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Xiaofang Fu,1,* JiangYing Guo,2,* Xiaofei Gu,1 Liyan Chen,1 Jiangang Ju,1 Huaqiong Huang2 1The First People’s Hospital of Hangzhou Linping District, Zhejiang University School of Medicine Second Affiliated Hospital Linping Hospital, Hangzhou, Zhejiang, People’s Republic of China; 2Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huaqiong Huang, The Second Affiliated Hospital of Zhejiang University School of Medicine, Shangcheng District, Hangzhou, Zhejiang, 310009, People’s Republic of China, Tel +8615005818703, Email zr_hhq@zju.edu.cn Jiangang Ju, The First People’s Hospital of Hangzhou Linping District, Zhejiang University School of Medicine Second Affiliated Hospital Linping Hospital, Linping District, Hangzhou, Zhejiang, People’s Republic of China, Tel +8615372002070, Email LL0731QQ0516@163.comBackground: Preserved ratio impaired spirometry (PRISm) is considered to be one of the early chronic obstructive pulmonary disease states, and there are few studies on PRISm prevention. We aimed to evaluate the relationship between physical activity and the risk of PRISm.Methods: A cross-sectional study was conducted using data from US adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2012. We examined the association between physical activity and PRISm using multivariable logistic regression models and a restricted cubic spline (RCS) model.Results: Compared to the normal and chronic obstructive pulmonary disease (COPD) groups, the PRISm group had lower levels of physical activity (3537.2 MET-min/week in the normal group vs 3452.1 MET-min/week in the COPD group vs 2841.5 MET-min/week in the PRISm group). Adjusted multivariable regression models revealed that greater physical activity dose (more than 4800 MET-min/week) was associated with lower odds of PRISm (adjusted odds ratio [aOR] = 0.77, 95% confidence interval [95% CI] = 0.61– 0.98; P = 0.031). The RCS curve revealed that there was a significant nonlinear negative dose–response relationship between the level of physical activity and the risk of PRISm (Pnon-linearity

Weichao Li,1,2 YuYan Liu,2 Xunhu Gu1 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Anesthesiology, Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, QingYuan, Guangdong, People’s Republic of ChinaCorrespondence: Xunhu Gu, Doctor of Medicine (MD), Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email 540523118@qq.comBackground: Catecholamine vasopressors are commonly used for intra- or post-operative hypotension for cardiac surgery, which have a side effect of new-onset atrial fibrillation (AF) and myocardial ischemia. However, it is not entirely clear whether catecholamine vasopressors increase the risk of new-onset AF after noncardiac surgery.Aim: The aim of this study was to analyze the association between the use of catecholamine vasopressors and the risk of developing new-onset AF after noncardiac surgery.Methods: In this prospective trial, available data from eligible elderly individuals receiving noncardiac surgery at a single center from November 2022 to January 2024 were gathered. Propensity score matching (PSM) was used to balance patient baseline characteristics and to control for confounders. To determine the association between catecholamine vasopressors and the risk of new-onset AF, univariate and multivariate logistic regression analyses were performed.Results: A total of 6000 subjects were included in this study (mean [SD] age, 70.73 [6.37] years; 910 [50.9%] males). After PSM, the patients were stratified into catecholamine vasopressor (n = 357) and comparator groups (n = 1432). A total of 18/357 patients in the catecholamine vasopressor group developed AF, and 25/1432 patients in the comparator group developed AF (incidence rate, 5.0% vs 1.7%). Compared with the comparator group, the catecholamine vasopressor group had an increased risk of new-onset AF (aOR, 2.77; 95% CI, 1.28– 5.89). Some sensitivity analyses also revealed consistent findings of increased new-onset AF risk associated with catecholamine vasopressor treatment.Conclusion: The findings from this study suggest that catecholamine vasopressor treatment is associated with an increased risk of new-onset AF and may help physicians select a modest medication for patients while also assessing the risk of new-onset AF. Keywords: catecholamine vasopressors, new-onset atrial fibrillation, risk, prospective trial, noncardiac procedures

Yujuan Mao,1,* Tianjiao Hao,2,* Hongxiu Zhang,2,* Xiaofei Gu,2 Jing Wang,1 Feifei Shi,1 Xiaolan Chen,1 Liuna Guo,1 Jie Gao,1 Yan Shen,2 JinLin Zhang,3 Shenglan Yu4 1Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, Jiangsu, 225300, People’s Republic of China; 2Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 3Jiangsu Institute for Food and Drug Control, Nanjing, Jiangsu Province, 210019, People’s Republic of China; 4College of Animal Medicine, Jiangsu Agri-Animal Husbandry Vocational College, Taizhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shenglan Yu; JinLin Zhang, Email slyu70@126.com; zjluser@126.comIntroduction: Eprinomectin offers promise against parasitic infections. This study develops Eprinomectin (EPR) mixed micelles for transdermal delivery, aiming to enhance efficacy and convenience against endoparasites and ectoparasites. Physicochemical characterization and pharmacokinetic studies were conducted to assess its potential as an effective treatment for parasitic infections.Methods: Blank and EPR mixed micelles were prepared using PEG-40 Hydrogenated castor oil (RH-40) and Nonyl phenol polyoxyethylene ether 40 (NP-40). Critical micelle concentrations (CMC) determined using the pyrene fluorescence probe method. Particle size, EE, DL, in vitro release, permeation, and skin irritation were evaluated. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley rats.Results: Results show that EPR mixed micelles present suitable stability, physicochemical properties, and safety. Moreover, the rapid release and high bioavailability of EPR mixed micelles have also been verified in the study. Pharmacokinetic experiments in vivo showed that an improvement in the transdermal absorption and bioavailability of EPR after encapsulation in mixed micelles formulations.Conclusion: The results proved that the novel mixed micelles are safe and effective and are expected to become a promising veterinary nano-delivery system.Keywords: eprinomectin, mixed micelles, transdermal delivery, pharmacokinetics

KaiMing Wei,1,2,* Yuan Cao,1,3,* XiangJin Kong,1,2 ChuanZhen Liu,1,2 XingHua Gu1,2 1Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 3National Key Laboratory for Innovation and Transformation of Luobing Theory; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences; Department of Cardiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: XingHua Gu, Email guxinghua@email.sdu.edu.cnBackground: Cardiovascular diseases, such as aortic valve calcification (AVC) and carotid atherosclerosis (CAS), impose substantial health challenges on a global scale. Both disorders have overlapping risk factors, which might trigger similar immune-inflammatory reactions in both diseases.Methods: Shared differentially expressed genes (DEGs) were identified in the AVC and CAS datasets from the Gene Expression Omnibus (GEO). Candidate hub genes associated with immunity were identified using LASSO and immune cell infiltration analysis, and single gene set enrichment analysis (GSEA) was performed on the datasets. Subsequently, the hub genes were confirmed by qRT‒PCR validation in tissue samples.Results: A total of 140 upregulated and 65 downregulated common genes were screened. Enrichment analyses highlighted immune system processes, response to stress, and cytokine pathways among the identified CEGs. LASSO identified candidate hub genes, including ANGPTL1, CX3CR1, and CCL4. Immune cell infiltration analysis emphasized the participation of immune cells, including macrophages, γδ T cells, and resting NK cells. The three hub genes were validated by qRT‒PCR analysis.Conclusion: Our study explored immunological processes, including immune-related genes and cells, involved in the development of AVC and CAS. In particular, the identified hub genes ANGPTL1, CX3CR1, and CCL4 play crucial roles in mediating immune-inflammatory responses, which are central to the pathogenesis of these cardiovascular diseases, and the involvement of these genes in key immune pathways suggests that they could serve as potential biomarkers for early diagnosis or as targets for therapeutic strategies.Keywords: aortic valve calcification, carotid atherosclerosis, immune-related genes

