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Yixin Liu,1 Feifei Ren,1 Shan Li,1 Xiangchen Li,1 Dongyan Shi,2 Zhiqing Zhang1 1Department of Pharmacy, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Clinical Laboratory, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Zhiqing Zhang, Department of pharmacy, the Second Hospital of Hebei Medical University, 215, Heping Road, Xinhua District, Shijiazhuang, Hebei, People’s Republic of China, Email 26500007@hebmu.edu.cn Dongyan Shi, Department of clinical laboratory, the Second Hospital of Hebei Medical University, 215, Heping Road, Xinhua District, Shijiazhuang, Hebei, People’s Republic of China, Email shidongyan73@126.comObjective: To define the antifungal activity of n-butylphthalide alone or in combination with fluconazole in Candida glabrata and Candida tropicalis.Methods: The antifungal activity of n-butylphthalide alone and in combination with fluconazole was investigated by the classical broth microdilution method and the time-killing curve method. The QRT-PCR method was used to determine gene expressions changes of mitochondrial respiratory chain enzymes, drug efflux pumps and drug target enzymes in Candida glabrata and Candida tropicalis after n-butylphthalide treatment.Results: The MIC values of n-butylphthalide against Candida glabrata and Candida tropicalis ranged from 16 to 64 μg·mL-1. The FICI value of the combination of n-butylphthalide and fluconazole against drug-resistant Candida glabrata and Candida tropicalis ranged from 0.5001 to 0.5315 with partial synergism. Time-killing curves showed that 256 μg·mL-1 n-butylphthalide significantly inhibited the growth of drug-resistant colonies of Candida glabrata and Candida tropicalis, and 128 μg·mL-1 n-butylphthalide combined with 1 μg·mL-1 fluconazole had an additive effect. N-butylphthalide could alter the expression of mitochondrial respiratory chain enzymes COX1, COX2, COX3, and CYTB genes in Candida glabrata and Candida tropicalis (P< 0.05) and downregulate the expression of the drug efflux pump genes CDR1 and CDR2 in drug-resistant Candida glabrata to 3.36% and 3.65%, respectively (P< 0.001), but did not affect the drug target enzyme ERG11 in drug-resistant Candida tropicalis.Conclusion: N-butylphthalide had antifungal activity against Candida glabrata and Candida tropicalis. N-butylphthalide improved the activity of fluconazole against drug-resistant Candida glabrata by affecting the expression of mitochondrial respiratory chain enzyme genes and reversing the high expression of drug efflux pump genes CDR1 and CDR2.Keywords: n-butylphthalide, fluconazole, drug resistance, Candida glabrata, Candida tropicalis, potentiation

Yanting Ma,1 Yongyuan Li,2 Zhanfeng Zhang,3 Guomei Du,4 Ting Huang,1 Zhi Zhong Zhao,5 Shou Liu,1 Zhancui Dang1 1Department of Public Health, Medical College, Qinghai University, Xining, Qinghai, People’s Republic of China; 2Disease Control department, Huangzhong District health Bureau, Xining, Qinghai, People’s Republic of China; 3Huangzhong District, Duoba County Health Services Center, Xining, Qinghai, People’s Republic of China; 4Clinical Laboratory, Qinghai Red Cross Hospital, Xining, Qinghai, People’s Republic of China; 5Disease Control Department, Qinghai Provincial Center for Endemic Disease Control and Prevention, Xining, Qinghai, People’s Republic of ChinaCorrespondence: Shou Liu; Zhancui Dang, Email liushou2004@aliyun.com; yxyyy2019@163.comPurpose: The prevalence of metabolic syndrome (MetS) is increasing worldwide, and early prediction of MetS risk is highly beneficial for health outcomes. This study aimed to develop and validate a nomogram to predict MetS risk in Qinghai Province, China, and it provides a methodological reference for MetS prevention and control in Qinghai Province, China.Patients and Methods: A total of 3073 participants living between 1900 and 3710 meters above sea level in Qinghai Province participated in this study between March 2014 and March 2016. We omitted 12 subjects who were missing diagnostic component data for MetS, ultimately resulting in 3061 research subjects, 70% of the subjects were assigned randomly to the training set, and the remaining subjects were assigned to the validation set. The least absolute shrinkage and selection operator (LASSO) regression analysis method was used for variable selection via running cyclic coordinate descent with 10-fold cross-validation. Multivariable logistic regression was then performed to develop a predictive model and nomogram. The receiver operating characteristic (ROC) curves was used for model evaluation, and calibration plot and decision curve analysis (DCA) were used for model validation.Results: Of 24 variables studied, 6 risk predictors were identified by LASSO regression analysis: hyperlipidaemia, hyperglycemia, abdominal obesity, systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI). A prediction model including these 6 risk factors was constructed and displayed good predictability with an area under the ROC curve of 0.914 for the training set and 0.930 for the validation set. DCA revealed that if the threshold probability of MetS is less than 82%, the application of this nomogram is more beneficial than both the treat-all or treat-none strategies.Conclusion: The nomogram developed in our study demonstrated strong discriminative power and clinical applicability, making it a valuable reference for meets prevention and control in the plateau areas of Qinghai Province.Keywords: metabolic syndrome, nomogram, prediction model, plateau section

Yu Xiao,1,2 Liang Liu,3 Ting-ting Chen,4 Zhou Zhang,5 Xiao-hong Wu6 1Psychosomatic Medical Center, The Fourth People’s Hospital of Chengdu, Chengdu, Sichuan Province, 610036, People’s Republic of China; 2Psychosomatic Medical Center, The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, 610036, People’s Republic of China; 3Department of Urology, Baoding No.1 Central Hospital, Baoding, Hebei Province, 071030, People’s Republic of China; 4Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610044, People’s Republic of China; 5Department of Gastroenterology, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang, Hubei Province, 441011, People’s Republic of China; 6Nursing Department, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliate Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan Province, 610041, People’s Republic of ChinaCorrespondence: Yu Xiao, The Fourth People’s Hospital of Chengdu, No. 8, Huli West Lane 1, Yingmenkou Road, Chengdu, Sichuan Province, 610036, People’s Republic of China, Tel +86-028-85641749, Email xiaoy3@outlook.comObjectives: Sexual harassment (SH) is a prevalent issue in various professional fields worldwide. The current study aims to investigate the incidence of SH targeting psychiatrists in China and explore its impact on quality of life (QOL).Methods: A consecutive recruitment of 1093 psychiatrists was conducted from 6 hospitals in China. The recorded data included participants’ socio-demographic characteristics, experiences of workplace SH within the previous year, and their QOL. SH comprised verbal harassment, physical harassment, and displaying of sexual organs. The Chinese version of the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) was employed to assess QOL. We compared the demographic characteristics and QOL between the SH group and the non-SH group. Multiple logistic regression analysis was used to identify independent demographic correlates of SH.Results: In total, 13.8% (n = 151) of the psychiatrists reported SH, with 5.8% reporting it once, 4.4% reporting it twice, and 3.6% reporting it three times or more. Psychiatrists who had encountered SH exhibited lower QOL across social, psychological, physical, and environmental domains. Multiple logistic regression analysis revealed that young physicians and those with shorter work experience had a higher likelihood of experiencing SH.Conclusion: The high prevalence of SH among Chinese psychiatrists is of concern. Given its detrimental effects on the well-being of physicians and the quality of medical care they provide, it is crucial to develop specialized employee training programs for this population to effectively manage workplace SH.Keywords: China, psychiatrists, quality of life, mental health professionals, sexual harassment, workplace safety

Zhihao Zhao,1,&ast; Diya Qi,1,&ast; Zeqing Zhang,2,&ast; Xin Du,3 Fengyun Zhang,2 Ruicong Ma,4 Yi Liang,1 Yuewu Zhao,1 Ying Gao,1 Yu Yang2 1Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 2Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Neurology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China; 4Graduate School, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Gao, Department of Cardiology, the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou, People’s Republic of China, Tel +86-13951461302, Email xzyygaoying@163.com Yu Yang, Department of Cardiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +86-15651359875, Email xuzhouyangyu@163.comPurpose: The aim of this study was to explore the relationship between inflammatory cytokines and the risk of heart failure (HF) readmission in patients with heart failure with preserved ejection fraction (HFpEF).Patients and Methods: We enrolled 429 patients with HFpEF admitted to the cardiology department in our hospital from January 2020 to July 2022. The patients were divided into the readmission or non-readmission groups according to whether they were readmitted for heart failure within 1 year of discharge. The clinical features and laboratory date of the subjects were collected and analyzed. Multivariate cox regression analysis was used to identify predictors of HF readmission. In addition, receiver operating characteristic (ROC) curves were used to determine the prognostic value of each factor.Results: The levels of IL-1β, IL-6, IL-10, IL-17, TNF-α, NT-proBNP, heart rate, total cholesterol and NYHA class were significantly higher in the readmission group than in the non-readmission group (p < 0.05). IL-1β, IL-6, IL-17, TNF-α, NT-proBNP, heart rate and NYHA class were identified as independent predictors of HF readmission.Conclusion: Inflammatory markers, including IL-1β, IL-6, IL-17 and TNF-α were related to the HF readmission in patients with HFpEF.Keywords: heart failure with preserved ejection fraction, inflammation, cytokine, readmission, risk assessment

Guofei Feng, Pan Zhuge, Yaping Zou, Zhifeng Zhang, Jiandong Guo, Junxiang Ma Department of ENT, Jinhua Central Hospital, Jinhua, Zhejiang, 321000, People’s Republic of ChinaCorrespondence: Guofei Feng, Department of ENT, Jinhua Central Hospital, No. 365, East Renmin Road, Jinhua, Zhejiang, 321000, People’s Republic of China, Tel/Fax +86 579 82552620, Email guofeifeng1781f@163.comObjective: To investigate the correlation between the levels of serum lipopolysaccharide (LPS), nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase 1 (HO-1) and cognitive impairment in patients with obstructive sleep apnoea (OSA).Methods: Serum LPS, Nrf2, HO-1 levels and cognitive impairment were measured using the Montreal Cognitive Assessment (MoCA) score in 56 patients in the “severe” group, 67 patients in the “mild-to-moderate” group and 100 healthy people in the “control” group. The differences in general conditions and serological indexes between the three groups were compared, the correlation between the MoCA scores and the serological indexes was explored and the independent predictors of the MoCA scores were analysed.Results: Serum LPS, Nrf2 and HO-1 levels were higher in the severe group than in the mild-to-moderate group and the control group (p < 0.05). A total of 71 patients with OSA had combined cognitive impairment, accounting for 57.7%, and the MoCA scores were lower in the severe group than in the mild-to-moderate group and the control group (p = 0.018). Serum LPS, Nrf2 and HO-1 levels were significantly higher in the severe group and mild-to-moderate group than in the control group (p < 0.05) and were negatively correlated with the MoCA scores. Lipopolysaccharide (p < 0.001) and HO-1 (p = 0.002) could be considered independent predictors of the MoCA score.Conclusion: Serum LPS and HO-1 levels are closely related to cognitive impairment in patients with OSA and have potential clinical value in the diagnosis.Keywords: obstructive sleep apnoea, cognitive impairment, lipopolysaccharide, nuclear factor erythroid 2-related factor 2, haem oxygenase 1

