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Yiwen Zhou,1,* Yuyan Huang,1,* Yingwen Wang,2 Xiaofeng Xu,1 Zhuowen Yu,1 Ying Gu3 1Department of Gastroenterology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China; 2Centre for Clinical Practice Guideline Production and Evaluation, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China; 3Nursing Department, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Gu, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China, Email guying0128@aliyun.com Zhuowen Yu, Department of Gastroenterology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai, 201102, People’s Republic of China, Email yzw100@126.comBackground: The Theoretical Domains Framework (TDF) is among the most extensively utilised foundational frameworks in implementation science. It was developed from 33 psychological theories, with the latest version identifying 14 domains encompassing 84 theoretical constructs. These domains and constructs capture the complexity of factors that affect behaviours, making the framework a valuable tool for designing and implementing interventions within health and social care settings.Objective: To summarise the development, hot topics, and future trends in TDF-related research and provide implementation practitioners with more information on the application of TDF.Methods: We used TDF as the topic and searched the ISI Web of Science Core Collection, identifying 1382 relevant publications. We used analytical tools such as Excel, Tableau, VOSviewer, and Citespace to conduct a bibliometric analysis of the relevant publication.Results: We identified the United Kingdom as the primary contributor, with University College London as the key institution. Susan Michie ranked highest in total citations. The analysis highlighted cancer and stroke as primary clinic medicine-related topics using TDF. Emerging themes encompass abuse, violence, maternal health, antenatal care, patient involvement, and trauma-informed care et al. “Nurse” and “qualitative research” emerged as recent and enduring hotspots, possibly indicating future research trends.Conclusion: This article represents the first attempt to summarise the TDF using bibliometric analysis. We suggest this method can be used to analyse other theoretical frameworks in scientific implementation of its objectivity and quantifiability. Overall, the application scope of TDF is shifting from public health towards more specialised clinical directions, although its application in the field of public health is continuously expanding. In the future, the number of users of TDF is also expected to expand from implementation scientists to professional technical personnel.Keywords: theoretical domains framework, bibliometric analysis, visualization, implementation science

Zijuan Ma,1,* Yunge Fan,1,* Zhijun Yu,1 Wenxuan Wu,1 Xiangting Zhang,1 Huolian Li,1 Shaochen Zhao,2 Yang Li,3 Yuanyuan Li,4 Dongfang Wang,1 Fang Fan1 1Center for Studies of Psychological Application, School of Psychology, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of China; 2Research Center for Guangdong-Hong Kong-Macao Policing Model Innovation, China People’s Police University, Guangzhou, People’s Republic of China; 3Department of Educational Psychology, Faculty of Education, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongfang Wang; Fang Fan, School of Psychology, South China Normal University, Shipai Road, Guangzhou, 510631, People’s Republic of China, Email wdfpsyc@126.com; fangfan@scnu.edu.cnPurpose: Although experimental psychopathology using PET, EEG, and fMRI is at the forefront of understanding the underlying mechanisms of sleep inertia, many questions concerning causality remain unanswerable due to ethical constraints and the use of small and heterogeneous samples in experimental methods. There is a pressing need for a novel perspective in a large and relatively homogeneous population to fully capture and elucidate longitudinal processes and dynamic causality that culminate in episodes of sleep inertia over time. Therefore, this study aimed to reveal the causal relationships between symptoms of sleep inertia across its distinct patterns.Patients and Methods: A total of 1636 intern nurses participated in the first survey (94.1% validity rate), then 1277 intern nurses were followed up (82.9% tracing rate). Symptoms of sleep inertia were self-reported using the Sleep Inertia Questionnaire. The cross-lagged panel network models were used to examine unique longitudinal relationships between symptoms of sleep inertia across distinct trajectories.Results: Four distinct trajectories of sleep inertia were established. Additionally, we found differences in those symptoms with the highest influence on other symptoms at the subsequent point across the networks of four trajectories, particularly, “Difficulty in concentrating” in the persistent-high group and “Feeling tense” in the deteriorating groups.Conclusion: The current study highlights changes in sleep inertia based on the long-term course over time. Notably, symptoms of “Difficulty in concentrating” and “Feeling tense” are imperative to address these specific symptoms within subpopulations.Keywords: sleep inertia, change patterns, network structures, intern nurse, shift work

Qichang Gao,1 Yiming Ma,1 Tuo Shao,1 Xiaoxuan Tao,2 Xiansheng Yang,1 Song Li,1 Jiaao Gu,1 Zhange Yu1 1Department of Spinal Surgery, The 1st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of China; 2Department of Radiotherapy, The 3st Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Zhange Yu, Email yuzhange1967@163.comBackground: Progress in research on expression profiles in osteoarthritis (OA) has been limited to individual tissues within the joint, such as the synovium, cartilage, or meniscus. This study aimed to comprehensively analyze the common gene expression characteristics of various structures in OA and construct a diagnostic model.Methods: Three datasets were selected: synovium, meniscus, and knee joint cartilage. Modular clustering and differential analysis of genes were used for further functional analyses and the construction of protein networks. Signature genes with the highest diagnostic potential were identified and verified using external gene datasets. The expression of these genes was validated in clinical samples by Real-time (RT)-qPCR and immunohistochemistry (IHC) staining. This study investigated the status of immune cells in OA by examining their infiltration.Results: The merged OA dataset included 438 DEGs clustered into seven modules using WGCNA. The intersection of these DEGs with WGCNA modules identified 190 genes. Using Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest algorithms, nine signature genes were identified (CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3), each demonstrating substantial diagnostic potential (areas under the curve from 0.701 to 0.925). Furthermore, dysregulation of various immune cells has also been observed.Conclusion: CDADC1, PPFIBP1, ENO2, NOM1, SLC25A14, METTL2A, LINC01089, L3HYPDH, NPHP3 demonstrated significant diagnostic efficacy in OA and are involved in immune cell infiltration.Keywords: osteoarthritis, machine learning, immune cells infiltration, diagnostic model

Danni Yang, Zhao Yu, Xianyou He Center for Studies of Psychological Application, South China Normal University, Guangzhou, People’s Republic of ChinaCorrespondence: Xianyou He, Email xianyouhe@163.comPurpose: The impact of moral beliefs on individuals’ moral judgments, particularly within the framework of contrasting cultural values such as collectivism and individualism, continues to be a subject of interest. This research delves into whether individuals with distinct values display differences in moral beliefs, with a specific focus on selflessness.Methods: Through experiment 1 and 2, we scrutinize the moral judgments of individuals with diverse values concerning pro-social behaviors driven by selflessness and in-group favoritism. Experiment 3 investigates the underlying mechanisms by examining reward expectations.Results: The findings from experiments 1 and 2 indicate that collectivists exhibit significantly higher moral judgment levels for selfless pro-social behaviors compared to individualists, highlighting a disparity in moral beliefs between the two value systems. Experimental 2 also found that collectivists’ moral judgments rose and fell as rescuers’ selflessness increased or decreased. However, individualist moral judgment did not change significantly with behavioral selflessness. The results reveal that collectivists hold higher reward expectations for selfless behavior, which contributes to their heightened moral judgment of selfless behavior.Conclusion: While it may be assumed that collectivists’ moral beliefs would be dominated by in-group preferences, aligning with the conceptual in-group preference of collectivism, this study unexpectedly found evidence of collectivists’ pursuit of selflessness in their moral beliefs. These findings offer initial evidence of distinct patterns of moral beliefs associated with collectivism and individualism, shedding light on potential reasons that lead collectivists to possess stronger moral beliefs about selflessness.Keywords: collectivism, individualism, moral beliefs, pro-social behavior, selflessness

Yun Han,1,* Jianping Zhu,1,* Jieqiong Liu,2 Ying Zheng,2 Gang Liang,1 Yi Yang,1 Lingyan Yu,3 Zhenwei Yu,1 Gang Han1 1Research Center for Clinical Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People’s Republic of China; 2The 903rd Hospital of PLA Joint Logistic Support Force, Hangzhou, People’s Republic of China; 3Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenwei Yu; Gang Han, Email yzw_srrsh@zju.edu.cn; 3199022@zju.edu.cnIntroduction: Recent studies suggested the potential benefits of extended infusion times to optimize the treatment efficacy of ceftazidime/avibactam, which indicated that the current pharmacokinetic/pharmacodynamic (PK/PD) target may not be sufficient, especially for severe infections. The purpose of this study is to assess the adequacy of dosing strategies and infusion durations of ceftazidime/avibactam when applying higher PK/PD targets.Methods: This study utilized published PK parameters to conduct Monte Carlo simulations. Different dosages including the recommended regimen based on renal function were simulated and evaluated by the probability of target attainment (PTA) and cumulative fraction of response (CFR). Different PK/PD targets were set for ceftazidime and avibactam. MIC distributions from various sources were used to calculate the CFR.Results: Multiple PK/PD targets have been set in this study, All recommended dosage could easily achieve the target of 50%fT ≥ MIC (ceftazidime) and 50%fT ≥ CT=1.0 mg/L (avibactam). However, for severe infection patients with normal renal function and augmented renal clearance at the recommended dosage (2000 mg/500 mg, every 8 hours), the infusion duration needs to be extended to 3 hours and 4 hours to achieve the targets of 100%fT ≥ MIC and 100%fT ≥ CT=1.0 mg/L. Only continuous infusion at higher dosages achieved 100%fT ≥ 4×MIC and 100%fT ≥ CT=4.0 mg/L targets to all currently recommended regimens. According to the varying MIC distributions, higher concentrations are needed for Pseudomonas aeruginosa, with the attainment rates vary across different regions.Conclusion: The current recommended dosing regimen of ceftazidime/avibactam is insufficient for severe infection patients, and continuous infusion is suggested.Keywords: ceftazidime, avibactam, pharmacokinetic/pharmacodynamic, probability of target attainment

Li Zhang,1,2 Zimu Yu,3 Yunfeng Zhang,1 Hengyu Wang,4,5 Juntao Cheng,6 Chao Shi1 1Department of Oncology, Gaoxin Branch Of The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2First School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, People’s Republic of China; 3Medical College of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 4Queen Mary College, Nanchang University, Nanchang, 330031, People’s Republic of China; 5School of Biological and Biomedical Sciences, Queen Mary University of London, London, UK; 6Peking University First Hospital, Peking University, Beijing, 100034, People’s Republic of ChinaCorrespondence: Chao Shi, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 151 7049 8679, Email ndyfy4540@ncu.edu.cnPurpose: Although brain metastasis (BM) from gastric cancer (GC) is relatively uncommon, its incidence has been increasing owing to advancements in treatment modalities. Unfortunately, patients diagnosed with BM from gastric cancer have poor life expectancy. Our study aims to establish a predictive model for brain metastasis in advanced gastric cancer patients, thus enabling the timely diagnosis of brain metastasis.Patients and Methods: The clinicopathological features of a cohort which included 40 GC patients with brain metastasis, 32 of whom from the First Affiliated Hospital of Nanchang University, 2 from Gaoxin Branch of the First Affiliated Hospital of Nanchang University, remaining 6 from Anyang District Hospital, and 80 non-metastatic advanced GC patients from the First Affiliated Hospital of Nanchang University between 2018 and 2022. Data were retrospectively analyzed.Results: Age, tumor size, differentiation, lymph node grade, tumor location, Lauren classification, liver metastasis, carbohydrate antigen 199 (CA199), lactate dehydrogenase (LDH), and human epidermal growth factor receptor 2 (Her-2) were associated with BM. A nomogram integrated with nine risk factors (tumor size, differentiation, lymph node grade, tumor location, Lauren classification, liver metastasis, CA-199, LDH, and Her-2) showed good performance (Area Under Curve 0.95, 95% CI: 0.91– 0.98).Conclusion: We developed and validated a nomogram that achieved individualized prediction of the possibility of BM from GC. This model enables personalized imaging review schedules for timely brain metastasis detection in advanced gastric cancer patients.Keywords: brain metastasis, gastric cancer, nomogram, risk factors

Kaiwu Xu,1 Cailing Xiang,1 Zhige Yu,1 Jia Li,2 Changjun Liu2 1Department of Gastrointestinal Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 410005, People’s Republic of China; 2Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan Province, 410005, People’s Republic of ChinaCorrespondence: Changjun Liu, Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), 61 Jiefang West Road, Changsha, Hunan Province, 410005, People’s Republic of China, Tel +86-0731-83928052, Email liuchangjun712@163.comPurpose: Strategies therapy for hepatocellular carcinoma (HCC) beyond oligometastasis are limited. The optimal sequence of systemic treatment for advanced HCC is not yet clear. Our study aims to evaluate the effectiveness of simultaneous lenvatinib combined PD-1 inhibitor on advanced HCC beyond oligometastasis.Patients and Methods: A total of 232 patients were enrolled in our retrospective study. Patients divided into three groups. (a) Lenvatinib plus simultaneous PD-1 inhibitor (Simultaneous group, n=58); (b) patients received PD-1 inhibitor before the tumor progression with continued lenvatinib administration (Before PD group, n=77); (c) patients received PD-1 inhibitor after the tumor progression (After PD group, n=97). To analyze overall survival (OS) and progression-free survival (PFS) among the three groups.Results: The estimated 6-, 12-, 18- and 24-mon OS for Simultaneous group patients were 100%, 93.1%, 63.4%, 48.3%, whereas the OS rates were 100%, 78%, 36.3%, 23.6% in Before PD group, and 99%, 61.2%, 22.1%, 7.5% in After PD group. The OS rates were obviously improved with the use of simultaneous PD-1 inhibitor among the three groups (P < 0.001). The estimated 3-, 6-, 9- and 12-month PFS rates for patients were 89.6%, 44.8%, 24.6%, 6% in After PD group, 90.9%, 59.7%, 27.3%, 12.4% in Before PD group and 98.3%, 81%, 51.7%, 39.7% in Simultaneous group, respectively. PFS rate was significantly different among the three groups (P < 0.001).Conclusion: Synchronous administration of lenvatinib and PD-1 inhibitors improved survival rate significantly. The synchronous combination could represent a promising strategy in HCC beyond oligometastasis.Keywords: lenvatinib, PD-1 inhibitor, hepatocellular carcinoma beyond oligometastasis, simultaneous, prognosis

