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Juan Gao,1 Jianyi Li,2,3 Yuqing Geng,1 Yan Yan1 1School of Business, Shanghai Dianji University, Shanghai, People’s Republic of China; 2Nursing Department, Guizhou Nursing Vocational College, Guizhou, People’s Republic of China; 3Institute of Innovative Development, Shanghai Dianji University, Shanghai, People’s Republic of ChinaCorrespondence: Jianyi Li, Email lijianyikf@foxmail.comAbstract: This study offers new insights into college students’ health education (CSHE) regarding its research status, hot spots, and trends by conducting a comprehensive bibliometric analysis of this field in the past decade (2014 to 2024). Specifically, we analyzed publication trends and used the bibliometric method with CiteSpace software to explore collaborative networks, detailed co-citation status, and co-occurrence dynamics based on 1358 Web of Science Core Collection articles. Our results indicate increased relevant publications and the collaboration networks show complex institutional and regional partnerships. At the same time, co-citation and co-occurrence analyses highlight interdisciplinary research themes that encompass public health. The study particularly underscores the emerging importance of mental health, global health, and innovative educational approaches. These findings reveal trends in CSHE research and provide crucial insights for future studies, stressing the need for interdisciplinary collaboration and creative strategies to tackle student health challenges. Moreover, in practice, this study contributes to promoting and practicing targeted health intervention policies and countermeasures aimed at enhancing student well-being, such as establishing dedicated health education courses, providing specialized training for teachers, conducting regular health assessments, and providing funding for CSHE.Keywords: college student, health education, global health, CiteSpace, systematic review

Yashi Ruan,1,* Lixia Guan,2,* Yuting Wang,2 Yifei Geng,2 Xiaoran Wang,2 Miao-Miao Niu,2 Li Yang,1 Cen Xu,1 Zhen Xu1 1Department of Urology, Reproductive Medicine and Oncology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, 225300, People’s Republic of China; 2Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Yang; Cen Xu, Department of Urology, Reproductive Medicine and Oncology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, 225300, People’s Republic of China, Email proyangli@163.com; cenxu263128@163.comPurpose: Dual inhibition of ataxia telangiectasia mutated (ATM) and histone deacetylase 2 (HDAC2) may be a potential strategy to improve antitumor efficacy in testicular cancer.Methods: A combined virtual screening protocol including pharmacophore modeling and molecular docking was used for screening potent dual-target ATM/HDAC2 inhibitors. In order to obtain the optimal lead compound, the dual ATM/HDAC2 inhibitory activity of the screened compounds was further evaluated using enzyme inhibition methods. The binding stability of the optimal compound to the dual targets was verified by molecular dynamics (MD) simulation. MTT assay and in vivo antitumor experiment were performed to validate antitumor efficacy of the optimal compound in testicular cancer.Results: Here, we successfully discovered six potent dual-target ATM/HDAC2 inhibitors (AMHs 1– 6), which exhibited good inhibitory activity against both ATM and HDAC2. Among them, AMH-4 showed strong inhibitory activity against both ATM (IC50 = 1.12 ± 0.03 nM) and HDAC2 (IC50 = 3.04 ± 0.08 nM). MD simulation indicated that AMH-4 binds to ATM and HDAC2 with satisfactory stability. Importantly, AMH-4 had significant antiproliferative activity on human testicular tumor cells, especially NTERA-2 cL.D1 cells, and no inhibitory effect on normal human testicular cells. In vivo experiments exhibited that AMH-4 was more effective than lartesertib and vorinostat in inhibiting the growth of NTERA-2 cL.D1 xenograft tumors with low toxicity.Conclusion: Overall, these results suggest that AMH-4 is an effective and low toxicity candidate for the treatment of testicular germ cell tumors.Keywords: ataxia telangiectasia mutated, histone deacetylase 2, dual-targeting inhibitors, testicular germ cell tumors, structure-based virtual screening

Shaoqiu Zhang,1,&ast; Qun Zhang,2,&ast; Jian Wang,1,3,&ast; Yifan Pan,4 Zhiyi Zhang,5 Yu Geng,1 Bei Jia,1 Bing Tian,2 Yali Xiong,1 Xiaomin Yan,1 Jie Li,1,3– 5 Huali Wang,6 Rui Huang,1,3– 5 Chao Wu1,3– 5 1Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Infectious Diseases, Affiliated Zhongda Hospital of Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of General Practice, Nanjing Second Hospital, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Wu; Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-25-83105890, Fax +86-25-83307115, Email dr.wu@nju.edu.cn; doctor_hr@126.comBackground: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease with high mortality rate. This study aimed to investigate the association of red blood cell distribution width (RDW) and mortality risk in hospitalized SFTS patients.Methods: Clinical data of SFTS patients was retrospectively collected from three hospitals between October 2010 and August 2022. Cox proportional hazards model was used to identity the risk factors for fatal outcome. The predictive value of RDW for fatal outcome was evaluated by the receiver operating characteristic (ROC) analysis and Kaplan–Meier methods.Results: Of 292 patients, the median age was 61.5 years. Non-survivors showed higher RDW value than survivors (13.6% vs.13.0%, P < 0.001). The mortality rate was 44.8% in patients with elevated RDW compared to 18.4% of patients with normal RDW, with a relative risk (RR) of 2.439. Elevated RDW was an independent risk factor of mortality (hazards ratio: 1.167, P = 0.019). Patients with elevated RDW had a higher cumulative mortality than patients with normal RDW. The area under the ROC curve (AUC) of RDW for the prediction of mortality was 0.690 (P < 0.001).Conclusion: Elevated RDW was associated with higher mortality risk for patients hospitalized for SFTS. RDW may be helpful for risk stratification in SFTS patients.Keywords: severe fever with thrombocytopenia syndrome, red blood cell distribution width, prognosis, survival