Jiongfeng Zhang,1,&ast; Xiaohui Luo,1,&ast; Ruiling Zhou,2,&ast; Chong Guo,1 Kai Xu,1 Gaoyang Qu,1 Le Zou,1 Wenye Yao,1 Shifan Lin,1 Zhiping Zhang1 1Department of Orthopedics, the 3rd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330008, People’s Republic of China; 2Department of Dermatology, Jiangxi Provincial Dermatology Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shifan Lin, Email 66031226@qq.com; Zhiping Zhang, Tel +86 791-88862249, Email ndsfy001425@ncu.edu.cnObjective: To explore the suitable population of CT value for predicting low bone mineral density (low-BMD).Methods: A total of 1268 patients who underwent chest CT examination and DXA within one-month period retrospectively analyzed. The CT attenuation values of trabecular bone were measured in mid-sagittal plane from thoracic vertebra 7 (T7). Receiver operating characteristic (ROC) curves were used to evaluate the ability to diagnose low-BMD.Results: The AUC for diagnosing low BMD was larger in women than in men (0.894 vs 0.744, p < 0.05). The AUC increased gradually with the increase of age but decreased gradually with the increase in height and weight (p < 0.05). In females, when specificity was adjusted to approximately 90%, a threshold of 140.25 HU has a sensitivity of 69.3%, which is higher than the sensitivity of 36.5% in males for distinguishing low-BMD from normal. At the age of 70 or more, when specificity was adjusted to approximately 90%, a threshold of 126.31 HU has a sensitivity of 76.1%, which was higher than that of other age groups.Conclusion: For patients who had completed chest CTs, the CT values were more effective in predicting low-BMD in female, elderly, lower height, and lower weight patients.Keywords: bone mineral density, chest computed tomography, dual-energy X-ray absorptiometry, attenuation value

Zhiyi Zhang,1,2,&ast; Baisheng Li,3,4,&ast; Huitao Huang,5 Yanmei Fang,5 Wenqiang Yang5 1School of Public Health, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China; 2Faculty of Health Sciences, University of Macau, Macao, People’s Republic of China; 3Institute of Microbiology, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Pathogen Detection for Emerging Infectious Disease Response, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, People’s Republic of China; 5Institute of Microbiology, Zhuhai Center for Disease Control and Prevention, Zhuhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenqiang Yang, Zhuhai Center for Disease Control and Prevention, Zhuhai, 519000, People’s Republic of China, Email 917461182@qq.comPurpose: This study was to identify and analyze the pathogen responsible for food poisoning in a tourist group traveling from Macao to Zhuhai.Patients and Methods: Samples were obtained from 27 patients of 96 cases, as well as samples of contaminated food in Macau. The collected samples were subjected to serological identification, drug sensitivity analysis, drug resistance gene identification, virulence factor analysis, and tracing.Results: Twenty-six isolates and the salad isolate were S. enteritidis ST11. Isolates from patients were exhibited significant resistance to Penicillin AMP (Ampicillin) and quinolones NAL (Nalidixic acid). Among these isolates, 21 strains were resistant to two or more antibiotics, indicating the multi-drug resistance (MDR). Genomic characteristics and phylogenetic analysis were performed on 9 of the isolates using whole genome sequencing (WGS). The analysis revealed that the resistance to AMP and NAL was primarily caused by a gryA mutation D87Y (9/9, 100%), and the presence of beta-lactam resistance genes blaOXA-1 (1/9, 11.11%), blaTEM-141 (1/9, 11.11%), and blaTEM-1B (8/9, 88.89%). It was also found a strains isolated from patients had two resistance genes to quinolones or beta-lactam drugs (1/8, 12.5%), respectively. The strains were found to possess 165 virulence genes, one adherence class virulence factor, one invasion class virulence factor and various pathogenicity islands, including SPI-1, SPI-2, SPI-3, SPI-4, SPI-5, SPI-9, SPI-10, SPI-13, SPI-14, SPI-15, SGI 1, CS54_island, and C63PI-1. Additionally, the virulence plasmids were detected, including IncFIB(s)-IncFII(s)-IncX1 (55.56%), IncFIB(s)-IncFII(s) (33.33%), and IncFIB(s)-IncFII(s)-IncHI2-IncHI2A (11.11%). PFGE (Pulsed Field Gel Electrophoresis) and phylogenetic tree analysis revealed a high degree of similarity between Salmonella isolates from patients and food samples from Macao.Conclusion: This study identified Salmonella enterica ST11 as the cause of the food poisoning outbreak. The findings highlight the importance of phenotypic characterization and next-generation sequencing (NGS) tools in epidemiological studies and emphasize the potential risk of a new emerging multi-antibiotic ST11 clone for S. enteritidis.Keywords: salmonella food poisoning, sequence type 11, whole-genome sequencing, antimicrobial resistance, multi-locus sequence typing

Zhanyi Zhang,1 Mengyuan Li,2 Yujia Geng,1 Wangshu Wang,1 Weihao Wang,1 Ying Shao1 1Department of Plastic and Reconstructive Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, 130000, People’s Republic of China; 2College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin Province, 130118, People’s Republic of ChinaCorrespondence: Ying Shao, Department of Plastic and Reconstructive Surgery, the First Hospital of Jilin University, Changchun, Jilin Province, 130000, People’s Republic of China, Email shao_ying@jlu.edu.cnPurpose: Previous studies have suggested a relationship between autoimmune diseases and the risk of facial skin aging. However, evidence from population-based studies on this topic is limited, leaving the causal association between these factors unknown. This study aimed to systematically evaluate the causal effects of 18 autoimmune diseases on the risk of facial skin aging, aim of providing strategies to mitigate early facial aging in patients with autoimmune diseases.Patients and Methods: We conducted univariate Mendelian randomization (UVMR) analyses to examine the causal relationship between 18 autoimmune diseases and facial aging using publicly available summary data from genome-wide association studies (GWASs). We also conducted multivariate Mendelian randomization (MVMR) analyses to adjust for confounding factors, including smoking, alcohol consumption, and body mass index (BMI).Results: The main inverse variance weighted (IVW) method revealed that genetically proxied ankylosing spondylitis (AS) (OR 1.017; 95% CI: 1.003– 1.031; P=0.018), sicca syndrome (SS) (OR 1.008; 95% CI: 1.005– 1.011; P= 2.66× 10− 6), systemic lupus erythematosus (SLE) (OR 1.006; 95% 1.001– 1.011; P=0.014), multiple sclerosis (MS) (OR 1.004; 95% CI: 1.001– 1.007; P=0.021), primary sclerosing cholangitis (PSC) (OR 1.002; 95% CI: 1.000– 1.004; P=0.023), and celiac disease (CeD) (OR 1.002; 95% CI: 1.001– 1.004; P=0.009) were significantly associated with higher risk of facial aging. After adjusting for potential confounding factors, the association persisted between AS, SLE, and CeD.Conclusion: These findings indicated that autoimmune diseases play a causal role in facial skin aging. Therefore, patients with autoimmune diseases should take appropriate measures to prevent early facial aging.Keywords: autoimmune disease, facial aging, Mendelian randomization, ankylosing spondylitis, systemic lupus erythematosus, celiac disease

Yinping Feng, Jing Guo, Shuirong Luo, Zunjing Zhang, Zhongda Liu Department of Tuberculosis, Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui Tuberculosis Clinical Medical Research Center, Lishui, Zhejiang, People’s Republic of ChinaCorrespondence: Zhongda Liu, Email liu_zd0578@126.comObjective: Exploring the risk factors for readmission of elderly patients with pulmonary tuberculosis (PTB) within one month using the propensity score matching(PSM).Methods: A retrospective analysis was conducted on the clinical data of elderly patients with PTB who were admitted to the Tuberculosis Department of Lishui Hospital of Traditional Chinese Medicine from January 2020 to October 2023. The patients were divided into two groups: non-readmission group and readmission group based on whether they were readmitted within one month after discharge. The PSM method was used to match the baseline data of the two groups of patients, and multivariate logistic regression analysis was conducted to explore the risk factors for readmission of elderly patients with PTB within one month after discharge.Results: A total of 1268 hospitalized elderly patients with PTB were included in the study, comprising 977 readmitted patients and 291 newly admitted patients (22.95%). Using the PSM, 288 pairs of patients were successfully matched. Following matching, there were no statistically significant differences between the two groups in terms of gender, age, occupation, body mass index(BMI), past medical history, etc. (all P> 0.05). Multivariate logistic regression analysis indicated that infection, drug-induced liver injury(DILI), acute heart failure(AHF), chronic kidney disease(CKD), and extrapulmonary tuberculosis(EPTB) were all identified as risk factors for readmission of elderly patients with PTB.Conclusion: After controlling for confounding factors through PSM, the study revealed that infection, DILI, AHF, CKD, and EPTB are risk factors for readmission among elderly patients with PTB, highlighting the need for early intervention.Keywords: elderly patients with pulmonary tuberculosis, aged, readmission, propensity score matching, risk factors

Jing Zhang,1,2 Yilin Hou,1 Zhaozi Zhang,1 Yihe Shi,1 Zhimin Wang,1 Guangyao Song1,2 1Department of Internal Medicine, Graduate School of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Guangyao Song; Jing Zhang, Email sguangyao2@163.com; gina_zhangjing@163.comBackground: Peroxidation is one of the important causes of insulin resistance (IR), and vitamin E is a natural antioxidant, and there may be some correlation between serum vitamin E levels and insulin resistance.Purpose: The correlation between serum vitamin E and insulin resistance in type 2 diabetes mellitus (T2DM) population.Methods: Two hundred and forty-two people (119 with T2DM) were included. One hundred and nineteen patients with T2DM were selected as the case group, and 123 people with non-T2DM were selected as the control group. People insulin resistance was detected by the homeostasis model assessment method (HOMA-IR) greater than 2.69 were included in the diabetic insulin resistance group, and those with HOMA-IR less than 2.69 were included in the diabetic non-insulin resistance group. Record the general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators. Correlation analysis, logistic regression, trend analysis, and restricted cubic spline (RCS) were performed using SPSS 25.0 and R 4.1.1 software. Correlation analysis, logistic regression, trend analysis, restricted cubic spline (RCS) analysis were conducted on general body indicators, biochemical indicators, hepatic function indicators, vitamin E, and other indicators.Results: The logistic regression results showed that after adjusting for confounding factors, vitamin E was an independent influencing factor for insulin resistance in T2DM patients (P < 0.001). The trend analysis results show that with the decrease of serum vitamin E levels, the risk of insulin resistance in T2DM patients gradually increases. The RCS results showed that the risk of insulin resistance was significantly increased when the serum vitamin E level was lower than 10,575.23 ng/mL.Conclusion: Serum vitamin E levels are lower in T2DM patients than in healthy populations; Vitamin E is an independent influencing factor for HOMA-IR in T2DM patients. The risk of insulin resistance gradually increases in T2DM patients as serum vitamin E levels decrease. Vitamin E is a risk factor for insulin resistance at serum vitamin E levels below 10,575.23 ng/mL. At higher serum vitamin E levels than 10,575.23 ng/mL, vitamin E is a protective factor for insulin resistance.Keywords: Vitamin E, type 2 diabetes mellitus, insulin resistance, oxidative stress

Shengchao Hou,1,2 Xiubo Wang,1 Zizhao Zhao,1 Yongqiang Ma,1 Jing Liu,3 Ziyun Zhang,2 Jingdong Ma1 1School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Administrative Office, Yuebei People’s Hospital, Shaoguan, People’s Republic of ChinaCorrespondence: Jingdong Ma, School of Medicine and Health Management, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan, 430030, People’s Republic of China, Email jdma@hust.edu.cnPurpose: Advancements in electronic health (eHealth) technology have profoundly impacted patient engagement. This study aimed to develop and validate the Electronic Patient Engagement Behavior (EPEB) scale to measure the conceptual and underlying framework of patient engagement behaviors in an eHealth context.Patients and Methods: Initial measurement items were generated based on a literature review and qualitative research. Two rounds of surveys, a pilot survey and validation survey, were conducted to evaluate the psychometric properties of the scale.Results: The EPEB scale consists of 15 items in four dimensions: disease information search, physician-patient interaction, social interaction between patients, and disease self-monitoring. In the pilot survey, the exploratory factor analysis revealed a four-factor model, explaining 69.411% of variance. In the validation survey, the Cronbach’s α coefficient of each sub-scale was 0.865, 0.904, 0.904, and 0.900 respectively. The Spearman-Brown split coefficient of the scale was 0.963. The results of the cross-sex measurement equivalence test indicate that all fit indices met the measurement criteria. The confirmatory factor analysis indicated second-order 4-factor model fit the data well. The EPEB has a good reliability and validity.Conclusion: The EPEB scale provides a reliable tool for measuring patient engagement behaviors in the eHealth context. The utilization of this scale may yield valuable insights into strategies for enhancing patient engagement and optimizing health outcomes.Keywords: patient engagement behaviors, electronic health, scale development, evaluation, validation