Fei Zhou,1,2 Liyuan Liu,1,2 Fei Wang,1,2 Lixiang Yu,1,2 Yujuan Xiang,1,2 Chao Zheng,1,2 Shuya Huang,1,2 Zhen Yang,1 Zhigang Yu1,2 1Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China; 2Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, 250033, People’s Republic of ChinaCorrespondence: Zhigang Yu, Department of Breast Surgery, The Second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China, Tel +86-531-85875048, Email yzg@medmail.com.cnPurpose: Periductal mastitis (PDM) is a chronic inflammatory lesion of the breast with an unknown etiology, and it is difficult for clinicians to differentiate it from granulomatous lobular mastitis (GLM), although they have different treatment strategies and prognosis. This study aimed to investigate the differences in their clinicopathologic features to inform treatment strategies.Patients and Methods: Between 2011 and 2020, 121 patients diagnosed with PDM and 57 patients with GLM were retrospective analysis. Patient data were extracted on demographics, clinical presentation, pathologic characteristics, treatments and clinical response. Histopathological evaluations were performed on core needle biopsy specimens. Immunohistochemical stains using antibodies against CD3, CD4, CD8, CD20, and CD138 was performed to define immune cell infiltration.Results: PDM patients had a higher median age compared to GLM patients (38 vs 32, p< 0.001). PDM was primarily located in the areolar area, while GLM predominantly affected the peripheral quadrant of the breast (56.20% vs 75.44%, p< 0.001). Histopathologically, more ductal dilatation (90.08% vs 3.51%, p< 0.001), ductal wall thickening (47.93% vs 1.75%, p< 0.001), and ductal rupture (44.63% vs 5.26%, p< 0.001) were observed in PDM. GLM presented with significantly more granuloma (94.74% vs 10.74%, p< 0.001), microabscess (68.42% vs 28.93%, p< 0.001), and lipid vacuole (40.35% vs 8.26%, p< 0.001) formation than PDM. Immunohistochemical analysis revealed a significant presence of CD20+ B lymphocytes in PDM and a higher prevalence of CD8+ T lymphocytes in GLM, indicating differing immune responses. Treatment outcomes varied, with PDM patients responding well to surgery and anti-mycobacterial therapy, while GLM patients showed favorable responses to steroid therapy.Conclusion: PDM is a specific entity with a similar clinical presentation but distinct histopathological features and immune profiles to GLM. Further research is needed to elucidate the pathogenesis and optimize therapeutic approaches for these breast inflammatory conditions.Keywords: etiology, granulomatous lobular mastitis, immunology, pathology, periductal mastitis

Zirui Bian,1,&ast; Tianzhe Bao,2,&ast; Xuequan Sun,3,4 Ning Wang,1 Qian Mu,5 Ting Jiang,6 Zhongxiang Yu,6 Junhang Ding,2 Ting Wang,7 Qihui Zhou2 1Department of Bone, Huangdao District Central Hospital, Qingdao, People’s Republic of China; 2Qingdao Key Laboratory of Materials for Tissue Repair and Rehabilitation, School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 3Weifang Eye Institute, Weifang Eye Hospital, Zhengda Guangming Eye Group, Weifang, People’s Republic of China; 4Zhengda Guangming International Eye Research Center, Qingdao Zhengda Guangming Eye Hospital, Qingdao University, Qingdao, People’s Republic of China; 5Department of Biomaterials, LongScience Biological (Qingdao) Co, LTD, Qingdao, People’s Republic of China; 6Heart Center, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao University, Qingdao, People’s Republic of China; 7Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qihui Zhou; Junhang Ding, Tel +86-17660670299, Email qihuizhou@uor.edu.cn; dingjunhang@uor.edu.cnIntroduction: The emergence and rapid spread of multidrug-resistant bacteria (MRB) caused by the excessive use of antibiotics and the development of biofilms have been a growing threat to global public health. Nanoparticles as substitutes for antibiotics were proven to possess substantial abilities for tackling MRB infections via new antimicrobial mechanisms. Particularly, carbon dots (CDs) with unique (bio)physicochemical characteristics have been receiving considerable attention in combating MRB by damaging the bacterial wall, binding to DNA or enzymes, inducing hyperthermia locally, or forming reactive oxygen species.Methods: Herein, how the physicochemical features of various CDs affect their antimicrobial capacity is investigated with the assistance of machine learning (ML) tools.Results: The synthetic conditions and intrinsic properties of CDs from 121 samples are initially gathered to form the raw dataset, with Minimum inhibitory concentration (MIC) being the output. Four classification algorithms (KNN, SVM, RF, and XGBoost) are trained and validated with the input data. It is found that the ensemble learning methods turn out to be the best on our data. Also, &epsiv;-poly(L-lysine) CDs (PL-CDs) were developed to validate the practical application ability of the well-trained ML models in a laboratory with two ensemble models managing the prediction.Discussion: Thus, our results demonstrate that ML-based high-throughput theoretical calculation could be used to predict and decode the relationship between CD properties and the anti-bacterial effect, accelerating the development of high-performance nanoparticles and potential clinical translation. Keywords: carbon dots, machine learning, antibacterial, minimum inhibitory concentration, classification algorithms

Xiaochen Chen,1,&ast; Jun Chen,2,&ast; Xue Zhao,2 Rongji Mu,1 Hongsheng Tan,1 Zhangsheng Yu1,3 1Clinical Research Institute & School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongsheng Tan, Clinical Research Institute & School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China, Email tanhs@shsmu.edu.cn Zhangsheng Yu, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 210240, People’s Republic of China, Email yuzhangsheng@sjtu.edu.cnAbstract: The coronavirus disease-2019 pandemic resulted in a major increase in depression and anxiety disorders worldwide, which increased the demand for mental health services. However, clinical interventions for treating mental disorders are currently insufficient to meet this growing demand. There is an urgent need to conduct scientific and standardized clinical research that are consistent with the features of mental disorders in order to deliver more effective and safer therapies in the clinic. Our study aimed to expose the challenges, complexities of study design, ethical issues, sample selection, and efficacy evaluation in clinical research for mental disorders. The reliance on subjective symptom presentation and rating scales for diagnosing mental diseases was discovered, emphasizing the lack of clear biological standards, which hampers the construction of rigorous research criteria. We underlined the possibility of psychotherapy in efficacy evaluation alongside medication treatment, proposing for a multidisciplinary approach comprising psychiatrists, neuroscientists, and statisticians. To comprehend mental disorders progression, we recommend the development of artificial intelligence integrated evaluation tools, the use of precise biomarkers, and the strengthening of longitudinal designs. In addition, we advocate for international collaboration to diversity samples and increase the dependability of findings, with the goal of improving clinical research quality in mental disorders through sample representativeness, accurate medical history gathering, and adherence to ethical principles.Keywords: clinical efficacy assessment, clinical trials, mental health, research design, statistical analysis

Zhenzhen Yu,1 Jianping Niu,1 Chen Wang2 1Department of Neurology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, People’s Republic of China; 2Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, People’s Republic of ChinaCorrespondence: Chen Wang, Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Zhenhai Road No. 55, Siming District, Xiamen, Fujian, 361000, People’s Republic of China, Email wangchen1986xm@163.com Jianping Niu, Department of Neurology, The Second Affiliated Hospital of Xiamen medical college, Shengguang Road No. 566, Jimei District, Xiamen, Fujian, 361000, People’s Republic of China, Email 549872685@qq.comObjective: This study aims to evaluate the epidemiological features of sexual dysfunction in people aged more than 65 years in parts of China, and to investigate the independent significant risk factors.Methods: According to the population distribution of five communities in Xiamen and Chongqing, we have randomly enrolled 2403 people more than 65 years-of-age. We collected data information through a questionnaire survey. Then demonstrated the current condition of sexual dysfunction in the samples by statistical analysis, and multivariable logistic regression was used to disclose the risk factors of sexual dysfunction in the older adults.Results: According to this study, about 10.48% of the elderly had sexual dysfunctions of different degrees and duration. The proportion of men was about twice that of women (14.5% of males and 7.3% of females). During the course of the disease, 3.19% (43/1344) of women and 3.31% (35/1059) of men had more than 15 years duration of sexual dysfunction. In severity, 5.7% (77/1344) of women and 7.0% (74/1059) of men had very severe sexual dysfunction. There were statistically significant differences in BMI, smoking, drinking history, hypertension, depression incidence or median (p< 0.05). Alcohol consumption history [OR = 1.711, 95% CI: 1.124– 2.604, p = 0.012] and depression [OR = 2.107, 95% CI: 1.109– 4.356, p =0.044] were independent risk factors for sexual dysfunction.Conclusion: The prevalence of sexual dysfunction was low among elderly in the southern part of China. But the course of the disease is long and the degree of the disease is very severe. Elderly with a history of drinking and depression are more prone to sexual dysfunction.Keywords: epidemiology, sexual dysfunction, elderly, prevalence, risk factor

Yuanyuan Su,1,* Ning Lu,2,* Pei Wang,3,* Qian Li,2 Hua Wen,2 Jie Zhang,2 Ling Fan,2 Jie Li,2 Zhaoxiang Yu,4 Manli Cui,2 Mingxin Zhang2 1Department of General Medicine, the People’s Hospital of Yubei District of Chongqing, Chongqing, People’s Republic of China; 2Department of Gastroenterology, the First Affiliated Hospital of Xi’an Medical College, Xi’an, Shaanxi, People’s Republic of China; 3Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, People’s Republic of China; 4Department of General Surgery, the First Affiliated Hospital of Xi’an Medical College, Xi’an, Shaanxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Manli Cui, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, Email cuiml1587@163.com; Mingxin Zhang, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, Email zmx3115@xiyi.edu.cn.Objective: This study aims to explore the nexus between students’ psychological well-being and the manifestation of gastrointestinal symptoms (GISs) amid the health lockdown enforced in Xi’an, focusing on the student populace of Xi’an Medical College and Shaanxi University of Traditional Chinese Medicine.Materials and methods: A survey encompassing psychological parameters and GISs was administered to a randomized cohort of 1327 college students drawn from Xi’an Medical College and Shaanxi University of Traditional Chinese Medicine. The survey instrument was developed utilizing the Questionnaire Star platform. Subsequent to data collection, analysis was performed using GraphPad Prism 9 and SPSS 22.0.Results: Comparative analysis revealed statistically significant disparities (P < 0.05) in various GISs between the periods during and preceding the health lockdown, encompassing symptoms such as nausea/vomiting, acid reflux, postprandial fullness/early satiety, anorexia, decreased appetite, bloating, abdominal discomfort, abdominal pain, diarrhea, and constipation. Notably, the mean score for Generalized Anxiety Disorder 7 (GAD-7) was 3.31± 3.92, indicating mild anxiety, while the mean score for Patient Health Questionnaire-2 (PHQ-2) was 1.15± 1.28, suggesting mild depression. Detailed evaluation of anxiety revealed prevalence rates of 34% among respondents, with 34.2% of these individuals reporting concurrent GISs, while among those evaluated for depression (38.8% of the sample), 44.2% reported concurrent GISs. Furthermore, multiple linear regression analysis unveiled a negative correlation between GISs during the health lockdown and lifestyle scores, while positive correlations were observed with GISs preceding the lockdown, anxiety, and depression. The formulated multiple linear regression equation for GISs during the health lockdown is delineated as follows: 14.693– 0.342 life style + 0.725GISs before health lockdown + 0.218anxiety + 0.564 depression.Conclusion: This investigation underscores the substantial impact of anxiety and depression on the student body, accentuating their role in precipitating GISs during health lockdown situations. The psychological well-being of medical students during exigent circumstances such as natural disasters warrants heightened attention, necessitating proactive measures aimed at emotional regulation to mitigate the onset of GISs.Keywords: COVID-19, health lockdown, gastrointestinal symptoms, anxiety, depression