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

Changbao Yan,1 Sheng Wang,2 Yaoguo Yang,2 Liang Zhao,1 Jie Zhang,1 Yanyang Wang,1 Dafang Liu,1 Yihe Geng,1 Zhong Chen2 1Department of Vascular Surgery, Capital Medical University Affiliated Luhe Hospital, Beijing, People’s Republic of China; 2Department of Vascular Surgery, Capital Medical University Affiliated Anzhen Hospital, Beijing, People’s Republic of ChinaCorrespondence: Zhong Chen, Tel /Fax +86-010-64456383, Email chenzhong8658@vip.sina.comAim: To evaluate the advantages and problems in the diagnosis and treatment of diabetic foot (DF) patients by analyzing the results of a 5-year follow-up of the organ system based (TOSF) treatment model.Methods: A retrospective study was conducted in 229 patients with diabetic foot. Chi-square test and rank-sum test were used to analyze the effects of patients’ general condition, behavioral and nutritional status, degree of infection (inflammatory markers), comorbidity, diabetic foot grade/classification, and revascularization on readmission rate, amputation rate, all-cause mortality, incidence of other complications, and wound healing time. Logistic regression was used to analyze the risk factors affecting the prognosis of diabetic foot. Kaplan-Meier survival curve was used to analyze the differences in amputation rate and mortality rate at each time point.Results: This study showed that nutritional status, degree of infection, and revascularization influenced readmission rates. General condition, behavior and nutritional status, degree of infection, Wagner grade and revascularization affect the amputation rate. General conditions, behavioral and nutritional status, degree of infection, comorbidities, classification and revascularization affect the mortality of patients. Age and white blood cell(WBC) count affected the incidence of other complications. Influence of infection degree and Wagner grade and revascularization in patients with wound healing time. Revascularization was an independent protective factor for readmission, amputation, and mortality.Elevated serum inflammatory markers are an independent risk factor for amputation. Hypoproteinemia is an independent risk factor for mortality.Conclusion: In the “TOSF” diagnosis and treatment pattern, diabetic foot patients have a good prognosis. Special attention should be paid to the screening and revascularization of lower extremity vascular disease in patients with diabetic foot.Keywords: diabetic foot, organ system, revascularization

Yimeng Geng,1,&ast; Peifen Zhang,1,&ast; Yanmeng Pan,1,&ast; Huaizhi Wang,2 Yi Chen,1 Jianbo Lai,1,3,4 Shaohua Hu1– 4 1Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Department of Psychiatry, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, 310003, People’s Republic of China; 4Brain Research Institute of Zhejiang University, Hangzhou, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaohua Hu, Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, The Key Laboratory of Mental Disorder’s Management, Brain Research Institute of Zhejiang University, Hangzhou, 310003, People’s Republic of China, Email dorhushaohua@zju.edu.cnPurpose: Venous thromboembolism (VTE) poses a significant threat to individuals’ health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE.Methods: We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings.Results: A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 μg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05).Conclusion: Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.Keywords: asymptomatic thromboembolism, D-dimer, psychiatric disorder, risk factors

The AR5 was published in 2014. The Paris Agreement and the 17 Sustainable Development Goals (SDGs) were adopted in 2015.An increasing number of countries have since announced ambitions to be carbon neutral by 2045–2060. The COVID-19 pandemic shocked the global economy in 2020 and motivated economic stimulus with demands for green recovery and concerns for economic security. All this has created a new context and a growing recognition that all industry, including the energy and emissions intensive industries, need to reach net zero GHG emissions. There is an ongoing mind shift around the opportunities to do so, with electrification and hydrogen emerging among key mitigation options as a result of renewable electricity costs falling rapidly. On the demand side there has been renewed attention to end-use demand, material efficiency, and more and better-quality recycling measures. This chapter takes its starting point in this new context and emphasises the need for deploying innovative processes and practices in order to limit the global warming to 1.5°C or 2°C (IPCC 2018a).

Yuhui Geng,1,&ast; Furong Li,2,&ast; Chen Chen,3 Zhuo Liu,1 Xiaojuan Ma,1 Xinya Su,1 Hua Meng,1 Wenwen Lu,1 Xingtian Wang,1 Dongfeng Pan,4 Peifeng Liang5 1School of Public Health, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Clinical Laboratory, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 3Department of Public Health, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 4Department of Emergency Medicine, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China; 5Department of Medical Records and Statistics, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peifeng Liang, Department of Medical Records and Statistics, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China, Tel +86 951 13895085519, Email doctor_pf@126.comPurpose: To investigate changes in the incidence of infections by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and analyzed whether there was an association between endogenous changes in the organism due to COVID-19 infection and the infections by ESBL-E.Patients and Methods: The study was a single-center retrospective case-control design. A total of 107 patients infected by ESBL-E during the COVID-19 pandemic were selected as the case group, while 214 uninfected patients selected by 1:2 propensity score matching (PSM) acted as the control group. Univariate analysis, LASSO logistic regression, and multivariate logistic regression were used to determine the risk factors for ESBL-E infection. An interrupted time series was used to analyze the changes in the incidence of ESBL-E infections in hospitalized patients during the COVID-19 pandemic.Results: The incidence of infection with ESBL-E showed a significant increase during COVID-19 (3.42 vs 4.92 per 1000 patients, p = 0.003). The incidence of ESBL-E infections increased at an average rate of 0.45 per 1000 patients per week compared to the pre-pandemic period (p = 0.022). Multivariate logistic regression analysis showed that a length of hospitalization ≥ 15 days (OR: 2.98 (1.07– 8.28), chronic kidney disease (OR: 4.25 (1.32– 13.70), white blood cell (WBC) > 9.5× 10^9/L (OR: 3.04 (1.54– 6.01), use of hormonal drugs (OR: 2.38 (1.04– 5.43), antibacterial drug use 1 type (OR: 5.38 (2.04– 14.21), antibacterial drug use 2 types (OR: 23.05 (6.71– 79.25) and antibacterial drug use ≥ 3 types (OR: 88.35 (8.55– 912.63) were independent risk factors for infection with ESBL-E, while chronic obstructive pulmonary disease (COPD) was a protective factor (OR: 0.14 (0.03– 0.66). COVID-19 was not an independent risk factor for infection by ESBL-E.Conclusion: During the COVID-19 pandemic, the incidence of infections by ESBL-E increased significantly. Increased exposure to traditional risk factors were the main reasons, however, COVID-19 was not an independent risk factor for ESBL-E infection.Keywords: β-lactamases, COVID-19, risk factor, antibacterial drugs, case-control study, LASSO