Zhihua Zhang,1 Yuhong Wang,2 Yankun Zhang,3 Shujun Geng,2 Haifeng Wu,4 Yanxin Shao,5 Guannan Kang6 1Department of Science & Education, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 2Department of Tuberculosis, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 3Department of Ophthalmology, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 4Clinical Laboratory, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 5Office of Clinical Pharmacological Center, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, Shijiazhuang, People’s Republic of China; 6Department of Tuberculosis, Hebei Chest Hospital, Shijiazhuang, People’s Republic of ChinaCorrespondence: Yanxin Shao, Office of Clinical Pharmacological Center, Hebei Chest Hospital, Hebei Provincial Key Laboratory of Lung Disease, No. 372, Sheng Li North Street, Shijiazhuang, Hebei, 050041, People’s Republic of China, Email shaoyanxin163@163.comBackground: Tuberculosis (TB) is one of the most infectious diseases caused by Mycobacterium tuberculosis (M. tb), and the diagnosis of active tuberculosis (TB) and latent TB infection (LTBI) remains challenging.Methods: Gene expression files were downloaded from the GEO database to identify the differentially expressed genes (DEGs). The ssGSEA algorithm was applied to assess the immunological characteristics of patients with LTBI and TB. Weighted gene co-expression network analysis, protein-protein interaction network, and the cytoHubba plug-in of Cytoscape were used to identify the real hub genes. Finally, a diagnostic model was constructed using real hub genes and validated using a validation set.Results: Macrophages and natural killer cells were identified as important immune cells strongly associated with TB. In total, 726 mRNAs were identified as DEGs. MX1, STAT1, IFIH1, DDX58, and IRF7 were identified as real hub immune-related genes. The diagnostic model generated by the five real hub genes could distinguish active TB from healthy controls or patients with LTBI.Conclusion: Our study may provide implications for the diagnosis and drug development of M. tb infections.Keywords: tuberculosis, latent tuberculosis infection, mycobacterium tuberculosis, immune, diagnostic model

Zhishuo Zhang,1,&ast; Lujia Tang,1,&ast; Yiran Guo,1 Xin Guo,2 Zhiying Pan,2 Xiaojing Ji,1,&ast; Chengjin Gao1,&ast; 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; 2School of Information Science and Technology, Sanda University, Shanghai, Pudong District, 201209, China&ast;These authors contributed equally to this workCorrespondence: Xiaojing Ji; Chengjin Gao, Email jixiaojing@xinhuamed.com.cn; gaochengjin@xinhuamed.com.cnBackground: As of 30 April 2023, the COVID-19 pandemic has resulted in over 6.9 million deaths worldwide. The virus continues to spread and mutate, leading to continuously evolving pathological and physiological processes. It is imperative to reevaluate predictive factors for identifying the risk of early disease progression.Methods: A retrospective study was conducted on a cohort of 1379 COVID-19 patients who were discharged from Xin Hua Hospital affiliated with Shanghai Jiao Tong University School of Medicine between 15 December 2022 and 15 February 2023. Patient symptoms, comorbidities, demographics, vital signs, and laboratory test results were systematically documented. The dataset was split into testing and training sets, and 15 different machine learning algorithms were employed to construct prediction models. These models were assessed for accuracy and area under the receiver operating characteristic curve (AUROC), and the best-performing model was selected for further analysis.Results: AUROC for models generated by 15 machine learning algorithms all exceeded 90%, and the accuracy of 10 of them also surpassed 90%. Light Gradient Boosting model emerged as the optimal choice, with accuracy of 0.928 ± 0.0006 and an AUROC of 0.976 ± 0.0028. Notably, the factors with the greatest impact on in-hospital mortality were growth stimulation expressed gene 2 (ST2,19.3%), interleukin-8 (IL-8,17.2%), interleukin-6 (IL-6,6.4%), age (6.1%), NT-proBNP (5.1%), interleukin-2 receptor (IL-2R, 5%), troponin I (TNI,4.6%), congestive heart failure (3.3%) in Light Gradient Boosting model.Conclusion: ST-2, IL-8, IL-6, NT-proBNP, IL-2R, TNI, age and congestive heart failure were significant predictors of in-hospital mortality among COVID-19 patients.Keywords: COVID-19, machine learning, prognosis model, ST2, IL-8, TNI, IL-6, IL-2R, congestive heart failure

Pan Gao,1,2 Xinyu Li,1,2 Ziqiu He,1,2 Hongbo Zhang,1,2 Zhi Zhang,1,2 Zonglai Liu1,2 1Department of Urology, Second People’s Hospital of Yichang, Yichang, Hubei Province, People’s Republic of China; 2Department of Urology, Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, People’s Republic of ChinaCorrespondence: Zonglai Liu, Department of Urology, Second People’s Hospital of Yichang, Second People’s Hospital of China Three Gorges University, 21 Xiling One Road, Yichang, 443000, Hubei Province, People’s Republic of China, Email 85538230@qq.comAbstract: Immune checkpoint inhibitors (ICI) have become a new hope for many patients with advanced cancer by blocking tumor immune escape. Bladder cancer is a common malignant tumor of the urinary tract epithelium that often relapses and metastasizes after surgery, chemotherapy, and radiotherapy. Immunotherapy has dramatically improved patient survival rates and clinical benefits as a new, potentially effective therapy. However, avoidance of various immune-related adverse events (irAEs) remains an implausible idea. ICI-induced myocarditis is different from viral myocarditis, and mortality is still high with the current treatment. We report the case of an 82-year-old female patient with ICI-induced fulminant myocarditis and myasthenia gravis. Although she actively accepted the current mainstream treatment for immune-related myocarditis and myasthenia, she died of heart and respiratory failure. Analyzing and reporting the patient’s disease development process and the changes in related indicators may help peers gain a deeper understanding of immune-related adverse events and reduce the mortality of immune-related myocarditis.Keywords: immune checkpoint inhibitors, immunotherapy, heart failure, multiple organs failure

Zhuoyuan Zhang,1,2,&ast; Dan Liu,1,2,&ast; Rui Lv,1,2,&ast; Haoyan Zhao,1,2,&ast; Tianjing Li,1,2 Yutao Huang,2 Zhicheng Tian,2 Xiangyu Gao,2 Peng Luo,2 Xin Li3 1Biochemistry and Molecular Biology, College of Life Science, Northwest University, Xi’an, 710127, People’s Republic of China; 2Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China; 3Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Luo; Xin Li, Email pengluo@fmmu.edu.cn; li_xin_mail@126.comPurpose: Neuroinflammation occurs in response to central nervous system (CNS) injury, infection, stimulation by toxins, or autoimmunity. We previously analyzed the downstream molecular changes in HT22 cells (mouse hippocampal neurons) upon lipopolysaccharide (LPS) stimulation. We detected elevated expression of Fibrillarin (FBL), a nucleolar methyltransferase, but the associated proinflammatory mechanism was not systematically elucidated. The aim of this study was to investigate the underlying mechanisms by which FBL affects neuroinflammation.Methods: RT-real-time PCR, Western blotting and immunofluorescence were used to assess the mRNA and protein expression of FBL in HT22 cells stimulated with LPS, as well as the cellular localization and fluorescence intensity of FBL. BAY-293 (a son of sevenless homolog 1 (SOS1) inhibitor), SR11302 (an activator protein-1 (AP-1) inhibitor) and KRA-533 (a KRAS agonist) were used to determine the molecular mechanisms underlying the effect of FBL. AP-1 was predicted to be the target protein of FBL by molecular docking analysis, and validation was performed with T-5224 (an AP-1 inhibitor). In addition, the downstream signaling pathways of FBL were identified by transcriptome sequencing and verified by RT-real-time PCR.Results: LPS induced FBL mRNA and protein expression in HT22 cells. In-depth mechanistic studies revealed that when we inhibited c-Fos, AP-1, and SOS1, FBL expression decreased, whereas FBL expression increased when KRAS agonists were used. In addition, the transcript levels of inflammatory genes in the NF-kB signaling pathway (including CD14, MYD88, TNF, TRADD, and NFKB1) were elevated after the overexpression of FBL.Conclusion: LPS induced the expression of FBL in HT22 cells through the RAS/MAPK signaling pathway, and FBL further activated the NF-kB signaling pathway, which promoted the expression of relevant inflammatory genes and the release of cytokines. The present study reveals the mechanism by which FBL promotes neuroinflammation and offers a potential target for the treatment of neuroinflammation.Keywords: FBL, neuroinflammation, LPS, molecular docking, transcriptome sequencing

Jing Zhang,1,2 Ke Ma,3 Jun Yan,4 Pingsheng Pan,5 Jiangshan Yin,6 Fuqing Lin,7 Hui Chen,8 Weiwei Zhao,1,2 Menglei Chen,1,2 Zhe Zhang,1,2 Minghui Liu,1,2 Xiaoli Gu,1,2 Xinghe Liao,1,2 Chenyue Zhang,1,2 Wenwu Cheng1,2 1Department of Integrated Therapy, Shanghai Cancer Center, Fudan University, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Department of Pain Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Oncology, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, People’s Republic of China; 5Department of Oncology, Fangta Hospital of Traditional Chinese Medicine in Songjiang District, Shanghai, People’s Republic of China; 6Department of Oncology, Fudan University Shanghai Cancer Center, Minhang Branch, Shanghai, People’s Republic of China; 7Department of Anaesthesiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 8Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Wenwu Cheng, Email cwwxxm@sina.comPurpose: This study aimed to assess the current status of clinical practice of refractory cancer pain (RCP) among a sample of physicians specializing in cancer pain management in Shanghai.Methods: From 2019 to 2021, a questionnaire survey was conducted among physicians engaged in diagnosis and treatment of cancer pain through the questionnaire WJX network platform in Shanghai, China.Results: A total of 238 responses participated in the survey. This survey reports physicians’ understanding and incidence rate of breakthrough cancer pain (BTCP). The choice of analgesics and satisfaction of analgesic effect were investigated. We also investigated doctors’ knowledge of the diagnostic criteria for RCP and their tendency to choose analgesics. Oral immediate-release morphine and intravenous or subcutaneous morphine injection have been the common treatment approach for transient cancer pain exacerbations. The main barriers to pain management are lack of standardized treatment methods for RCP, lack of knowledge related to RCP, and single drug dosage form. Doctors believe the most necessary measures to improve the current situation of poor cancer pain control include improving medical staff’s understanding and treatment techniques for RCP, updating treatment techniques and methods, and improving the configuration of drug types in medical institutions. Clinicians expect to improve understanding and treatment techniques through systematic training.Conclusion: Despite multiple available analgesic measures, the treatment of RCP remains challenging. Improving the understanding of medical staff towards RCP, improving treatment techniques, and increasing the accessibility of multiple drug types are important ways to improve the satisfaction of cancer pain management in the future.Keywords: refractory cancer pain, breakthrough cancer pain, pain management, opioid drugs

