emerges as a cost-effective choice for the first-line treatment of NSCLC patients ineligible for platinum-based chemotherapy.Keywords: atezolizumab, cost-effectiveness, NSCLC, IPSOS

Bennan Zhao,1,&ast; Qingxiao Liu,2,&ast; Qing Du,3 Jun Kang,1 Rong Tang,4 Yalan Tu,5 Dafeng Liu1 1The First Ward of Internal Medicine, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 2Department of Neurology, Hospital of Chengdu University of TCM, Chengdu, People’s Republic of China; 3The Second Ward of ICU, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 4Department of Integrated Chinese and Western Medicine, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 5Scientific Research and Teaching Department, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dafeng Liu, The First Ward of Internal Medicine, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China, Tel +86 1 309 449 4836, Email ldf312@126.com Yalan Tu, Scientific Research and Teaching Department, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China, Tel +86 1 501 326 6454, Email tyl950330@163.comPurpose: To date, there are few reports about mpox case series in China, and scarce information is available about the in-vivo kinetics of T-cell responses in the early stage of mpox infection. This study aims to investigate the clinical difference among mpox patients with and without human immunodeficiency virus (HIV) infection.Patients and Methods: A total of 56 patients diagnosed with mpox by Chengdu Center for Disease Control and Prevention (CDC) and hospitalized in Public Health Clinical Center of Chengdu were retrospectively included and divided into an HIV-infected group (n=23) and a non-HIV-infected group (n=33). Clinical characteristics and serum chemistry findings of mpox patients were collected in order to analyze the differences between the HIV-infected group and the non-HIV-infected group.Results: Multiple laboratory abnormalities, including elevated C-reactive protein (69.1%), hypocalcemia (50.9%), elevated CD3+CD8+T counts (47.0%) and inverted ratio of CD3+CD4+T to CD3+CD8+T (64.7%) were common in mpox cases. There were statistically significant differences (all P < 0.05) in age, serum calcium levels, CD3+CD4+T counts, the ratio of CD3+CD4+T to CD3+CD8+T, proportion with > 10 rashes, incidence of proctitis anus and time from rash growth to rash scab shedding between HIV-infected group and non-HIV-infected group. In the early stage of mpox infection, the median of CD3+CD8+T counts in the non-HIV-infected group was significantly higher than that in healthy donors (P< 0.001), and the median of CD3+CD4+T/CD3+CD8+T ratio was significantly lower (P< 0.001). The median of CD3+CD4+T counts in mpox patients co-infected with HIV significantly decreased compared to the pre-infection level (p =0.033).Conclusion: Our study indicates that mpox co-infected with HIV patients have longer lasting rash lesions and a higher incidence of proctitis anus. T-cell responses may be different between HIV-infected and non-HIV-infected individuals in the early stage of mpox infection.Keywords: mpox, HIV, clinical characteristics, complication, T-cell response