Zhe Yu,1– 3 Ruoqi Ding,1– 3 Qiuju Yan,1– 3 Menghan Cheng,1– 3 Teng Li,1– 4 Fei Zheng,5 Lin Zhu,1– 4 Yang Wang,1– 4 Tao Tang,1– 4 En Hu1– 4 1Institute of Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 2NATCM Key Laboratory of TCM Gan, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 3Center for Interdisciplinary Research in Traditional Chinese Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 4Xiangya Hospital, Central South University, Nanchang, Jiangxi, 330004, People’s Republic of China; 5The College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410008, People’s Republic of ChinaCorrespondence: En Hu; Ruoqi Ding, Integrative Medicine, Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China, Email znxyhe@csu.edu.cn; ruoqi_ding@outlook.comPurpose: Many herbs can promote neurological recovery following traumatic brain injury (TBI). There must lie a shared mechanism behind the common effectiveness. We aimed to explore the key therapeutic targets for TBI based on the common effectiveness of the medicinal plants.Material and methods: The TBI-effective herbs were retrieved from the literature as imputes of network pharmacology. Then, the active ingredients in at least two herbs were screened out as common components. The hub targets of all active compounds were identified through Cytohubba. Next, AutoDock vina was used to rank the common compound-hub target interactions by molecular docking. A highly scored compound-target pair was selected for in vivo validation.Results: We enrolled sixteen TBI-effective medicinal herbs and screened out twenty-one common compounds, such as luteolin. Ten hub targets were recognized according to the topology of the protein-protein interaction network of targets, including epidermal growth factor receptor (EGFR). Molecular docking analysis suggested that luteolin could bind strongly to the active pocket of EGFR. Administration of luteolin or the selective EGFR inhibitor AZD3759 to TBI mice promoted the recovery of body weight and neurological function, reduced astrocyte activation and EGFR expression, decreased chondroitin sulfate proteoglycans deposition, and upregulated GAP43 levels in the cortex. The effects were similar to those when treated with the selective EGFR inhibitor.Conclusion: The common effectiveness-based, common target screening strategy suggests that inhibition of EGFR can be an effective therapy for TBI. This strategy can be applied to discover core targets and therapeutic compounds in other diseases.Keywords: traditional Chinese medicine, medicinal plants, luteolin, AZD3759, epidermal growth factor receptor, astrocyte

Zhao Liu,1,&ast; Ling Wang,2,&ast; Jiabing Sun,1,&ast; Qinghuan Zhang,3 Yue Peng,1 Susu Tang,1 Limei Zhang,4 Xiaobin Li,4,5 Zhijian Yu,1 Tao Zhang6 1Department of Otolaryngology, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of China; 2Department of Obstetrics, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, 519000, People’s Republic of China; 3Department of Clinical Laboratory, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, 519000, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of China; 5Zhuhai Precision Medical Center, Zhuhai Hospital Affiliated with Jinan University (Zhuhai People’s Hospital), Zhuhai, People’s Republic of China; 6Department of Otolaryngology, The First Affiliated Hospital of Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Zhang; Zhijian Yu, Email 18045681156@163.com; yzjent@163.comObjective: Staphylococcus haemolyticus can cause a series of infections including otitis media (OM), and the oxacillin-resistant S. haemolyticus has become a serious health concern. This study aimed to investigate the genomic characteristics of two strains of oxacillin-resistant and mecA-positive S. haemolyticus isolated from the samples of ear swabs from patients with OM and explore their acquired antibiotic resistance genes (ARGs) and the mobile genetic elements (MGEs).Methods: Two oxacillin-resistant S. haemolyticus strains, isolated from ear swab samples of patients with OM, underwent antimicrobial susceptibility evaluation, followed by whole-genome sequencing. The acquired ARGs and the MGEs carried by the ARGs, harbored by the genomes of two strains of S. haemolyticus were identified.Results: The two strains of oxacillin-resistant S. haemolyticus (strain SH1275 and strain SH9361) both carried the genetic contexts of mecA with high similarity with the SCCmec type V(5C2& 5) subtype c. Surprisingly, the chromosomal aminoglycoside resistance gene aac(6’)-aph(2”) harbored by S. haemolyticus strain SH936 was flanked by two copies of IS 256, forming the IS 256-element (IS 256-GNAT-[aac(6’)-aph(2”)]-IS 256), which was widely present in strains of both Staphylococcus and Enterococcus genus. Furthermore, the two strains of oxacillin-resistant and MDR S. haemolyticus were found to harbor antimicrobial resistance plasmids, including one 26.9-kb plasmid (pSH1275-2) containing msr(A)–mph(C)) and qacA, one mobilizable plasmid pSH1275-3 harboring vga(A)LC, one plasmid (pSH9361-1) carrying erm(C), and one plasmid (pSH9361-2) carrying qacJ.Conclusion: The systematic analysis of whole-genome sequences provided insights into the mobile genetic elements responsible for multi-drug resistance in these two strains of oxacillin-resistant and mecA-positive S. haemolyticus, which will assist clinicians in devising precise, personalized, and clinical therapeutic strategies for treating otitis media caused by multi-drug resistant S. haemolyticus.Keywords: Staphylococcus haemolyticus, ear swabs, mecA, antimicrobial resistance plasmid, whole genome sequence

Jinchun Liu,1 Zhijun Yu,2,3 Guohua Wang2 1Department of Medicine, Henan Vocational College of Nursing, Anyang, Henan Province, 455000, People’s Republic of China; 2Department of Neurophysiology and Neuropharmacology, Institute of Special Environmental Medicine and Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226019, People’s Republic of China; 3Department of Thoracic Surgery, Nantong Second People’s Hospital, Nantong, Jiangsu, 226001, People’s Republic of ChinaCorrespondence: Guohua Wang, Email wgh036@hotmail.comAbstract: Coronary artery fistulae (CAF) are a rare anomaly characterized by abnormal connections between a coronary artery and a cardiac chamber or a great vessel, with most patients remaining asymptomatic. Despite being predisposed to severe complications like heart failure, patients with CAF infrequently experience severe stenosis in the coronary artery. This study delineates a case involving a 46-year-old male presenting with a fistula bridging the right coronary artery (RCA) and right atrium (RA), manifesting a pronounced 99% stenosis at the right extremity of the coronary artery proximal to the fistula. Concurrently, the individual exhibits six conventional risk factors: age over 40, male gender, hypertension, diabetes, smoking, and hypertriglyceridemia. Following pharmaceutical intervention, the patient was discharged and subjected to extended follow-up. This case highlights the dual processes of “accelerating damage” and “retarding renewal” in the progression of atherosclerosis. Factors such as shear stress, smoking, and hypertension are posited to expedite endothelial cell damage, while aging and diabetes may impede the renewal and repair of these cells. Together with the concept of secondary atherosclerotic plaque healing, this case prompts the introduction of a “Double Endothelial Healings” hypothesis, proposing a potential pathogenetic mechanism for coronary artery atherosclerosis.Keywords: coronary artery fistulae, atherosclerosis, pathogenesis, plaque healing, endothelial injury

Yanping Guo,1 Zhangbin Yu,2 Huiying Tu,2 Biying Zheng,1 Jiamin Li,1 Ying Liu1 1Department of Pediatrics, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Neonatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Yanping Guo; Ying Liu, Tel +86-15919990131 ; +86-13902992158, Email guoyanping1223@163.com; 13902992158@139.comBackground and Objectives: To examine the correlation between the concentration of vitamin D (VD) in venous blood at approximately 4 weeks of age (± 4 weeks of age) and neonatal outcomes in preterm infants (birth weight < 1500 g or gestational age < 32 weeks) in two neonatal intensive care units (NICUs) located in Shenzhen, China.Methods and Study Design: Preterm infants were split into two groups based on their VD concentration at ± 4 weeks of age: VD insufficiency (VDI) group (≤ 20 ng/mL) and VD sufficient (VDS) group (> 20 ng/mL). Binary logistic regression analysis was used to examine relationships between outcomes and VDI.Results: Of 230 infants in total, 119 (51.7%) were assigned to the VDI group and 111 to the VDS group (48.3%). No correlation was found between serum VD at ± 4 weeks of age and gestational age (p> 0.05). The starting point of the two groups for oral VD intake did not differ significantly (p> 0.05). At ± 4 weeks of age, oral VD dose (P< 0.05) was greater in the VDS group. Gestational diabetes mellitus was associated with VDI (OR=1.94, 95% CI 1.01– 3.75, p=0.047) after controlling for this risk. Following correction for gestational age and oral VD dosage at ± 4 weeks old, VDI was also linked to a significant risk of retinopathy of prematurity (OR=2.00, 95% CI 1.08– 3.68, p< 0.027).Conclusion: Preterm newborns (gestational age < 32 weeks or birth age < 1500 g) in NICUs in Shenzhen, China continue to have significantly high VDI. Higher VDI is associated with gestational diabetes mellitus and retinopathy of prematurity.Keywords: very preterm birth, very low birth weight infant, vitamin D, 4 weeks of age, outcome

Yueliang Chen,1,&ast; Yun Han,2,3,&ast; Feng Guo,1 Zhenwei Yu2,3 1Intensive Care Unit, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Research Center for Clinical Pharmacy, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Guo; Zhenwei Yu, Email 3408003@zju.edu.cn; yzw_srrsh@zju.edu.cnAbstract: Imipenem is a broad-spectrum antibiotic that has been used in treating severe infections and exhibits a time-dependent PK/PD profile. Its dose should be adjusted based on renal function. However, there is little experience with imipenem dosing in obese adolescent patients with augmented renal clearance (ARC) and history of schizophrenia. This case reported successful dosing of imipenem in an obese adolescent patient with ARC based on therapeutic drug monitoring (TDM) and model-informed precision dosing (MIPD). A 15-year-old male adolescent patient with history of schizophrenia was diagnosed with ventilator-associated pneumonia due to carbapenem-susceptible Klebsiella pneumoniae and received imipenem treatment (0.5 g every 8 hours with a 1-hour infusion). However, the exposure of imipenem was suboptimal due to ARC, and there is no available model for MIPD in this patient. Thus, we utilized prediction error to find a population pharmacokinetic model that fit this patient and ran Maximum a posteriori Bayesian estimation and Monte Carlo simulation based on screened models to predict changes in drug concentrations. The dose of imipenem was adjusted to 0.5 g every 6 hours with a 2-hour infusion, and subsequent TDM revealed that dosing adjustment was accurate and successful. Finally, the patient’s status of infection improved. This study will be beneficial to imipenem dosing in similar cases in the future, thereby improving the safety and effectiveness of imipenem or other antibiotics.Keywords: case report, imipenem, therapeutic drug monitoring, population pharmacokinetic

Zhijun Zhang,1,2 Tiehong Yang,2 Jingwei Wang,2 Zhe Yu,2 Youbei Qiao,2 Chaoli Wang,2 Zhenggang Yue,1 Hong Wu2 1School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, People’s Republic of China; 2Department of Medicine Chemistry and Pharmaceutical Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of ChinaCorrespondence: Hong Wu, Department of Medicine Chemistry and Pharmaceutical Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of China, Tel/Fax +86 29 84776823, Email wuhong@fmmu.edu.cn Zhenggang Yue, School of Pharmacy, Shaanxi University of Chinese Medicine, Xi’an, People’s Republic of China, Tel +86 18092086211, Email liuxingjian1981@163.comPurpose: The remarkable peroxidase-like activity of single-atom nanozymes (SAzymes) allows them to catalyze the conversion of H2O2 to •OH, rendering them highly promising for antibacterial applications. However, their practical in vivo application is hindered by the near-neutral pH and insufficient H2O2 levels present in physiological systems. This study was aimed at developing a SAzyme-based nanoreactor and investigating its in vivo antibacterial activity.Methods: We developed a hollow mesoporous molybdenum single-atom nanozyme (HMMo-SAzyme) using a controlled chemical etching approach and pyrolysis strategy. The HMMo-SAzyme not only exhibited excellent catalytic activity but also served as an effective nanocarrier. By loading glucose oxidase (GOx) with HMMo-SAzyme and encapsulating it with hyaluronic acid (HA), a nanoreactor (HMMo/GOx@HA) was constructed as glucose-triggered cascade catalyst for combating bacterial infection in vivo.Results: Hyaluronidase (HAase) at the site of infection degraded HA, allowing GOx to convert glucose into gluconic acid and H2O2. An acid environment significantly enhanced the catalytic activity of HMMo-SAzyme to promote the further catalytic conversion of H2O2 to •OH for bacterial elimination. In vitro and in vivo experiments demonstrated that the nanoreactor had excellent antibacterial activity and negligible biological toxicity.Conclusion: This study represents a significant advancement in developing a cascade catalytic system with high efficiency based on hollow mesoporous SAzyme, promising the advancement of biological applications of SAzyme. Keywords: nanozyme, nanocarrier, glucose oxidase, reactive oxygen species, bacterial infection

Wanchun Cheng,1 Mohammad Mofatteh,2 José Fidel Baizabal-Carvallo,3,4 Shaohuan Lu,1 Ping Su,1 Yimin Chen,5,6 Luoming Li,1 Lizhi Qin,1 Xingmei Zuo,1 Yifeng Lan,7 Yue Huang,8 Zhihui Yu,9 Zirui Luo,10,&ast; Gang Chen10,&ast; 1Department of Neurology and National Stroke Center, The 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 2School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Belfast, UK; 3Parkinson’s Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA; 4Department of Sciences and Engineering, University of Guanajuato, León, Mexico; 5Department of Neurology and Advanced National Stroke Center, Foshan Sanshui District People’s Hospital, Foshan, People’s Republic of China; 6Neuro International Collaboration (NIC), Foshan, People’s Republic of China; 7Department of Radiology, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 8Department of Emergency, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 9Department of Laboratory Medicine, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China; 10Dean’s Office, the 5th People’s Hospital of Foshan City, Foshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zirui Luo; Gang Chen, Dean’s Office, the 5th People’s Hospital of Foshan City, Foshan, Guangdong Province, 528211, People’s Republic of China, Email ziruiluo@126.com; vikingsaga@163.comPurpose: Intravenous thrombolysis has emerged as an effective approach to improve the long-term survival and functional status of patients with ischemic stroke. The aim of this study was to assess the impact of a national stroke project on the door-to-needle-time (DNT).Patients and Methods: The patients were divided into pre-construction and construction periods. Construction Measures were performed during the construction period. The DNT and onset-to-needle time (ONT) were compared in two period groups.Results: After participating in the National Stroke Center Project and effective measurements, the thrombolysis treatment metrics were improved significantly. The DNT (IQR) was shortened from 65.0 (54.5,85.0) minutes in the Pre-Construction period to 40.0 (33.0,53.0) minutes in the Construction period (p < 0.001). Similarly, the ONT was reduced from 157.0 (IQR) (115.0,184.0) minutes to 116.0 (87.8,170.0) minutes (p = 0.035).Conclusion: The DNT time and ONT time can be shortened by National Stroke Center Construction projects. More suitable hospitals should be encouraged to participate as the National Stroke Center.Keywords: acute ischemic stroke, intravenous thrombolysis, door-to-needle time, onset-to-needle time

