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Guojun Shen,1,* Xueying Li,2,3,* Anqi Zheng,2 Mingxing Gong,4 Zhanhui Wang,2 Baolin Liao5 1Hepatology Unit, the Third People′s Hospital of Jiujiang City, Jiujiang, People’s Republic of China; 2Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 3Department of Gastroenterology, Shenzhen Qianhai Taikang Hospital, Shenzhen, People’s Republic of China; 4Department of Infectious Diseases, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 5Department of Hepatology, Guangzhou Medical Research Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baolin Liao, Department of Hepatology, Guangzhou Medical Research Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, No. 8 Huaying Road, Guangzhou, 510440, People’s Republic of China, Email polinlbl@163.com Zhanhui Wang, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Blvd, Guangzhou, 510515, People’s Republic of China, Email wangzhh@smu.edu.cnBackground: Nucleos(t)ide analogues (NAs) as the first-line treatment for chronic hepatitis B (CHB) have been shown to partially restore the antiviral immunity of the patients. However, hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients have a relatively longer duration of HBV infection and lower level of HBV DNA. Whether NAs treatments have a different effect on their immune repertoires between CHB and HCC patients remains to be determined.Patients and Methods: In this study, 126 CHB patients and 85 HBV-related HCC patients who received or did not receive NAs treatment, as well as 361 healthy individuals were enrolled to analyze the effect of NAs treatment on T cell receptor β chain (TCRβ) and B cell receptor heavy chain (BCRh) repertoires in peripheral blood of the patients.Results: We found that after NAs therapy, the richness and evenness of TCRβ and BCRh repertoires in CHB patients were significantly lower than those in untreated patients and healthy controls, while the diversity of TCRβ and BCRh repertoires was stable in HCC patients. The alanine aminotransferase and HBV DNA levels were not correlated with the TCR or BCR diversity in CHB and HCC patients.Conclusion: The results suggest that NAs therapy could influence the overall T cell and B cell repertoires diversity in CHB patients but has minimal impact on HCC patients, indicating a significant difference in the potential to restore antiviral immunity between CHB and HCC patients by NAs treatment.Keywords: chronic hepatitis B, Nucleos(t)ide analogue, T cell receptor, immune repertoire, hepatocellular carcinoma

Zhuang Zhou,1 Xiaogang Zhou,1 Gang Shen,2 Ahmad Zamri Khairani,1 Jamalsafri Saibon1 1School of Educational Studies, Universiti Sains Malaysia, Penang, Malaysia; 2School of Physical Education, Changzhou University, Changzhou, People’s Republic of ChinaCorrespondence: Jamalsafri Saibon; Xiaogang Zhou, School of Educational Studies, Universiti Sains Malaysia, Penang, 11800, Malaysia, Email jamalsafri@usm.my; brucechou123456@gmail.comBackground and Objective: Bullying is notably prevalent among children and adolescents, especially within the context of physical education (PE) environments. Understanding the underlying factors that trigger bullying behavior is essential in designing strategies to prevent bullying and formulating more effective interventions in PE. There is a lack of integrated findings regarding the wide range of correlates of bullying behavior among children and adolescents within the PE context. Therefore, this systematic review aimed to synthesize the correlates of bullying behavior among children and adolescents within the context of PE.Methods: We conducted a systematic search across four databases (EBSCOhost, PubMed, Scopus, Web of Science) for relevant studies published before August 2023. Two reviewers independently examined the articles, assessed their methodological quality, and performed data extraction.Results: A total of 23 articles met the inclusion criteria. It is found that demographic, physical movement, physical appearance, psycho-cognitive, teacher-related, and contextual factors emerged as six prominent influential factors affecting adolescent bullying behavior. Specifically, demographic factors mainly encompassed age and gender; physical movement factors primarily include physical activity, sedentary behavior, physical exercise, and sports competence; physical appearance factors primarily include being overweight, too thin, too tall, or too short; psycho-cognitive factors chiefly involved cognitive empathy, motivation, enjoyment of physical activity; teacher-related factors primarily comprised activity choices, teachers competence, controlling style, autonomy support; and contextual factors primarily cover desolate climate, perceived caring climate, strong sense of competition and winning setting.Conclusion: The results indicate that bullying is a complex and multifaced behavior primarily determined by demographic, physical movement, physical appearance, psycho-cognitive, teacher-related, and contextual factors. Future studies need to enhance the diversity of research samples and comparative studies on the factors influencing bullying behavior among children and adolescents in different countries. Additionally, a more extensive range of intervention studies addressing bullying behavior among children and adolescents is warranted.Keywords: bullying behavior, physical education, children, adolescents, psycho-cognitive factors, sports competence