Zhenhu Zhang,1,&ast; Bin Shang,1,&ast; Xinyu Mao,1 Yamin Shi,2 Guodong Zhang,1 Dong Wang1 1Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 2School of Foreign Languages, Shandong University of Finance and Economics, Jinan, 250014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Wang, Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 Jing Wu Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +8615168863605, Email sdphwd@163.comBackground: Esophageal squamous cell carcinoma (ESCC) is an aggressive and fatal malignancy that leads to epithelial cancer. The association between epithelial cell heterogeneity, prognosis, and immune response in this cancer remains uncertain. This study aimed to investigate epithelial cell heterogeneity in ESCC and develop a predictive risk model using the identified cell types.Methods: Single-cell RNA sequencing (scRNA-seq) and differential ESCC gene data were accessed from the Gene Expression Omnibus. Functional enrichment analysis, inferCNV, cell development trajectories, and intercellular communication were analyzed following epithelial cell characterization. Differentially expressed ESCC (n = 773) and epithelial cell marker genes (n = 3407) were intersected to obtain core genes, and epithelial cell-related prognostic genes were identified. LASSO regression analysis was used to construct a prognostic model. The external dataset GSE53624 was used to further validate the stability of the model. Drug sensitivity predictions, and immune cell infiltration were analyzed. Molecular docking clarified the possible therapeutic role of β-sitosterol in ESCC. Finally, wound healing assay, cell colony, and transwell assay were constructed to detect the effects of the core gene PDLIM2 on ESCC cell proliferation, invasion, and migration.Results: Eight cell clusters were identified, and epithelial cells were categorized into tumor and paratumor groups. The tumor group possessed more chromosomal variants than the paratumor group. Epithelial cells were associated with multiple cell types and significantly correlated with the Wnt, transforming growth factor, and epidermal growth factor signaling pathways. From 231 intersected genes, five core genes were screened for use in the risk model: CTSL, LAPTM4B, MYO10, NCF2, and PDLIM2. These genes may contribute to the cancerous transformation of normal esophageal epithelial cells and thereby act as biomarkers and potential therapeutic targets in patients with ESCC. β-Sitosterol furthermore displayed excellent docking potential with these genes. Meanwhile, further experiments demonstrated that the gene PDLIM2 plays a major role in the progression of oesophageal squamous carcinoma.Conclusion: We successfully developed a risk model for the prognosis of ESCC based on epithelial cells that addresses the response of ESCC to immunotherapy and offers novel cancer treatment options.Keywords: ESCC, epithelial cells, risk signature, β-sitosterol, TME

Mei Xiao,1 Guangwen Luo,1 Zhaowei Zhang,1 Yanfen Liu,2 Rui Gong,3 Jianghuan Ke1 1Department of Pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 2Department of Endocrinology and Metabolism, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, People’s Republic of ChinaCorrespondence: Guangwen Luo, Department of pharmacy, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, People’s Republic of China, Tel +86-0579-82552760, Email lgw2018@126.comPurpose: To investigate the correlation between thyroid-related hormones and diabetic retinopathy (DR) in euthyroid patients with type 2 diabetes mellitus (T2DM).Patients and Methods: Patients with T2DM admitted to our hospital between January 2023 and June 2023 were retrospectively analyzed. The patients were divided into DR and non-diabetic retinopathy (NDR) groups according to whether DR occurred. Thyroid function-related hormones (TSH, FT3, and FT4), blood glucose indices (FBG and HbA1c), and blood lipid indices (HDL-C, LDL-C, TC, and TG) of the two groups were analyzed by univariate and multivariate logistic regression to explore the risk factors for DR. Pearson correlation analysis and multiple stepwise regression analysis were used to investigate the correlation of TSH or FT3 with FBG, HbA1c, and TG in DR patients.Results: Of the 286 patients with T2DM included in this study, 101 (35.31%) developed DR and 185 (64.69%) did not. High TG, FBG, HbA1c, and TSH and low FT3 levels were independent risk factors for DR in T2DM patients. TSH positively correlated with TG, whereas FT3 negatively correlated with TG and HbA1c in T2DM patients with DR.Conclusion: Higher TSH and lower FT3 in T2DM patients with normal thyroid function may affect glucose and lipid metabolism, thereby increasing the risk of DR.Keywords: type 2 diabetes mellitus, diabetic retinopathy, thyroid-stimulating hormone, free triiodothyronine, glucose and lipid metabolism

Lina Yu,1,&ast; Zidan Xu,1,&ast; Guanxiong Zhu,1,&ast; Liting Zeng,1 Zeyu Zhang,1 Yang Yu,2 Siran Wang,1 Xin Zhang,3 Na Zhou,3 Lu Liang1,4 1Department of Preventive Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Sports and Health, Guangzhou Sport University, Guangzhou, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wailong, Taipa, Macau, People’s Republic of China; 4Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lina Yu; Lu Liang, Email yulina@gzhmu.edu.cn; lliangaa@gzhmu.edu.cnBackground: The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare.Methods: Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites.Results: The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites.Conclusion: The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.Keywords: photodynamic therapy, verteporfin, RGD sequence, tumor-specific drug delivery

Shasha Zhang,1,&ast; Jianhua Wu,2,&ast; Yue Zhao,3 Jingjing Zhang,1 Xiaoyun Zhang,1 Chensi Wu,3 Zhidong Zhang,4 Zhanjun Guo1 1Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 2Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 4Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhidong Zhang, Department of Surgery, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Email zzd407@163.com Zhanjun Guo, Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Tel +86 311 86095734, Email zjguo5886@aliyun.comPurpose: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy.Patients and methods: Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test.Results: Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P< 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS.Conclusion: IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.Keywords: endocrine adverse event, malignancies, monoclonal antibody therapy, immune-related side effects, treatment efficacy

Liqun Yang,1– 3 Zhimei Zhang,3 Yunfeng Zhen,3 Jing Feng,3 Jinhu Chen,3 Guangyao Song1– 3 1Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Hebei Key Laboratory of Metabolic Disease, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Guangyao Song, Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China, Tel +86-0311-8598-8556, Email sguangyao2@163.comPurpose: Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism.Patients and Methods: 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism.Results: In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219– 0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032).Conclusion: The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.Keywords: sirtuin, postprandial hypertriglyceridemia, insulin resistance, genetics

Zixian Liu, Tianming Lu, Ruoning Qian, Zian Wang, Ruogu Qi, Zhengguang Zhang School of Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, People’s Republic of ChinaCorrespondence: Zhengguang Zhang; Ruogu Qi, Email zhengguangzhang@njucm.edu.cn; rqi@njucm.edu.cnBackground: Cancer continues to be a prominent issue in the field of medicine, as demonstrated by recent studies emphasizing the significant role of autophagy in the development of cancer. Traditional Chinese Medicine (TCM) provides a variety of anti-tumor agents capable of regulating autophagy. However, the clinical application of autophagy-modulating compounds derived from TCM is impeded by their restricted water solubility and bioavailability. To overcome this challenge, the utilization of nanotechnology has been suggested as a potential solution. Nonetheless, the current body of literature on nanoparticles delivering TCM-derived autophagy-modulating anti-tumor compounds for cancer treatment is limited, lacking comprehensive summaries and detailed descriptions.Methods: Up to November 2023, a comprehensive research study was conducted to gather relevant data using a variety of databases, including PubMed, ScienceDirect, Springer Link, Web of Science, and CNKI. The keywords utilized in this investigation included “autophagy”, “nanoparticles”, “traditional Chinese medicine” and “anticancer”.Results: This review provides a comprehensive analysis of the potential of nanotechnology in overcoming delivery challenges and enhancing the anti-cancer properties of autophagy-modulating compounds in TCM. The evaluation is based on a synthesis of different classes of autophagy-modulating compounds in TCM, their mechanisms of action in cancer treatment, and their potential benefits as reported in various scholarly sources. The findings indicate that nanotechnology shows potential in enhancing the availability of autophagy-modulating agents in TCM, thereby opening up a plethora of potential therapeutic avenues.Conclusion: Nanotechnology has the potential to enhance the anti-tumor efficacy of autophagy-modulating compounds in traditional TCM, through regulation of autophagy.Keywords: autophagy, nano-delivery, anti-cancer, traditional Chinese medicine

Wenrong Zhang,1,2,&ast; Haining Wang,1,&ast; Tong Wu,1 Xintao Gao,1 Yuting Shang,1 Zhifang Zhang,1 Xingjian Liu,1 Yinü Li1 1National Key Laboratory of Agricultural Microbiology, Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, People’s Republic of China; 2College of Life Sciences, Capital Normal University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingjian Liu; Yinü Li, Tel/Fax +861082109854 ; +861082105495, Email liuxingjian@caas.cn; liyinv@caas.cnPurpose: COVID-19 is rampant throughout the world, which has caused great damage to human lives and seriously hindered the development of the global economy. Aiming at the treatment of SARS-CoV-2, in this study, we proposed a novel fenobody strategy based on ferritin (Fe) self-assembly technology.Methods: The neutralizing nanobody H11-D4 of SARS-CoV-2 fused to the C-terminus of end-modified human ferritin was expressed in E. coli and silkworm baculovirus expression systems. A large number of nanoparticles were successfully self-assembled in silkworms, while relatively few nanoparticles can be observed in the treated products from E. coli by electron microscopy. Subsequently, the fenobody’s expression level and neutralizing activity were then evaluated.Results: The results showed that the IC50 of H11-D4 and fenobody Fe-H11-D4 expressed in E. coli were 171.1 nmol L− 1 and 20.87 nmol L− 1, respectively. However, the IC50 of Fe-HD11-D4 expressed in silkworms was 1.46 nmol L− 1 showing better neutralization activity.Conclusion: Therefore, fenobodies can be well self-assembled in silkworm baculovirus expression system, and ferritin self-assembly technology can effectively improve nanobody neutralization activity.Keywords: COVID-19, ferritin, fenobody, baculovirus expression system, silkworm

Qun Ding,1– 4,&ast; Congcong Yu,2,3,&ast; Xiang Xu,1,3 Yinjiao Hou,1,3 Yingwen Miao,2,3 Sijue Yang,2,3 Shihua Chen,2,3 Xuelin Ma,2,3 Zhou Zhang,2,3 Yan Bi1– 3 1Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Branch of National Clinical Research Centre for Metabolic Diseases, Nanjing, People’s Republic of China; 4Department of Endocrinology, the Second People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhou Zhang, Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Branch of National Clinical Research Centre for Metabolic Diseases, No. 321, Zhongshan Road, Nanjing, 210008, People’s Republic of China, Tel + 86 25-83106666, Email zhangzhou@smail.nju.edu.cn Yan Bi, Department of Endocrinology, Endocrine and Metabolic Disease Medical Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Branch of National Clinical Research Centre for Metabolic Diseases, No. 321, Zhongshan Road, Nanjing, 210008, People’s Republic of China, Tel + 86 25-83105313, Email biyan@nju.edu.cnAim: Numerous evidence suggests that diabetes increases the risk of cognitive impairment. This study aimed to develop and validate a multivariable risk score model to identify mild cognitive impairment (MCI) in patients with type 2 diabetes mellitus (T2DM).Methods: This cross-sectional study included 1256 inpatients (age: 57.5 ± 11.2 years) with T2DM in a tertiary care hospital in China. MCI was diagnosed according to the criteria recommended by the National Institute on Aging-Alzheimer’s Association Workgroup, and a MoCA score of 19– 25 indicated MCI. Participants were randomly allocated into the derivation and validation sets at 7:3 ratio. Logistic regression models were used to identify predictors for MCI in the derivation set. A scoring system based on the predictors’ beta coefficient was developed. Predictive ability of the risk score was tested by discrimination and calibration methods.Results: Totally 880 (285 with MCI, 32.4%) and 376 (167 with MCI, 33.8%) patients were allocated in the derivation and validation set, respectively. Age, education, HbA1c, self-reported history of severe hypoglycemia, and microvascular disease were identified as predictors for MCI and constituted the risk score. The AUCs (95% CI) of the risk score were 0.751 (0.717, 0.784) in derivation set and 0.776 (0.727, 0.824) in validation set. The risk score showed good apparent calibration of observed and predicted MCI probabilities and was capable of stratifying individuals into 3 risk categories by two cut-off points (low risk: ≤ 3, medium risk: 4– 13, and high risk ≥ 14).Conclusion: The risk score based on age, education, HbA1c, self-reported history of severe hypoglycemia, and microvascular disease can effectively assess MCI risk in adults with T2DM at different age. It can serve as a practical prescreening tool for early detection of MCI in daily diabetes care.Keywords: mild cognitive impairment, type 2 diabetes mellitus, risk score, prescreening tool