Yi Geng,1 Yu-Jie Sun,1 Hao Song,1 Qiu-Ju Miao,1 Yi-Fei Wang,1 Jin-Liang Qi,2 Xiu-Lian Xu,1 Jian-Fang Sun1 1Institute of Dermatology, Peking Union Medical College and Chinese Academy of Medical Sciences, Nanjing, 210042, People’s Republic of China; 2State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, People’s Republic of ChinaCorrespondence: Xiu-Lian Xu; Jian-Fang Sun, Email xxlqjl@sina.com; fangmin5758@aliyun.comBackground: Skin cutaneous melanoma (SKCM) is the deadliest dermatology tumor. Ongoing researches have confirmed that the NOD-like receptors (NLRs) family are crucial in driving carcinogenesis. However, the function of NLRs signaling pathway-related genes in SKCM remains unclear.Objective: To establish and identify an NLRs-related prognostic signature and to explore its predictive power for heterogeneous immune response in SKCM patients.Methods: Establishment of the predictive signature using the NLRs-related genes by least absolute shrinkage and selection operator-Cox regression analysis (LASSO-COX algorithm). Through univariate and multivariate COX analyses, NLRs signature’s independent predictive effectiveness was proven. CIBERSORT examined the comparative infiltration ratios of 22 distinct types of immune cells. RT-qPCR and immunohistochemistry implemented expression validation for critical NLRs-related prognostic genes in clinical samples.Results: The prognostic signature, including 7 genes, was obtained by the LASSO-Cox algorithm. In TCGA and validation cohorts, SKCM patients with higher risk scores had remarkably poorer overall survival. The independent predictive role of this signature was confirmed by multivariate Cox analysis. Additionally, a graphic nomogram demonstrated that the risk score of the NLRs signature has high predictive accuracy. SKCM patients in the low-risk group revealed a distinct immune microenvironment characterized by the significantly activated inflammatory response, interferon-α/γ response, and complement pathways. Indeed, several anti-tumor immune cell types were significantly accumulated in the low-risk group, including M1 macrophage, CD8 T cell, and activated NK cell. It is worth noting that our NLRs prognostic signature could serve as one of the promising biomarkers for predicting response rates to immune checkpoint blockade (ICB) therapy. Furthermore, the results of expression validation (RT-qPCR and IHC) were consistent with the previous analysis.Conclusion: A promising NLRs signature with excellent predictive efficacy for SKCM was developed.Keywords: cutaneous melanoma, NLR proteins, immune, survival analysis, prognosis

Yunbo Chen,1,2 Yuanyuan Dai,3 Yizheng Zhou,4 Ying Huang,5 Yan Jin,6 Yan Geng,7 Bing Ji,8 Rong Xu,9 Wencheng Zhu,10 Shuyan Hu,11 Zhuo Li,12 Jinhua Liang,13 Yonghong Xiao1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China; 3Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 4Clinical Laboratory, Jingzhou Central Hospital, Jingzhou, People’s Republic of China; 5Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Clinical Laboratory, Shandong Provincial Hospital, Jinan, People’s Republic of China; 7Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 8Clinical Laboratory, Affiliated Hospital of Binzhou Medical College, Binzhou, People’s Republic of China; 9Clinical Laboratory, People’s Hospital of Yichun City, Yichun, People’s Republic of China; 10Clinical Laboratory, Lu’an Civil Hospital, Lu’an, People’s Republic of China; 11Clinical Laboratory, People’s Hospital of Qingyang, Qingyang, People’s Republic of China; 12Clinical Laboratory, The First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 13Clinical Laboratory, The Affiliated Hongqi Hospital of Mudanjiang Medicine College, Mudanjiang, People’s Republic of ChinaCorrespondence: Yonghong Xiao, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel/Fax +86 571 87236421, Email xiao-yonghong@163.comPurpose: Blood cultures (BCs) are essential laboratory tests for diagnosing blood stream infections. BC diagnostic improvement depends on several factors during the preanalytical phase outside of innovative technologies. In order to evaluate the impact of an educational program on BC quality improvement, a total of 11 hospitals across China were included from June 1st 2020 to January 31st 2021.Methods: Each hospital recruited 3 to 4 wards to participate. The project was divided into three different periods, pre-implementation (baseline), implementation (educational activities administered to the medical staff) and post-implementation (experimental group). The educational program was led by hospital microbiologists and included professional presentations, morning meetings, academic salons, seminars, posters and procedural feedback.Results: The total number of valid BC case report forms was 6299, including 2739 sets during the pre-implementation period and 3560 sets during the post-implementation period. Compared with the pre-implementation period, some indicators, such as the proportion of patients who had 2 sets or more, volume of blood cultured, and BC sets per 1000 patient days, were improved in the post-implementation period (61.2% vs 49.8%, 18.56 vs 16.09 sets, and 8.0 vs 9.0mL). While BC positivity and contamination rates did not change following the educational intervention (10.44% vs 11.97%, 1.86% vs 1.94%, respectively), the proportion of coagulase negative staphylococci-positive samples decreased in BSI patients (6.87% vs 4.28%).Conclusion: Therefore, medical staff education can improve BC quality, especially increasing volume of blood cultured as the most important variable to determine BC positivity, which may lead to improved BSI diagnosis.Keywords: blood culture, bloodstream infection, medical education, medical staff, quality improvement

Qingsong Li,1– 3,&ast; Cheng Hu,1– 3,&ast; Shengfa Su,1– 3 Zhu Ma,1,2 Yichao Geng,1– 3 Yinxiang Hu,1– 3 Huiqin Li,1,2 Bing Lu1– 3 1Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Thoracic Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3Teaching and Research Department of Oncology, Clinical Medical College of Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Lu, Department of Thoracic Oncology, Affiliated Hospital of Guizhou Medical University and Affiliated Cancer Hospital of Guizhou Medical University, 1 Beijing Road West, Guiyang, 550004, People’s Republic of China, Tel +86-851-86513076, Email lbgymaaaa@163.comPurpose: The impact of primary tumour radiotherapy on the prognosis for non-small-cell lung cancer (NSCLC) with controlled malignant pleural effusion (MPE-C) (MPE-C-NSCLC) is unclear. This study aimed to analyze the efficacy and safety of primary tumor radiotherapy in patients with MPE-C-NSCLC.Patients and Methods: A total of 186 patients with MPE-C-NSCLC were enrolled and divided into two groups. The patients in the D group were treated with only drugs. Those in the RD group were treated with drugs plus primary tumour radiotherapy. The Kaplan-Meier method was used for survival analysis, and the Log rank test was used for between-group analysis and univariate prognostic analysis. The Cox proportional hazards model was used to perform multivariate analyses to assess the impacts of factors on survival. Propensity score matching (PSM) was matched based on clinical characteristics, systematic drug treatment and drug response to further adjust for confounding factors.Results: The overall survival (OS) rates at 1, 2, and 3 years for the RD group and D group were 54.4%, 26.8%, and 13.3% and 31.1%, 11.5%, and 4.4%, respectively; the corresponding MSTs were 14 months and 8 months, respectively (χ2=15.915, p< 0.001). There was a significant difference in survival by PSM (p=0.027).Before PSM, multivariate analysis showed that metastasis status (organ≤ 3 and metastasis≤ 5), primary tumour radiotherapy, chemotherapy cycles≥ 4, and drug best response (CR+PR) were independent predictors of prolonged OS. After PSM, primary tumour radiotherapy and drug best response (CR+PR) were independent predictors of prolonged OS were still independent predictors of prolonged OS. There were no grade 4– 5 radiation toxicities.Conclusion: For MPE-C-NSCLC, the response of systemic drug treatment plays a crucial role in survival outcomes, and we also should pay attention to primary tumour radiotherapy in addition to systematic drug treatment.Keywords: non-small cell lung cancer, controlled malignant pleural effusion, radiotherapy, overall survival, prognosis