Yihua Jin,1,* Zhimin Geng,1,2,* Kun Lin,1 Xinyu Gu,1 Xiwei Feng,1 Songling Fu,1 Wei Wang,1 Chunhong Xie,1 Yujia Wang,1 Fangqi Gong1 1Department of Cardiology, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Pediatric Cardiovascular Diseases Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangqi Gong; Yujia Wang, Email gongfangqi@zju.edu.cn; wangyujia@zju.edu.cnPurpose: Kawasaki disease (KD) is an acute systemic vasculitis that is associated with dysregulated immune responses. Monocytes play a central role in innate immunity. Our previous single-cell RNA sequencing of peripheral blood mononuclear cells (PBMC) revealed a new subset of monocytes in children with KD called L-Selectin+ classical monocytes (SELL+ CM). Therefore, we aimed to investigate the correlation between KD and SELL+ CM.Patients and Methods: Peripheral blood samples were collected from 81 KD patients, 18 febrile patients and 36 healthy children before treatment. Among them, ten KD patients were followed up, and samples were obtained before and after intravenous immunoglobulin (IVIG) treatment. Analysis of SELL+ CM was performed using flow cytometry. Additionally, ROC curve analysis was conducted to assess the diagnostic value of SELL+ CM for KD.Results: Classical monocytes (CM) expressed the highest levels of L-selectin in children with KD. The ratio of SELL+ CM in CM was significantly higher in KD patients than in febrile and healthy children. Following IVIG treatment, the ratio of SELL+ CM in CM showed a downward trend. The receiver operating characteristic (ROC) curve analysis (the area under the curve, AUC = 0.71) indicated the potential diagnostic value of SELL+ CM in KD. The correlation analysis suggested that SELL+ CM may serve as a new clinical index for patients with KD.Conclusion: In KD, the ratio of SELL+ CM in CM significantly increases during the acute phase, which may become a potential biomarker and help facilitate KD diagnosis based on clinical features.Keywords: Kawasaki disease, monocyte subsets, L-Selectin, coronary artery lesions

Kehua Jiang,1 Qing Wang,1 Xiao-Long Chen,1 Xiaodong Wang,1 Xiaoya Gu,1 Shuangshuang Feng,1 Jian Wu,2 Haojie Shang,2 Xiaozhuo Ba,2 Yanlong Zhang,1 Kun Tang2 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 2Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Yanlong Zhang, Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China, Email ylzhang3030@163.com Kun Tang, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Email tangsk1990@163.comAbstract: Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.Keywords: indoleamine 2, 3-dioxygenase 1, IDO1, IDO1 inhibitors, nanodrugs, nanodelivery, cancer immunotherapy, combination therapy

Xia Gu,1,2,* Hui Zhou,1,* Mengyue Miao,1 Daifeng Hu,1 Xinyue Wang,3 Jing Zhou,4 Alexander Tobias Teichmann,1 Youzhe Yang,1,5 Chunyan Wang1 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Gynaecology and Obstetrics, Leshan People’s Hospital, Leshan, 614003, People’s Republic of China; 3The Basic Medical College, Army Medical University, Chongqing, 400038, People’s Republic of China; 4Department of Endocrinology, Chengdu Third People’s Hospital, Chengdu, 610014, People’s Republic of China; 5Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Youzhe Yang; Chunyan Wang, The Affiliated Hospital of Southwest Medical University, NO. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email yangyouzhe@swmu.edu.cn; wangchunyan6813@swmu.edu.cnAbstract: Endometriosis (EMS) is defined as the appearance, growth, infiltration, and repeated bleeding of endometrioid tissue (glands and stroma) outside the uterus cavity, which can form nodules and masses. Endometriosis is a chronic inflammatory estrogen-dependent disease and occurs in women of reproductive age. This disorder may significantly affect the quality of life of patients. The pathogenic processes involved in the development and maintenance of endometriosis remain unclear. Current treatment options for endometriosis mainly include drug therapy and surgery. Drug therapy mainly ties to the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hormonal drugs. However, these drugs may produce adverse effects when used for long-term treatment of endometriosis, such as nausea, vomiting gastrointestinal reactions, abnormal liver and kidney function, gastric ulcers, and thrombosis. Although endometriosis lesions can be surgically removed, the disease has a high recurrence rate after surgical resection, with a recurrence rate of 21.5% within 2 years and 40% to 50% within 5 years. Thus, there is an urgent need to develop alternative or additional therapies for the treatment of endometriosis. In this review, we give a systematic summary of therapeutic multiple component prescriptions (including traditional Chinese medicine and so on), bioactive crude extracts of plants/herbs and purified compounds and their newly found mechanisms reported in literature in recent years against endometriosis.Keywords: endometriosis, treatment, multiple component prescriptions, extracts of plants/herbs, purified compounds, mechanisms

Yanwu Zhang,1,* Buasiyamu Abudunaibi,2,* Yunkang Zhao,2 Dongliang Zhang,1 Yanru Chu,1 Song Lei,1 Xiaomin Gu,1 Xuying Lao,1 Xianhao Wu,1 Weitao Yao,1 Yi Chen,1 Feng Tong1 1Department of Infectious Disease Control and Prevention, Ningbo Prefectural Center for Disease Control and Prevention, Ningbo, Zhejiang Province, People’s Republic of China; 2State Key Laboratory of Vaccines for Infectious Diseases, Xiang’ an Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng Tong; Yi Chen, Ningbo Prefectural Center for Disease Control and Prevention, Ningbo, Zhejiang Province, People’s Republic of China, Email tongfeng1031@163.com; 30279068@qq.comObjective: To conduct a comprehensive evaluation of the Dengue Fever Surveillance and Early Warning System deployed in Ningbo City during 2023, focusing on its capacity for timely identification and reporting of dengue fever cases, particularly imported cases from endemic regions.Methods: A detailed data of patient clinical features and blood profile trends was collected from clinical records and surveillance reports, focusing on the rapid diagnostic processes and surveillance rigor. This study assessed the effectiveness of the system in identifying and reporting dengue cases and identified the limitations of the existing framework through a basic statistical approach.Results: The system demonstrated timely identification and reporting of dengue fever cases, with a particular emphasis on imported cases. However, several limitations were identified, including the need for more precise monitoring criteria and improved coordination with medical entities.Conclusion: The study underscores the critical role of public health bodies in managing disease outbreaks and advocates for enhanced methodologies to refine epidemic control efforts. The findings contribute to the advancement of early warning mechanisms and the improvement of proactive infectious disease monitoring in metropolitan environments, providing valuable insights for fortifying the Dengue Fever Surveillance and Early Warning System in Ningbo City.Keywords: Dengue fever, Imported, Surveillance, Early-warning