Hang Qiu,1 Yinghua Zhu,1 Guoqi Shen,1 Zhen Wang,1 Wenhua Li1,2 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Wenhua Li, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China, Tel +86 18052268293, Email xzwenhua0202@163.comPurpose: Development and validation of a nomogram model to predict the risk of Contrast-Induced Acute Kidney Injury (CI-AKI) after emergency percutaneous coronary intervention (PCI) in elderly patients with acute ST-segment elevation myocardial infarction (STEMI).Patients and Methods: Retrospective analysis of 542 elderly (≥ 65 years) STEMI patients undergoing emergency PCI in our hospital from January 2019 to June 2022, with all patients randomized to the training cohort (70%; n=380) and the validation cohort (30%; n=162). Univariate analysis, LASSO regression, and multivariate logistic regression analysis were used to determine independent risk factors for developing CI-AKI in elderly STEMI patients. R software is used to generate a nomogram model. The predictive power of the nomogram model was compared with the Mehran score 2. The area under the ROC curve (AUC), calibration curves, and decision curve analysis (DCA) was used to evaluate the prediction model’s discrimination, calibration, and clinical validity, respectively.Results: The nomogram model consisted of five variables: diabetes mellitus (DM), left ventricular ejection fraction (LVEF), Systemic immune-inflammatory index (SII), N-terminal pro-brain natriuretic peptide (NT-proBNP), and highly sensitive C-reactive protein(hsCRP). In the training cohort, the AUC is 0.84 (95% CI: 0.790– 0.890), and in the validation cohort, it is 0.844 (95% CI: 0.762– 0.926). The nomogram model has better predictive ability than Mehran score 2. Based on the calibration curves, the predicted and observed values of the nomogram model were in good agreement between the training and validation cohort. Decision curve analysis (DCA) and clinical impact curve showed that the nomogram prediction model has good clinical utility.Conclusion: The established nomogram model can intuitively and specifically screen high-risk groups with a high degree of discrimination and accuracy and has a specific predictive value for CI-AKI occurrence in elderly STEMI patients after PCI.Keywords: nomogram, elderly, risk prediction model, ST-segment elevation myocardial infarction, percutaneous coronary intervention, contrast-induced acute kidney injury

Yinghua Zhu,1,&ast; Haiyan He,2,&ast; Hang Qiu,1 Guoqi Shen,1 Zhen Wang,1 Wenhua Li1,3 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Cardiology, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenhua Li, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +86 18052268293, Email xzwenhua0202@163.comObjective: Our aim was to assess systemic immune-inflammation index (SII) and NT-proBNP value either in singly or in combination to predict acute ST-elevation myocardial infarction (STEMI) patient prognosis.Methods: Analyzed retrospectively the clinical features and laboratory data of STEMI confirmed patients in our hospital from January to December 2020. The levels of SII and NT-proBNP were detected. The Kaplan-Meier approach and Spearman’s rank correlation coefficient were used to construct the overall major adverse cardiac event (MACE) curve. Multivariate Cox regression analysis was applied to detect MACE predictors. In addition, the Delong test and receiver operating characteristic (ROC) curve analyzed each factor performance on its own and composite multivariate index to predict MACEs.Results: The MACE group showed statistically significant differences in SII, NT- proBNP in comparison to the non-MACE group (P=0.003, P < 0.001). Based on Kaplan-Meier analysis, SII and NT-proBNP showed positive correlation with MACE (log-rank P < 0.001). SII and NT-proBNP were independent predicting factors for long-term MACEs in multivariate Cox regression analysis (P < 0.001, HR: 2.952, 95% CI 1.565– 5.566; P < 0.001, HR: 2.112, 95% CI 1.662– 2.683). SII and NT-proBNP exhibited a positive correlation (R = 0.187, P < 0.001) in correlation analysis. According to the ROC statistical analysis, the combination exhibited 78.0% sensitivity and 88.0% specificity in the prediction of MACE. According to the results of the AUC and Delong test, the combined SII and NT-proBNP performed better as a prognostic index than each of the individual factor indexes separately (Z = 2.622, P = 0.009; Z = 3.173, P < 0.001).Conclusion: SII and NT-proBNP were independent indicators of clinical prognosis in acute STEMI patients, and they correlated positively. These factors could be combined to improve clinical prognosis.Keywords: systemic immune-inflammation index, NT-proBNP, STEMI, MACEs, risk assessment

Yanrui Liang,1,&ast; Weihong Guo,1,&ast; Chuangji Li,1,&ast; Guodong Shen,1,&ast; Haoxian Tan,2 Peiwen Sun,2 Zhian Chen,1 Huilin Huang,1 Zhenhao Li,1 Zhenyuan Li,1 Yingxin Ren,1 Guoxin Li,1 Yanfeng Hu1 1Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoxin Li; Yanfeng Hu, Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Ave, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1681 ; +86-20-6164-1682, Fax +86-20-6164-1681, Email yfenghu@qq.com; gzliguoxin@163.comPurpose: Lymphadenectomy with lymph node (LN) mapping is essential for surgical removal of solid tumors. Existing agents do not provide accurate multimodal mapping and antitumor therapy for metastatic LNs; therefore, we fabricated a polydopamine (PDA) nanoparticle (NP)-based tumor-targeted LN mapping agent capable of multimodal mapping and guided photothermal therapy (PTT) for metastatic LNs.Materials and Methods: PDA NPs modified with polyethylene glycol (PEG) were obtained by polymerization under alkaline conditions. The PEG-PDA NPs were loaded with the circular tripeptide Arg-Gly-Asp (cRGD) to achieve tumor-targeting capacity and with the fluorescent dye IR820 and magnetic resonance imaging (MRI) contrast Gd(NH2)2 for in situ detection. The resulting cRGD-PEG-PDA@IR820/Gd(NH2)2 (cRGD-PPIG) NPs were tested for their biosafety and metastatic LN mapping ability. They were drained specifically into LNs and selectively taken up by gastric MKN45 cells via αvβ 3 integrin-mediated endocytosis.Results: This phenomenon enabled MR/optical/near-infrared fluorescence multimodal metastatic LN mapping, guiding the creation of accurate and highly efficient PTT for gastric cancer metastatic LNs in mice.Conclusion: In summary, we fabricated tumor-targeted cRGD-PPIG NPs with MR/optical/near-infrared fluorescence multimodal metastatic LN mapping capacity for surgery and efficient PTT guidance post-surgery.Keywords: multimodal imaging, lymph node mapping, metastatic lymph node, photothermal therapy