Jie Bai,1– 3,&ast; Bibo Wu,1– 3,&ast; Shasha Zhao,1– 3,&ast; Gang Wang,1– 3,&ast; Shengfa Su,1– 3 Bing Lu,1– 3 Yinxiang Hu,1– 3 Yichao Geng,1,3 Zhengneng Guo,1– 3 Jun Wan,2,3 Weiwei OuYang,1– 3 Cheng Hu,1– 3 Jie Liu1– 3 1Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengfa Su, Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China, Tel +8613608550432, Fax +86513076, Email sushengfa2005@163.comPurpose: To explore the effect of PD-1 inhibitors combined with irradiation on myocardial injury and the changes of HMGB1-associated inflammatory markers.Methods: Four groups of five mice were used, each groupformed by randomly dividing 20 mice (group A control; group B PD-1 inhibitors; group C Irradiation; group D PD-1 inhibitors+irradiation; n = 5 for each). The mice were treated with either PD-1 inhibitors or a 15 Gy dose of single heart irradiation, or both. Hematoxylin-eosin staining assessed the morphology and pathology of heart tissue; Masson staining assessed heart fibrosis; Tunel staining evaluated heart apoptosis; flow cytometry detected CD3+, CD4+, and CD8+ T lymphocytes in heart tissues; enzyme linked immunosorbent assay evaluated IL-1β, IL-6, and TNF-ɑ of heart tissue; Western blot and quantitative real-time PCR (qPCR) detected the expression of protein and mRNA of HMGB1, TLR-4, and NF-κB p65 respectively.Results: The degree of heart injury, collagen volume fraction (CVF) and apoptotic index (AI) in groups B, C, and D were higher than group A, but the differences between the CVF and AI of group A and group B were not statistical significance (P> 0.05). Similarly, the absolute counts and relative percentage of CD3+ and CD8+ T lymphocytes and the concentrations of IL-1β, IL-6, and TNF-α in heart tissue with group D were significantly higher than the other groups (P< 0.05). In addition, compared with group A, the expression of protein and mRNA of HMGB1 and NF-κB p65 in other groups were higher, and the differences between each group were statistically significant while TLR4 was not. In addition, interaction by PD-1 inhibitors and irradiation was found in inflammatory indicators, especially in the expression of the HMGB1 and CD8+ T lymphocytes.Conclusion: PD-1 inhibitors can increase the expression of HMGB1-associated inflammatory cytokines and aggravate radiation-induced myocardial injury.Keywords: HMGB1, PD-1 inhibitors, radiotherapy, heart injury

BackgroundTreatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries.Patients and methodsIn this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation.ResultsA total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (

Yi Xiong,1 Ye He,2 Yan Peng,3 Yun Geng4 1Department of Orthopaedic, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei, People’s Republic of China; 2Department of Preventive Treatment of Diseases,Shaanxi Meixian Hospital of Traditional Chinese Medicine, Shaanxi, People’s Republic of China; 3Department of Medical Examination, Yili Kazak Autonomous Prefecture Hospital of Traditional Chinese Medicine, Xinjiang, People’s Republic of China; 4Department of Pharmacology, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong, People’s Republic of ChinaCorrespondence: Yun Geng, Tel/Fax +86-531-59556066, Email gengyunsd@163.comPurpose: Osteoporotic vertebral compression fracture (OVCF) is a common disease in the elderly, and genetic factors play a key role in its occurrence. The present study was conducted to investigate the association between interleukin-6 (IL-6) and the transforming growth factor (TGF-β) gene polymorphisms and the occurrence of thoracolumbar OVCF.Patients and Methods: This case–control study recruited 146 patients with OVCF and 144 osteoporosis patients as the control group. Genotypes of the IL-6 rs1800796 and TGF-β rs1982073 were analyzed by sequencing. Genotype distribution and allelic frequencies were investigated by the χ2 test. Odds ratios (OR) and 95% confidence intervals (CI) evaluated the relationship of IL-6 or TGF-β polymorphism and OVCF susceptibility.Results: Allele G and genotype GG of IL-6 rs1800796 was more frequent in patients with OVCF (40.07% vs.28.47%; 19.18% vs.7.64%) compared with controls. GG genotype (OR=3.394, 95% CI=1.560– 7.385, P < 0.001) and G allele (OR=1.680, 95% CI=1.187– 2.376, P < 0.001) of IL-6 rs1800796 was significantly associated with increased risk of OVCF. What is more, CT and TT genotypes (41.78 vs.51.39; 19.86 vs.26.39) and allele T (40.75 vs 52.08) of TGF-β rs1982073 were less frequent in OVCFs, more common in controls and protective against OVCF risk (OR=0.436, 95% CI=0.228– 0.835, P = 0.012; OR=0.615, 95% CI=0.443– 0.855, P = 0.004).Conclusion: Our results suggest that the G allele and GG genotype of IL-6 rs1800796 may contribute to increased susceptibility to OVCF in elderly Chinese. In contrast, CT and TT genotypes and the T allele of TGF-β rs1982073 may contribute to lower susceptibility of OVCF.Keywords: OVCF, IL-6, TGF-β, gene polymorphisms