Lili Liu,1,* Feifei Li,2,3,* Xinyu Gu,2,3 Runkai Jiao4,5 1School of Education, Changchun Normal University, Changchun, Jilin, People’s Republic of China; 2College of Education, Wenzhou University, Wenzhou, Zhejiang, People’s Republic of China; 3Center for Psychological and Behavioral Research, Wenzhou University, Wenzhou, Zhejiang, People’s Republic of China; 4School of Psychology, Northeast Normal University, Changchun, Jilin, People’s Republic of China; 5National Training Center for Kindergarten Principals, Ministry of Education, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feifei Li, Wenzhou University, Chashan Higher Education Park, Wenzhou, Zhejiang Province, 325035, People’s Republic of China, Tel +8615143003119, Email 20220053@wzu.edu.cnPurpose: Possessing a calling to teach is a core and essential quality of good kindergarten teachers, and it is critical to explore which factors positively impact kindergarten teachers’ career calling. Developing a career calling is a meaning-making process that can be influenced by the actions of others in the workplace. During the frequent parent-teacher interactions, parent-initiated support may serve as significant interpersonal cues for kindergarten teachers in developing their career calling. Thus, the present study examined the effect of parent-initiated support on kindergarten teachers’ career calling. Further, we investigated the multiple mediating roles of global and specific basic psychological need satisfaction based on the self-determination theory (SDT).Methods: Cross-sectional data were collected from 629 kindergarten teachers in China and analyzed using Mplus 8.3 software and the Process 3.5 macro of SPSS 26.0 software. Before testing the hypothesis, we used Mplus 8.3 to save factor scores from the Bifactor model of basic psychological need satisfaction and two uni-dimensional models of parent-initiated support and career calling. Subsequently, using the Process 3.5 macro within SPSS 26.0 software, we conducted path analysis to examine the total and mediating effects between parent-initiated support and kindergarten teachers’ career calling.Results: The results revealed a positive effect of parent-initiated support on teachers’ career calling. Teachers’ global and specific competence need satisfaction partially mediated this positive effect, while the mediating effects of teachers’ specific autonomy and relatedness need satisfaction were non-significant.Conclusion: These findings suggest that parent-initiated support is an important job resource for kindergarten teachers’ development of career calling. In addition to satisfying global psychological needs, satisfying specific needs (eg, competence need) provides additional benefits to kindergarten teachers’ experience of career calling.Keywords: parent-initiated support, career calling, basic psychological need satisfaction, kindergarten teacher, self-determination theory

Jiangpei Shi,1,* Rongguang Zhang,1,* Yu Wang,1 Yingwei Sun,1 Xiaoyan Gu,1 Yu An,1 Xinyu Chai,1 Xiaoyu Wang,2 Zhi Wang,1 Yaqi Lyu,1 Teng Guo,1 Nianping Feng,1 Ying Liu1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China*These authors contributed equally to this workCorrespondence: Nianping Feng; Ying Liu, Email npfeng@shutcm.edu.cn; debbyly@shutcm.edu.cnBackground: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging.Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb–nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum–Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid–polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC–Orbitrap–MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated.Results: The HNS reduced particle–mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer’s patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-β 1, which altered the TME in 4T1 tumor-bearing mice.Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.Keywords: herb–nanoparticle hybrid system, intestinal biological barrier, tumor microenvironment, breast cancer lung metastasis

Yuanyuan Cheng,* Tengfei Qi,* Xin Gu Department of Sexually Transmitted Disease, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Gu, Department of Sexually Transmitted Disease, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, No. 1278 Baode Road, Shanghai, 200443, People’s Republic of China, Tel +86-18017336858, Email gx3014@163.comAbstract: Syphilis is a complex, systemic infectious disease caused by Treponema pallidum subspecies pallidum. Secondary syphilitic lesions typically manifest within 3 months following initial exposure to T. pallidum. The predominant cutaneous manifestations of secondary syphilis are macula and papule. Certain individuals with syphilis may present with an atypical rash during the secondary stage owing to immunosuppression and other factors. Herein, we report a rare case of atypical recurrent secondary syphilis around the anus in a 65-year-old woman. Based on cerebrospinal fluid findings and skin biopsy results, the patient was ultimately diagnosed as neurosyphilis and recurrent secondary syphilis. Following intravenous antibiotic therapy, the patient’s rash improved significantly. This case underscores the importance for physicians to remain vigilant regarding the possibility of syphilis when encountering cases exhibiting unusual clinical manifestations, as a definitive diagnosis necessitates a comprehensive evaluation.Keywords: recurrent secondary syphilis, perianal annular rash, neurosyphilis, definitive diagnosis

You Zhang,1,* Chi Geng,1,* Yulun Zhou,1,* Feng Li,1 Siliang Peng,1 Xinru Guo,1 Xiaosong Gu,1 Jing Li,2 Hui Li1 1Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 2Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Li, Department of Cardiology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, 215006, People’s Republic of China, Email 9911263@163.com Jing Li, Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, People’s Republic of China, Email 18862130763@163.comBackground: Vascular adhesion protein-1 (VAP-1), an inflammation-inducible endothelial cell molecule, was reported to be implicated in a variety of cardiovascular diseases. However, the clinical significance of circulating VAP-1 levels in patients with coronary heart disease (CHD) remains less studied.Patients and Methods: We retrospectively analyzed clinical data of 336 hospitalized patients in the Second Affiliated Hospital of Soochow University from May 2020 to September 2022, 174 of which were diagnosed with CHD. Serum VAP-1 was measured by enzyme-linked immunosorbent assay at enrollment. The primary end point of this study was the occurrence of major adverse cardiovascular events (MACE). The coronary stenosis and clinical manifestations of CHD were assessed and recorded from medical records or follow-up calls. The relevant results were obtained, and the reliability of the conclusions was verified through regression analysis, curve fitting, and survival curve.Results: After adjusting for potential confounders, higher serum VAP-1 level was associated with increased risk of MACE in patients with CHD [(HR = 5.11, 95% CI = 1.02– 25.59), (HR = 5.81, 95% CI = 1.16– 29.11)]. The results of curve fitting and survival analysis were consistent with those of regression analysis. However, no significant association was observed between VAP-1 and MACE in the entire study population [(HR = 5.11, 95% CI = 0.41– 1.93), (HR = 1.17, 95% CI = 0.52– 2.62)]. Furthermore, the level of VAP-1 did not show a significant correlation with coronary stenosis and the clinical manifestations of CHD.Conclusion: These findings suggested that CHD patients with higher serum levels of VAP-1 are at a higher risk of adverse cardiovascular outcomes.Keywords: vascular adhesion protein-1, atherosclerosis, coronary heart disease, major adverse cardiovascular events