Zhiliang Zhang,1,&ast; Zhongxiang Ding,2,&ast; Fenyang Chen,2 Rui Hua,3 Jiaojiao Wu,3 Zhefan Shen,2 Feng Shi,3 Xiufang Xu1 1School of Medical Imaging, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Department of Radiology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou, People’s Republic of China; 3Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Shi; Xiufang Xu, Email feng.shi@uii-ai.com; 1996033011@hmc.edu.cnBackground: Cerebral small vessel disease lacks specific clinical manifestations, and extraction of valuable features from multimodal images is expected to improve its diagnostic accuracy. In this study, we used deep learning techniques to segment cerebral small vessel disease imaging markers in multimodal magnetic resonance images and analyze them with clinical risk factors.Methods and results: We recruited 211 lacunar stroke patients and 83 control patients. The patients’ cerebral small vessel disease markers were automatically segmented using a V-shaped bottleneck network, and the number and volume were calculated after manual correction. The segmentation results of the V-shaped bottleneck network for white matter hyperintensity and recent small subcortical infarction were in high agreement with the ground truth (DSC> 0.90). In small lesion segmentation, cerebral microbleed (average recall=0.778; average precision=0.758) and perivascular spaces (average recall=0.953; average precision=0.923) were superior to lacunar infarct (average recall=0.339; average precision=0.432) in recall and precision. Binary logistic regression analysis showed that age, systolic blood pressure, and total cerebral small vessel disease load score were independent risk factors for lacunar stroke (P< 0.05). Ordered logistic regression analysis showed age was positively correlated with cerebral small vessel disease load score and total cholesterol was negatively correlated with cerebral small vessel disease score (P< 0.05).Conclusion: Lacunar stroke patients exhibited higher cerebral small vessel disease imaging markers, and age, systolic blood pressure, and total cerebral small vessel disease score were independent risk factors for lacunar stroke patients. V-shaped bottleneck network segmentation network based on multimodal deep learning can segment and quantify various cerebral small vessel disease lesions to some extent.Keywords: lacunar stroke, cerebral small vessel disease, imaging markers, deep learning, quantification, image segmentation, clinical risk factors

Fei Shu,&ast; Hong Chen,&ast; Zhihao Zhang, Zhiyue Dun, Weijin Lv, Wangxinyue Sun, Mei Liu Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Liu, Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, People’s Republic of China, Tel +86-25-69593081, Fax +86-25-69593186, Email liumei2017@njmu.edu.cnIntroduction: Poor interfacial bonding between the fibers and resin matrix in fiber-reinforced composites (FRCs) is a significant drawback of the composites. To enhance the mechanical properties of FRC, fibers were modified by depositing SiO2 nanofilms via the atomic layer deposition (ALD) technique. This study aims to evaluate the effect of ALD treatment of the fibers on the mechanical properties of the FRCs.Methods: The quartz fibers were modified by depositing different cycles (50, 100, 200, and 400) of SiO2 nanofilms via the ALD technique and FRCs were proposed from the modified fibers. The morphologies, surface characterizations of nanofilms, mechanical properties, and cytocompatibility of FRCs were systematically investigated. Moreover, the shear bond strength (SBS) of FRCs to human enamel was also evaluated.Results: The SEM and SE results showed that the ALD-deposited SiO2 nanofilms have good conformality and homogeneity. According to the results of FTIR and TGA, SiO2 nanofilms and quartz fiber surfaces had good chemical combinations. Three-point bending tests with FRCs showed that the deposited SiO2 nanofilms effectively improved FRCs’ strength and Group D underwent 100 deposition cycles and had the highest flexural strength before and after aging. Furthermore, the strength of the FRCs demonstrated a crescendo-decrescendo tendency with SiO2 nanofilm thickness increasing. The SBS results also showed that Group D had outstanding performance. Moreover, the results of cytotoxicity experiments such as cck8, LDH and Elisa, etc., showed that the FRCs have good cytocompatibility.Conclusion: Changing the number of ALD reaction cycles affects the mechanical properties of FRCs, which may be related to the stress relaxation and fracture between SiO2 nanofilm layers and the built-up internal stresses in the nanofilms. Eventually, the SiO2 nanofilms could enhance the FRCs’ mechanical properties and performance to enamel by improving the interfacial bonding strength, and have good cytocompatibility. Keywords: atomic layer deposition, SiO2 nanofilms, surface modification, interfacial bonding

Qiong Ge,1,&ast; Zhewen Zhang,2,&ast; Zhiming Cao,2 Dan Wu,3 Changping Xu,1 Jianbiao Yao,3 Jian Gao,1 Yan Feng1 1Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou, Zhejiang, 310057, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Feng, Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China, Tel/Fax +86-571-87115204, Email yfeng@cdc.zj.cnPurpose: This study aims to investigate the in vitro antiviral effects of the aqueous solution of Changyanning (CYN) tablets on Enterovirus 71 (EV71), and to analyze its active components.Methods: The in vitro anti-EV71 effects of CYN solution and its herbal ingredients were assessed by testing the relative viral RNA (vRNA) expression level and the cell viability rates. Material basis analysis was performed using HPLC-Q-TOF-MS/MS detection. Potential targets and active components were identified by network pharmacology and molecular docking. The screened components were verified by in vitro antiviral experiments.Results: CYN solution exerted anti-EV71 activities as the vRNA is markedly reduced after treatment, with a half maximal inhibitory concentration (IC50) of 996.85 μg/mL. Of its five herbal ingredients, aqueous extract of Mosla chinensis (AEMC) and leaves of Liquidambar formosana Hance (AELLF) significantly inhibited the intracellular replication of EV71, and the IC50 was tested as 202.57 μg/mL and 174.77 μg/mL, respectively. Based on HPLC-Q-TOF-MS/MS results, as well as the comparison with the material basis of CYN solution, a total of 44 components were identified from AEMC and AELLF. Through network pharmacology, AKT1, ALB, and SRC were identified as core targets. Molecular docking performed between core targets and the components indicated that 21 components may have anti-EV71 effects. Of these, nine were selected for in vitro pharmacodynamic verification, and only rosmarinic acid manifested in vitro anti-EV71 activity, with an IC50 of 11.90 μg/mL. Moreover, rosmarinic acid can stably bind with three core targets by forming hydrogen bonds.Conclusion: CYN solution has inhibitory effects on EV71 replication in vitro, and its active component was identified as rosmarinic acid. Our study provides a new approach for screening and confirmation of the effective components in Chinese herbal preparation.Keywords: antiviral effects, material basis analysis, component-target-pathway-disease network, protein–protein interaction network, core targets, rosmarinic acid

Qiwei Li,1 Zhiyun Zhang,1,2 Jiajia Fang1 1Department of Neurology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, 322000, People’s Republic of China; 2Department of Neurology, The Mianyang Central Hospital, Mianyang, Sichuan Province, 621000, People’s Republic of ChinaCorrespondence: Jiajia Fang, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, 322000, People’s Republic of China, Email fangjjiaj@zju.edu.cnAbstract: Epilepsy is a prevalent neurological disorder among women globally, often requiring long-term treatment. Hormonal fluctuations in women with epilepsy (WWE) can have reciprocal effects on epilepsy and antiseizure medications (ASMs), posing significant challenges for WWE. Notably, WWE commonly experience endocrine alterations such as thyroid dysfunctions, low bone metabolism, and reproductive hormone irregularities. On the one hand, the presence of hormones in women with epilepsy affects their susceptibility to epilepsy as well as the metabolism of antiseizure medications in various ways. On the other hand, epilepsy itself and the use of antiseizure medications impact the production, secretion, and metabolism of hormones, resulting in low fertility, increased risk of pregnancy complications, negative offspring outcomes, and so on. In order to develop more precise treatment strategies in the future, it is necessary to comprehend the explicit relationships between hormones, epilepsy, and antiseizure medications, as well as to elucidate the currently known mechanisms underlying these interactions.Keywords: women with epilepsy, antiseizure medications, endocrine, hormonal changes

Zhendong Zhang,1,&ast; Yonghuan Chen,2,3,&ast; Lei Zhang3,4 1School of Physical Education, Zhengzhou Sias University, Zhengzhou, People’s Republic of China; 2Department of Marine Sports, Pukyong National University, Busan, South Korea; 3School of Physical Education (Main Campus), Zhengzhou University, Zhengzhou, People’s Republic of China; 4Department of Sports Science, Jeonbuk National University, Jeonju-si, South Korea&ast;These authors contributed equally to this workCorrespondence: Lei Zhang, Email zhanglei@zzu.edu.cnPurpose: To explore the relations among personality traits, sports commitment, and exercise behavior of Chinese college students. To test whether sports commitment plays an intermediary role in the process of personality traits affecting exercise behavior. To explore the factors that affect Chinese college students’ exercise behavior from the psychological level, to promote college students to actively participate in physical exercise.Methods: A questionnaire survey was conducted on 1200 students from 6 universities using the “Personality Trait Scale”, “Sports Commitment Scale” and “Exercise Behavior Scale”. SPSS was used to analyze the differences between genders and urban and rural areas; and correlation analysis was conducted on the personality traits, sports commitment, and exercise behaviors of college students. Finally, AMOS was used to establish a structural equation model to test the mediating role of sports commitment.Results: There are significant differences between different genders in each factor of personality traits (P< 0.05); there is no significant difference between different genders in the participation opportunities of sports commitment (P=0.734), and there are significant differences in other factors. There were significant differences in each factor of exercise behavior (P< 0.05). There were no significant differences in personality traits, sports commitment, and exercise behavior between urban and rural students (P> 0.05). There was a significant correlation among personality traits, sports commitment, and exercise behavior (P < 0.01). The direct effect of personality traits on exercise behavior was not significant (P > 0.05), but there was only the mediating effect of sports commitment.Conclusion: There is a significant correlation among Chinese college students’ personality traits, sports commitment, and exercise behavior. Sports commitment plays an intermediary role between personality traits and sports commitment. Improving the level of sports commitment can encourage Chinese college students to participate in physical exercise.Keywords: personality traits, sports commitment, exercise behavior, AMOS

Fengmei Huang,1,&ast; Yumei Shi,1,&ast; Li Ding,2 Jingui Huang,1 Zhaoli Zhang2 1Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 2Nursing Department, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaoli Zhang, Nursing Department, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, People’s Republic of China, Tel +86-23-65079129, Email 2671004746@qq.comPurpose: Learned helplessness (LH) is the psychological state in which an individual experiences multiple failures and setbacks and experiences a sense of loss when facing the current situation. It is a significant burden for lung cancer patients that can impair quality of life and lead to physical, social, and psychological difficulties. Thus, this study aimed to determine the level of LH among patients with lung cancer and identify factors associated with LH.Patients and Methods: From August 2022 to March 2023, 237 patients with lung cancer from Chongqing University Cancer Hospital were selected for this study. A general information questionnaire, the LH scale, the Brief Illness Perception questionnaire, the Strategies Used by People to Promote Health questionnaire, the Medical Coping Modes questionnaire, and the Self-esteem scale were used for the investigation. Multiple linear regression was employed to identify influencing factors for LH in patients with lung cancer.Results: The total LH score of patients with lung cancer was 52.19± 11.20. Multiple linear regression analysis showed that illness perception (β=0.249, P=0.001), self-efficacy (β=− 0.194, P=0.017), and resignation coping mode (β=0.267, P< 0.001) were the main influencing factors of LH (P< 0.05), which explained 42.0% of the total variance.Conclusion: The score of LH in patients with lung cancer was at a moderate level in this study. Illness perception, self-efficacy, and resignation coping mode have been found to impact LH among patients with lung cancer. Healthcare professionals should implement effective interventions, such as promoting self-efficacy, encouraging positive coping, and reducing illness perception, to alleviate LH.Keywords: lung cancer, learned helplessness, risk factors, psychology