Yu Z, Chan S, Wang X, et al. Drug Des Devel Ther. 2023;17:993–1006. At the authors request, the Editor and Publisher of the journal Drug Design, Development and Therapy have retracted the published article. Following publication of the article, the authors raised concerns about the duplication of images from Figure 4. Specifically, The images for Figure 4G, HCT116, RUT and 5-FU, have been duplicated. The authors wished to apologize for this error and no longer have confidence in the data and corresponding findings. To maintain academic standards, the authors requested to retract the article and the Editor and Publisher agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Hao Qin,1,&ast; Wenjun Wang,2,&ast; Longlong Hu,1 Zuozhong Yu,1 Yang Chen,1 Yuanbin Zhao,1 Yanhui Liao,1 Renqiang Yang1 1Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Respiratory Diseases, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renqiang Yang, Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86-13979117790, Fax +86-0791-87357375, Email yangrenqiangcn@163.comBackground: Ischemic heart disease is one of the leading causes of death in the world, of which ST-segment elevation myocardial infarction (STEMI) is an important type. Inappropriate activation and accumulation of platelets typically induced thrombosis, which may result in acute vessel occlusion and STEMI. Multiple cytokines have been shown to regulate platelet activation, but the relationship between HMGB2 and platelet activation has not been elucidated.Methods: We collected peripheral blood of STEMI patients and healthy adults, and mass spectrometry analysis of platelet proteins was conducted. The “edgeR” package was used to identify the differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the significantly changed pathways. Western blot and ELISA were used to detect the expression of a high mobility group box 2 (HMGB2). Flow cytometric analysis and platelet aggregation rate were performed to evaluate the activation of platelets.Results: We identified ALOX5, HIST1H1B, S100A11, HMGB2, and RPS15A were the top five up-regulated proteins by differential expression analysis. Western blot verified that the relative protein expression of HMGB2 in platelet was significantly higher in STEMI patients compared with control adults, and the results of ELISA indicated that the serum HMGB2 level increased and significantly correlated with neutrophil count in STEMI patients. Further investigation showed that the platelet aggregation induced by ADP, the activation of integrin αIIbβ 3 and CD62P expression on platelet surface were all enhanced by the recombinant HMGB2 (rHMGB2).Conclusion: In conclusion, HMGB2 may be the key molecule to regulate platelet activation in patients with STEMI, which may serve as a potential therapeutic target for STEMI.Keywords: ST-segment elevation myocardial infarction, STEMI, proteomics analysis, platelet, HMGB2

Mengyuan Sui,1 Zhongbiao Yu,2 Mingxing Zhou1 1School of Administration and Law, Hunan Agricultural University, Changsha, People’s Republic of China; 2School of Management, University of Sanya, Sanya, People’s Republic of ChinaCorrespondence: Zhongbiao Yu, Email zhongbiaoyu@sanyau.edu.cnIntroduction: The report of the 20th Party Congress proposes to build a high-quality cadre capable of taking on the important task of national rejuvenation. Grassroots civil servants are facing great pressure and challenges, and alleviating burnout has become an important issue in the construction of grassroots civil servants. Empirically analysing the impact of psychological contract on burnout of grassroots civil servants in the Chinese context will help to build a high-quality grassroots civil service team.Methods: Using a sample of 1824 grassroots civil servants in China, this study empirically examined the effect of the psychological contract on burnout among grassroots civil servants using the OLS methodology, conducted a robustness test by way of substituting variables and research methods, and then discussed the mediating effect of physical and mental health in the psychological contract and burnout among grassroots civil servants.Results: The study showed that grassroots civil servants’ psychological contract had a significant negative impact on burnout; transactional psychological contract was positively related to burnout, and relational and developmental psychological contracts were negatively related to burnout in grassroots civil servants. The results of the heterogeneity analysis showed that the effect of psychological contract on burnout differed by age, gender, exercise frequency, and sleep status. The results of the mediation analysis showed that higher psychological contract scores were related to better physical and mental health, thus inhibiting burnout among grassroots civil servants. This indicates a significant mediation effect of physical and mental health in the relationship between psychological contract and burnout of grassroots civil servants.Conclusion: The psychological contract of grassroots civil servants has a significant negative effect on burnout, and physical and mental health mediate between the two. These conclusions are of great theoretical and practical significance for alleviating the stress of grassroots civil servants and improving their work performance.Keywords: psychological contract, grassroots civil servants, burnout, physical and mental health

Ao Li,1,2 Jinhua Yan,3 Ya Zhao,2 Zhenping Yu,4 Shane Tian,5 Abdul Haseeb Khan,2 Yuanzheng Zhu,2 Andong Wu,2 Cuntai Zhang,3 Xiao-Li Tian2 1Queen Mary School, Nanchang University, Nanchang, Jiangxi, 330031, People’s Republic of China; 2Aging and Vascular Diseases, Human Aging Research Institute (HARI) and School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang, Jiangxi, 330031, People’s Republic of China; 3Department of Geriatrics, Institute of Gerontology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Institute of Translational Medicine, School of Life Science, Nanchang University, and Jiangxi Key Laboratory of Human Aging, Nanchang, Jiangxi, 330031, People’s Republic of China; 5Department of Biochemistry/Chemistry, Ohio State University, Columbus, OH, USACorrespondence: Xiao-Li Tian; Cuntai Zhang, Email tianxiaoli@ncu.edu.cn; ctzhang@tjh.tjmu.edu.cnAbstract: Vascular aging represents a collection of structural and functional changes in a blood vessel with advancing age, including increased stiffness, vascular wall remodeling, loss of angiogenic ability, and endothelium-dependent vasodilation dysfunction. These age-related alterations may occur earlier in those who are at risk for or have cardiovascular diseases, therefore, are defined as early or premature vascular aging. Vascular aging contributes independently to cardio-cerebral vascular diseases (CCVDs). Thus, early diagnosis and interventions targeting vascular aging are of paramount importance in the delay or prevention of CCVDs. Here, we review the direct assessment of vascular aging by examining parameters that reflect changes in structure, function, or their compliance with age including arterial wall thickness and lumen diameter, endothelium-dependent vasodilation, arterial stiffness as well as indirect assessment through pathological studies of biomarkers including endothelial progenitor cell, lymphocytic telomeres, advanced glycation end-products, and C-reactive protein. Further, we evaluate how different types of interventions including lifestyle mediation, such as caloric restriction and salt intake, and treatments for hypertension, diabetes, and hyperlipidemia affect age-related vascular changes. As a single parameter or intervention targets only a certain vascular physiological change, it is recommended to use multiple parameters to evaluate and design intervention approaches accordingly to prevent systemic vascular aging in clinical practices or population-based studies.Keywords: vascular aging, arterial stiffness, endothelial function, arterial wall thickness, therapeutic intervention

Yefu Yu,1,&ast; Guier Yang,2,&ast; Yanan Wang,1 Faxiang Jin,1 Huiyu Wang,1 Zhongqiang Yu,3 Lanqing Li,4 Xiangcheng Li,4 Junshun Gao,4 Wenfang Xu1 1Department of Clinical Laboratory, Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 2Emergency Ward of Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 3Department of Imaging, Affiliated Hospital of Shaoxing University, Shaoxing, 312000, People’s Republic of China; 4Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, 310016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenfang Xu, Department of Clinical Laboratory, Affiliated Hospital of Shaoxing University, 999 Zhongxing South Road, Yuecheng District, Shaoxing, People’s Republic of China, Tel +8613857589470, Email 0052019050@usx.edu.cn Junshun Gao, Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, 3 Qingchun East Road, Shangcheng District, Hangzhou, People’s Republic of China, Email gjs_919@zuaa.zju.edu.cnBackground: Actinomadura geliboluensis was first isolated in 2012 in Gelibolu, Canakkale, Turkey, and has not been reported to be isolated from humans until now. We have isolated it from the bronchoalveolar lavage fluid (BLF) of a patient with pneumonia and found its drug resistance. It is the first time that Actinomadura geliboluensis has been isolated from humans since its discovery and naming. This case may provide new ideas and methods for the clinical diagnosis and treatment of pulmonary actinomycosis.Case Description: The patient was a 75-year-old male who was hospitalized in a township hospital and failed to improve after penicillin treatment. After admission to our hospital, the patient was treated with piperacillin/tazobactam according to clinical guidelines for 14 days. Actinomadura geliboluensis was isolated from the patient’s BLF and was identified by 16S rRNA sequencing. This report shows the biological characteristics and in vitro drug susceptibility testing, as well as the genomics analysis based on next-generation sequencing (NGS). The results demonstrated that Actinomadura geliboluensis was easy to be mistakenly identified as Actinomyces dental caries by using the Merieux ANC identification card. Based on the MIC test, Actinomadura geliboluensis was susceptible to tetracyclines, quinolones and sulfonamides, but resistant to carbapenems, penicillins and cephalosporins. The K-B test results showed Actinomadura geliboluensis was highly sensitive to piperacillin/tazobactam. Genomic analysis based on NGS showed that the Actinomadura geliboluensis belongs to Planobispora rosea EF-Tu mutants conferring resistance to inhibitor GE2270A, AAC(3)-VIIa, vanRO, chrB, and mexY.Conclusion: Actinomycetes is generally sensitive to Penicillin but Actinomadura geliboluensis is not. In vitro drug susceptibility test is needed to support individualized drug use to avoid delay in the disease.Keywords: Actinomadura geliboluensis, pulmonary actinomycosis, antibiotic resistance, next generation sequencing, genomics

Fenglei Wang, Zhiying Yu, Shasha Xue, Yunxiao Wang, Lin Li, Dabo Wang, Ling Wang Department of Ophthalmology, the Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Ling Wang, Department of Ophthalmology, the Affiliated Hospital of Qingdao University, University, No. 16 Jiangsu Road, Shinan District, Qingdao, 266003, People’s Republic of China, Tel +86 18661806679, Email tsingtaowl@hotmail.comPurpose: To investigate the differences in parameters related to angle configuration and lens position in patients with cortical age-related cataract by ultrasound biomicroscopy (UBM) in different body positions.Methods: Prospective study with 55 patients with cortical age-related cataract proposed for phacoemulsification, examined using a Compact Touch STS UBM (Quantel Medical, France). UBM bag/balloon technology was applied to measure the central anterior chamber depth (ACD) and lens vault (LV) in horizontal and vertical orientation in sitting and supine positions, angle opening distance (AOD500), trabecular iris angle (TIA) and iris lens angle (ILA) in four quadrants: superior, inferior, nasal, and temporal.Results: We found no significant difference in ACD between sitting and supine positions (p = 0.053); LV was significantly greater in the supine position (p < 0.001); AOD500 in superior and inferior quadrants were significantly longer in the sitting position (p = 0.001; p < 0.001); TIA in superior and inferior quadrants was significantly greater in the sitting position (p < 0.001; p < 0.001), and TIAmax-min was significantly smaller in the sitting position (p = 0.001); ILA in temporal quadrant was significantly larger in the sitting position (p = 0.015) and ILAmax-min was significantly smaller in the sitting position (p < 0.001).Conclusion: The anterior chamber angle was narrower and the lens was positioned more anteriorly in the supine than in the sitting position in cortical age-related cataract. Different positions may affect the angle configuration and the relative space of lens through different directions of mechanics and modes of action.Keywords: angle configuration, body position, ultrasound biomicroscopy, cortical age-related cataract