Xin He,1 Jiping Sun,2 Chao Liu,2 Xiaoyang Yu,2 Huixian Li,2 Wenjing Zhang,2 Yan Li,2 Yingzhou Geng,2 Zhigang Wang2 1Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Department of Nephrology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaCorrespondence: Zhigang Wang, First Affiliated Hospital of Xi’an Jiaotong University, West Yanta Road 277, Xi’an, 710061, People’s Republic of China, Email wangzhigang2017@xjtu.edu.cnPurpose: Emerging evidence has revealed that gut microbiota plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). However, few studies have used metagenomic sequencing to analyze the alterations of gut microbiota community in patients with early-stage DKD.Methods: We carried out metagenomic sequencing in fecal samples of 10 DKD patients (DKD group) and 10 T2DM patients who appeared to be less prone to DKD (non-DKD group), aiming to compare the composition and function of gut microbiota between the DKD and non-DKD groups.Results: The gut microbial community of the DKD group was significantly different from that of the non-DKD group, characterized by a marked increase in phylum Proteobacteria, genus Selenomonadales, Neosynechococcus, Shigella, Bilophila, Acidaminococcus, species, Escherichia coli, Bacteroides plebeius, Megasphaera elsdenii, Acidaminococcus unclassified, and Bilophila wadsworthia. The amounts of species Citrobacter farmeri and Syntrophaceticus schinkii were significantly and positively correlated with the urinary albumin creatinine ratio in the DKD group. Furthermore, functional analysis based on dbCAN and KEGG databases showed aberrant lipopolysaccharide (LPS) biosynthesis and carbohydrate metabolism in the gut microbiome of the DKD group.Conclusion: Our findings provided evidence for alterations in the composition and function of gut microbiota in patients with DKD versus the non-DKD group. These data may contribute to a more comprehensive understanding of the pathological mechanisms of DKD.Keywords: diabetic kidney disease, gut microbiota, metagenomics, type 2 diabetes mellitus

Model performance has been significantly enhanced by channel attention. The average pooling procedure creates skewness, lowering the performance of the network architecture. In the channel attention approach, average pooling is used to collect feature information to provide representative values. By leveraging the central limit theorem, we hypothesize that the strip-shaped average pooling operation will generate a one-dimensional tensor by considering the spatial position information of the feature map. The resulting tensor, obtained through average pooling, serves as the representative value for the features, mitigating skewness during the process. By incorporating the concept of the central limit theorem into the channel attention operation process, this study introduces a novel attention mechanism known as the "Central Attention Mechanism (CAM)." Instead of directly using average pooling to generate channel representative values, the central attention approach employs star-stripe average pooling to normalize multiple feature representative values into a single representative value. In this way, strip-shaped average pooling can be utilized to collect data and generate a one-dimensional tensor, while star-stripe average pooling can provide feature representative values based on different spatial directions. To generate channel attention for the complementary input features, the activation of the feature representation value is performed for each channel. Our attention approach is flexible and can be seamlessly incorporated into various traditional network structures. Through rigorous testing, we demonstrate the effectiveness of our attention strategy, which can be applied to a wide range of computer vision applications and outperforms previous attention techniques. [ABSTRACT FROM AUTHOR]

In recent years, remote sensing object detection has become a research hotspot in computer vision tasks. However, previous approaches for remote sensing object detection often overlook the rich contextual information in images, which is crucial for accurately detecting occluded or interconnected objects using convolutional neural networks. To capture this contextual information, we propose a method called the Large Kernel Disassembling (LKD) Attention Mechanism. LKD breaks down large convolutional kernels to provide a larger receptive field to the convolutional neural networks, enabling them to capture rich contextual information in remote sensing images and enhance their performance. We employ an adaptive channel submodule and a deep convolutional spatial submodule. The adaptive channel submodule helps the network learn relationships between different channels, while the deep convolutional spatial submodule aids in extracting rich spatial features. We evaluate the proposed attention mechanism on the DIOR dataset and compare it with several recent attention mechanisms on the SSDD dataset. Experimental results demonstrate the superiority of LKD in terms of performance over other methods, validating the effectiveness of the Large Kernel Disassembling attention mechanism in remote sensing object detection tasks. [ABSTRACT FROM AUTHOR]

Li Xue,1 Li Tao,1 Haifeng Sun,2 Yan Wang,1 Yanping Zhang,1 Na Lei,1 Zeshi Liu,1 Hua Zhang,1 Li Jin,1 Ting Zhang,1 Jing Zhang,1 Hao Meng,1 Fang Huang,1 Yan Geng,1 Ming Li3 1Department of Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 2Third Department of Medical Oncology, Shaanxi Provincial Cancer Hospital Affiliated to Medical College of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 3Department of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaCorrespondence: Yan GengDepartment of Clinical Laboratory, The Second Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaEmail gengyanjyk@126.comMing LiDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaEmail minglil@126.comBackground: Platelet (PLT) and red blood cell (RBC) have been demonstrated to play a critical role in inflammatory processes. This study aimed to evaluate the association of blood PLT and RBC related parameters with the disease activity in rheumatoid arthritis (RA) patients, and also to investigate the role of these indices in differentiating among RA patients with different disease activity.Methods: Clinical data from RA patients were retrospectively analyzed. RA patients were divided into inactive group and active group according to DAS28-CRP. The relationship between blood PLT and RBC counts-related indices and DAS28-CRP was detected by Spearman correlation. ROC curve was used to assess the diagnostic value of these indices in differentiating active RA from inactive RA.Results: Active RA patients exhibited higher level of PLT counts but significantly lower levels of RBC counts, hemoglobin (Hb), red blood cells-platelet ratio (RPR) and hemoglobin-platelet ratio (HPR) compared with inactive RA. PLT counts were positively but RBC counts, Hb, RPR and HPR were negatively related with DAS28-CRP.Conclusion: Blood PLT and RBC related indices were significantly associated with RA disease activity. These indices may be used to distinguish active RA from inactive RA.Keywords: rheumatoid arthritis, platelets, red blood cells, hemoglobin