Jiameng Gao,1,2,&ast; Zhiyuan Zhang,1,2,&ast; Jing Yu,1,2,&ast; Nan Zhang,1,2 Yu Fu,1,2 Xuemei Jiang,1,2 Zheyu Xia,3 Qingqing Zhang,1,2 Zongmei Wen1,2 1Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Lung Transplantation, Shanghai, People’s Republic of China; 3School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongmei Wen; Qingqing Zhang, Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel +86 13761635280 ; +86 13764542055, Email wzm1103@126.com; elfe666@163.comPurpose: Ischemia reperfusion injury (IRI) unavoidably occurs during lung transplantation, further contributing to primary graft dysfunction (PGD). Neutrophils are the end effectors of IRI and activated neutrophils release neutrophil extracellular traps (NETs) to further amplify damage. Nevertheless, potential contributions of NETs in IRI remain incompletely understood. This study aimed to explore NET-related gene biomarkers in IRI during lung transplantation.Methods: Differential expression analysis was applied to identify differentially expressed genes (DEGs) for IRI during lung transplantation based on matrix data (GSE145989, 127003) downloaded from GEO database. The CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were utilized to identify key modules associated with neutrophil infiltration. Moreover, the least absolute shrinkage and selection operator regression and random forest were applied to identify potential NET-associated hub genes. Subsequently, the screened hub genes underwent further validation of an external dataset (GSE18995) and nomogram model. Based on clinical peripheral blood samples, immunofluorescence staining and dsDNA quantification were used to assess NET formation, and ELISA was applied to validate the expression of hub genes.Results: Thirty-eight genes resulted from the intersection between 586 DEGs and 75 brown module genes, primarily enriched in leukocyte migration and NETs formation. Subsequently, four candidate hub genes (FCAR, MMP9, PADI4, and S100A12) were screened out via machine learning algorithms. Validation using an external dataset and nomogram model achieved better predictive value. Substantial NETs formation was demonstrated in IRI, with more pronounced NETs observed in patients with PGD ≥ 2. PADI4, S100A12, and MMP9 were all confirmed to be up-regulated after reperfusion through ELISA, with higher levels of S100A12 in PGD ≥ 2 patients compared with non-PGD patients.Conclusion: We identified three potential NET-related biomarkers for IRI that provide new insights into early detection and potential therapeutic targets of IRI and PGD after lung transplantation.Keywords: ischemia reperfusion injury, neutrophil extracellular traps, lung transplantation, primary graft dysfunction, WGCNA, machine learning

Jiaxing Zhang,1,2,&ast; Liwei Gu,3,&ast; Yumao Jiang,4,&ast; Yun Ma,5,&ast; Ziyue Zhang,3 Shengnan Shen,3 Shuo Shen,3 Qing Peng,6 Wei Xiao2,7 1Institute of Digestive Disease, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Qingyuan, Guang Dong, People’s Republic of China; 2School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guang Dong, People’s Republic of China; 3Artemisinin Research Center and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 4Gannan Medical University, Ganzhou, Jiang Xi, People’s Republic of China; 5Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, Guang Dong, People’s Republic of China; 6Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 7Key Laboratory of Glucolipid Metabolic Disorder, Ministry of Education, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Peng; Wei Xiao, Email pengqing85@163.com; xw7688@smu.edu.cnBackground: Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from Artemisia annua L. that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy.Methods: In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored.Results: T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1.Conclusion: T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI. Keywords: artesunate, liposomes, AKI, cisplatin, oxidative stress, inflammation

Chengying Hong,1 Yihan Xiong,2 Jinquan Xia,3 Wei Huang,4 Andi Xia,1 Shunyao Xu,1 Yuting Chen,1 Zhikun Xu,1 Huaisheng Chen,1 Zhongwei Zhang5 1Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 2Neurology Department, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 3Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 4Department of Clinical Microbiology, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China; 5Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Huaisheng Chen, Department of Critical Care Medicine, Shenzhen People’s Hospital, Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, 518020, People’s Republic of China, Email sunshinic@hotmail.com Zhongwei Zhang, Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email 716461751@qq.comObjective: The objective of this study was to utilize LASSO regression (Least Absolute Shrinkage and Selection Operator Regression) to identify key variables in septic patients and develop a predictive model for intensive care unit (ICU) mortality.Methods: We conducted a cohort consisting of septic patients admitted to the ICU between December 2016 and July 2019. The disease severity and laboratory index were analyzed using LASSO regression. The selected variables were then used to develop a model for predicting ICU mortality. AUCs of ROCs were applied to assess the prediction model, and the accuracy, sensitivity and specificity were calculated. Calibration were also used to assess the actual and predicted values of the predictive model.Results: A total of 1733 septic patients were included, among of whom 382 (22%) died during ICU stay. Ten variables, namely mechanical ventilation (MV) requirement, hemofiltration (HF) requirement, norepinephrine (NE) requirement, septicemia, multiple drug-resistance infection (MDR), thrombocytopenia, hematocrit, red-cell deviation width coefficient of variation (RDW-CV), C-reactive protein (CRP), and antithrombin (AT) III, showed the strongest association with sepsis-related mortality according to LASSO regression. When these variables were combined into a predictive model, the area under the curve (AUC) was found to be 0.801. The AUC of the validation group was 0.791. The specificity of the model was as high as 0.953. Within the probability range of 0.25 to 0.90, the predictive performance of the model surpassed that of individual predictors within the cohort.Conclusion: Our findings suggest that a predictive model incorporating the variables of MV requirement, HF requirement, NE requirement, septicemia, MDR, thrombocytopenia, HCT, RDW-CV, CRP, and AT III exhibiting an 80% likelihood of predicting ICU mortality in sepsis and demonstrates high accuracy.Keywords: sepsis, mortality, LASSO regression, predictive model, ICU

Enyi Zhu,1,2,&ast; Ming Zhong,3,&ast; Tiantian Liang,4,&ast; Yu Liu,3,&ast; Keping Wu,1,2 Zhijuan Zhang,1,2 Shuping Zhao,1,2 Hui Guan,5 Jiasi Chen,6 Li-Zhen Zhang,7 Yimin Zhang1,2 1The Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, 510000, People’s Republic of China; 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, 510000, People’s Republic of China; 3Department of Nephrology, Center of Kidney and Urology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, 517108, People’s Republic of China; 4Nephrology Division, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510630, People’s Republic of China; 5Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China; 6Department of Nephrology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510030, People’s Republic of China; 7Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yimin Zhang, The Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, People’s Republic of China, Email zhangyim@mail.sysu.edu.cn Li-Zhen Zhang, Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China, Email zhanglzh3@mail2.sysu.edu.cnObjective: Diabetic nephropathy (DN) represents the principal cause of end-stage renal diseases worldwide, lacking effective therapies. Fatty acid (FA) serves as the primary energy source in the kidney and its dysregulation is frequently observed in DN. Nevertheless, the roles of FA metabolism in the occurrence and progression of DN have not been fully elucidated.Methods: Three DN datasets (GSE96804/GSE30528/GSE104948) were obtained and combined. Differentially expressed FA metabolism-related genes were identified and subjected to DN classification using “ConsensusClusterPlus”. DN subtypes-associated modules were discovered by “WGCNA”, and module genes underwent functional enrichment analysis. The immune landscapes and potential drugs were analyzed using “CIBERSORT” and “CMAP”, respectively. Candidate diagnostic biomarkers of DN were screened using machine learning algorithms. A prediction model was constructed, and the performance was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The online tool “Nephroseq v5” was conducted to reveal the clinical significance of the candidate diagnostic biomarkers in patients with DN. A DN mouse model was established to verify the biomarkers’ expression.Results: According to 39 dysregulated FA metabolism-related genes, DN samples were divided into two molecular subtypes. Patients in Cluster B exhibited worse outcomes with a different immune landscape compared with those in Cluster A. Ten potential small-molecular drugs were predicted to treat DN in Cluster B. The diagnostic model based on PRKAR2B/ANXA1 was created with ideal predictive values in early and advanced stages of DN. The correlation analysis revealed significant association between PRKAR2B/ANXA1 and clinical characteristics. The DN mouse model validated the expression patterns of PRKAR2B/ANXA1.Conclusion: Our study provides new insights into the role of FA metabolism in the classification, immunological pathogenesis, early diagnosis, and precise therapy of DN.Keywords: diabetic nephropathy, fatty acid metabolism, molecular subtypes, immune landscape, pharmacotherapy, diagnostic model

Huifeng Wu,1 Xiaodong Wu,2 Mengdan Zhao,3 Jingjing Yan,3 Chaoqun Li,3 Zhewei Zhang,1 Sangsang Tang,2 Rong Wang,3 Weidong Fei3 1Department of Urology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Gynecologic Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of China; 3Department of Pharmacy, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, People’s Republic of ChinaCorrespondence: Weidong Fei; Rong Wang, Email feiweidong@zju.edu.cn; 5521085@zju.edu.cnAbstract: During the past decade, “membrane lipid therapy”, which involves the regulation of the structure and function of tumor cell plasma membranes, has emerged as a new strategy for cancer treatment. Cholesterol is an important component of the tumor plasma membrane and serves an essential role in tumor initiation and progression. This review elucidates the role of cholesterol in tumorigenesis (including tumor cell proliferation, invasion/metastasis, drug resistance, and immunosuppressive microenvironment) and elaborates on the potential therapeutic targets for tumor treatment by regulating cholesterol. More meaningfully, this review provides an overview of cholesterol-integrated membrane lipid nanotherapeutics for cancer therapy through cholesterol regulation. These strategies include cholesterol biosynthesis interference, cholesterol uptake disruption, cholesterol metabolism regulation, cholesterol depletion, and cholesterol-based combination treatments. In summary, this review demonstrates the tumor nanotherapeutics based on cholesterol regulation, which will provide a reference for the further development of “membrane lipid therapy” for tumors. Keywords: cholesterol, tumor, plasma membrane, nanotherapeutics

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

Shuaijun Cao,1,&ast; Xiaoying Jiang,2,&ast; Jinshan Suo,3 Yanyan Lu,2 Mohan Ju,2 Qixiang Zeng,1 Qingru Zheng,1 Zuoyan Zhang,1 Wenqi Tang1 1Department of Critical Care Medicine, Shanghai Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuoyan Zhang; Wenqi Tang, Department of Critical Care Medicine, Shanghai Sixth People’s Hospital, No. 600 Yishan Road, Shanghai, 200000, People’s Republic of China, Tel +86 021-24058331, Email 18930177049@189.cn; zhang_zy1969@163.comIntroduction: Carbapenem-Resistant Enterobacteriaceae (CRE) has posed a significant threat to humans.The aim of this study was to investigate the molecular characteristics of blaKPC-producing Escherichia coli in a university-affiliated tertiary hospital.Methods: Polymerase chain reaction (PCR) and BLAST+ software were used to detect the prevalence of blaKPC in E. coli and Klebsiella pneumoniae. Whole-genome sequencing was performed for the blaKPC-harboring clinical E. coli isolates. Antimicrobial resistance genes, MLSTs, KPC-carrying plasmid typing and genetic environment of blaKPC were analyzed. A maximum likelihood core single nucleotide polymorphism (SNP)-based phylogeny tree was constructed to determine the evolutionary relationships within this ST131 collection. Conjugation experiments were performed to determine the mobilization of blaKPC. The minimal inhibitory concentrations of the common antimicrobial agents were determined using the broth microdilution method.Results: The prevalence of blaKPC in 424 clinical E. coli isolates and 1636 E. coli strains from GenBank database were 2.2% (45/2060) whereas the detection rate of blaKPC in K. pneumoniae from the GenBank database was 29.8% (415/1394). The blaKPC-harboring conjugants exhibited resistance to multiple β-lactams, except for cefepime-zidebactam and ceftazidime-avibactam. All blaKPC-carring E. coli isolates were susceptible to tigecycline and polymyxin B. ST131 was the dominant sequence type of blaKPC-carring E. coli, accounting for 40.0% (18/45). Most of the blaKPC-producing ST131 E. coli (89.5%,17/19) belonged to clade C ST131 lineage. Genetic environment analysis revealed that 57.8% (26/45) of blaKPC gene was linked to Tn 4401-associated structure ISKpn6-blaKPC-ISKpn7. IncN was the most common plasmid type in KPC-producing E. coli whereas IncFII was the dominant plasmid type in KPC-producing K. pneumoniae.Conclusion: The detection rate of blaKPC was lower in E. coli compared with K. pneumoniae. The dominant sequence and plasmid types of blaKPC-harboring isolates differed between E. coli and K. pneumoniae. Further studies about the role of the defense system in acquisition of KPC-plasmids in E. coli will be performed to provide new insights into the low prevalence of blaKPC.Keywords: Escherichia coli, blaKPC, carbapenemases, plasmids typing