Yi Zhang,1,2 Yulin Zhang,3,&ast; Li Zhu,4,&ast; Zixiang Yu,5 Fangting Lu,1 Zhen Wang,1 Qiu Zhang1 1Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 3The Second Clinical Medical College, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 4Department of Endocrinology, Chaohu Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 5The First Clinical Medical College, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu Zhang, Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China, Email zhangqiu@ahmu.edu.cnIntroduction: Obesity in adults is a problem, particularly when paired with other metabolic abnormalities. Previous research have linked various screening approaches to diabetes, but additional evidence points to the relevance of combining diabetes screening methods with obesity and its effects. This research examined the impact of thyroid hormones (TSHs) and health risk factors (HRFs) in screening for obesity and diabetes in Chinese populations, and whether age can modulate this association.Methods: From March to July 2022, the Hefei Community Health Service Center connected with the First Affiliated Hospital of Anhui Medical University was chosen, and the multi-stage cluster sample approach was utilized to test adults aged 21– 90 in each community. Latent category analysis (LCA) was performed to investigate the clustering patterns of HRFs. A one-way ANOVA was used to examine waist circumference (WC), biochemical markers, and general data. Furthermore, multivariate logistic regression analysis was utilized to investigate the relationship between health risk variables and WC.Results: A total of 750 individuals without a history of major problems who had a community health physical examination were chosen, with missing data greater than 5% excluded. Finally, 708 samples were included in the study with an effective rate of 94.4%. The average WC was (90.0± 10.33) cm, the prevalence in the >P75, P50~P75, P25~P50, and ≤P25 groups were 24.7%, 18.9%, 28.7% and 27.7%, respectively. The average TSH was (2.76± 2.0) μIU/mL. Male (β=1.91), HOMA-IR (β=0.06), TyG (β=2.41), SBP (β=0.08), TG (β=0.94) and UA (β=0.03) were more likely to have a higher prevalence of WC level. The analyses revealed significant correlations between HRFs, TSH, age, other metabolic indexes and WC (P < 0.05).Discussion: Our findings suggest that the quality of metabolic-related indicators used to successfully decrease diabetes in Chinese individuals with high HRFs levels should be prioritized. Comprehensive indicators might be a useful and practical way for measuring the metabolic evolution of diabetes level levels.Keywords: health risk factors, diabetes mellitus, metabolic indicators, TSH, WC, diabesity

Wenwen Zhai,&ast; Huili Liu,&ast; Zhuoying Yu, Ye Jiang, Jing Yang, Min Li Department of Anesthesiology, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Li, Department of Anesthesiology, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 13522757239, Email liminanesth@bjmu.edu.cnPurpose: Cesarean section (C-section) is associated with moderate-to-severe postoperative pain. Many studies on pain management after C-section have been published in recent decades, many of which focused on new regional techniques. The purpose of this study is to outline the connections within the dynamic evolution of postcesarean delivery analgesia research publications using retrospective bibliometric analysis.Patients and Methods: Published studies on postoperative pain management of C-section were retrieved from the Science Citation Index Expanded (SCI-E) of Web of Science (WOS) Core collection database. All papers published from 1978 to October 22, 2022 were searched. The research progress and growing trend were quantitatively analyzed by total publications, research institutions, journal impact factors, and author’s contribution. Total citations frequency, average citations per item and h-index were used for evaluating literature quantity. Top 20 journals with the highest number of publications were charted. The keywords co-occurrence overlay map was visualized by the VOSviewer software.Results: From 1978 to 2022, a total of 1032 articles in postcesarean delivery analgesia research field were published, with 23,813 times cited, average citations of 23.07 per item, and an h-index of 68. The most high-yield publication year, countries, journals, authors, institutions were 2020 (n=79), the United States (n=288), Anesthesia and Analgesia (n=108), Carvalho B (n=25), and Stanford University (n=33), respectively. The United States had the most cited papers. The future research interest might be “prescription”, “quadratus lumborum block”, “postnatal depression”, “persistent pain”, “dexmedetomidine”, “enhanced recovery”, and “multimodal analgesia”.Conclusion: By employing the online bibliometric tool and VOSviewer software, we found that studies on postcesarean analgesia had grown markedly. The focus had evolved to nerve block, postnatal depression, persistent pain, and enhanced recovery.Keywords: postcesarean section, analgesia, bibliometric analysis, keywords analysis

Huan Liu,1,2,&ast; Zhiping Yu,3,&ast; Yueguang Liu,4 Mingzhen Li,1,2 Cheng Chen,1,2 Zhiyu Zhu,4 Fang Liu,4 Liming Tan2,3 1Department of Precision Medicine Center, The Second People’s Hospital of Huaihua, Huaihua, People’s Republic of China; 2Key Laboratory of Cancer Prevention and Treatment of Huaihua, Huaihua, People’s Republic of China; 3School of Pharmacy, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Department of Clinicopathology Center, The Second People’s Hospital of Huaihua, Huaihua, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liming Tan, The Second People’s Hospital of Huaihua, Lulin Road, Huaihua, 418000, People’s Republic of China, Email tanliming1973@126.comPurpose: C-type lectin domain family 4 member M (CLEC4M) has been found to be involved in the occurrence and development of cancer, but its role in NSCLC remains to be fully explored. Our work aims to evaluate the diagnostic and prognostic value of CLEC4M in NSCLC and to investigate the underlying mechanisms of CLEC4M in the immune microenvironment of NSCLC.Methods: Integrating publicly accessible data and clinical tissue samples to verify the expression of CLEC4M in NSCLC. The diagnostic value of CLEC4M was determined by receiver operating characteristic (ROC) curve. Kaplan–Meier survival analysis, nomogram plot, univariate and multivariate Cox regression models were performed to evaluate the prognostic impact of CLEC4M on NSCLC patients. The correlation between CLEC4M and tumor immune infiltration was estimated using TIMER and UALCAN databases. Functional assessments including GO, KEGG pathway and GSEA analyses were implemented to illustrate the potential mechanisms of CLEC4M in NSCLC.Results: CLEC4M was significantly downregulated in NSCLC tissue, as confirmed by immunohistochemistry of clinical tissues. The high AUC value of ROC curves demonstrated the diagnostic accuracy of CLEC4M in NSCLC. Additionally, low CLEC4M expression was associated with poor survival in NSCLC patients. Furthermore, CLEC4M was found to be significantly associated with tumor immune infiltration, and CLEC4M may be involved in immune activation and proliferation inhibition through the functional assessment, suggesting that CLEC4M may be a therapeutic target for NSCLC patients.Conclusion: Our findings reveal CLEC4M is significantly downregulated in NSCLC tissues, and illustrate the diagnostic and prognostic value of CLEC4M in NSCLC, as well as its potential serve as an immune-related therapeutic target.Keywords: CLEC4M, non-small cell lung carcinoma, NSCLC, prognosis, diagnosis, tumor immune microenvironment

Zhen Yu,1,&ast; Shixin Chan,2,&ast; Xu Wang,2 Rui Sun,2 Ming Wang,1 Zhenglin Wang,2 Xiaomin Zuo,2 Jiajie Chen,3 Huabing Zhang,4 Wei Chen1,2,5 1Department of General Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 3Department of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 4Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China; 5Anhui Provincial Institute of Translational Medicine, Hefei, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huabing Zhang, Department of Biochemistry & Molecular Biology, School of Basic Medicine, Anhui Medical University, Hefei, 230032, People’s Republic of China, Email slzhang1977@163.com; huabingzhang@ahmu.edu.cn Wei Chen, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 13966711566, Fax +86 0551-63633742, Email chenwei366@126.com; chenwei366@ahmu.edu.cnPurpose: To evaluate the effect of 5-fluorouracil (5-FU) combined with rutaecarpine (RUT) on the antiproliferative, anti-migratory, and apoptosis-promoting ability of colorectal cancer (CRC) cells and explore the underlying mechanism.Methods: The antiproliferative effects of RUT and 5-FU on CRC cells were evaluated using MTT and colony formation assays. Anti-migration was assessed by cell scratch and transwell tests. The synergistic effect of RUT and 5-FU was assessed by isobologram and combination index analysis using CompuSyn software. The effects of RUT and 5-FU on cell apoptosis were detected by flow cytometry. Differences in protein expression levels with or without RUT and/or 5-FU treatment were assessed by Western blot. Moreover, a mouse xenograft model of CRC was established to investigate the antitumor effect of RUT and 5-FU in vivo, and Ki67 and cleaved caspase-3 expression was detected by immunofluorescence.Results: In this study, we found that 5-FU combined with RUT can inhibit the proliferative, migratory, and antiapoptotic abilities of CRC cells to a significantly greater extent than either RUT or 5-FU alone both in vivo and in vitro. Western blot analysis showed that the level of signal transducer and activator of transcription 3 (STAT3) phosphorylation in CRC cells was significantly reduced after combination therapy compared with that seen with the respective monotherapies. In addition, combination therapy influenced the STAT3 signaling pathway, namely, it inhibited the expression of c-Myc, CDK4, and Bcl-2 while enhancing that of the proapoptotic protein cleaved caspase-3. Immunofluorescence staining further showed that the expression of Ki67 and cleaved caspase-3 was significantly downregulated and upregulated, respectively, in tumor tissues of mice treated with combination therapy compared with that observed with 5-FU treatment alone.Conclusion: Combined therapy with 5-FU and RUT exerted a superior curative effect in CRC than treatment with either single drug alone and has potential as a novel therapeutic modality for the treatment of CRC.Keywords: 5-fluorouracil, colorectal cancer, rutaecarpine, signal transducer and activator of transcription 3, synergistic therapy

Han Zhang,1– 3 Yefan Zhang,1– 3 Sen Sheng,1,2 Yang Xing,4 Zhongchen Mou,5 Yanqiu Zhang,1– 3 Zhixue Shi,1– 3 Zhenjie Yu,1,2 Qianqian Gao,1– 3 Weiqin Cai,1– 3 Qi Jing1– 3 1School of Management, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2“Health Shandong” Collaborative Innovation Center for Severe Social Risk Prediction and Governance, Weifang, People’s Republic of China; 3China Academy of Rehabilitation and Health, Weifang Medical University, Weifang, People’s Republic of China; 4Weifang People’s Hospital, Weifang, People’s Republic of China; 5School of Psychology, Weifang Medical University, Weifang, People’s Republic of ChinaCorrespondence: Weiqin Cai; Qi Jing, School of Management, Weifang Medical University, No. 7166 Baotongxi Street, Weifang, 261053, People’s Republic of China, Tel +8618106369128, Email caiwq@wfmc.edu.cn; jingq@wfmc.edu.cnObjective: Although physical exercise has been shown to boost physical, psychological, and psychiatric conditions in older adults, there is a relative lack of research on the mechanisms involved in this process for older adults with type 2 diabetes mellitus (T2DM). We thus evaluated whether sleep quality and depression mediated the relationship between physical exercise and cognitive impairment in older adults with T2DM by focusing on the exercise–physiology–psychology and psychiatry connection.Methods: Self-reported data were collected from 2646 older adults with T2DM in Weifang, Shandong, China. Regression and bootstrap analyses were conducted to explore the chain mediator model including physical exercise, cognitive impairment, sleep quality, and depression.Results: Engaging in physical exercise (coefficient = − 0.6858, p < 0.001), high levels of sleep quality (coefficient = − 0.3397, p = 0.015), and low levels of depression (coefficient = 0.3866, p < 0.001) were significantly associated with a low level of cognitive impairment. Sleep quality and depression mediated the chain effect between physical exercise and cognitive impairment (total effect = − 1.0732, 95% CI [− 1.3652, − 0.7862]; direct effect = − 0.6858, 95% CI [− 0.9702, − 0.3974]; indirect effect = − 0.3875, 95% CI [− 0.5369, − 0.2521]).Conclusion: Physical exercise may improve sleep quality in older adults with T2DM, alleviating depression and delaying the development of cognitive impairment. Physical exercise can enhance patients’ ability to resist depression and cognitive impairment, and creating comfortable sleep environments can also reinforce the effects of this process. These findings have important implications for promoting healthy aging in older adults with T2DM.Keywords: physical exercise, cognitive impairment, older adults, depression, sleep quality, type 2 diabetes

Hai Feng,1,&ast; Yunhui Zhuo,2,&ast; Xuemei Zhang,2 Yuyao Li,1 Yue Li,1 Xiangjuan Duan,2 Jia Shi,1 Chengbin Xu,3 Yueqiu Gao,1,2 Zhuo Yu2 1Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Informatics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yueqiu Gao, Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email gaoyueqiu@shutcm.edu.cn Zhuo Yu, Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email zhuoyu@shutcm.edu.cnAbstract: Hepatocellular carcinoma (HCC) remains a serious medical therapeutic challenge as conventional curative avenues such as surgery and chemotherapy only benefit for few patients with limited tumor burden. Immunotherapy achieves clinical progress in the treatment of this prevalent malignant disease by virtue of the development of tumor immunology; however, most patients have experienced minimal or no clinical benefit in terms of overall survival. The complexity and diversity of tumor microenvironment (TME) built by immune and stromal cell subsets has been considered to be responsible for the insufficiency of immunotherapy. The advance of bioanalytical technology boosts the exploration of the composition and differentiation of these infiltrated cells, which reflect the immune state of the TME and impact the efficacy of the antitumor immune response. Targeting these cells to remodel the TME is one of the important immunotherapeutic approaches to improve HCC treatment. In this review, we focused on the role of these non-cancerous cells in the tumor progression, and elaborated their function on cancer immunotherapy when manipulating them as potential targets.Keywords: immune cells, stromal cells, tumor microenvironment, hepatocellular carcinoma, immunotherapy