Yichao Geng,1– 3,* Shengfa Su,2,3,* Li Cao,2,* Ting Yang,4 Weiwei Ouyang,2,3 Lingfeng Liu,2,3 Bibo Wu,2,3 Qiuning Zhang,5 Bing Lu,2,3 Xiaohu Wang1,5 1The First School of Clinical Medicine, Lanzhou University, Lanzhou, People’s Republic of China; 2Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 3Department of Oncology, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 4Department of Pathophysiology, Guizhou Medical University, Guiyang, People’s Republic of China; 5Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaohu WangThe First School of Clinical Medicine, Lanzhou University, Lanzhou, People’s Republic of China, Tel +8613909407551,Fax +86 931 5196196, Email xhwang@impcas.ac.cn; Bing Lu Department of Oncology, The Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China, Tel +8613809432527, Fax +86 851 6513076, Email lbgymaaaa@163.comPurpose: This study was designed to evaluate the effects of PD-1 inhibitor on lung tissue morphology and the immune system in a mouse model of radiation-induced lung injury (RILI) and to assess interactions between radiation therapy and PD-1 inhibition.Methods: Twenty C57BL/6 mice were divided randomly into four groups of five mice each. Mice were treated with an anti-mouse PD-1 monoclonal antibody, whole thorax irradiation, both or neither. Lung tissue morphology and pathological changes were assessed by hematoxylin-eosin staining; lung fibrosis was assessed by Masson staining and analysis of hydroxyproline; CD3+, CD4+, and CD8+ T lymphocytes in lung tissues were detected immunohistochemically; and the concentrations of transforming growth factor-β 1 (TGF-β 1) and interleukin-6 (IL-6) in lung tissue were evaluated by cytokine multiplex analysis.Results: Lung injury scores and indicators of pulmonary fibrosis were higher in mice administration whole thorax irradiation than in control mice. Inflammatory infiltrate scores, alveoli deformation scores, collagen volume fractions and hydroxyproline contents in lung tissues were all significantly higher in mice administered PD-1 inhibitor plus irradiation than in the other three groups. Similarly, the percentages of CD3+ and CD8+T cells and the concentrations of IL-6 and TGF-β 1 in lung tissue were significantly higher in mice treated with radiation and PD-1 inhibitor than in the other groups. However, PD-1 inhibitor and irradiation interacted significantly only in the elevation of TGF-β 1 level.Conclusion: Whole thorax X-ray irradiation in mice can cause pulmonary injury and fibrosis, which could be exacerbated by PD-1 inhibitors. Radiotherapy combined with PD-1 inhibitors may aggravate RILI by synergistically upregulating TGF-β 1 expression, thereby affecting the immune-inflammatory microenvironment in the lungs.Keywords: PD-1 inhibitors, radiotherapy, radiation fibrosis, lung injury, transforming growth factor-β 1

Linjue Shangguan,1,&ast; Peipei Zhang,1 Shengwei Fang,1 Kaili Xiang,1 Yawen Geng,1 Dingcun Luo,2,&ast; Chunlei Zhao1,&ast; 1Department of Nuclear Medicine, Hangzhou Cancer Hospital, Hangzhou, 310002, People’s Republic of China; 2Department of Tumor Surgery, Hangzhou First People’s Hospital, Hangzhou, 310006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunlei ZhaoDepartment of Nuclear Medicine, Hangzhou Cancer Hospital, 34 Yanguan Lane, Shangcheng District, Hangzhou, 310002, People’s Republic of ChinaEmail clzhaocl@hotmail.comDingcun LuoDepartment of Tumor Surgery, Hangzhou First People’s Hospital, 261 Huansha Road, Shangcheng District, Hangzhou, 310000, People’s Republic of ChinaEmail ldc65@163.comObjective: To investigate the relationship of BRAF mutation with the outcome of the first postoperative 131I treatment and malignant biological characteristics in papillary thyroid carcinoma (PTC).Methods: Thirty-three patients with PTC who underwent their first 131I treatment after total thyroidectomy were enrolled in this study. BRAF mutation in postoperative tumor tissue and circulating tumor DNA (ctDNA) in peripheral blood at the time of 131I treatment were detected. According to the status of BRAF mutation, all patients were divided into 2 groups in each category of tumor tissues and ctDNA, respectively: 1) BRAF mutation, 2) BRAF wild-type. The Fisher’s exact test was performed to analyze the relationship of BRAF mutation in either tumor tissue or ctDNA with the outcome of the first 131I treatment and malignant characteristics of PTC.Results: BRAF mutation was detected in tumor tissues in 25 patients (25/33,75.8%), and all the patients had single mutation site. In ctDNA, BRAF mutation was detected in 5 patients (5/33, 15.2%), and all the patients had single mutation site. In both tumor tissues and ctDNA, BRAF mutation showed no relationship with the outcome of first 131I treatment and the malignant biological characteristics (P> 0.05).Conclusion: The value of BRAF mutation alone might be limited in predicting therapeutic outcome of the first 131I treatment in PTC. No definitive relevance was found between BRAF mutation and malignant biological features in PTC.Keywords: gene mutation, BRAF, radiotherapy, papillary thyroid carcinoma

Yi Zhao,1,2 Li Zhang,1 Yarui Geng1 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, People’s Republic of China; 2Department of Drug Clinical Trials, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, People’s Republic of ChinaCorrespondence: Yi ZhaoDepartment of Drug Clinical Trials, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, People’s Republic of ChinaTel/Fax +86 571-87061501Email zhaoyi1124@zju.edu.cnObjective: This study aimed at investigating the factors influencing clinical drug trial participation by pregnant women and their spouses.Methods: This hospital-based cross-sectional study was conducted at Women’s Hospital, School of Medicine, Zhejiang University, from July to September 2020. A self-administered questionnaire was distributed to pregnant women and their spouses in the maternity ward. The questionnaire consisted of two sections: The first part was aimed at collecting demographic information data while the second part consisted of 10 open-ended questions regarding clinical drug trial knowledges, financial compensation, risk awareness, psychological impact, and pregnancy outcomes.Results: A total of 206 questionnaires (115 from pregnant women and 91 from their spouses) were included in the statistical analysis. About 50% of pregnant women and their spouses had heard of clinical trials (50.43% vs 49.45%, p=0.888). Compared to their spouses, the proportion of pregnant women who thought that there is a need for the development of drugs during pregnancy was significantly higher (94.78% vs 16.48%, p=0.008). Moreover, a significant number of full-time employed pregnant women believed that clinical drug trials will increase the possibility of disease cure, relative to part-time/not employed pregnant women (98.21% vs 88.13%, p=0.030). Spouses whose education levels were below high school and those whose education level was high school or above exhibited significant differences regarding whether financial compensation will motivate their participation in clinical trials (77.78% vs 58.90%, p=0.044). Pregnant women and their spouses had no significant differences regarding various aspects: drug treatment during pregnancy, clinical trial drugs should be free, the need to increase the protection of pregnant women in clinical trials.Conclusion: Due to fetus-associated concerns, most pregnant women are reluctant to be included in clinical trials. However, pregnant women and their spouses agree that medical treatment should be accessible for illnesses during pregnancy, and clinical drug trials during pregnancy should be performed. The usage of untested or sub-therapeutic drug regimens in clinical practice paradoxically increases the risk for fetuses. When recruiting pregnant volunteers for clinical drug trials, researchers should conduct in-depth consultations and comprehensively inform the pregnant women and their families on the pros and cons of their involvement.Keywords: pregnancy, clinical trials, drug safety, participation, attitudes