Dingyue Wang, Gaosen Zhang, Yana Yu, Zhen Zhang Department of Ultrasound, the First Affiliated Hospital China Medical University, Shenyang City, Liaoning Province, 110001, People’s Republic of ChinaCorrespondence: Zhen Zhang, Email zhangzhen@cmu.edu.cnAbstract: Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass, muscular strength, and muscle function. In older adults, type 2 diabetes mellitus (T2DM) constitutes a significant health burden. Skeletal muscle damage and deterioration have emerged as novel chronic complications in patients with diabetes, often linked to their increased longevity. Diabetic sarcopenia has been associated with increased rates of hospitalization, cardiovascular events, and mortality. Nevertheless, effectively managing metabolic disorders in patients with T2DM through appropriate therapeutic interventions could potentially mitigate the risk of sarcopenia. Utilizing imaging technologies holds substantial clinical significance in the early detection of skeletal muscle mass alterations associated with sarcopenia. Such detection is pivotal for arresting disease progression and preserving patients’ quality of life. These imaging modalities offer reproducible and consistent patterns over time, as they all provide varying degrees of quantitative data. This review primarily delves into the application of dual-energy X-ray absorptiometry, computed tomography, magnetic resonance imaging, and ultrasound for both qualitative and quantitative assessments of muscle mass in patients with T2DM. It also juxtaposes the merits and limitations of these four techniques. By understanding the nuances of each method, clinicians can discern how best to apply them in diverse clinical scenarios.Keywords: diagnostic imaging, older adults, sarcopenia, skeletal muscle mass, type 2 diabetes mellitus

Sicheng Zhao, Tingyan Wu, Mingjing Fu, Zhe Zhang Department of Dermatology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, People’s Republic of ChinaCorrespondence: Sicheng Zhao, Department of Dermatology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, No. 118 Wansheng Street, Suzhou Industrial Park, Suzhou, Jiangsu, 215028, People’s Republic of China, Email zscba@163.comBackground: Psoriasis is a chronic inflammatory skin disease characterized by erythema, papules, and plaques. Adiponectin (ADIPOQ) is an important protein hormone secreted by adipose tissue. Here, we aimed to explore the expression of ADIPOQ in psoriasis patients and the moderation effect of histone lactylation on ADIPOQ.Methods: The GSE78097 data set was downloaded from GEO database to analyze the differentially expressed genes (DEGs) in psoriasis. A total of 36 psoriasis patients were recruited to obtain the skin samples. The ADIPOQ protein levels, global lactylation and histone lactylation (H3K18lac) levels were detected by Western blot assay. Chromatin immunoprecipitation (CHIP) assay was performed to detect the combination between H3K18lac and promoter regions of the ADIPOQ. The receiver operating curve (ROC) analysis was used to evaluate the diagnostic value of ADIPOQ in psoriasis.Results: ADIPOQ was decreased in the skin tissues of psoriasis patients. In addition, the global lactylation and H3K18lac levels were significantly decreased in the skin tissues of psoriasis patients. In HaCaT cells, promoting the global lactylation and H3K18lac levels increased the ADIPOQ protein levels, while si-LDHA transfection decreased the ADIPOQ protein levels. The CHIP results indicated that lactylation promoted the binding of promoter regions of the ADIPOQ and H3K18lac. Finally, the ROC analysis showed that ADIPOQ exhibited diagnostic value in psoriasis.Conclusion: This study demonstrated ADIPOQ was decreased in the skin tissues of psoriasis patients, and ADIPOQ has diagnostic value for psoriasis. Furthermore, down-regulation of H3K18lac levels inhibited the transcription of ADIPOQ, which was the key factor of decrease of ADIPOQ levels in psoriasis patients.Keywords: psoriasis, ADIPOQ, histone, lactylation

Yixiu Zhong,1 Youfan Zhang,2 Beibei Lu,1 Zhenjun Deng,1 Zhiwen Zhang,2 Qi Wang,2 Jianglin Zhang1 1Department of Dermatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 2Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Yixiu Zhong; Jianglin Zhang, Email 846783501@qq.com; zhang.jianglin@szhospital.comAbstract: Hypertrophic scars and keloids are common fibroproliferative diseases following injury. Patients with pathologic scars suffer from impaired quality of life and psychological health due to appearance disfiguration, itch, pain, and movement disorders. Recently, the advancement of hydrogels in biomedical fields has brought a variety of novel materials, methods and therapeutic targets for treating hypertrophic scars and keloids, which exhibit broad prospects. This review has summarized current research on hydrogels and loaded components used in preventing and treating hypertrophic scars and keloids. These hydrogels attenuate keloid and hypertrophic scar formation and progression by loading organic chemicals, drugs, or bioactive molecules (such as growth factors, genes, proteins/peptides, and stem cells/exosomes). Among them, smart hydrogels (a very promising method for loading many types of bioactive components) are currently favoured by researchers. In addition, combining hydrogels and current therapy (such as laser or radiation therapy, etc.) could improve the treatment of hypertrophic scars and keloids. Then, the difficulties and limitations of the current research and possible suggestions for improvement are listed. Moreover, we also propose novel strategies for facilitating the construction of target multifunctional hydrogels in the future. Keywords: hydrogel, wound healing, hypertrophic scar, keloid

Xiaoming Yang,&ast; Zhongda Liu,&ast; Xiaojing Liu, Quan Li, Hui Huang, Zunjing Zhang Department of Respiratory and Critical Care Medicine, Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui, 323000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zunjing Zhang, No. 800 Zhongshan Road, Liandu District, Lishui, Zhejiang Province, People’s Republic of China, Tel +8613884387661, Email 382149034@qq.comPurpose: Sangju-Yin, supplemented with some drugs, has frequently demonstrated therapeutic efficacy against colds, albeit its effect on Mycoplasma pneumoniae (MP) infection remains unknown. Therefore, we aimed to elucidate the treatment efficacy and influencing factors of a Sangju cough mixture on MP infection in adults.Patients and Methods: Between January 2021 and December 2022, 150 adult patients with MP infection at the Lishui Hospital of Traditional Chinese Medicine Affiliated with Zhejiang University of Traditional Chinese Medicine were assigned to the treatment (administered Sangju cough mixture and moxifloxacin tablets) or the control (administered moxifloxacin tablets) groups.Results: When compared with the control group, the treatment group exhibited significantly improved traditional Chinese medicine syndrome scores, increased CD4+ T cell levels, and decreased CD8+ T cell levels (all P < 0.05). After 7 days of treatment, the negative conversion rate of the MP-specific immunoglobulin M (MP-IgM) antibody of the treatment group was not significantly different from that of the control group (P > 0.05); however, after 14 days of treatment, the rate was significantly higher in the treatment group (P < 0.05). The univariate regression analysis revealed that combined chronic respiratory disease, failure to take Sangju cough mixture, combined pneumonia, Nutritional Risk Screening 2002 (NRS 2002) score of at least 3 points, and age were associated with the negative conversion of the MP-IgM antibody (all P < 0.05). Nevertheless, the multivariate regression model revealed that the NRS 2002 score of at least 3 points was not an independent risk factor (P > 0.05).Conclusion: Sangju cough mixture can improve symptoms, accelerate the negative conversion time of MP-IgM antibody, and promote rehabilitation of the patients.Keywords: Mycoplasma pneumoniae infection, Sangju cough mixture, moxifloxacin, negative conversion time, influencing factors

Zheng Tian,1,&ast; Yachen Jiang,1,&ast; Nan Zhang,1 Zhijun Zhang,2 Lan Wang1 1School of Nursing, Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 2Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lan Wang, Email wangl0423@tmu.edu.cmBackground and Aim: COPD nursing plays a crucial role in alleviating disease symptoms, prolonging patient survival, and is therefore of paramount importance. However, authoritative research findings, research hotspots, and development trends in the field of COPD are still unclear. This study aimed to examine authoritative research findings, research hotspots, and trends in the field of COPD nursing. Descriptive statistics and bibliometric and visual analyses of the literature were conducted.Methods: Bibliometric data were obtained from the Web of Science database. Citespace was used to explore publication trends, countries, institutions, journals, authors, keywords, and co-citation characteristics of the included literature in order to summarize the key research in the field of COPD nursing.Results: In total, 693 articles on COPD nursing were published. 1998– 2014 showed a rapid growth period in this research field, which stabilized in 2015– 2022. The research content could mostly be summarized into five categories: acute exacerbation, quality of life, risk, evidence-based nursing, and pulmonary rehabilitation. The research hotspots in 1998– 2014 included randomized controlled trials, education, elderly patients, nursing home residents, nursing homes, rehabilitation, and prevalence. Research in 2015– 2022 focused on impact, palliative care, needs, and predictors. In recent years, research mainly concentrated on symptom management models, cost-effectiveness, and cumulative meta-analysis.Conclusion: Bibliometric analysis of COPD nursing articles indicates that the focus of COPD nursing research is shifting from tertiary prevention to primary and secondary prevention. Helping patients achieve self-management of symptoms, reducing the financial burden of COPD on healthcare, and summarizing research evidence by meta-analyses will likely remain the focus of future research.Keywords: bibliometric analysis, COPD, nursing, Citespace, research hotspots

Yunyan Chen,1,2 Ziwei Zhang,1,2 Zhilei Qian,3 Rui Ma,1,2 Minna Luan,1,2 Yu Sun1 1School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 2Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu, 241002, People’s Republic of China; 3The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Yunyan Chen; Yu Sun, School of Pharmacy, Wannan Medical College, Wuhu, 241002, People’s Republic of China, Tel +86 553 3932492, Email cyy1206@163.com; whsunyu@163.comBackground: A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue.Methods: TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L.Results: TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study.Conclusion: Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.Keywords: celastrol, tetrandrine, sequentially released liposomes, anti-liver cancer

Zhengjia Zhang,1,&ast; Xinyi Luo,1,&ast; Xiaoxia Xue,1 Mingshi Pang,1 Xiangpeng Wang,1 Liuchunyang Yu,1 Jinxiu Qian,1 Xiaoyu Li,1 Meng Tian,1 Aiping Lu,2 Cheng Lu,3 Yuanyan Liu1 1School of Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hongkong, People’s Republic of China; 3Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanyan Liu; Cheng Lu, Email yyliu_1980@163.com; lv_cheng0816@163.comBackground: The morbidity and mortality of triple-negative breast cancer (TNBC) are still high, causing a heavy medical burden. CCL5, as a chemokine, can be involved in altering the composition of the tumor microenvironment (TME) as well as the immunosuppressive degree, and has become a very promising target for the treatment of TNBC. Dysregulation of microRNAs (miRNAs) in tumor tissues is closely related to tumor progression, and its utilization can be used to achieve therapeutic purposes. Engineered exosomes can avoid the shortcomings of miRNAs and also enhance their targeting and anti-tumor effects through engineering. Therefore, we aimed to create a cRGD-modified exosome for targeted delivery of miR-588 and to investigate its effect in remodeling immunosuppressive TME by anchoring CCL5 in TNBC.Methods: In this study, we loaded miR-588 into exosomes using electroporation and modified it with cRGD using post insertion to obtain cRGD-Exos/miR-588. Transmission electron microscopy (TEM), nanoparticle tracking assay technique (NTA), Western Blots, qPCR, and flow cytometry were applied for its characterization. CCK-8, qPCR and enzyme-linked immunosorbent assay (ELISA), in vivo fluorescence imaging system, immunohistochemistry and H&E staining were used to explore the efficacy as well as the mechanism at the cellular level as well as in subcutaneous graft-tumor nude mouse model.Results: The cRGD-Exos/miR-588 was successfully constructed and had strong TNBC tumor targeting in vitro and in vivo. Meanwhile, it has significant efficacy on TME components affected by CCL5 and the degree of immunosuppression, which can effectively control TNBC with good safety.Conclusion: In this experiment, cRGD-Exos/miR-588 was prepared to remodel immunosuppressive TME by anchoring CCL5, which is affected by the vicious cycle of immune escape. Overall, cRGD-Exos/miR-588 explored the feasibility of targeting TME for the TNBC treatment, and provided a competitive delivery system for the engineered exosomes to deliver miRNAs for antitumor therapy drug.Keywords: engineered exosome, triple negative breast cancer, miR-588, CCL5, tumor environment