Jichan Shi,1,&ast; Gexin Gao,2,&ast; Zhijie Yu,3,&ast; Kaihuai Wu,4 Youquan Huang,5 Lian-Peng Wu,6 Zhengxing Wu,1 Xinchun Ye,1 Chaochao Qiu,1 Xiangao Jiang1 1Department of Infectious Disease, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2Department of Nursing School, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Hematology, Wenzhou Key Laboratory of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 4Departments of Infectious Diseases, Taishun People’s Hospital, Wenzhou, 325000, People’s Republic of China; 5Departments of Infectious Diseases, Yongjia People’s Hospital, Wenzhou, 325000, People’s Republic of China; 6Department of Laboratory, Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangao Jiang, Department of Infectious Disease of Wenzhou Central Hospital, The Dingli Clinical Institute of Wenzhou Medical University, 252 Baili East Road, Lucheng District, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel +86 13587691822, Fax +86 577 88070007, Email jiang_xiangao@126.comBackground: Tuberculosis (TB) is still the single pathogen infectious disease with the largest number of deaths worldwide. The relationship that intestinal microbiota disorder and de novo fatty acid synthesis metabolism have with disease progression in multi-drug resistant TB (MDR-TB) has not yet been fully studied.Objective: To investigate the effects of long periods of MDR-TB, pre-extensively drug-resistant TB (pre-XDR-TB), or rifampicin-resistant TB (RR-TB) on gut microbiome dysbiosis and advanced disease.Methods: The sample was chosen between March 2019 and September 2019 in Wenzhou Central Hospital and comprised 11 patients with pre-XDR-TB, 23 patients with RR-TB, and 28 patients with MDR-TB. Healthy individuals were chosen as the control group (CK group). An overnight fast blood sample was drawn via venipuncture into tubes without anticoagulant. For analysis, 300 mg of faeces from patients from the same group was mixed and analysed using DNA extraction, NGS sequencing, and bioinformatics. A QIAamp Fecal DNA Mini Kit was used to isolate the DNA. The extracted DNA was stored at − 20°C.Results: Advanced TB was concurrent with an elevated level of the proportions of acetyl-CoA carboxylase (ACC1) to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and fatty acid synthase (FASN) to GAPDH in de novo fatty acids synthesis, and Eubacterium, Faecalibacterium, Roseburia, and Ruminococcus were increased significantly in RR-TB patients compared to healthy individuals, whereas their abundance in the pre-XDR-TB and MDR-TB groups showed little change in comparison with the control group. Proteobacteria levels were greatly increased in the RR-TB and MDR-TB patient groups but not in the patients with pre-XDR-TB or the healthy subjects. The pre-XDR-TB group exhibited alterations of the intestinal microbiome: coliform flora showed the highest abundance of Verrucomicrobiales, Enterobacteriales, Bifidobacteriales and Lactobacillales. De novo fatty acids synthesis was enhanced in patients and was associated with the gut microbiome dysbiosis induced by the antimicrobials, with Bacteroidetes, Bacteroidales, and Bacteroidaceae displaying the most important correlations on a phylum, order, and family level, respectively.Conclusion: The progression to advanced TB was observed to be a result of the interaction between multiple interrelated pathways, with gut–lung crosstalk potentially playing a role in patients with drug-resistant TB.Keywords: multi-drug resistant TB disease, gut commensal, microbial imbalance, de novo fatty acids synthesis, microbiome biosignature alterations

Hao Cheng,1 Zhen Yu,1 Cheng-lan Yan,1 Hui-dan Yang,1 Chong Gao,2 Hong-yan Wen1 1Department of Rheumatology, Shanxi Medical University, the Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USACorrespondence: Hong-yan Wen, Email wenhongyan@sxmu.edu.cnBackground: Patients with systemic sclerosis (SSc) have poor prognosis without cure methods. We began, 10 years ago, to relieve active SSc using short-term intravenous high-dose methylprednisolone pulse (MP-Pulse) and then maintain remission using long-term and low-dose oral glucocorticoids (LTLD-GC).Methods: Total 46 of SSc patients with interstitial lung disease (ILD) and induration of skin during January 2006 to December 2019 were analyzed retrospectively, who were followed up for 10 years or more. The patients were treated with MP-Pulse (15 mg/kg/day, 4 days/week, for 2 weeks) with (n=21) or without (n=25) LTLD-GC (prednisone 5– 10 mg/day or methylprednisolone 4– 8 mg/day). The biographic and clinical data, including occurrence of infection or any adverse reactions, were collected at baseline, 6 months, 1 year, and annually through 10 years after treatment.Results: From baseline to 10 years, compared with MP-Pulse alone, MP-Pulse/LTLD-GC significantly reduced skin and lung fibrosis and improved lung function: Rodnan skin score (mRSS: 22.1± 12.4 to 8.16± 2.5, P< 0.001), forced vital capacity (FVC: 71.7% to 89.83%, P< 0.001), forced expiratory volume in the first second (FEV1: 75.7% to 87.88%, P< 0.001), diffusing capacity of the lung for carbon monoxide (DLCO: 63.4% to 87.73%, P< 0.001), and high-resolution chest computerized tomography scan (HRCT score: 3.96± 2.81 to 1.42± 0.83, P< 0.001). None of the 46 patients had femoral head necrosis, compression fracture, death, or life-threatening adverse events.Conclusion: These outcomes indicate that intravenous MP-Pulse combined with oral LTLD-GC could achieve significant remission and better long-term (10 years) efficacy without severe adverse effects in SSc patients with ILD and induration of skin.Keywords: glucocorticoids, low-dose, pulse, systemic sclerosis, safety

Chunyan Shao,1– 5,&ast; Ziwei Yu,1– 5,&ast; Tongwang Luo,1– 5,&ast; Bin Zhou,1– 5 Quanjiang Song,1– 5 Zhuoyue Li,1– 5 Xiaoqiang Yu,1– 5 Sheng Jiang,1– 5 Yingshan Zhou,1– 5 Wanyu Dong,1– 5 Xingdong Zhou,1– 5 Xiaodu Wang,1– 5 Houhui Song1– 5 1Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Hangzhou, Zhejiang, 311300, People’s Republic of China; 2Zhejiang Provincial Engineering Research Center for Animal Health Diagnostics & Advanced Technology, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, Hangzhou, Zhejiang, 311300, People’s Republic of China; 4China-Australia Joint Laboratory for Animal Health Big Data Analytics, Hangzhou, Zhejiang, 311300, People’s Republic of China; 5College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houhui Song; Xiaodu Wang, College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, Zhejiang, 311300, People’s Republic of China, Tel +86 15064890670 ; +86 18806537583, Email songhh@zafu.edu.cn; xdwang@zafu.edu.cnIntroduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication.Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot.Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi.Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.Keywords: chitosan-coated selenium nanoparticles, PRRSV, apoptosis, ROS, JNK signaling pathways

Yue Wang,1,&ast; Shuang Tan,2,&ast; Evenki Pan,3 Yutong Ma,3 Xue Wu,3 Zhe Yu,1 Kui Jiang1 1Department of Medical Oncology, the Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Department of Gynecology, the Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Geneseeq Research Institute, Nanjing Geneseeq Technology Inc, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kui Jiang; Zhe Yu, Department of Medical Oncology, the Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China, Tel +8617709873696 ; +8618641103913, Email jk0411@163.com; deepriveryu@outlook.comAbstract: Hormonal therapy is an important treatment option for estrogen receptor (ER)-positive patients with advanced ovarian cancer. Although ER overexpression has been previously used as an indicator for hormonal therapy, the clinical outcomes of advanced ovarian cancer patients receiving hormonal therapy remain unsatisfactory. Additional biomarkers for screening patients are needed to improve its efficacy. In this study, we reported a metastatic ovarian cancer case with estrogen receptor 1 (ESR1) gene amplification and protein overexpression, which showed sustained partial response to hormonal therapy, including letrozole and tamoxifen, and displayed an overall survival of 47 months. The response to the therapy was evaluated by imageological examinations, cancer antigen-125 (CA-125) tests, and circulating tumor DNA (ctDNA) sequencing using capture-based hybrid next-generation sequencing. Our clinical data suggested that ESR1 amplification might be a potential predictor of response to hormonal therapy in ovarian cancer. The combination of tumor detection techniques including imaging, CA-125 and ctDNA would enable confirmation of tumor response with high confidence.Keywords: ESR1 amplification, ovarian cancer, hormonal therapy, letrozole, tamoxifen, circulating tumor DNA

Jie Li,1,&ast; Siwen Chen,1,&ast; Hui Xue,2,&ast; Haoyi Wang,3,&ast; Tianwei Huang,4 Hongya Xie,5 Jiang He,6 Cai Ke,3 Zhaonan Yu,3 Bin Ni4 1Department of General Medical Ward, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of Oncology Medical Ward, Hanzhong Central Hospital, Hanzhong, People’s Republic of China; 3Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China; 4Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 5Department of Thoracic Surgery, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 6Department of Thoracic Surgery, Suzhou Wuzhong People’s Hospital, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Ni, Department of Thoracic Surgery, First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Tel +86 17774015977, Email bin_ni@163.com Zhaonan Yu, Hangzhou D.A. Medical Laboratory, Hangzhou, People’s Republic of China, Tel +86 15558078770, Email yuzhaonan870213@163.comIntroduction: From an oncologic perspective, genetic detection is becoming a frontline clinical test, used to identify actionable alterations for targeted therapy, monitor molecular clonal tumor evolution, indicate disease progression and prognosis, and predict medication efficacy and resistance. From analysis of both tumor tissue and cell-free DNA from a large cohort of non-small cell lung cancer patients in East-China, we characterized the full spectrum of genomic alterations.Methods: The study comprised 3000 unpaired samples including 1351 tumor tissue DNA (tDNA) and 1649 cell-free circulating tumor DNA (cfDNA) samples, from which 67 cancer-related genes were sequenced and the genetic alteration profiles were depicted. Integrative molecular analyses identified the frequently mutated genes, uncovered co-occurring somatic alterations, described the distribution of hotspot variants, analyzed the frequency of variant alleles, and notably distinguished actionable, novel variants.Results: The most commonly affected genes were EGFR, TP53, KRAS, CDKN2A, and PIK3CA in both tDNA and cfDNA samples. EGFR and CTNNB1, PIK3CA and PTEN, ERBB2 and SMO were found to have frequent co-occurring alterations in tDNA samples, while EGFR and SMO, KRAS and PDGFRA, PIK3CA and KDR were in cfDNA samples. A large number of primary druggable variants were identified in tDNA samples, while numerous drug-resistance variants, rare actionable variants, and non-EGFR actionable variants were detected in cfDNA samples. Novel variants were enriched in KDR, KIT, TP53, ABL1, FGFR1 in tDNA samples while the majority of novel variants were distributed in PDGFRA, EGFR, KIT, ROS1, BRCA2 in cfDNA samples. Variant allele frequency in tDNA samples was significantly (P < 0.001) higher than that in cfDNA samples.Conclusion: The results revealed considerable differences in the alteration characteristics between the two kinds of specimens. To date, this study represents the largest real-world investigation of its kind, derived from the largest number of patients in East-China. It reinforced and expanded the mechanism of molecular analysis of neoplastic genetic profiles.Keywords: real world study, non-small cell lung cancer patients in East-China, tumor tissue DNA, cell-free circulating tumor DNA, next-generation-sequencing, genetic alteration

Yue Liu,1,2 Bidong Fu,2 Zichuan Yu,2 Gelin Song,2 Hong Zeng,2 Yiyang Gong,2 Yongqi Ding,2 Da Huang3 1Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 2Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China; 3Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of ChinaCorrespondence: Da Huang, Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 13576113993, Email danmo0904@163.comPurpose: Hepatocellular carcinoma (HCC) is a malignancy with high incidence, but its prognosis is not optimistic. KRBA1 is a member of the KRAB family and participates in the regulation of gene transcription. However, no studies have focused on the role of KRBA1 in HCC.Patients and Methods: In this study, we first analyzed the expression of KRBA1 in HCC using TCGA and ICGC databases and validated by Immunohistochemistry in clinical HCC samples. The Wilcoxon rank-sum test was used to determine the relationship between KRBA1 expression and clinicopathological features. Subsequently, we used Kaplan-Meier online website analysis and Cox regression model to predict the prognostic value of KRBA1 in HCC patients. Furthermore, the functions of KRBA1 were identified by enrichment analysis. TIMER and GSCALite were used to investigate the relationship between KRBA1 expression in HCC and immune infiltration and drug targets, respectively. Finally, the relationship between KRBA1 expression and m6A modification in HCC was analyzed using the TCGA and ICGA datasets.Results: The results showed that KRBA1 was upregulated in HCC and was associated with many clinicopathological features. High KRBA1 causes poor overall survival and may be an independent risk factor for HCC. KRBA1 tends to be hypermethylated and associated with poor prognosis in HCC compared with normal tissues. Enrichment analysis indicates that KRBA1 is associated with cell cycle and immune processes, and TIMER analysis shows that KRBA1 expression is associated with infiltration levels and immune characteristics of various immune cells. Silenced KRBA1 evidently reduced three chemokine expression in HCC cells. Drug sensitivity analysis showed that KRBA1 was sensitive to 39 drug small molecules. KRBA1 showed a strong positive correlation with five m6A related genes.Conclusion: KRBA1 is a prognostic biomarker associated with HCC immunity and m6a modification, serving as an effective target for the diagnosis and treatment of HCC.Keywords: KRBA1, prognosis, biomarker, immune infiltration, hepatocellular carcinoma, m6A modification