Kai Ma,* Jing Li,* Guoqi Shen, Di Zheng, Yongli Xuan, Yuan Lu, Wenhua Li Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenhua Li, Tel +86 18052268293, Email xzwenhua0202@163.comObjective: To establish a nomogram model to predict the risk of contrast-induced acute kidney injury (CI-AKI) by analyzing the risk factors of CI-AKI and to evaluate its effectiveness.Methods: Retrospectively analyze the clinical data of non-ST-elevation acute coronary syndrome (NSTE-ACS) patients who underwent percutaneous coronary intervention (PCI) in our cardiology department from September 2018 to June 2021. Of these, patients who underwent PCI in an earlier period formed the training cohort (70%; n = 809) for nomogram development, and those who underwent PCI thereafter formed the validation cohort (30%; n = 347) to confirm the model’s performance. The independent risk factors of CI-AKI were determined by LASSO regression and multivariable logistic regression analysis. By using R software from which nomogram models were subsequently generated. The nomogram was developed and evaluated based on discrimination, calibration, and clinical efficacy using the concordance statistic (C-statistic), calibration plot, and decision curve analysis (DCA), respectively.Results: The nomogram consisted of six variables: age > 75, left ventricular ejection fraction, diabetes mellitus, fibrinogen-to-albumin ratio, high-sensitive C-reactive protein, and lymphocyte count. The C-index of the nomogram is 0.835 (95% CI: 0.800– 0.871) in the training cohort and 0.767 (95% CI: 0.711– 0.824) in the validation cohort, respectively. The calibration plots exhibited that the nomogram was in good agreement between prediction and observation in the training and validation cohorts. Decision curve analysis and clinical impact curve suggested that the predictive nomogram had clinical utility.Conclusion: The nomogram model established has a good degree of differentiation and accuracy, which is intuitively and individually to screen high-risk groups and has a certain predictive value for the occurrence of CI-AKI in NSTE-ACS patients after PCI.Keywords: nomogram, risk forecasting model, non-ST-elevation acute coronary syndrome, percutaneous coronary intervention, contrast-induced acute kidney injury

Guangtai Shen, 1 Xiaoqiang Yu, 1 Tianyang Sun, 1 Tian Hou, 1 Heping He, 1 Tubuxin Bai, 1 Zhipeng Zhang, 1 Xiaoli Ding, 1 Qingping Li, 2 Ying Liang, 3 Yuhua Ma 4 1Department of Breast and Thyroid Surgery, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of China; 2Department of Operating Room, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of China; 3Department of Pathology, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of China; 4Department of Anesthesiology, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of ChinaCorrespondence: Xiaoqiang YuDepartment of Breast and Thyroid Surgery, Inner Mongolia Xing’an League People’s Hospital, Ulanhot, Inner Mongolia, 137400, People’s Republic of ChinaTel/Fax +86 0482-8413761Email yuxq66_dr@163.comObjective: To verify the volume similarity between unilateral mammary gland and autologous omentum in adult females.Methods: A total of 63 patients diagnosed with stage 0–II breast cancer and partial non-lactating multi-fistula mastitis in the breast surgery department of Inner Mongolia Xing’an League People’s Hospital from 2007 to 2020 were enrolled in the study, including 52 cases of stage 0–II breast cancer and 11 cases of non-lactating multi-fistula mastitis. The volume of the resected mammary gland and the omentum were measured by a “soft tissue measuring cylinder” and recorded. The appearance of the reconstructed breast was compared with that of the healthy side. The correlation between unilateral mammary gland volume and autologous omentum volume was analyzed by linear regression.Results: Valid data were obtained for 60 cases. Affected breast size, curve, texture, nipple, and inframammary fold after omentum breast reconstruction were similar and symmetrical to those of the unaffected side. Postoperative complications occurred in most patients; the majority of these (76.67%) involved numbness of the nipple, and other complications were few. Patient satisfaction with postoperative appearance, feel, and movement of the breast, as well as total treatment costs, was over 75.0%. Linear regression analysis indicates a linear relationship between subcutaneous gland volume (x) and autologous omentum volume (y): y = 0.9847x - 1.2132, R 2 = 0.9742.Conclusion: Only when the dissociated pedicled omentum is completely obtained under laparoscopy can the whole subcutaneous residual cavity of the mammary gland be filled to the same volume. This study verifies that the volume of the unilateral mammary gland is similar to that of the autologous omentum in adult females.Keywords: unilateral mammary gland, omentum, volume, similarity, laparoscope, breast reconstruction