Wangmei Liu,&ast; Jing Guo,&ast; Qiaomin Jiang, Guangnao Zhou, Yanyu Dong, Biqing Xu, Zhongda Liu, Zunjing Zhang, Jianjun Liu Department of Tuberculosis, Lishui Hospital of Traditional Chinese Medicine, Lishui, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianjun Liu; Zunjing Zhang, Department of Tuberculosis, Lishui Hospital of Traditional Chinese Medicine, No. 800 Zhongshan Street, Liandu District, Lishui, 323000, People’s Republic of China, Tel +86 13757835027 ; +86 13884387661, Email jianjunliu888@126.com; zunjingzhangzj@126.comObjective: The purpose of this study is to examine the effect of quality control circle (QCC) activities on increasing the mask-wearing compliance of hospitalized patients diagnosed with tuberculosis (TB) during external examinations.Methods: To assess the mask-wearing compliance of patients diagnosed with TB admitted to a ward in our hospital in 2019, who visited other departments, we conducted activities in accordance with the ten steps of the QCC. We outlined the causes of non-compliance and developed and implemented improvement plans. We compared the results obtained before and after the implementation of the QCC to assess the enhancement in patient compliance concerning wearing masks during external examinations, particularly among individuals diagnosed with pulmonary tuberculosis.Results: The compliance rate for mask-wearing during external examinations rose from an initial 32.61% (45/138) prior to the intervention to 83.71% (149/178) following the intervention. The difference between the two groups was statistically significant (χ2 = 85.635, P

Tianwei Qian,1– 5,&ast; Qiaoyun Gong,1– 5,&ast; Yiyang Shu,1– 5 Hangqi Shen,1– 5 Xia Wu,1– 5 Weijun Wang,1– 5 Zhihua Zhang,1– 5 Hui Cao,1– 5 Xun Xu1– 5 1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2National Clinical Research Center for Eye Diseases, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, People’s Republic of China; 4Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, People’s Republic of China; 5Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Disease, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Cao; Zhihua Zhang, Tel +86 (0) 13611878111 ; +86 (0) 13817901235, Fax +86 021-63240090, Email drcaohui@126.com; drzhihuazhang@126.comPurpose: To evaluate the effectiveness and safety of diazepam in maintaining stable intraoperative blood pressure (BP) in hypertensive patients undergoing vitrectomy under nerve block anesthesia.Methods: A total of 180 hypertensive patients undergoing vitrectomy with nerve block anesthesia were randomized into two groups. The intervention group was given oral diazepam 60 min before operation, while the control group was given oral placebo 60 min before operation. The primary outcome is the effective rate of intraoperative BP control, defined as systolic blood pressure (SBP) during the operation maintained < 160 mmHg at all timepoints. The logistic regression model will be performed to analyze the compare risk factors for ineffective BP control.Results: The effective rate of intraoperative SBP control in the diazepam group was significant higher than that in the placebo group from 15 min to 70 min of the surgery (P < 0.05). The proportion of patients with SBP ≥ 180 mmHg at any timepoint from operation to 1 h postoperation was higher in the placebo group (12.22%) than in the diazepam group (2.22%) (P = 0.0096). We observed that the change in SBP from baseline consistently remained higher in the placebo group than in the diazepam group. In the logistic regression analysis, age, years of diagnosed hypertension and SBP 1h before surgery were significant risk factors for ineffective BP control.Conclusion: This study provides robust evidence supporting the effectiveness of oral diazepam as a pre-surgery intervention in maintaining stable blood pressure during vitrectomy in hypertensive patients.Trial Registration: Chinese Clinical Trial Registry (ChiCTR), ChiCTR2100041772.Keywords: nerve block anesthesia, vitrectomy, diazepam, blood pressure stabilization

Zhilin Zhang,1,2 Aldrin D Calderon,1 Xingyu Huang,1 Axin Huang1 1School of Mechanical Manufacturing and Energy Engineering, Mapúa University, Manila, 0900, Philippines; 2School of Physics and Telecommunications Engineering, Yulin Normal University, Yulin, 537000, People’s Republic of ChinaCorrespondence: Aldrin D Calderon, Email adcalderon@mapua.edu.phAbstract: About 80% of stroke patients have hand motor dysfunction, and wearing finger rehabilitation machinery can enable patients to carry out efficient passive rehabilitation training independently. At present, many typical finger rehabilitation machines have been developed, and clinical experiments have confirmed the effectiveness of mechanically assisted finger rehabilitation. In this paper, the finger rehabilitation machinery will be classified in the actuation mode, and the terminal traction drive/motor drive/spring drive/rope drive/memory alloy drive/electroactive material drive/hydraulic drive/pneumatic drive technology and its typical applications are analyzed. Study the structure, control methods, overlap between mechanical bending nodes and finger joints, training modes, response speed, and driving force of various types of finger rehabilitation machinery. The advantages and disadvantages of various actuation methods of finger rehabilitation machinery are summarized. Finally, the difficulties and opportunities faced by the future development of finger rehabilitation machinery are prospected. In general, with the continuous improvement of quality of life, stroke patients need flexible, segmented control, accurate bending, multi-training mode, fast response, and good driving force finger rehabilitation machinery. This will also be a future hot research direction.Keywords: fingers, machinery, rehabilitation, actuation

Wan Tang,1,2 Hongdou Chen,1,2 Zixin Zhang,1,2 Gang Wu,1,2 Yanquan Lin1– 3 1Pharmacy, Suqian Hospital of Nanjing Drum-Tower Hospital Group, Suqian, People’s Republic of China; 2Pharmacy, Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, People’s Republic of China; 3Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Hongdou Chen, Email chenhongdou2000@aliyun.comObjective: To analyse the relationship between the adverse drug reactions (ADRs) of essential drugs and visits, based on the recorded annual increase in ADRs associated with essential medicines in China, to provide a reliable theoretical basis for further analysis and optimization of the safety of essential drugs.Methods: The data of adverse reactions of essential drugs in China from 2011 to 2020, time series analysis was conducted, and vector autoregressive (VAR) model was established. The relationship between the number of ADRs and visits was explored empirically through Granger causality test, impulse response function and variance decomposition.Results: There was a long-term cointegration relationship and one-way causality between the number of visits and ADRs caused by essential medicines. In the initial stage, the ADR response to the number of visits increased sharply, but with an increase in the number of lag periods, the impact remained basically stable, even showing a slight decreasing trend.Conclusion: The number of visits impacts ADRs caused by essential medicines, but this impact remains basically stable after reaching a certain level.Keywords: essential medicines, adverse drug reactions, vector autoregressive model, time-series analysis

Xing Li, Zhuyuan Zhang, Wen Cai, Xuexin Zhou, Yan Zhang, Cailiang Wu, Xianming Xu, Hao Wu Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of ChinaCorrespondence: Hao Wu; Xianming Xu, Email zhuwy2007@126.com; xuxm11@163.comBackground: The relationship of iron deficiency and thyroid hormone has been researched a lot among pregnant or other healthy population. However, invisible iron deficiency, namely shortage of serum ferritin (sFer) level, has been barely investigated among Chinese pregnant women. This study aimed to explore the effects of sFer status on thyroid function and pregnancy outcomes in a population-based upper first-class hospital.Methods: A total of 781 singleton pregnant women of gestation in Shanghai General Hospital took part in this retrospective cohort study. The participants were divided into four groups by quartiles of serum ferritin levels (Q1– 4). Binary logistic regressions were used to examine the strength of association between the different traits and the serum ferritin (sFer) quartiles separately, where Q1 (lowest ferritin quartile) was taken as the base reference. One-way ANOVA was adopted to compare the averages of the different variables across sFer quartiles. Categorical measures were compared by Fisher exact test or chi-square test.Results: As the sFer concentration rises, incidence of premature birth (15.8%vs 12.3% vs 9.20% vs 6.20% p = 0.016) as well as threatened miscarriage (14.8% vs 7.2% vs 8.70% vs 6.70% p = 0.021) presented a downward trend. Compared with the other sFer group, subjects of the low sFer group were older, more often to be found to have lower serum γT3 and FT4 levels in early pregnancy but not in middle pregnancy.Conclusion: sFer concentration in the first trimester can affect thyroid function. The correction of invisible iron deficiency with inadequate sFer status prior to pregnancy or during early pregnancy is imperative, not only to prevent anemia, but also for maintaining optimum thyroid function and normal fetal development. For clinicians, sFer status of pregnant women should be attached great importance apart from attention to iron level.Keywords: serum ferritin, thyroid hormone, subclinical hypothyroidism, thyroid-stimulating hormone, pregnant women

Chang Tang,1,2,&ast; Lanting Wang,1,2,&ast; Zihua Chen,1,2,&ast; Jin Yang,1,2 Haiqing Gao,1,2 Chenggong Guan,1,2 Qiaozhi Gu,1,2 Shan He,1,2 Fanping Yang,1,2 Shengan Chen,1,2 Li Ma,1,2 Zhen Zhang,1,2 Ying Zhao,1,2 Lin Tang,1,2 Yu Xu,1,2 Yue Hu,3 Xiaoqun Luo1,2 1Department of Allergy & Immunology, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 2Department of Dermatology, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 3Department of Clinical Laboratory, Huashan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqun Luo, 12 Wulumuqi Zhong Road, Jing’an District, Shanghai, People’s Republic of China, Tel +86 13918825230, Email luoxiaoqun913@126.comPurpose: Several in vivo experiments have shown that molecular hydrogen is a promising therapeutic agent for interstitial lung diseases (ILD). In this study, hydrogen therapy was investigated to determine whether it is superior to N-Acetylcysteine (NAC) for the treatment of patients with early-stage ILD.Patients and Methods: A prospective, single-center, randomized, controlled clinical trial was conducted in 87 patients with early-stage ILD. Hydrogen or NAC therapy was randomly assigned (1:1 ratio) to the eligible patients. The primary endpoint was the change in the high-resolution computed tomography (HRCT) and composite physiologic index (CPI) scores from baseline to week 48. Pulmonary function was evaluated as a secondary endpoint, and adverse events were recorded for safety analysis.Results: The rate of HRCT image improvement from the baseline in the HW group (63.6%) was higher than that in the NAC group (39.5%). A significant decrease in CPI and improvement in DLCO-sb were observed in the hydrogen group compared with those in the control group. Changes in other pulmonary function parameters, including FVC, FEV1, FEV1/FVC%, and TLC, were not significantly different between the two groups. Adverse events were reported in 7 (15.9%) patients in the HW group and 10 (23.3%) patients in the NAC group, but the difference was not significant (P=0.706).Conclusion: Hydrogen therapy exhibits superior efficacy and acceptable safety compared with NAC therapy in patients with early-stage ILD.Keywords: hydrogen, N-acetylcysteine, interstitial lung disease, therapeutic effects