Daifeng Hu,1,* Mengyue Miao,1,* Hui Zhou,1 Xia Gu,1,2 Xuedan Wang,3 Alexander Tobias Teichmann,1 Qin Wang,1 Youzhe Yang1,2 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China; 3Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Wang; Youzhe Yang, The Affiliated Hospital of Southwest Medical University, NO. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email wangq@swmu.edu.cn; yangyouzhe@swmu.edu.cnAbstract: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors originating from perivascular epithelioid cells. In gynecological system, the uterus is one of the most common sites affected by PEComas. Most PEComas are benign, and patients usually have a good prognosis. However, malignant uterus PEComa is rare, and better comprehensive epidemiological investigations are needed. To date, there are a few reported cases of uterus PEComa. We herein report a rare case of malignant PEComa occurred in the uterine corpus and cervix, possibly accompanied by pulmonary lymphangioleiomyomatosis (PLAM). In addition, 55 cases of malignant uterus PEComa were picked out and collected in the data base of PubMed and Medline. On the one hand, the age of onset, population distribution, clinical manifestations, metastatic sites and routes of metastasis were analysed. On the other hand, a summary of the epidemiology, pathogenesis, diagnosis, and treatments of uterus PEComa was given.Keywords: perivascular epithelioid cell tumors, uterus, malignant, rare case, cervix

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

Suyang Guo,1 Wenqi Bai,1 Fengjie Cui,1 Xin Chen,1 Xiaojing Fang,1 Honghong Shen,2 Xianhua Gu1 1Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of China; 2Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical University, Bengbu, People’s Republic of ChinaCorrespondence: Honghong Shen, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical University, 287 Changhuai Road, Bengbu, Anhui, 233004, People’s Republic of China, Tel +8613385681156, Email shenhonghong1984@163.com Xianhua Gu, Department of Oncology Gynecology, The First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, 287 Changhuai Road, Bengbu, Anhui, 233004, People’s Republic of China, Tel +8613385680722, Email guxianhua1986@163.comIntroduction: GRHL1 belongs to the family of Grainyhead-like (GRHL). Previous studies have shown that dysregulation of growth and survival pathways is associated with the GRHL family of gene cancers. Immunotherapy with checkpoint inhibitors has changed the treatment paradigm for many tumors, including endometrial cancer (EC). However, the effect of GRHL1 on immunotherapy in EC and its relationship with immune cell infiltration are poorly understood.Methods: Differential expression of GRHL1 between EC and normal EC tissues was analyzed by searching the TCGA database, and the results were verified utilizing immunohistochemistry analyses. Next, the relationship between GRHL1, CD8+ T cells and tumor microenvironment (TME) was also investigated, and the effect of GRHL1 expression on immunotherapy in EC was evaluated.Results: According to the findings, EC tissues had elevated expression levels of GRHL1 relative to normal tissues. Patients with EC who expressed GRHL1 at high levels experienced worse overall survival (OS) and Progression-free survival (PFS) than those whose expression was lower. In addition, GRHL1 expression was negatively correlated with CD8+ T cells, and patients with high GRHL1 expression were less effective in receiving immunotherapy.Conclusion: The expression of GRHL1 was high in EC patients, and high expression of GRHL1 inhibits the proliferation of CD8+ T cells in the tumor microenvironment of EC and affect the efficacy of immunotherapy.Keywords: GRHL1, endometrial cancer, tumor microenvironment, CD8+ T cells, immunotherapy

Hui Yu,1 Xinyi He,1 Jinmeng Yao,1 Xiaoya Gu,1 Lin Zhou,1 Li Gao,1,2 Jia Wang1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Jia Wang; Li Gao, Email wangjia_80@163.com; gaoli23@mail.xjtu.edu.cnBackground: Molybdenum diselenide (MoSe2), as a nano near-infrared absorber, has been widely studied in the field of photothermal therapy of cancer. However, there is little research on its application in the treatment of human choriocarcinoma.Methods and Results: In this paper, a new type of carbon-coated MoSe2 (MEC) nanoparticles was prepared by a one-step hydrothermal method. The chemical characterization including SEM, TEM, EDS, XRD, FT-IR, TGA, Roman, and XPS showed that MEC was successfully synthesized. MEC exhibited a high photothermal conversion efficiency (50.97%) and extraordinary photothermal stability under laser irradiation. The cell experiment results showed that MEC had good biocompatibility on normal cells while significant photothermal effect on human choriocarcinoma (JEG-3) cells, achieving a good anticancer effect. The level of reactive oxygen species (ROS) in JEG-3 cells was significantly increased under the combination of MEC nanoparticles and near-infrared radiation. MEC nanoparticles could induce apoptosis of JEG-3 cells in combination with near-infrared radiation. Finally, transcriptomic analysis verified that MEC combined with laser radiation could inhibit DNA replication and induce apoptosis, thus improving its therapeutic effect on human choriocarcinoma.Conclusion: MEC nanoparticles exert an excellent photothermal effect and may become an important candidate drug for the treatment of human choriocarcinoma.Keywords: MoSe2, carbon-coated, biocompatibility, human choriocarcinoma, photothermal therapy

Yanjie Zhu,1,2 Xinkun Zhang,1,2 Guangfei Gu,1,2 Yunshan Fan,1,2 Zhi Zhou,1,2 Chaobo Feng,1,2 Xin Gu,3 Shisheng He1,2 1Department of Orthopedic, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Spinal Pain Research Institute, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Orthopedic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Shisheng He, Department of Orthopedic, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, 301 Yanchang Road, Shanghai, 200072, People’s Republic of China, Email tjhss7418@tongji.edu.cn Xin Gu, Department of Orthopedic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Shanghai, 200050, People’s Republic of China, Email guxin2004ty@163.comPurpose: To investigate the clinical outcomes of percutaneous transforaminal endoscopic discectomy assisted with selective nerve root block for treating radicular pain with diagnostic uncertainty in the elderly.Methods: A total number of 36 elderly patients were included in the study. Clinical outcomes collected for analysis include operative time, hospital stay time, Visual Analog Scale, and Oswestry Disability Index before and after the surgery, the global outcome based on the Macnab outcome criteria.Results: Seventeen males and nineteen females with a mean age of 73.72 ± 7.15 were included in this study. Radicular pain was the main complaint of all the patients with the least symptom duration of two months. Radiological findings showed that 80.6% of the patients with multilevel disc herniation, 16.7% received lumbar fusion surgery before, and 8.3% with degenerative scoliosis. Besides, 69.4% of the patients have at least one comorbidity. 85.4% of the patients showed a positive response to selective nerve root block, and 91.6% of the patients reported a favorable outcome at the last follow-up. The mean value of pre-operative leg pain was 7.56 ± 0.74 and dramatically decreased after surgery (2.47 ± 0.81, P < 0.001). Besides, the mean value of Oswestry Disability Index decreased from 43.03 ± 4.43 to 5.92 ± 5.24 (P < 0.001) one year after the surgery.Conclusion: Multilevel degeneration of the lumbar spine is common in elderly patients. Identifying the responsible segment and decompressing the nerve root through minimally invasive surgery can provide a satisfactory clinical outcome for those with radicular pain as their primary complaint. And selective nerve root block is a reliable diagnostic tool for those with an ambiguous diagnosis.Keywords: percutaneous transforaminal endoscopic discectomy, selective nerve root block, radicular pain, elderly, clinical outcome