Chengyang Tang,1,&ast; Qiang Liu,2,&ast; Yaxuan Zhang,1 Guihu Liu,1 Guangsi Shen1 1Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Institution of Sports Medicine, Peking University Third Hospital, Beijing Key Laboratory of Sports Injuries, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangsi ShenDepartment of Orthopaedics, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of ChinaTel +86-18962113353Email shenguangsi@suda.edu.cnPurpose: Osteoarthritis (OA) is the most common chronic joint disorder in elderly individuals. This study aimed to identify immune-related diagnostic gene signatures for OA.Methods: First, we performed single-sample gene set enrichment analysis (ssGSEA) to evaluate the infiltration of immune cells in OA expression data from the Gene Expression Omnibus (GEO) database. Then, weighted gene coexpression network analysis (WGCNA) was performed to identify hub modules and genes related to immune cell types with significant infiltration. Finally, we screened diagnostic markers from the differentially expressed genes (DEGs) in both the OA group and the hub module using least absolute shrinkage and selection operator (LASSO) logistic regression.Results: Immune filtration analysis showed that immature B cells, mast cells, natural killer T cells, myeloid-derived suppressor cells (MDSCs), and type 2 T helper cells were dysregulated in OA samples. In WGCNA, a total of 120 genes were selected as hub genes associated with mast cell infiltration.The enrichment analysis showed that spliceosome, positive regulation of cell migration, and response to mechanical stimulus were mainly involved. The LASSO regression model for the GSE117999 dataset revealed 15 DEGs for predicting OA. Finally, two genes were obtained by intersection for further investigation.Conclusion: Cold-inducible RNA-binding protein (CIRBP) and transient receptor potential vanilloid 4 (TRPV4) were identified as diagnostic biomarkers for OA, and both were positively correlated with mast cell infiltration.Keywords: osteoarthritis, bioinformatics analysis, immune infiltration, WGCNA

Lisha Chi,1,&ast; Guojing Zhao,2,&ast; Naiche Chen,3,&ast; Guanghui Shen,4 Kai Huang,4 Xiaoyu Xia,1 Yijing Chen,1 Jian Liu,1 Ran Xu,5 Yanhan Chen,6 Weijie Dong,7 Jiexia Zheng8 1School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Institute of China Innovation and Entrepreneurship Education, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Renji College, Wenzhou Medical University, Wenzhou, People’s Republic of China; 4School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Department of Natural Science, Affiliated School of Wenzhou University Town, Wenzhou, People’s Republic of China; 6School of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 7The 1th School of Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China; 8Department of Student Affairs, Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiexia ZhengDepartment of Student Affairs, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of ChinaEmail zhengjiexia2021@163.comBackground: Vaccination is an effective strategy to mitigate the spread of COVID-19. This study aimed to compare predictors of vaccination intention between healthcare workers (HCWs) and non-healthcare workers (non-HCWs) in China.Methods: A web-based cross-sectional survey was conducted among HCWs and non-HCWs. Several bivariate analysis techniques, eg, crosstab with Chi-square, independent t-test and single factor ANOVA, were performed to analyze the correlation. After that, a series of multivariate binary regressions were employed to determine predictors of vaccination intention.Results: Intention was closely and significantly related with gender, perceived vaccination knowledge, perceived importance and effectiveness of vaccine to prevent COVID-19. HCWs and non-HCWs were heterogeneous, since vaccination intention, perceived knowledge, and attitudes (eg, importance, severity, risk) toward COVID-19 or vaccine had statistically significant difference between the two groups. With comparison of predictors of vaccination intention, for HCWs, demographic factors were the major predictors of COVID-19 vaccination intention. Female HCWs and HCWs with a Master’s or higher degree were more hesitant about vaccination (P = 0.01 and P < 0.001, respectively), while HCWs had greater vaccination intention as their age increased (P = 0.02). For non-HCWs, perceived vaccination knowledge was the major predictor of COVID-19 vaccination intention (P < 0.001). Additionally, perceived importance and effectiveness of vaccine were predictors for both HCWs and non-HCWs.Conclusion: Vaccination intention of HCWs was greater than that of non-HCWs in China. Measures should be taken to improve the vaccination rate based on the predictors of vaccination intention identified in this study. For HCWs, especially those with a high level of education or who were females, the safety and effectiveness of vaccines in use may reinforce their vaccination intention. For non-HCWs, popularization of general medical knowledge, including of vaccine-preventable diseases, may increase their vaccination intention.Keywords: COVID-19 vaccine, intention, predictor, HCWs, non-HCWs