Yuanyuan Geng,1,&ast; Weiwei Wu,2,3,&ast; Rouyu Li,4– 6 Juan Xu,1 Ruixue Gu,1 Jiejie Lu,2 Wenai Zheng,7 Fei Zhao,1 Jianzhong Zhang,1 Jie Gong1 1National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China; 3National Clinical Research Center for Skin and Immune Disease, Beijing, People’s Republic of China; 4Department of Dermatology, Peking University First Hospital, Beijing, People’s Republic of China; 5Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, People’s Republic of China; 6Research Center for Medical Mycology, Peking University, Beijing, People’s Republic of China; 7Department of Laboratory Medicine, The Fifth People’s Hospital of Hainan Province, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Gong Tel +86 10 5890 0368Email gongjie@icdc.cnBackground: Founder events have been observed among numerous plants and animal species living on oceanic islands due to the geographic separation of these islands and the small amount of original life they harbor. However, there has been little research on the ecological characteristics of pathogenic microorganisms on islands. Trichophyton rubrum ranks the most common isolated dermatophyte causing dermatophytosis in clinic and has become an epidemic strain worldwide in recent decades.Objective: To study the phylogenetic characteristics and the distribution pattern of genetic polymorphism of T. rubrum in China, which further provide theoretical basis for the prevention and control of T. rubrum.Methods: In the present study, we sequenced and analyzed the genetic characteristics of 204 T. rubrum isolates from Hainan Island and other sites in China. Phylogenetic analysis and genetic polymorphisms were studied based on a total of 41,409 high-quality whole-genome SNPs.Results: The majority of the isolates from Hainan Island clustered together. Mixed T. rubrum population differentiation was observed among the strains of different geographical origins. In addition, the genetic diversity (π) of the Hainan isolates was low and showed no significant difference from that of isolates from other sites.Conclusion: This study is the first to discuss general ecological and evolutionary principles related to pathogenic fungi. Our findings reveal a founder effect during the origination of T. rubrum on Hainan Island and provide guidance regarding prevention and treatment strategies.Keywords: founder effects, Trichophyton rubrum, genetic diversity, population differentiation

Changli Tu,1,* Guojie Wang,2,* Yayuan Geng,3 Na Guo,3 Ning Cui,4 Jing Liu1 1Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China; 2Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China; 3Huiying Medical Technology Co., Ltd, Room A206, B2, Dongsheng Science and Technology Park, Beijing, People’s Republic of China; 4Medical Imaging Center, Shiyan Taihe Hospital, Shiyan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Cui; Jing LiuDepartment of Pulmonary and Critical Care Medicine (PCCM), Fifth Affiliated Hospital of Sun Yat-sen University, 52 East Meihua Road, Zhuhai, People’s Republic of ChinaTel +867562528733Email cuixitong@139.com; liujing25@mail.sysu.edu.cnBackground: Coronavirus disease 2019 (COVID-19) is a worldwide public health pandemic with a high mortality rate, among severe cases. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. It is important to ensure early detection of the virus to curb disease progression to severe COVID-19. This study aims to establish a clinical-nomogram model to predict the progression to severe COVID-19 in a timely and efficient manner.Methods: This retrospective study included 202 patients with COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University and Shiyan Taihe Hospital from January 17 to April 30, 2020. The patients were randomly assigned to the training dataset (n = 163, with 43 progressing to severe COVID-19) or the validation dataset (n = 39, with 10 progressing to severe COVID-19) at a ratio of 8:2. The optimal subset algorithm was applied to filter for the clinical factors most relevant to the disease progression. Based on these factors, the logistic regression model was fit to distinguish severe (including severe and critical cases) from non-severe (including mild and moderate cases) COVID-19. Sensitivity, specificity, and area under the curve (AUC) were calculated using the R software package to evaluate prediction performance. A clinical nomogram was established and performance assessed using the discrimination curve.Results: Risk factors, including demographic data, symptoms, laboratory and image findings, were recorded for the 202 patients. Eight of the 53 variables that were entered into the selection process were selected via the best subset algorithm to establish the predictive model; they included gender, age, BMI, CRP, D-dimer, TP, ALB, and involved-lobe. AUC, sensitivity, and specificity were 0.91, 0.84 and 0.86 for the training dataset, and 0.87, 0.66, and 0.80 for the validation dataset.Conclusion: We established an efficient and reliable clinical nomogram model which showed that gender, age, and initial indexes including BMI, CRP, D-dimer, involved-lobe, TP, and ALB could predict the risk of progression to severe COVID-19.Keywords: clinical nomogram model, COVID-19, progression risk, logistic regression

Ting Zhang,1– 4,* Chengchen Yin,1– 3,* Yongchen Geng,1– 3 Yan Zhou,1– 3 Shusen Sun,5 Fushan Tang1– 3 1Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 3The Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 4Department of Pharmacy, Guiyang Hospital of Stomatology, Guiyang 550000, People’s Republic of China; 5College of Pharmacy and Health Sciences, Western New England University, Springfield, MA 01119, USA*These authors contributed equally to this workCorrespondence: Fushan TangDepartment of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaTel/ Fax +86 851 2864 2334Email fstang@vip.163.comObjective: To set up a psychological contract scale for hospital pharmacists to strengthen the management of pharmacists and improve the occupational health of pharmacists.Methods: A psychological contract scale for hospital pharmacists with structured questionnaires was designed according to the professional characteristics of hospital pharmacists and validated through the investigation of pharmacists in 77 public medical institutions in Zunyi, China, which were included through stratified random sampling. Kaiser-Meyer-Olkin (KMO) Measure of Sampling Adequacy and Bartlett’s Test of Sphericity were used to assess the suitability of the sample for factor analysis. Validity of the dimensions was investigated with exploratory factor analysis. The principal component analysis and varimax rotation methods were used to identify the factor structure. The internal consistency was assessed by the Cronbach’s alpha coefficient.Results: The psychological contract scale for hospital pharmacists was composed of pharmacists’ perceptions regarding the hospital, pharmacists themselves, and government/society responsibility. The KMO values of the three perceptions were 0.957, 0.930 and 0.917, respectively, all greater than 0.6. The significance probability of the Bartlett spherical test was 0.000, indicating good structural validity. The Cronbach’s alpha coefficient and half coefficient of the responsibilities in three sub-scales were all greater than 0.6, indicating good internal reliability of the scale. The average scores of the pharmacist responsibility, the hospital responsibility and the government/society responsibility in the pharmacists’ perception were 5.42± 0.637, 4.64± 1.069 and 4.49± 1.134, respectively. In the pharmacists’ perception, their own responsibility has been better fulfilled than those of hospitals and government/society.Conclusion: The psychological contract scale for hospital pharmacists can be a useful tool to evaluate the psychological contract of hospital pharmacists for research and occupational health assessments and management in the area of hospital pharmacy.Keywords: pharmacist, psychological contract, questionnaire