Lien Wang,1,2 Xiaowei Chen,1 Xiaojing Gu,1 Heidi De Smedt,3 Vanina Popova,3 Dong-Jing Fu,4 Carla M Canuso,4 Wayne C Drevets,2 Guang Chen2 1Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Shanghai, People’s Republic of China; 2Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Brisbane, CA, USA; 3Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Beerse, Belgium; 4Janssen Research & Development, LLC, Janssen Pharmaceutical Companies of Johnson & Johnson, Raritan, NJ, USACorrespondence: Guang Chen, Janssen Fellow, Scientific Director, Translational Research, Mood DAS, Neuroscience Therapeutic Area, Janssen R & D, LLC, Janssen Pharmaceutical Companies of Johnson and Johnson, 3210 Merryfield Row, Room 1908, San Diego, CA, 92121, USA, Tel +1 (240) 602 7950, Email guangchenmd@gmail.comPurpose: This meta-analysis assessed whether atypical antipsychotics (AAPs) and esketamine nasal spray (ESK-NS), which are mechanistically distinct, differ in antidepressant outcomes.Patients and Methods: Data were extracted from 12 trials of ESK-NS or AAPs in depressed patients (4276) with inadequate response or resistance to conventional antidepressants. Montgomery-Åsberg Depression Rating Scale (MADRS) score reductions from baseline and response rates (≥ 50% reduction) were analyzed.Results: At endpoint, the estimated MADRS score reduction of pooled ESK-NS arms was greater than pooled AAP arms (+9.16 points, p < 0.0001). The reduction also was greater in the pooled control arms of the ESK-NS trials than the pooled control arms of the AAP trials (+7.57 points, p < 0.0001). The mean difference in the reductions between pooled ESK-NS and control arms was 1.87 points greater than that between pooled AAP and control arms, but this difference was not significant (95% CI: − 4.49, 0.74, p = 0.16). Relative to their respective control arms, the mean difference in response rates was 25% for the pooled ESK-NS and 9% for the pooled AAP arms; the mean response rate was 16% greater in the pooled ESK-NS studies than the pooled AAP studies (p = 0.0004). Comparisons against specific AAPs showed mean differences in the MADRS score reductions at 1 week between the experimental and control arms that were numerically larger in the ESK-NS trials than in the aripiprazole trials (mean difference of 1.71 points, p = 0.06) and the brexpiprazole trials (mean difference of 2.05 points, p = 0.02).Conclusion: The ESK-NS arms showed numerically larger MADRS score reductions at week-1 and endpoint, and a significantly larger response rate compared with AAP arms. Prospective studies involving direct comparisons are warranted to compare the relative efficacy between these treatment regimens.Keywords: major depressive disorder, treatment resistant depression, adjunctive and conjunctive treatment, atypical antipsychotics, esketamine nasal spray, rapid-acting

Xingchen Shang,1,2,&ast; Linfei Ye,1,&ast; Xiaohua Gu,3 Aihua Zhou,4 Yunmei Xu,5 Yiran Zhang,1 Yuexia Liao,1 Lin Li6 1School of Nursing, Yangzhou University, Yangzhou, People’s Republic of China; 2School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 3Delivery Room, Yangzhou Maternal and Child Care Service Centre, Yangzhou, People’s Republic of China; 4Delivery Room, Taizhou Second People’s Hospital, Taizhou, People’s Republic of China; 5Obstetrics and Gynecology Department, Baoying People’s Hospital, Yangzhou, People’s Republic of China; 6Department of Nursing, The Affiliated Hospital of Yangzhou University, Yangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Li, Department of Nursing, The Affiliated Hospital of Yangzhou University, No. 368, Hanjiang Middle Road, Yangzhou, 225000, People’s Republic of China, Tel +86 13585233313, Email 361350908@qq.comBackground: Most pregnant women do not reach the recommendation for physical activity (PA). As a subcategory of PA, exercise is also essential. Evidence on pregnant women’s attitudes and barriers to PA and exercise self-efficacy in China is scarce.Aim: To explore the levels and influencing factors of attitudes and barriers to PA and exercise self-efficacy among pregnant women.Methods: A cross-sectional study of 311 pregnant women was conducted from August to December 2022. Individual characteristics, pregnant women’s attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy were measured using the self-designed demographic questionnaire, pregnant women’s attitudes toward exercise questionnaire, barriers to prenatal PA and exercise questionnaire, and the pregnancy exercise self-efficacy scale, respectively.Results: More than 90% of pregnant women believed exercise benefits themselves and their babies, and 40.8% of pregnant women did not know how to exercise. Women encounter different types of barriers to PA and exercise. Intrapersonal barriers included the proportion of feelings of tiredness (56.6%), low energy (54.7%), lack of interest or motivation (49.2%), feelings of illness and morning sickness (46.6%), and large body weight (43.7%). Interpersonal barriers included pregnant women being advised to avoid PA and exercise (49.2%), lack of clear advice about the intensity and dose of exercise (41.8%), no one to exercise with (38.9%), and lack of advice from healthcare professionals (38.6%). Weather conditions were the most significant environmental barriers (41.2%). The total score of pregnancy exercise self-efficacy was (38.50± 7.33). Education level, parity, and attitudes toward exercise independently predict pregnant women’s attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy, respectively.Conclusion: Pregnant women have a favorable attitude toward exercise and relatively good exercise self-efficacy but lack knowledge of exercise. They face numerous barriers. Medical professionals should encourage pregnant women with lower levels of education to exercise and assist multipara in overcoming obstacles.Keywords: attitudes, barriers, exercise self-efficacy, physical activity, pregnancy