Zhiquan Hu,1,&ast; Jingjing Li,2,&ast; Chunguang Yang,1 Fen Chen,3 Zhihua Wang,1 Ping Lei,4 Guanxin Shen4 1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunguang YangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan, 430030, People’s Republic of ChinaTel +86-13871084024Fax +86-27-83663460Email cgyang-hust@hotmail.comFen ChenDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaEmail 54113447@qq.comBackground: COVID-19 outbreak began in Wuhan and pandemics occur. Although SARS-CoV-2-specific immunoglobulins have been detected in serum of COVID-19 patients, their dynamics and association with outcomes have not been fully characterized.Methods: This retrospective cohort study investigated the association between SARS-CoV-2-specific immunoglobulins and clinical outcomes of COVID-19 patients. We recruited 137 participants who were diagnosed with COVID-19 in four wards of the Tongji Hospital in Wuhan, China. Among the 137 participants, 81 patients were recovered, 23 patients died, and 33 patients remained hospitalized by the end of the study. SARS-CoV-2-specific immunoglobulins were analyzed by chemiluminescence assays. Laboratory and radiological characteristics, and clinical outcomes were compared between the recovered group and the deceased group. Furthermore, a matched cohort study was conducted in which each non-survivor was matched to two recovered patients of similar age.Results: SARS-CoV-2-specific IgM levels peaked in the fourth week after the onset of COVID-19, while serum IgG levels rose earlier and remained high up to the eighth week. In the age-matched cohort study, the serum IgM, but not IgG levels, were higher among the non-survivors than in the recovered group (P = 0.006). The area under the ROC curve for the IgM and IgG levels was 0.702 (95% CI: 0.560– 0.845, P = 0.006) and 0.596 (95% confidence interval: 0.449– 0.744, P = 0.194), respectively. We also showed that patients with COVID-19 who had high IgM or IgG levels (stratified according to best cut-off) exhibited significantly lower overall survival (Kaplan–Meier survival curves, P < 0.05).Discussion: These results indicate the association between immunoglobulins and outcome in patients with COVID-19 and demonstrated that elevated serum IgM levels could indicate poor outcomes in patients with COVID-19. Further, the information about the profile of SARS-CoV-2-specific IgGs may be useful for the future epidemiological investigations of COVID-19 therapies.Keywords: SARS-CoV-2, COVID-19, immunoglobulin, prognosis, antibodies, IgM, IgG, diagnosis

Chao-lei Chen,1,* Lin Liu,1,* Jia-yi Huang,1 Yu-ling Yu,1 Geng Shen,1 Kenneth Lo,1,2 Yu-qing Huang,1 Ying-qing Feng1 1Department of Cardiology, Hypertension Research Laboratory, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, People’s Republic of China; 2Centre for Global Cardiometabolic Health, Department of Epidemiology, Brown University, Providence, RI, USA*These authors contributed equally to this workCorrespondence: Yu-qing Huang; Ying-qing Feng Department of Cardiology, Hypertension Research Laboratory, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular InstituteGuangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 106, Zhongshan Second Road, Yuexiu District, Guangzhou 510080, People’s Republic of ChinaTel/Fax +86-20-83827812Email hyq513@126.com; 651792209@qq.comPurpose: The relationship between thigh circumference and all-cause and cause-specific mortality has not been consistent. We aimed to examine how thigh circumference associates with all-cause, cardiovascular, and cerebrovascular mortality among US adults.Patients and Methods: This cohort study included 19,885 US adults who participated in the 1999– 2006 National Health and Nutrition Examination Survey (NHANES) with thigh circumference being measured at baseline, and survival status was ascertained until 31 December 2015. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for mortality according to thigh circumference in quartiles. Kaplan–Meier survival curve and restricted cubic spline regression were performed to evaluate the prospective association. Finally, subgroup analyses by age, gender, body mass index (BMI), and medical history at baseline were conducted.Results: During a median follow-up of 11.9 years, 3513 cases of death, 432 death cases due to cardiovascular disease, and 143 death cases due to cerebrovascular disease have occurred. Multivariate Cox regression indicated that every 1cm increase in thigh circumference was related to 4% and 6% decreased risk of all-cause mortality and cardiovascular mortality, respectively. Compared to the reference group, the highest quartile of thigh circumference significantly decreased all-cause mortality by 21% (HR 0.79, 95% CI 0.62– 1.00, P< 0.05). However, the association of thigh circumference with cerebrovascular mortality was not significant. BMI was a significant effect modifier among individuals with a BMI of less than 25 kg/m2 (P< 0.0001).Conclusion: A low thigh circumference appears to be associated with increased risk of all-cause and cardiovascular mortality, but not cerebrovascular mortality.Keywords: thigh circumference, all-cause mortality, cardiovascular mortality, cerebrovascular mortality

YiXuan Lin,1 Jinju Li,1 Di Wu,1 FanJing Wang,1 ZhaoHui Fang,2,3 GuoMing Shen1 1Graduate School of Anhui University of Chinese Medicine, Hefei, Anhui, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, People’s Republic of China; 3Anhui Academic of Traditional Chinese Medicine Diabetes Research Institute, Hefei, Anhui, People’s Republic of ChinaCorrespondence: ZhaoHui Fang; GuoMing Shen Tel +86-13085513100Email fangzhaohui9097@163.com; shengm_66@163.comBackground: Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases in the world with complicated pathogenesis. This study aimed to identify differentially expressed genes (DEGs) and molecular pathways in T2DM using bioinformatics analysis.Materials and Methods: To explore potential therapeutic targets for T2DM, we analyzed three microarray datasets (GSE50397, GSE38642, and GSE44035) acquired from the Gene Expression Omnibus (GEO) database. DEGs between T2DM islet and normal islet were picked out by the GEO2R tool and Venn diagram software. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) to identify the pathways and functional annotation of DEGs. Then, protein–protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes/Proteins (STRING).Results: In total, we identified 36 DEGs in the three datasets, including 32 up-regulated genes and four down-regulated genes. The improved functions and pathways of the DEGs enriched in cytokine–cytokine receptor interaction, pathways in cancer, PI3K-Akt signaling pathway, and Rheumatoid arthritis. Among them, ten hub genes with a high degree of connectivity were selected. Furthermore, via the re-analysis of DAVID, four genes (IL6, MMP3, MMP1, and IL11) were significantly enriched in the Rheumatoid arthritis pathway.Conclusion: Our study, based on the GEO database, identified four significant up-regulated DEGs and provided novel targets for diagnosis and treatment of T2DM.Keywords: bioinformatics analysis, microarray, differentially expressed genes, type 2 diabetes mellitus