Jing Zhao, Qianqian Kong, Minghuan Wang, Hao Huang, Xirui Zhou, Yinping Guo, Yi Zhang, Lingshan Wu, Zhiyuan Yu, Xiang Luo Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Xiang Luo, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Tel +86 27-83663337, Email flydottjh@163.comPurpose: Excessive daytime sleepiness (EDS) and cerebral small vessel disease (CSVD) are common problems among older adults; however, their association is not clear. The present study aimed to investigate the frequency of EDS in CSVD patients and the relationship between EDS and neuroimaging markers of CSVD.Patients and Methods: We conducted a cross-sectional study among 1076 community-dwelling older adults aged 55– 85 years. EDS was measured using the Epworth Sleepiness Scale (ESS), and EDS was defined as an ESS score greater than 10. Binary logistic regression was performed to assess the association between EDS and neuroimaging markers of CSVD.Results: Of the 1076 participants (mean age: 65.58 ± 6.46 years, 60.5% female), the prevalence of EDS was 10.0%. EDS was more frequent in participants with CSVD than in the total sample (20.0% vs 10.0%, p < 0.001). In fully adjusted models, EDS was significantly correlated with CSVD burden (OR = 1.39, 95% CI 1.16 to 1.68, p < 0.001), the severity of white matter hyperintensities (WMH) (OR = 1.33, 95% CI 1.14 to 1.54, p < 0.001), and presence of lacunes (OR = 2.47, 95% CI 1.53 to 4.00, p < 0.001) but not with the presence of cerebral microbleeds (CMBs) (OR=1.54, 95% CI 0.92 to 2.56, p = 0.099) or severity of enlarged perivascular spaces (EPVS) in basal ganglia (OR = 1.16, 95% CI 0.70 to 1.92, p = 0.564).Conclusion: We found a high frequency of EDS symptoms in CSVD individuals. Further, EDS was significantly associated with WMH, lacunes, and CSVD burden. Our findings further suggest patients with CSVD may exhibit abnormal sleep-wake patterns.Keywords: cerebral small vessel disease, daytime sleepiness, sleep disorders, white matter hyperintensities, lacunes

Yijin Chen,1,2,&ast; Hongtao Liu,2,3,&ast; Zhikang Yu,2,4 Yang Yang,1,2 Qingyan Huang,2,4 Changqing Deng,1,2 Hui Rao,2,4 Heming Wu2,4 1Department of Gastroenterology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Gastrointestinal Surgery, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heming Wu, Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of China, Tel +86 753-2131-591, Email wuheming1986@126.comBackground: Alcoholics are prone to alcoholic cirrhosis (ALC). Aldehyde dehydrogenase 2 (ALDH2) is involved in alcohol metabolism. Herein, the relationship between ALDH2 genotypes and ALC was analyzed among Hakka alcoholics in southern China.Methods: A total of 213 alcoholics and 214 non-alcoholics were included in the study. The ALDH2 gene rs671 polymorphism was analyzed, life history, disease history, and auxiliary examination results of these participants were collected.Results: The alcoholics had higher level of total serum protein, and serum globulin, lower level of serum albumin, serum albumin/globulin ratio, serum prealbumin, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) than non-alcoholics. In the 213 alcoholics, 180 developed ALC. There were 206 non-ALC persons in the 214 non-alcoholics. The proportion of the ALDH2 rs671 G/G homozygous (&ast;1/&ast;1) was significantly lower in ALC patients (83.3%) than that of other groups (100.0% in non-ALC in alcoholics, 95.6% in non-ALC in non-alcoholics), while the proportion of the G/A heterozygous (&ast;1/&ast;2) was significantly higher in ALC patients (16.7%) than that of other groups (0% in non-ALC in alcoholics, 4.4% in non-ALC in non-alcoholics). Logistic regression analysis indicated that participants with low level of NLR (adjusted OR 5.543, 95% CI 2.964– 10.368, P< 0.001), LMR (adjusted OR 9.256, 95% CI 4.740– 18.076, P< 0.001), and PLR (adjusted OR 6.047, 95% CI 3.372– 10.845, P< 0.001), and ALDH2 G/A genotype (adjusted OR 6.323, 95% CI 2.477– 16.140, P< 0.001) had a significantly higher risk of ALC.Conclusion: ALDH2 polymorphism rs671 &ast;1/&ast;2 genotype is a potential risk factor for the development of ALC among Hakka alcoholics.Keywords: ALDH2, alcoholics, alcoholic liver cirrhosis, gene polymorphism, Hakka

Shirui Li,1 Zhihui Gao,1 Meihan Zhong,1 Zhujun Yu,1 Jianan Li,2 Haoran Bi1,3,4 1Department of Biostatistics, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Key Laboratory of Environment and Health, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Center for Medical Statistics and Data Analysis, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Haoran Bi, Department of Biostatistics, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262660, Email bihaoran1989@sina.com Jianan Li, Key Laboratory of Environment and Health, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou, Jiangsu, 221004, People’s Republic of China, Tel/Fax +86-0516-83262659, Email lijianan512133@163.comPurpose: The emergence of the mutant virus has exacerbated the COVID-19 epidemic, and vaccines remain an effective and viable means of resistance. As a socially influential young group, university students’ awareness and acceptance of the COVID-19 vaccine are crucial to achieving herd immunity. This study aimed to assess the awareness and acceptance of the COVID-19 vaccine among Chinese university students and identify possible factors associated with their awareness level and vaccine hesitancy.Patients and Methods: An anonymous cross-sectional survey was conducted among Chinese university students between 10 and 28 June 2021. We collected information on the demographic characteristics, awareness and acceptance of the COVID-19 vaccine, and influencing factors. Sleep disturbances and anxiety disorders were also evaluated. Multinomial logistic regression analyses were performed.Results: Among the 721 participants (aged 18 to 23 years) with a female predominance (68.9%), 40.4% of cases exhibited moderate awareness the COVID-19 vaccine, and 87.4% of cases expressed high acceptance of the vaccine. Participants’ awareness of the COVID-19 vaccine was associated with gender, ethnicity, region of residence, grade level, satisfaction with current state of pandemic control, the perceived likelihood of a COVID-19 pandemic rebound, the source number of COVID-19 information, concerns about differences in vaccine manufacturers, acceptance of current state-approved vaccines and insomnia level. Furthermore, age, preferred channels for vaccination and the acceptance of current state-approved vaccines were significantly associated with their acceptance of the vaccine.Conclusion: This study reflected Chinese university students’ high acceptance, but insufficient awareness of the COVID-19 vaccine, some students have insomnia and anxiety problems. These require the government to take measures such as individualized publicity and education, adding professional psychological counseling courses to improve the university students’ awareness of vaccines and public health events, and comprehensively promote vaccination to cope with the ever-changing situation of the COVID-19 epidemic.Keywords: university students, COVID-19 vaccine, mental health, vaccine hesitancy

Yu Luo,1,2,&ast; Heming Wu,2,3,&ast; Qingyan Huang,2,3 Hui Rao,2,3 Zhikang Yu,2,3 Zhixiong Zhong2,3 1Department of Gynaecology, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Center for Precision Medicine, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhikang Yu; Zhixiong Zhong, Center for Precision Medicine, Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou People’s Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, People’s Republic of China, Tel +753-2131-591, Email yuzhikang01@126.com; zhongzhixiong01@126.comObjective: To investigate the frequencies of BRCA1 and BRCA2 mutations in Chinese Hakka patients with ovarian cancer.Methods: The protein coding regions and exon intron boundary regions of the BRCA gene were sequenced using genomic DNA isolated from the lymphocytes of patients with next-generation sequencing. The patients’ family history and clinical records were collected.Results: A total of 195 patients with ovarian cancer were included in the study, and 52 distinct variants of the BRCA gene were identified. It was found that 64 patients (64/195, 32.8%) had BRCA gene mutations, including 32 patients (50.0%) with BRCA1 mutation, 27 patients (42.2%) with BRCA2 mutation, and 5 patients (7.8%) with both mutations. Furthermore, 22 pathogenic mutations were detected in 26 patients, 2 likely pathogenic variants in 2 patients, 12 variants of uncertain significance in 20 patients, and 16 likely benign variants in 24 patients. The mutations were mainly found to occur in exons 8, 14, and 17 of BRCA1 and exons 10, 11, 14, and 15 of BRCA2. The results showed that the BRCA genes possess different mutation hotspots in different ethnic groups. In addition, recurrent mutations were noted in many patients. BRCA1 c.536 A>T, considered a founder mutation, was identified in 10 patients (15.63%, 10/64), followed by BRCA1 c.2635 G>T (6.25%, 4/64) and BRCA2 c.2566 T>C (6.25%, 4/64).Conclusion: The BRCA1 c.536 A>T could be considered to be a founder mutation in this ovarian cancer population. This recurrent BRCA1 mutation has rarely been observed in other ethnic groups. Our findings are expected to provide valuable data for clinical consultation and for designing individualized treatment for ovarian cancer.Keywords: BRCA gene, ovarian cancer, variants, Hakka population

Lu Zhang,1 Zitong Yu,2 Qingxi Qu,1 Xiao Li,1 Xue Lu,1 Hui Zhang1 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Department of Obstetrics, Shouguang People’s Hospital, Shouguang, 262700, People’s Republic of ChinaCorrespondence: Hui Zhang, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 107 Wenhua West Road, Jinan, 250012, People’s Republic of China, Email williamzh@126.comBackground: Long non-coding RNA (lncRNA) and exosomes are implicated in endometriosis development. We measured the expression of an exosomal lncRNA, homeobox transcript antisense RNA (HOTAIR), and explored its molecular mechanism in endometriosis progression.Methods: Expression of HOTAIR and microRNA (miR)-761 in different endometrial tissues was measured. Exosomes were isolated from a culture medium of endometrial stromal cells (ESCs). RT-qPCR was used to measure HOTAIR expression in different exosome types. CCK-8, Edu, wound healing, transwell assays, flow cytometry and tube formation were used to detect the role of exosomal HOTAIR on ESCs and human umbilical vein endothelial cells (HUVECs). The relationship among miR-761, HOTAIR, and histone deacetylase 1 (HDAC1) was verified by dual-luciferase reporter assay. ESCs were transfected with miR-761 mimics or HDAC1 small interfering RNA (si-RNA) to ascertain if alterations in expression of miR-761 or HDAC1 could reverse the effect of exosomal HOTAIR. Then, we detected the effect of the HOTAIR/miR-761/HDAC1 axis on signal transducer and activator of transcription 3 (STAT3)-mediated inflammation. In vivo experiments were conducted to verify in vitro results.Results: HOTAIR expression was upregulated and miR-761 expression was downregulated in ectopic endometrium tissues. HOTAIR was packaged into exosomes and transported from ESCs to surrounding cells. Exosomal HOTAIR promoted the proliferation, migration, and invasion, and inhibited the apoptosis of ESCs. Angiogenesis of HUVECs was enhanced after cultured with exosomal HOTAIR. HOTAIR acted as a competing endogenous RNA to downregulate miR-761 and increase HDAC1 expression. miR-761 overexpression or HDAC1 knockdown reversed the role of exosomal HOTAIR on ESCs and HUVECs. The HOTAIR/miR-761/HDAC1 axis could activate STAT3-related proinflammatory cytokines and stattic (inhibitor of phosphorylated-STAT3) could reverse the effect of HOTAIR on ESCs and HUVECs. In vivo experiments suggested that exosomal HOTAIR promoted the growth of endometrial lesions in vivo.Conclusion: Exosomal HOTAIR promoted the progression and angiogenesis of endometriosis by regulating the miR-761/HDAC1 axis and activating STAT3-mediated inflammation in vitro and in vivo, which may provide promising treatment for endometriosis.Keywords: endometriosis, HOTAIR, exosomes, miR-761, HDAC1, STAT3, inflammation

Yuyao Li,1,&ast; Yue Li,1,&ast; Jinghao Zhang,2 Longshan Ji,3 Man Li,3 Xuehua Sun,2 Hai Feng,1 Zhuo Yu,2 Yueqiu Gao1,2 1Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Laboratory of Cellular Immunity, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuo Yu; Yueqiu Gao, Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Pudong New District, Shanghai, 201203, People’s Republic of China, Tel +86 21 2025 6507, Fax +86 21 20256699, Email zhuoyu@shutcm.edu.cn; gaoyueqiu@shutcm.edu.cnAbstract: Hepatocellular carcinoma (HCC) is one of the leading lethal tumors worldwide, and the treatment remains a great medical challenge. Surgery and chemotherapy are current standard curative methods for patients with HCC, but the prognosis is still dismal. Based on unique medical theories and rich practical experience, traditional Chinese medicine (TCM) has been broadly employed to effectively treat HCC for a long history. Recently, systematic clinical trials have been well designed to study the efficacy of TCMs in the treatment of HCC, and the underlying antitumor mechanisms were also deeply explored. Here, we reviewed the published clinical evaluation of some commonly used TCMs in the treatment of HCC, and the related anti-HCC mechanisms through in vitro and in vivo study, promoting the modernization of TCM study in oncology for achieving a substantial reduction of HCC burden in the future.Keywords: traditional Chinese medicine, hepatocellular carcinoma, antitumor mechanism, tumor therapy, active ingredient