Xue Gu,1 Xia Shen,1 Jiang-Hui Chu,2 Ting-Ting Fang,2 Lei Jiang3 1Wuxi School of Medicine, Jiangnan University, Wuxi, People’s Republic of China; 2Department of Cardiothoracic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, People’s Republic of China; 3Department of Radiology, Huadong Sanatorium, Wuxi, People’s Republic of ChinaCorrespondence: Lei Jiang, Department of Radiology, Huadong Sanatorium, Wuxi, People’s Republic of China, Tel +86 13921272670, Email jiang178dajishan@163.comBackground: Lung cancer patients will have lung damage after surgery, need rehabilitation exercise. Common-sense model has shown the impact of patients’ perception of illness on health behaviors. However, for patients with lung cancer after thoracoscopic surgery, there has been no relevant exploration of disease perception.Objective: The purpose of this study was to investigate the clinical status of patients with lung cancer patients who have undergone thoracoscopic surgery, and to explore the correlation between frailty, disease perception, and lung functional exercise compliance.Methods: The cross-sectional study included 218 patients with lung cancer after thoracoscopic surgery. We collected participants’ frailty, disease perception, exercise adherence, and relevant clinical information. T-test, Chi-square, Linear regression, Pearson’s correlation, and mediation analysis were used for statistical analysis of patient data.Results: We analyzed the data by disease perception with high and low median scores and found significant differences in lymphatic dissection, stool within three days, pain, thoracic drainage tube placement time. Linear regression results show that, after controlling for confounding factors, frailty and disease perception were significantly associated with pulmonary function exercise compliance. The higher the frailty score, the worse the compliance, and the higher the disease perception negative score, the less exercise. Illness perception played a partially mediating role in the association between frailty and lung functional exercise adherence.Conclusion: Frailty and disease perception have an impact on exercise adherence, therefore, we need to consider these factors in the intervention to improve exercise compliance after thoracoscopic surgery for lung cancer.Keywords: frailty, illness perception, patient compliance, thoracoscopy, lung neoplasms

Jian Jun Gu,1,2,&ast; Tian Jian Du,1,2,&ast; Li Na Zhang,3,&ast; Jing Zhou,4 Xiang Gu,2 Ye Zhu2 1Department of Cardiology, Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Department of Cardiology, Northern Jiangsu People’s Hospital, Yangzhou, Jiangsu, People’s Republic of China; 3Department of Cardiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 4Key Laboratory of Animal Breeding Reproduction and Molecular Design for Jiangsu Province, College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Zhu; Xiang Gu, Department of Cardiology, Northern Jiangsu People’s Hospital, 98 Nantong West Road, Yangzhou, Jiangsu, People’s Republic of China, Email 307971331@qq.com; DZ120210035@yzu.edu.cnBackground: Heart failure (HF) is a common clinical syndrome due to ventricular dysfunction and is a major cause of mortality worldwide. Ferroptosis, marked by excessive iron-dependent lipid peroxidation, is closely related to HF. Therefore, the purpose of this study is to explore and validate ferroptosis-related markers in HF by bioinformatics analysis and animal experiments validation.Materials and Methods: The gene expression profiles (GSE36074) of murine transverse aortic constriction (TAC) were obtained from the Gene Expression Omnibus (GEO); From the FerrDb database, ferroptosis-related genes (FRGs) were identified. Using GEO2R, differential expressed genes (DEGs) were screened. An overlapping analysis was conducted among DEGs and FRGs to identify ferroptosis-related DEGs (FRDEGs). We then performed clustering, functional enrichment analysis, and protein-protein interaction (PPI) analyses. In addition, the key FRDEGs were extracted by cytoHubba plugin and the networks of transcription factors (TFs)-key FRDEGs and microRNA-key FRDEGs were constructed. Lastly, the key FRDEGs were carried by quantitative reverse transcription PCR (RT-qPCR) and immunohistochemistry (IHC).Results: Fifty-nine FRGs showing significantly different expression were identified from a total of 1918 DEGs in mice heart by transverse aortic constriction. GO and KEGG functional enrichment analysis revealed that these 59 ferroptosis-related DEGs mostly associated with positive regulation of apoptotic process, FoxO signaling pathway, VEGF signaling pathway, Apoptosis, Ferroptosis. Five key FRDEGs (Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2) were identified using PPI networks; Based on TFs-key FRDEGs networks, we found that Mapk14, Hif1a, Tlr4 and Ptgs2 were regulated by 3, 4, 5, and 29 TFs, respectively; however, Ddit3 was not regulated by any TF; By analyzing the miRNA–key FRDEGs networks, we found that 39, 74, 11, 28, and 18 miRNAs targets regulate the expression of Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2, respectively. Lastly, five key FRDEGs were validated at the mRNA and protein levels by RT-qPCR and IHC, which were in line with our bioinformatics analysis.Conclusion: Our findings reveal that Mapk14, Hif1a, Ddit3, Tlr4 and Ptgs2 may be involved in the development of HF through regulating ferroptosis and as potential targets for HF.Keywords: heart failure, transverse aortic constriction, ferroptosis, bioinformatics, key genes

Shamik Bafna,1 Xiaolin Gu,2 Helene Fevrier,3 Mohinder Merchea2 1Cleveland Eye Clinic, Brecksville, OH, USA; 2Alcon Vision LLC, Fort Worth, TX, USA; 3Verana Health, San Francisco, CA, USACorrespondence: Shamik Bafna, Cleveland Eye Clinic, 7001 S Edgerton Road, Brecksville, OH, 44141, USA, Tel +1 216-287-2060, Email sbafna@midwestvision.comPurpose: To determine the incidence of pseudophakic monovision among patients bilaterally implanted with monofocal intraocular lenses (IOLs) and to characterize the distribution of myopic offsets achieved.Patients and Methods: This retrospective database study included data on patients receiving care from ophthalmologists who contributed to the Academy IRIS® (Intelligent Research In Sight) Registry. Anonymized data were collected, including patient age, ethnicity, procedure data (CPT code, date, laterality), and postoperative manifest refractive spherical equivalent (MRSE) in both eyes implanted with monofocal or monofocal toric IOLs. No data regarding IOL manufacturer, model, or power were collected. One primary outcome measure was the percentage of patients achieving monovision (defined as emmetropia within ± 0.25 diopters [D] in one eye and a myopic offset of ≥ 0.50 D in the fellow eye) among all patients receiving bilateral monofocal IOLs at the time of cataract surgery between January 1, 2016, and September 1, 2019, with at least 90 days of follow-up. Other primary outcomes included the distribution and frequency of myopic offsets (anisometropia) between eyes.Results: Of the 16,765 people receiving bilateral monofocal IOLs within the study period, 4796 (28.6%) achieved emmetropia in at least one eye, as defined by an MRSE within ± 0.25 D. The incidence of monovision among these patients was 34.2% (1638/4796). One-quarter (24.7%; 405/1638) of patients who achieved monovision had a myopic offset between 0.50 and 0.74 D, with more than one-third (35.2%; 576/1638) falling within 0.75– 1.24 D and 18.0% within 1.25– 1.74 D. A myopic offset ≥ 1.75 D was observed in 22.1% (362/1638) of patients who achieved monovision.Conclusion: Pseudophakic monovision for presbyopia correction was achieved in ~34% of patients in the IRIS Registry bilaterally implanted with monofocal IOLs, with myopic offsets typically ranging from 0.5 to 1.24 D.Keywords: presbyopia, monovision, monofocal IOLs, myopic offset, diopter correction