Chen Xu,1,2,* Rijin Song,1,* Pei Lu,1,* Jianchun Chen,2 Yongqiang Zhou,2 Gang Shen,2 Minjun Jiang,2 Wei Zhang1 1Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Urology, Affiliated Wujiang Hospital of Nantong Univerisity, Suzhou 215200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Zhang Email weizhangsir@126.comMinjun Jiang Email 463161688@qq.comIntroduction: Poor cell uptake and incomplete intracellular drug release are the two major challenges for polymeric prodrug-based drug delivery systems (PPDDSs) in cancer treatment.Methods: Herein, a PPDDS with pH-induced surface charge-reversal and reactive oxygen species (ROS) amplification for ROS-triggered self-accelerating drug release was developed, which was formed by encapsulating a ROS generation agent (vitamin K3 (VK3)) in pH/ROS dual-sensitive polymetric prodrug (PEG-b-P(LL-g-TK-PTX)-(LL-g-DMA)) based micelle nanoparticles (denoted as PVD-NPs).Results: The surface charge of the PVD-NPs can change from negative to positive for enhanced cell uptake in response to tumor extracellular acidity pH. After internalization by cancer cells, PVD-NPs demonstrate dual drug release in response to intracellular ROS-rich conditions. In addition, the released VK3 can produce ROS under the catalysis by NAD(P)H:quinone oxidoreductase-1, which facilitates tumor-specific ROS amplification and drug release selectively in cancer cells to enhance chemotherapy.Conclusion: Both in vitro and in vivo experiments demonstrated that the PVD-NPs showed significant antitumor activity in human prostate cancer.Keywords: charge-reversal, dual-responsive, ROS generation, cancer specific chemotherapy

Ying Cui, Guihua Shen, Dan Zhou, Fengli Wu Department of Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing City 100730, People’s Republic of ChinaCorrespondence: Ying CuiDepartment of Gynecology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, No. 1 Dahua Road, Dongcheng District, Beijing City 100730, People’s Republic of China 100730 Email uvh1528@163.comIntroduction: It is known that CASC11 can promote colorectal cancer. However, the function of CASC11 in ovarian carcinoma (OC) remains elusive.Methods: In this study, we measured the expression levels of CASC11 and miR-182 in both OC and healthy control samples by performing qPCR. The interaction between CASC11 and miR-182 was analyzed by the overexpression experiment and qPCR. Cell apoptosis was analyzed by cell apoptosis assay, and the prognostic value of CASC11 for OC was analyzed by survival curve analysis.Results: We found that CASC11 and microRNA-182 (miRNA-182) were upregulated in OC. Plasma CASC11 was upregulated in OC patients and predicted early-stage OC. Follow-up study revealed that high plasma levels of CASC11 were closely correlated with poor survival conditions of OC patients. CASC11 and miRNA-182 were positively correlated in OC. Overexpression of CASC11 mediated the upregulation of miRNA-182 in cells of OC cell lines, while miRNA-182 overexpression did not significantly affect CASC11 expression. Overexpression of CASC11 and miRNA-182 promoted cancer cell proliferation and inhibited cancer cell apoptosis.Conclusion: Therefore, CASC11 overexpression predicts poor prognosis and CASC11 regulates cell proliferation and apoptosis as well as microRNA-182 expression in ovarian carcinoma.Keywords: ovarian carcinoma, CASC11, miRNA-182, proliferation, apoptosis

Chen Xu,1,* Ri-jin Song,2,* Pei Lu,2,* Jian-chun Chen,1 Yong-qiang Zhou,1 Gang Shen,1 Min-jun Jiang,1 Wei Zhang2 1Department of Urology, The First People’s Hospital of Wujiang City, Suzhou, China; 2Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China *These authors contributed equally to this work Aim: To significantly promote cancer cell uptake and to achieve combination therapy and on-demand drug release, a pH-triggered charge-switchable and redox-responsive drug-release nanovehicle was developed in this study. Materials and methods: The nanocarrier was constructed by conjugating 3,3'-dithiodipropionic acid-modified doxorubicin (DTPA-DOX) and 2,3-dimethylmaleic anhydride (DMA) to the side amino groups of poly(ethylene glycol)-b-poly(L-lysine) (PEG-b-PLL) and by encapsulating triptolide (TRI) into the hydrophobic core. The surface charge of the obtained nanocarriers (DA-ss-DT) can change from negative to positive in response to tumor extracellular acidity pH, and the nanocarriers capably release two drugs in response to intracellular high glutathione (GSH) environment. Results: Compared to the control group, the in vitro cellular uptake of DA-ss-DT by human prostate cancer PC-3 cells was significantly promoted in slightly acidic conditions, and the drug could be rapidly released in the high concentration of GSH conditions. The in vitro and in vivo antitumor experiments exhibited that the DA-ss-DT nanoparticles have a great antitumor effect in comparison to the control group. Conclusion: These findings demonstrated that the DA-ss-DT nanoparticles supply a useful strategy for promoting cellular uptake and synergetic anticancer therapy. Keywords: combination therapy, charge reversal, redox-responsive, pH-responsive