Traidit Thianthanyakij,1,2,&ast; Yinghui Zhou,1,&ast; Mengyi Wu,3,&ast; Yuting Zhang,4 Jui-Ming Lin,1 Yan Huang,4 Yuou Sha,1 Jiayi Wang,1 Sirapath Peter Kong,2 Jinran Lin,1 Qingmei Liu,1 Wenyu Wu1,5,6 1Department of Dermatology, Huashan Hospital, Fudan University, Shanghai Institute of Dermatology, Shanghai, 200040, People’s Republic of China; 2Faculty of Medicine, Thammasat University (Rangsit Campus), Pathumthani, 12120, Thailand; 3Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 4State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, 200433, People’s Republic of China; 5Department of Dermatology, Jing’an District Central Hospital, Shanghai, 200040, People’s Republic of China; 6Academy for Engineering and Technology, Fudan University, Shanghai, 200433, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingmei Liu; Wenyu Wu, Email liuqing.mei@163.com; wenyu_wu@fudan.edu.cnBackground: Existing research links oxidative stress and inflammation to hair loss. Salvianolic acid B (SAB) is known for its anti-oxidative, anti-inflammatory, and other beneficial pharmacological properties.Objective: To assess the efficacy of SAB in modulating hair growth.Methods: In vivo experiments were conducted using C57BL/6 mice to evaluate the effects of SAB on hair and skin parameters. The study involved ex vivo analysis of human hair follicles (HFs) for hair shaft length and hair growth cycle assessment. In vitro, human dermal papilla cells (hDPCs) were cultured with SAB, and their proliferation, protection against H2O2-induced oxidative damage, and gene/protein expression alterations were examined using various analytical techniques, including Real-Time Cell Analysis (RTCA), DCFH-DA Assay, RNA-seq, and KEGG pathway analysis.Results: SAB treatment in mice significantly improved hair growth and vascularization by day 21. In human HFs, SAB extended hair shaft length and delayed the transition to the catagen phase. SAB-treated hDPCs showed a notable decrease in the expression of oxidation-antioxidation-related genes and proteins, including reduced phosphorylation levels of ERK and p38.Conclusion: The study indicates that SAB promotes hDPC proliferation and offers protection against oxidative stress, highlighting its potential as a therapeutic agent for enhancing hair growth and treating hair loss.Keywords: salvianolic acid B, hair growth, hair cycle, hair follicle, dermal papilla cells

Xue-Jun Dou,1,&ast; Run-Yang Ma,1,&ast; De-Wang Ren,1 Qiang Liu,2 Peng Yan3 1Department of Thoracic Surgery, Aerospace Center Hospital, Beijing, 100049, People’s Republic of China; 2Department of Thoracic Surgery, Peking University International Hospital, Beijing, 102206, People’s Republic of China; 3Department of Respiratory Medicine, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Liu, Department of Thoracic Surgery, Peking University International Hospital, Beijing, 102206, People’s Republic of China, Tel +86 15901472799, Email liuqiang8548@163.com Peng Yan, Department of Respiratory Medicine, China Aerospace Science & Industry Corporation 731 hospital, Beijing, 100071, People’s Republic of China, Email yanpeng301@163.comObjective: This study aimed to investigate the effectiveness and tolerability of anlotinib plus PD-1 blockades in patients with previously immunotherapy treated advanced non-small-cell lung cancer (NSCLC).Methods: A total of 67 patients with previously immunotherapy treated advanced NSCLC who received anlotinib plus PD-1 blockades in clinical practice were screened retrospectively. All the PD-1 blockades used in this study were approved in China and consisted of sintilimab, camrelizumab, tislelizumab and pembrolizumab. Effectiveness and safety of anlotinib plus PD-1 blockades were assessed, and all patients were followed up regularly. Clinical significance between response status to previous immune-related treatment regimens and therapeutic outcomes of anlotinib plus PD-1 blockades was further explored.Results: The best overall response among the 67 patients suggested that a partial response was observed in 16 patients, stable disease was noted in 41 patients and progressive disease was found in 10 patients, which yielded an objective response rate of 23.9% (95% CI: 14.3– 35.9%) and a disease control rate of 85.1% (95% CI: 74.3– 92.6%). Prognostic outcomes indicated that the median progression-free survival (PFS) was 6.1 months (95% CI: 2.37– 9.83) and the median overall survival (OS) was 16.5 months (95% CI: 10.73– 22.27). Exploratory analysis highlighted that patients who were intolerant to previous immune-related regimens (17 patients) might have a superior prognosis (median OS: 22.3 months vs 12.5 months, P=0.024). Additionally, adverse reactions with any grades during anlotinib plus PD-1 blockades administration were observed in 62 patients (92.5%), of which 31 patients (46.3%) had ≥grade 3 adverse reactions. Most common adverse reactions were fatigue, hypertension, diarrhea and hepatotoxicity.Conclusion: Anlotinib plus PD-1 blockades demonstrated promising effectiveness and tolerable safety in patients with previously immunotherapy treated advanced NSCLC. Those who were intolerant to previous immune-related regimens might benefit significantly from treatment with anlotinib plus PD-1 blockades. This conclusion should be confirmed in future studies.Keywords: previously immunotherapy treated NSCLC, anlotinib, PD-1 blockades, effectiveness, safety