Xianhua Gu,1,&ast; Honghong Shen,2,&ast; Guangzheng Zhu,3 Xinwei Li,2 Yue Zhang,2 Rong Zhang,1 Fang Su,2 Zishu Wang2 1Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 2Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 3Department of Surgical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Su; Zishu Wang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, 287 Changhuai Road, Bengbu, Anhui, 233004, People’s Republic of China, Tel +8613605523272 ; +86 18909620171, Email sufang2899@163.com; wzshahbb@163.comIntroduction: The complement system is integral to the innate and adaptive immune response, helping antibodies eliminate pathogens. However, the potential role of complement and its modulators in the tumor microenvironment (TME) of gastric cancer (GC) remains unclear.Methods: This study assessed the expression, frequency of somatic mutations, and copy number variations of complement family genes in GC derived from The Cancer Genome Atlas (TCGA). Lasso and Cox regression analyses were conducted to develop a prognostic model based on the complement genes family, with the training and validation sets taken from the TCGA-GC cohort (n=371) and the International Gene Expression Omnibus (GEO) cohort (n=433), correspondingly. The nomogram assessment model was used to predict patient outcomes. Additionally, the link between immune checkpoints, immune cells, and the prognostic model was investigated.Results: In contrast to patients at low risk, those at high risk had a less favorable outcome. The prognostic model-derived risk score was shown to serve as a prognostic marker of GC independently, as per the multivariate Cox analysis. Nomogram assessment showed that the model had high reliability for predicting the survival of patients with GC in the 1, 3, 5 years. Additionally, the risk score was positively linked to the expression of immune checkpoints, notably CTLA4, LAG3, PDCD1, and CD274, according to an analysis of immune processes. The core gene C5aR1 in the prognostic model was found to be upregulated in GC tissues in contrast to adjoining normal tissues, and patients with elevated expressed levels of C5aR1 had lower 10-year overall survival (OS) rates.Conclusion: Our work reveals that complement genes are associated with the diversity and complexity of TME. The complement prognosis model help improves our understanding of TME infiltration characteristics and makes immunotherapeutic strategies more effective.Keywords: complement genes, tumor microenvironment, gastric cancer, immune checkpoints, prognostic model

Yan Lan,1,2,&ast; Yu-Kun Zheng,3,&ast; Liu-Yi Wu,3 Zi-Jun Zhou,3 Ruo-Xin Guan,3 Heng Xu,3 Ji-Yuan Tu,3 Xin Gu,3 Rui Wang,3 Nan Jiang,3 Yuan Wu,4 Cheng-Ren Shu,1,2 Zhong-Shi Zhou3 1Department of Pharmacy, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Huangshi, Hubei, People’s Republic of China; 2Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention, Hubei, People’s Republic of China; 3College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, Hubei, People’s Republic of China; 4Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cheng-Ren Shu, Department of Pharmacy, Huangshi Central Hospital, NO. 141, Tianjin Road, Huangshi, Hubei, People’s Republic of China, Tel +86-27-13986590438, Email 397112615@qq.com Zhong-Shi Zhou, College of Pharmacy, Hubei University of Chinese Medicine, No. 1, Huangjiahu West Road, Hongshan District, Wuhan City, Hubei Province, People’s Republic of China, Tel +86-27-15871745189, Email monkeyzzs@126.comObjective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism.Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses.Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues.Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.Keywords: Polygonum cuspidatum, network pharmacology, MAPK/ERK, analgesic

Xiayan Xu,1– 3,&ast; Yun Xie,2– 4,&ast; Xia Gu,5– 7,&ast; Yang Zhou,2,3 Yu Kang,2,3,8 Jin Liu,2,3 Wenguang Lai,2– 4 Hongyu Lu,2,3 Shiqun Chen,2,3 Jun-yan Xu,2,3,9 Feng Lin,10 Yong Liu1– 3 1School of Medicine, South China University of Technology, Guangzhou, 510006, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, People’s Republic of China; 4School of Biology and Biological Engineering South China University of Technology, Guangzhou, 510006, People’s Republic of China; 5Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 6The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang, 150086, People’s Republic of China; 7Cardiovascular Imaging Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 8Shantou University Medical College, Shantou, 515041, People’s Republic of China; 9Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, College of Emergency and Trauma, Hainan Medical University, Haikou, 571199, People’s Republic of China; 10Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Lin, Shenzhen People’s Hospital, Shenzhen, 518020, People’s Republic of China, Email linfeng3085@163.com Yong Liu, South China University of Technology, No. 382, Waihuan East Road, University City, Panyu District, Guangzhou, Guangdong Province, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email liuyong@gdph.org.cnBackground: Blood glucose levels significantly affect the clinical prognosis of patients with coronary artery disease (CAD), and systemic immune inflammation is a common risk factor for both CAD and diabetes. However, the relationship between immune inflammation levels and poor prognosis in patients with CAD with different glucose metabolic statuses remains unclear.Methods: Between January 2007 and December 2020, we recruited 84,645 patients with CAD. The systemic immune inflammation index (SII) was used to comprehensively reflect the immune and inflammatory levels of patients and was calculated using the following formula: neutrophils × platelets/lymphocytes. The patients were classified into nine groups according to their glucose metabolism status (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]). Cox regression models and competing risk Fine and Gray models were used to investigate the association between SII and clinical outcomes.Results: During the follow-up period, 12,578 patients died, including 5857 cardiovascular-related and 1251 cancer-related deaths. The risk of all-cause and cause-specific mortality increased with increasing SII tertiles in CAD patients with NGR, pre-DM, and DM. When considering glucose metabolism status, the multivariate cox regression revealed that CAD patients with DM and SII-H levels had the highest risk of all-cause mortality (1.69 [1.56– 1.83]), cardiovascular mortality (2.29 [2.02– 2.59]), and cancer mortality (1.29 [1.01– 1.66]). Moreover, incorporating the SII into traditional risk factor models significantly improved the C-index for predicting all-cause and cardiovascular mortality.Conclusion: Systemic immune inflammation levels on admission were correlated with a higher risk of all-cause and cause-specific mortality in patients with CAD, particularly in those with DM.Keywords: systemic immune inflammation index, coronary artery disease, type 2 diabetes, prognosis, mortality