Chen Shen,1 Jun Li,1 Yi Zhang,1 Yuce Li,2 Guanxin Shen,3 Jintao Zhu,2 Juan Tao1 1Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; 2School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, China; 3Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Abstract: Vaccines have shown great success in treating and preventing tumors and infections, while adjuvants are always demanded to ensure potent immune responses. Polyethylenimine (PEI), as one of the well-studied cationic polymers, has been used as a transfection reagent for decades. However, increasing evidence has shown that PEI-based particles are also capable of acting as adjuvants. In this paper, we briefly review the physicochemical properties and the broad applications of PEI in different fields, and elaborate on the intracellular processes of PEI-based vaccines. In addition, we sum up the proof of their in vivo and clinical applications. We also highlight some mechanisms proposed for the intrinsic immunoactivation function of PEI, followed by the challenges and future perspectives of the applications of PEI in the vaccines, as well as some strategies to elicit the desirable immune responses. Keywords: cationic polymers, APCs, immunoactivation, danger signals, anti-infection, anticancer

Chunguang Yang,1,* Xueyou Ma,1,* Zhihua Wang,1 Xing Zeng,1 Zhiquan Hu,1 Zhangqun Ye,1 Guanxin Shen2 1Department of Urology, Tongji Hospital, 2Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Background: Curcumin induces apoptosis and autophagy in different cancer cells. Moreover, chemical and biological experiments have evidenced that curcumin is a biologically active iron chelator and induces cytotoxicity through iron chelation. We thus hypothesized that curcumin may induce apoptosis and autophagy in castration-resistant prostate cancer (CRPC) cells through its iron-chelating properties.Materials and methods: CRPC cells were loaded with curcumin alone or in combination with ferric ammonium citrate (FAC). Cytotoxicity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was assessed by flow cytometry, terminal deoxynucleotidyl transferase nick end labeling (TUNEL) assay and caspase activity. Autophagy status was analyzed by the detection of autophagosomes and light chain 3-II (LC3-II) using transmission electron microscopy and Western blot. Iron-binding activity of curcumin was assessed by spectrophotometry and MTT assay. The expression levels of transferrin receptor 1 (TfR1) and iron regulatory protein 1 (IRP1) were examined by Western blot.Results: Curcumin induced apoptosis and autophagy in CRPC cells. Combining curcumin with autophagy inhibitors (3-methyladenine [3-MA]) synergized the apoptotic effect of curcumin. Moreover, curcumin bound to FAC at a ratio of ~1:1, as assessed by spectrophotometry and MTT assay. Apoptosis and autophagy induced by curcumin were counteracted by equal amounts of FAC. At apoptosis- and autophagy-inducing concentrations, curcumin enhanced the expression levels of TfR1 and IRP1, indicative of iron deprivation induced by curcumin.Conclusion: Together, our results indicate that curcumin induces apoptosis and protective autophagy in CRPC cells, which are at least partially dependent on its iron-chelating properties. Keywords: curcumin, castration-resistant prostate cancer, apoptosis, autophagy, iron chelation

Zhiguo Liu,1,* Shufang Yu,1,* Di Chen,1 Guoliang Shen,1 Yu Wang,1 Leping Hou,2 Dan Lin,1 Jinsan Zhang,1 Faqing Ye1 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 2Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: FGFR1 is well known as a molecular target in anticancer drug design. TKI258 plays an important role in RTK inhibitors. Utilizing TKI258 as a lead compound that contains a quinazolinone nucleus, we synthesized four series of 3-vinyl-quinoxalin-2(1H)-one derivatives, a total of 27 compounds. We further evaluated these compounds for FGFR1 inhibition ability as well as cytotoxicity against four cancer cell lines (H460, B16-F10, Hela229, and Hct116) in vitro. Some compounds displayed good-to-excellent potency against the four tested cancer cell lines compared with TKI258. Structure–activity relationship analyses indicated that small substituents at the side chain of the 3-vinyl-quinoxalin-2(1H)-one were more effective than large substituents. Lastly, we used molecular docking to obtain further insight into the interactions between the compounds and FGFR1. Keywords: FGFR1, synthesis, quinoxaline, antitumor activity, kinase inhibitor