Kaifang Yao,1,&ast; Zhihan Chen,1,&ast; Yanwei Li,1 Baomin Dou,1 Zhifang Xu,1– 3 Yajing Ma,1 Simin Du,1 Jiangshan Wang,1 Jiangjiang Fu,1 Qi Liu,1 Zezhi Fan,1 Yangyang Liu,1– 3 Xiaowei Lin,1– 3 Yuan Xu,1– 3 Yuxin Fang,1– 3 Shenjun Wang,1– 3 Yi Guo1,3,4 1Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China; 2School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China; 3National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin City, People’s Republic of China; 4School of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Guo; Shenjun Wang, School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of China, Tel +86 22-5959-6290, Email guoyi_168@163.com; shenjunwang@163.comPurpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia.Patients and Methods: We injected complete Freund’s adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1−/− mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1.Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1−/− ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated.Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.Keywords: acupuncture, TRPA1, ST36, inflammation, immune, analgesia

Chang Chen,1 Qian Mei,2 Qi Liu,3 Meichen Lu,4 Lu Hou,1 Xiaohong Liu,3 Xuezheng Gao,3 Limin Chen,3 Zhenhe Zhou,1– 4 Hongliang Zhou5 1Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Wuxi City, People’s Republic of China; 2School of Humanities and Management Science, Wannan Medical College, Wuhu City, People’s Republic of China; 3Grade 2021 Class 3, First Clinical Medical College of Jinzhou Medical University, Jinzhou City, People’s Republic of China; 4Department of Psychiatry, The Affiliated Mental Health Center of Jiangnan University, Wuxi City, People’s Republic of China; 5Department of Psychology, The Affiliated Hospital of Jiangnan University, Wuxi City, People’s Republic of ChinaCorrespondence: Zhenhe Zhou, Wuxi Mental Health Center, No. 156, Qianrong Road, Binhu District, Wuxi City, Jiangsu Province, People’s Republic of China, Tel +86-1-335-811-8986, Fax +86-510-83219366, Email zhouzh@njmu.edu.cn Hongliang Zhou, The Affiliated Hospital of Jiangnan University, No. 200, Huihe Road, Binhu District, Wuxi City, Jiangsu Province, People’s Republic of China, Tel +86-1-536-525-1126, Fax +86-510-85808820, Email Hongliangzh2022@hotmail.comPurpose: Schizophrenia patients show impaired conditional reasoning. This study was to investigate event-related potential (ERP) characteristics of the conditional reasoning in schizophrenia.Patients and methods: Participants included 24 schizophrenia patients and 30 normal controls (NCs), and the measurements of ERPs were conducted during the Wason selection task.Results: Results showed that NCs consistently outperformed schizophrenia patients in terms of accuracy. Among the different rule types of the task, the precautionary type experiment yielded the highest accuracy rates. In contrast, both the descriptive and abstract type experiments resulted in lower accuracy. The RTs of the abstract type experiment were the shortest among the four experiments. In the abstract type of the Wason selection task, the NCs exhibited higher amplitudes for both the N1 and P2 components compared to the schizophrenia patients. At the parietal lobe, the N2 amplitudes were higher for the social contract type of the task compared to the precautionary version. At the frontal lobe, the N2 amplitudes were highest for the abstract type of the task. In the abstract type, the N2 amplitude at the parietal lobe was higher than that at the central lobe. The NCs displayed lower amplitudes for both the P3 and slow wave compared to the schizophrenia patients. Differences were observed between the NC and schizophrenia groups in terms of the latencies for N1, P2, N2, P3 and slow wave components across different experiment types and regions of interest.Conclusion: In conclusion, the observed ERP patterns provide valuable insights into the neural mechanisms underlying the Wason selection task, highlighting the differences between NCs and patients with schizophrenia.Keywords: event-related potential, wason selection task, schizophrenia, conditional reasoning, neural mechanism