Xiao Ran,1 Dao Wen Wang,2 Zhen Yu,1 Rongxue Wu,3 Qin Zhang4 1Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China; 2The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China; 3Department of Biological Sciences Division/ Cardiology, University of Chicago, Chicago, IL, 60637, USA; 4Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of ChinaCorrespondence: Qin Zhang Email qzhang8@tjh.tjmu.cnAim: Tissue kallikrein (TK) exerts protective effects on cardiac cerebrovascular diseases (CCVDs). Changes in TK level in plasma are associated with ischemic stroke and coronary artery disease (CAD); however, a causal correlation could not be established. Therefore, we investigated the association between TK levels and CCVDs in a community-based cross-sectional study in China.Methods: A total of 6043 subjects (4242 men and 1801 women) were enrolled in this community-based cross-sectional study. Then, TK levels were measured using an enzyme-linked immunosorbent assay kit. Multivariate linear regression model and logistic regression were used to assess the correlations between TK levels and CCVDs. Subsequently, the receiver operating characteristic (ROC) curve was drawn to assess the value of TK level in evaluating the risk of ischemic stroke. Finally, the influence of various medications was evaluated on TK levels.Results: The TK level was significantly lower in subjects with ischemic stroke (P < 0.001) and hypertension (P < 0.001) and negatively associated with ischemic stroke (P < 0.001) but not associated with hypertension, coronary heart disease, and diabetes compared to the traditional risk factors. The diagnostic accuracy for ischemic stroke, as quantified by the area under the curve, was 0.892 (95% CI, 0.884– 0.900) for TK level, deeming it as a promising assessment tool. Moreover, no appreciable influence of various drugs therapy was found in TK levels (P = 0.222) except for those taking antilipemic agents.Conclusion: TK is a strong and independent endogenous protective factor against ischemic stroke in the Chinese population and could be a promising biomarker for the risk of ischemic stroke.Keywords: tissue kallikrein, ischemic stroke, cardiac cerebral vascular disease, risk factor

Zaoqin Yu,1,&ast; Wei Li,1,&ast; Xiaofang Shangguan,2 Yuanxuan Cai,2 Qianyan Gao,1 Ximin Wang,1 Yuan Chen,3 Dong Liu,1 Chengliang Zhang1 1Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Liu; Chengliang ZhangDepartment of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of ChinaTel/Fax +86-27-83663643; +86-27-83663519Email ld2069@outlook.com; clzhang@tjh.tjmu.edu.cnBackground: Despite the great signs of progress in cancer pain management in China, the associated pain remains under-treated. Poor knowledge among the medical staff is an important factor contributing to the under-treatment of cancer pain. This study aimed to evaluate the knowledge, practices, and perceived barriers in cancer pain management among the medical staff at oncology units in China.Patients and Methods: A cross-sectional survey was conducted with the medical staff (including physicians, nurses, and pharmacists) at oncology units in tertiary hospitals of China between December 2020 and January 2021. The questionnaire assessed the knowledge, practices, and perceived barriers in cancer pain management.Results: A total of 1262 medical staff responded to the questionnaire; the response rate was 94.2%. Most participants had good knowledge of the three-step analgesic ladder of the World Health Organization (WHO) and the National Comprehensive Cancer Network (NCCN) guidelines for Adult Cancer Pain. Knowledge deficit was prominent in questions on opioid dose titration and rotation and adverse effects of opioids; the correct response rate was less than 40%. Training, work experience in oncology, and education level were significantly related to knowledge of cancer pain management (all P < 0.001). In clinical practice for cancer pain management, approximately 57.2% of medical staff were unfamiliar with opioid dose titration and rotation; only 14.4% treated cancer pain through multidisciplinary collaboration. Poor medication compliance, difficult individualized analgesia protocols, and insufficient multidisciplinary participation were the most frequently perceived barriers by the medical staff for pain management.Conclusion: These findings suggested a further need for integrating recent guidelines to strengthen continued training (especially among juniors and those with low education levels) and patient education to improve the knowledge and clinical practices of cancer pain management among the medical staff in China. Multi-disciplinary management is required for the effective treatment of cancer pain.Keywords: cancer pain, medical staff, knowledge, practices, barriers, multi-disciplinary management

Xin Liu,1– 3,&ast; Yize Zhang,2,3,&ast; Zenghan Wang,1– 3 Liwen Liu,1– 3 Guizhen Zhang,1– 3 Jianhao Li,1– 3 Zhigang Ren,1– 3 Zihui Dong,2,3 Zujiang Yu1– 3 1Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 3Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zujiang Yu; Zihui Dong Email johnyuem@zzu.edu.cn; donghellen@163.comPurpose: Hepatocellular carcinoma (HCC) has high morbidity and poor prognosis due to the propensity of recurrence and metastasis. Emerging studies have confirmed that proline-rich coiled-coil2A (PRRC2A) plays a crucial role in tumorigenesis and immunoregulation. However, its expression status and biological functions in HCC remain poorly documented.Methods: The presence and prognostic value of PRRC2A were determined by a tissue microarray (TMA) cohort and multiple databases, mainly from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC). Functional enrichment analysis was applied to identify the mechanisms of PRRC2A in HCC. The biological function of PRRC2A in HCC progression in vitro was determined by CCK-8, colony formation, EdU, transwell migration and invasion assays. Moreover, the Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE), single-sample gene set enrichment analysis (ssGSEA), tumor immune dysfunction and exclusion (TIDE) algorithms, immunophenoscore (IPS) and public available immunotherapy cohorts were performed to classify their associations with tumor-infiltrating immune cells and immunotherapy.Results: PRRC2A was upregulated in HCC at both mRNA and protein levels. High PRRC2A expression was correlated with poor prognosis and could be an independent risk factor. Functional enrichment analysis demonstrated that elevated PRRC2A was significantly correlated with the activation of various oncogenic pathways. Additionally, in vitro experiments confirmed that silencing PRRC2A could suppress the proliferation and metastasis capacities of HCC cells. More importantly, PRRC2A was negatively associated with many anti-tumor immune cells, but positively related to the expression of markers of exhaustive T cells. And HCC patients with high PRRC2A were more likely to be nonresponsive to immunotherapy.Conclusion: This study explored the predictive value and biological roles of PRRC2A in HCC progression and indicated that it might be a potential biomarker for HCC patients and a predictor for immunotherapy.Keywords: hepatocellular carcinoma, PRRC2A, prognosis, immune infiltration, immunotherapy

Zhe Yu,1,&ast; Wei Wei,1,&ast; Hongruo Liu,1 Evenki Pan,2 Peng Yang,2 Kui Jiang1 1Department of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2Nanjing Genesseq Technology Inc., Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kui JiangDepartment of Medical Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of ChinaEmail jk0411@163.comAbstract: Metastatic castration resistant prostate cancer (mCRPC), the advanced stage of prostate cancer (PCa), develops resistance to first line androgen deprivation therapy (ADT). Aberrant androgen receptor (AR) and PI3K-Akt-mTOR signaling pathway are responsible for the development and progression of mCRPC. We herein describe a case of a 64-year-old male mCRPC patient with somatic AKT1 and AR mutations. The patient, who had been heavily pretreated by ADT and AR inhibitors, showed stable disease progression when he received everolimus, an mTOR inhibitor. The PSA level dropped drastically from 1493.0 ng/mL to 237.6 ng/mL, after 3 months of treatment. The overall survival (OS) was 43 months, of which the progression-free survival (PFS) with everolimus treatment was 7 months. The administration of mTOR inhibitor, everolimus, could achieve good clinical responses along with prolonging PFS for mCRPC patients harboring AKT1 mutations. Technology in precision medicine, such as targeted next-generation sequencing (NGS) of cancer-relevant genes, has promising function in personalized therapy.Keywords: castration resistant prostate cancer, androgen receptor, everolimus, next-generation sequencing

Jing Hu,1,&ast; Juanfen Gu,1,&ast; Zhiyan Yu,1 Xianxu Yang,1 Jian Fan,1 Lingying You,1 Qinyan Hua,1 Yuting Zhao,1 Yuerong Yan,1 Weiwei Bai,2 Zipeng Xu,3 Lina You,1 Chaobo Chen3,4 1Department of Postpartum Rehabilitation Center, Xishan People’s Hospital of Wuxi City, Wuxi, Jiangsu, People’s Republic of China; 2Department of Ultrasound, Xishan People’s Hospital of Wuxi City, Wuxi, Jiangsu, People’s Republic of China; 3Department of General Surgery, Xishan People’s Hospital of Wuxi City, Wuxi, Jiangsu, People’s Republic of China; 4Department of Immunology, Ophthalmology and ORL, Complutense University School of Medicine, Madrid, 28040, Spain&ast;These authors contributed equally to this workCorrespondence: Lina You; Chaobo Chen Tel +86 13812052853; +86 13585000831Email 21721140@qq.com; bobo19820106@gmail.comPurpose: The incidence of diastasis rectus abdominis (DRA) in parturients is continuously increasing, which may cause uncomfortable and affect the quality of life. The present study aims to retrospectively summarize the experience and efficacy in the treatment of DRA via standardized rehabilitation procedures in Eastern China.Methods: This retrospective study included the parturients with DRA admitted to the Xishan People’s Hospital of Wuxi between January 2017 and May 2021. Patients were separated into standardized rehabilitation group (SR) and non-standardized rehabilitation group (non-SR). The outcomes were the change in rectus abdominis separation and Physical Functioning Scale (PFS). Measurement data were compared between the two groups, and multivariate linear regression was used to analyze the factors associated with the standardized rehabilitation process. P values < 0.05 were considered statistically significant.Results: Among a total of 294 patients with DRA who were included in the study, 171 patients were treated with SR (SR), and the other 123 patients were treated without SR process (non-SR). Compared with non-SR, the separation of the rectus abdominis was significantly reduced in SR after standardized rehabilitation treatment (p value < 0.0001). The multiple linear regression model analysis results suggested that standardized rehabilitation was an independent factor influencing the prognosis of DRA in parturients (p < 0.0001). In addition, the quality of life of the study group was significantly improved (p < 0.0001).Conclusion: Standardized rehabilitation method revealed high efficiency in treating DRA in postpartum women and could improve the quality of life of parturients.Keywords: diastasis rectus abdominis, postpartum women, rehabilitation, Physical Functioning Scale

Weikang Chen,1,&ast; Wenhao Zhang,2,3,&ast; Tao Zhou,1,&ast; Jian Cai,1 Zhixian Yu,1 Zhigang Wu1 1Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Urology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixian Yu; Zhigang WuDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Road Lucheng District, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaEmail yuzx515@163.com; andrologywzg@wmu.edu.cnBackground: Bladder cancer (BC), as the most common urinary system tumor type and the main cause of tumor-related death, has an unsatisfactory prognosis. In recent years, related literature has proposed that cell pyroptosis is an inflammatory form of programmed cell death. However, in BC, the relationship between the expression of pyroptosis-related genes and the prognosis has not been elucidated.Methods: We got the RNA sequencing data from TCGA and GEO datasets. Fifty-two pyroptosis-related genes were extracted for further explore. Then, we compared the gene expression levels between the normal bladder and BC tissues. After that, we develop and validate a pyroptosis-related gene prognostic model and made following functional enrichment analysis and single-sample gene set enrichment analysis of the differentially expressed genes between the high- and low-risk groups.Results: Twenty-nine differentially expressed genes (DEGs) were found between normal and tumor tissues. Based on the median score calculated by the risk score formula from 8 pyroptosis-related genes, 414 patients were equally divided into low- and high-risk subgroups. The survival probability of BC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001). Through multivariate analysis, our risk score is an independent factor predicting OS in BC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis show that high-risk populations are rich in immune-related genes and have a decreased immune status. All the above results have been externally verified from GEO cohort.Conclusion: Pyroptosis-related genes are closely related to tumor immunity and are a potential prognostic tool for predicting BCs.Keywords: pyroptosis, bladder cancer, immune, prognosis, TCGA

Rui Shi, Ziwei Wang, Jun Zhang, Zhicheng Yu, Lanfen An, Sitian Wei, Dilu Feng, Hongbo Wang Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of ChinaCorrespondence: Dilu Feng; Hongbo WangDepartment of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, People’s Republic of ChinaTel +86 027 85350583Fax +86 278 572 6362Email fengdilu@126.com; hb_wang1969@sina.comPurpose: Endometrial cancer (EC) is a common gynaecologic malignancy with an increasing incidence rate and mortality in recent years. N6-methylandenosine (m6A)-related long noncoding RNA (lncRNA) plays a vital role in EC, emerging as one of the most abundant RNA modifications.Materials and Methods: The Cancer Genome Atlas (TCGA) database and UCSC Xena were used to download data related to EC. Survival and univariate and multifactorial prognostic analyses were performed for m6A-related lncRNAs. The expression levels of the three lncRNAs were verified using q-PCR. A nomogram was used to create a clinical tool to assess overall survival. To investigate the relationship between m6A-related lncRNA and EC, we downloaded differential genes related to EC from the TCGA database and mined three m6A-related lncRNAs, namely SCARNA9, TRAF3IP2-AS1, and AL133243.2. The data were categorized into high- and low-risk groups based on m6A-associated lncRNA.Results: Survival analysis revealed that the high-risk group had a lower survival rate. Survival analysis of three m6A-associated lncRNAs revealed that cases with high expression of SCARNA9 tended to have a poorer prognosis, whereas the opposite was true for TRAF3IP2-AS1, AL133243.2. Univariate and multifactorial prognostic analyses suggested statistical differences in patients’ age, FIGO stage, pathological grade, risk score, and prognosis of EC, which was confirmed by results of the separate prognostic factor analysis for the three lncRNAs. Risk status was validated as an independent prognostic indicator, and the prognostic nomogram combined patient age, pathological stage, and FIGO classification to assess 3– 5-year survival. Cases from high- and low-risk groups were analysed for the tumour microenvironment and immune cell scores, and stromal cell scores were found to be lower in the high-risk group. Correlations were analysed using different databases for immune cell classification.Conclusion: m6A-related lncRNAs may play a key role in the diagnosis and treatment of EC as targets of prognosis and the immune microenvironment.Keywords: N6-methylandenosine, long noncoding RNAs, endometrial cancer, tumour microenvironment