Xiaochen Zhang,1 Zhiyuan Zhang,1 Gang Shen,2 Jun Zhao2 1Department of Oral and Maxillofacial Surgery, 2Department of Orthodontics, College of Stomatology, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China Abstract: To enhance biocompatibility and osseointegration between titanium implants and surrounding bone tissue, numerous efforts have been made to modify the surface topography and composition of Ti implants. In this paper, Lenti-BMP-2-loaded TiO2 nanotube coatings were fabricated by lyophilization in the presence of trehalose to functionalize the surface. We characterized TiO2 nanotube layers in terms of the following: surface morphology; Lenti-BMP-2 and trehalose release; their ability to induce osteogenesis, proliferation, and anti-inflammation in vitro; and osseointegration in vivo. The anodized TiO2 nanotube surfaces exhibited an amorphous glassy matrix perpendicular to the Ti surface. Both Lenti-BMP-2 and trehalose showed sustained release over the course of 8 days. Results from real-time quantitative polymerase chain reaction studies demonstrated that lyophilized Lenti-BMP-2/TiO2 nanotubes constructed with trehalose (Lyo-Tre-Lenti-BMP-2) significantly promoted osteogenic differentiation of bone marrow stromal cells but not their proliferation. In addition, Lyo-Tre-Lenti-BMP-2 nanotubes effectively inhibited lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α production. In vivo, the formulation also promoted osseointegration. This study presents a promising new method for surface-modifying biomedical Ti-based implants to simultaneously enhance their osteogenic potential and anti-inflammatory properties, which can better satisfy clinical needs. Keywords: osteogenesis, anti-inflammation, TiO2 nanotube layers, Lenti-BMP-2, lyophilization, trehalose

The ecosystem service value on Ximen Island was calculated using the value table of ecosystem services proposed by Xie et al. according to the land use data from 2006–2017. The STIRPAT model was used to analyze the driving mechanisms of ecosystem services on Ximen Island. The results show that the ecosystem service value of Ximen Island has gradually decreased from 2006 to 2017, and the value of ecosystem services has decreased by 15.842 million Yuan over 10 years. Applying the principal component analysis method can effectively eliminate the collinearity problem in the process of regression analysis. The value of ecosystem services has a high correlation with socio-economic variables. The total population, GDP per capita, the increased rate of forestry output, the proportion of primary industry, and the Engel coefficient are all important driving factors that affect the change of valuable ecosystem services on Ximen Island. Among them, the proportion of primary industry is positive, and the other 4 indicators are negative. The rate of increase in forestry output has the greatest negative impact. A 1% increase in the total population, in the GDP per capita, in the rate of forestry output, in the proportion of primary industry, and in the Engel coefficient results in ecosystem service values varying by 0.199%, 0.165%, 0.289%, -0.144%, and 0.252%, respectively.

Background: In Australia, the profession of pharmacy has undergone many changes to adapt to the needs of the community. In recent years, concerns have been raised with evidence emerging of workforce saturation in traditional pharmacy practice sectors. It is not known how current final year pharmacy students’ perceive the different pharmacy career paths in this changing environment. Hence investigating students’ current experiences with their pharmacy course, interaction with the profession and developing an understanding of their career intentions would be an important step, as these students would make up a large proportion of future pharmacy workforce Objective: The objective of this study was thus to investigate final year students’ career perspectives and the reasons for choosing pharmacy, satisfaction with this choice of pharmacy as a tertiary course and a possible future career, factors affecting satisfaction and intention of future career paths. Methods: A quantitative cross sectional survey of final year students from 3 Australian universities followed by a qualitative semi-structured interview of a convenience sample of final year students from the University of Sydney. Results: ‘Interest in health and medicine’ was the most important reason for choosing pharmacy (n=238). The majority of students were ‘somewhat satisfied’ with the choice of pharmacy (35.7%) as a course and possible future career. Positive associations were found between satisfaction and reasons for joining pharmacy such as ‘felt pharmacy is a good profession’ (p=0.003) while negative associations included ‘joined pharmacy as a gateway to medicine or dentistry’ (p=0.001). Quantitate and qualitative results showed the most frequent perception of community pharmacy was ‘changing’ while hospital and pharmaceutical industry was described as ‘competitive’ and ‘research’ respectively. The highest career intention was community followed by hospital pharmacy. Conclusion: Complex factors including university experiences are involved in shaping students’ satisfaction and perception of career. This may relate to challenges in the community pharmacy sector, job opportunities in hospital and limited understanding of the pharmaceutical industry. The results offer insight for the profession in terms of entry into various roles and also to pharmacy educators for their roles in shaping curricula and placement experiences that attract future graduates to defined career pathways in pharmacy.

In smart warehouses, logistics robots need to continuously execute tasks, and therefore traditional onetime multi-robot path planning cannot meet practical needs. To address this challenge, we proposed Prejudgment Conflicts Search (SPC) algorithm. The SPC algorithm is divided into two layers: the higher layer allocates tasks to robots based on priority rules, and the lower layer plans paths for these robots with an improved A* algorithm, which includes vertex and edge collision checks during path searching and effectively prevents collisions among robots. We simulated SPC and Conflict-Based Search (CBS) on random maps and warehouse maps. The results show that compared to CBS, SPC provides nearly optimal paths with a significantly reduced computation time. Additionally, as the number of robots increases, SPC exhibits better scalability, offering a practical solution for continuous multi-robot path planning in smart warehouses, with the potential to enhance logistics efficiency. [ABSTRACT FROM AUTHOR]