Jin Wang,1,2 Ye Qian,2 Xuemin Gao,3 Na Mao,3 Yucong Geng,4 Gaojie Lin,3 Guibin Zhang,2 Han Li,3 Fang Yang,3 Hong Xu3 1Department of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai 201700, People’s Republic of China; 2Hebei Key Laboratory for Chronic Diseases, Tangshan Key Laboratory for Preclinical and Basic Research on Chronic Diseases, School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, People’s Republic of China; 3Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, Hebei 063210, People’s Republic of China; 4Department of Pathology, Haigang Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Hong XuMedical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, Hebei 063210, People’s Republic of ChinaTel +86-315-8816236Fax +86-315-8816238; Email xuhong@ncst.edu.cnBackground: N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a short peptide with an anti-silicosis effect. However, the short biological half-life and low plasma concentration of Ac-SDKP hamper discovery of specific targets in organisms and reduce the anti-silicosis effect. A novel peptide, Ac-SDK (biotin) proline, termed “Ac-B”, with anti-fibrotic properties was synthesized.Methods: Ac-B was detected quantitatively by high-performance liquid chromatography. Phagocytosis of Ac-B by the alveolar epithelial cell line A549 was investigated by confocal laser scanning microscopy and flow cytometry. To further elucidate the cellular-uptake mechanism of Ac-B, chemical inhibitors of specific uptake pathways were used. After stimulation with transforming growth factor-β 1, the effects of Ac-B on expression of the myofibroblast marker vimentin and accumulation of collagen type I in A549 cells were analyzed by Western blotting. Sirius Red staining and immunohistochemical analyses of the effect of Ac-B on expression of α-smooth muscle actin (SMA) in a rat model of silicosis were undertaken.Results: Ac-B had good traceability during the uptake, entry, and distribution in cells. Ac-B treatment prevented an increase in α-SMA expression in vivo and in vitro and was superior to that of Ac-SDKP. Caveolae-mediated uptake of Ac-B by A549 cells led to achieving anti-epithelial–mesenchymal transformation (EMT) effects.Conclusion: Ac-B had an anti-fibrotic effect and could be a promising agent for the fibrosis observed in silicosis in the future.Keywords: Ac-SDKP, biotin, epithelial–mesenchymal transformation, phagocytosis, anti-fibrotic function

Focal malformations of cortical development, including focal cortical dysplasia (FCD) and hemimegalencephaly (HME), are important causes of intractable childhood epilepsy. Using targeted and exome sequencing on DNA from resected brain samples and nonbrain samples from 53 patients with FCD or HME, we identified pathogenic germline and mosaic mutations in multiple PI3K/AKT pathway genes in 9 patients, and a likely pathogenic variant in 1 additional patient. Our data confirm the association of DEPDC5 with sporadic FCD but also implicate this gene for the first time in HME. Our findings suggest that modulation of the mammalian target of rapamycin pathway may hold promise for malformation-associated epilepsy. Ann Neurol 2015;77:720-725

The two-color laser filamentation technique serves as a high-quality, laser-based strong-field terahertz source. However, the terahertz energy obtained from this method tends to saturate at high laser intensity, limiting its ability to fully exploit the advantage of the extremely strong field offered by relativistic lasers. Here, we proposed a novel approach based on photon deceleration in plasma to obtain controllable terahertz radiations with two-color relativistic femtosecond laser pulses. In our method, an 800-nm laser drives the plasma wave and controls the plasma density distribution, while the other 10.6- μ m laser experiences a strong frequency downshift in the plasma wave and converts to a multi-cycle terahertz pulse, whose central frequency is adjustable by altering the parameters of laser and plasma. The conversion efficiency from the 10.6- μ m laser to terahertz radiation can be over 12%, potentially unlocking novel applications in the terahertz domain. [ABSTRACT FROM AUTHOR]

Ling Pu,1 Zuoyi Jian,2 Fen Pan,3 Yang Geng,4 Miao He,5 Pu Liao1,6 1Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education of China), College of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Bioinformatics, Novogene Biotechnology Co., Ltd, Sichuan, People’s Republic of China; 3Department of Clinical Laboratory, Shanghai Children’s Hospital, Shanghai, People’s Republic of China; 4College of Life Sciences, Sichuan University, Sichuan, People’s Republic of China; 5Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, Sichuan, People’s Republic of China; 6Department of Clinical Laboratory, Chongqing People’s Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Pu LiaoCollege of Laboratory Medicine, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing 400016, People’s Republic of ChinaTel +86 0 236 848 5240Fax +86 0 236 848 5240Email liaopu2015@163.com Miao HeInstitute of Blood Transfusion, Chinese Academy of Medical Sciences, No. 26, Huacai Road, Chengdu 610052, Sichuan, People’s Republic of ChinaTel +86 0 286 164 8549Fax +86 0 286 164 8556Email messa1022@126.comIntroduction: Multidrug-resistance in Acinetobacter baumannii has emerged as a serious problem to public health. There is still a significant gap in the understanding of the multidrug-resistance and the genome diversity evolutionary process of A. baumannii in China, especially in the central and western regions.Methods: Ten A. baumannii strains were collected from three hospitals in Chongqing, China. Whole-genome re-sequencing was used to obtain differences in genomic levels among strains. The diversity were determined by multi-locus sequence typing method, and investigate the genetic relationship between the ten strains and others by phylogenetic analysis. Comparative analysis focused on resistance genes related to insertions and deletions (InDels) and single-nucleotide polymorphisms (SNPs) was performed.Results: The overall G+C% content was 39.05%∼39.43%, the average sequencing depth was 273.95∼428.99, and the alignment ratio of the sequencing data was 92.93%∼99.27%. A total of 42 InDels and 11,387 SNPs were detected in the coding sequence region of the isolates. Phylogenetic tree shows that the 10 A. baumannii isolates were divided into four relative groups, and there exist the possibility of cross-regional spread pattern. A total number of 19 drug resistance genes had been found in each strain, and efflux pump-related genes accounted for the most. Only AacA4 underwent a change in InDel. Six types of drug resistance genes were found in the SNPs resistance gene-related loci, among which gene ANT(3’’)-II and QacE mutations were found in each strain.Conclusion: In this study, the main mechanism of A. baumannii multi-drug resistance is due to the multi-drug efflux pump related genes. The point mutations at the SNPs sites of the six types of resistance genes are the main differences in A. baumannii between Chongqing and the eastern coastal areas of China.Keywords: Acinetobacter baumannii, antimicrobial resistance, genome-wide re-sequencing, MLST, phylogenetic analysis, SNP