Hongyu An,1,&ast; Xiao Gu,2,&ast; Bojan Obrenovic,3,4,&ast; Danijela Godinic5,&ast; 1School of Journalism and Communication, Shanghai International Studies University, Shanghai, 201620, People’s Republic of China; 2Media Literacy Research Institute, Communication University of Zhejiang, Hangzhou, Zhejiang, 310018, People’s Republic of China; 3Zagreb School of Economics and Management, Zagreb, 10000, Croatia; 4Luxembourg School of Business, Luxembourg, 2453, Croatia; 5Faculty of Humanities and Social Sciences, University of Zagreb, Zagreb, 10000, Croatia&ast;These authors contributed equally to this workCorrespondence: Xiao Gu, Media Literacy Research Institute, Communication University of Zhejiang, Hangzhou, Zhejiang, 310018, People’s Republic of China, Tel +8613364104382, Fax +8613364104382, Email guxiao0705@163.com Bojan Obrenovic, Zagreb School of Economics and Management, Zagreb, 10000, Croatia, Email bojan.obrenovic@zsem.hrPurpose: The purpose of this study is to examine the combined effects and relationships between social media exposure, job insecurity, job stress, and anxiety among individuals and to propose an innovative model exploring how these factors contribute to increased anxiety.Patients and Methods: This empirical research paper focuses on understanding the role of job insecurity, social media exposure, and job stress in predicting anxiety levels. The study was conducted on a sample of 292 white-collar employees in various organizations and institutions across the United States amid the COVID-19 pandemic and the ongoing economic crisis, during the broader transition to a digital working environment. A self-report Likert-type questionnaire was administered to measure employees’ job stress, uncertainty, anxiety levels and social media exposure. The present study employed theoretical background of Lazarus’ Theory of Psychological Stress and the JDR Model. Structural equation modeling (SEM) was used to examine the relationships between these constructs, while confirmatory factor analysis (CFA) was conducted to assess the validity of the measurement model.Results: The study provides empirical support for the claim that employees with pervasive job stress will likely develop anxiety symptoms. It also highlights the mechanisms by which social media exposure increases employees’ anxiety levels and how management and policymakers can buffer the stressors.Conclusion: The research emphasizes the importance of addressing occupational mental health problems, and the implications of the findings indicate the need for managerial interventions in securing effective measures for buffering stress and controlled social media usage. This study contributes to the body of knowledge by informing managers and policymakers on key aspects to consider in promoting psychological balance and a healthy organizational climate.Keywords: anxiety, job stress, social media use, JDR-model, Lazarus theory of stress, psychological wellbeing

Xianhua Gu,1,&ast; Honghong Shen,2,&ast; Zheng Xiang,3 Xinwei Li,2 Yue Zhang,2 Rong Zhang,1 Fang Su,2 Zishu Wang2 1Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 2Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 3Department of Surgical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Su; Zishu Wang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, 287 Changhuai Road, Bengbu, Anhui, 233004, People’s Republic of China, Tel +8613605523272 ; +86 18909620171, Email sufang2899@163.com; wzshahbb@163.comIntroduction: GPR176, an orphan G protein-coupled receptor (GPCR), is essential for the progression of gastrointestinal cancers. However, it is still unclear how GPR176 affects tumor immunity and patient prognosis in gastric cancer (GC).Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were searched in this investigation to assess the expression patterns of GPR176 in GC tissues and normal gastric mucosa. The findings were further verified using immunohistochemical tests and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). The Kaplan-Meier method, univariate logistic regression, and Cox regression were then used to investigate the relationship between GPR176 and clinical traits. Additionally, the potential correlation between GPR176, immune checkpoint genes, and immune cell infiltration levels was investigated.Results: As per the research findings, GC tissues had higher levels of GPR176 than normal tissues. Additionally, individuals with high expression of GPR176 had a worse 10-year overall survival (OS), in contrast with those having a low expression of GPR176 (p < 0.001). The OS of GC can be predicted using a validated nomogram model. The expression of GPR176 demonstrated a negative correlation with CD8+ T cells. When compared to the low-expression group of GPR176, Tumor Immune Dysfunction and Exclusion (TIDE) analysis demonstrated that the high-expression group had a considerably higher risk of immune evasion. A remarkable difference (variation) was observed in the levels of GPR176 expression across both groups, ie, low and high-risk groups, as determined by the immune phenomenon scores (IPS) immunotherapy assessment.Conclusion: By examining GPR176 from various biological perspectives, it was determined that GPR176 can act as a predictive biomarker for poor patient prognosis in GC. Additionally, it was observed that GPR176 is capable of suppressing the proliferation of CD8+ T cells and facilitating immune evasion.Keywords: GPR176, gastric cancer, tumor microenvironment, immunotherapy, immune escape

Tao Jiang,1,&ast; Yuan Chen,1,&ast; Xia Gu,1,2 Mengyue Miao,1 Daifeng Hu,1 Hui Zhou,1 Jing Chen,3 Alexander Tobias Teichmann,1 Youzhe Yang1,2 1Sichuan Provincial Center for Gynaecology and Breast Diseases, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Luzhou, 646000, People’s Republic of China; 3Reproductive Medicine Center, The Second People’s Hospital of Yibin, Yibin, 644000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Alexander Tobias Teichmann; Youzhe Yang, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou, 646000, People’s Republic of China, Email alexandertobiasteichmann@swmu.edu.cn; yangyouzhe@swmu.edu.cnAbstract: Endometriosis is a hormone-dependent inflammatory disease characterized by the existence of endometrial tissues outside the uterine cavity. Pharmacotherapy and surgery are the current dominant management options for endometriosis. The greater incidence of recurrence and reoperation after surgical treatment as well as the adverse effects of medical approaches predispose patients to potential limitations for their long-term usage. Consequently, it is essential to explore novel supplementary and alternative drugs to ameliorate the therapeutic outcomes of endometriotic patients. Resveratrol is a phenolic compound that has attracted increasing interest from many researchers due to its pleiotropic biological activities. Here, we review the possible therapeutic efficacies and molecular mechanisms of resveratrol against endometriosis based on in vitro, animal, and clinical studies. The potential mechanisms of resveratrol include anti-proliferative, pro-apoptotic, anti-angiogenic, anti-oxidative stress, anti-invasive and anti-adhesive effects, thereby suggesting that resveratrol is a promising candidate for endometriosis. Because most studies have investigated the effectiveness of resveratrol on endometriosis via in vitro trials and/or experimental animal models, further high-quality clinical trials should be undertaken to comprehensively estimate the clinical application feasibility of resveratrol on endometriosis.Keywords: endometriosis, resveratrol, therapeutic efficacies, molecular mechanisms, clinical application

Honghong Shen,1,&ast; Xianhua Gu,2,&ast; Huiyuan Li,1 Mingyue Tang,1 Xinwei Li,1 Yue Zhang,1 Fang Su,1 Zishu Wang1 1Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China; 2Department of Gynecology Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fang Su; Zishu Wang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, 287 Changhuai Road, Bengbu, Anhui, 233004, People’s Republic of China, Tel +8613605523272 ; +86 18909620171, Email sufang2899@163.com; wzshahbb@163.comIntroduction: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer. It is the fourth leading cause of cancer-related death worldwide. Deregulation of the ATF/CREB family is associated with the progression of metabolic homeostasis and cancer. Because the liver plays a central role in metabolic homeostasis, it is critical to assess the predictive value of the ATF/CREB family in the diagnosis and prognosis of HCC.Methods: Using data from The Cancer Genome Atlas (TCGA), this research evaluated the expression, copy number variations, and frequency of somatic mutations of 21 genes in the ATF/CREB family in HCC. A prognostic model based on the ATF/CREB gene family was developed via Lasso and Cox regression analyses, with the TCGA cohort serving as the training dataset and the International Cancer Genome Consortium (ICGC) cohort serving as the validation set. Kaplan-Meier and receiver operating characteristic analyses verified the accuracy of the prognostic model. Furthermore, the association among the prognostic model, immune checkpoints, and immune cells was examined.Results: High-risk patients exhibited an unfavorable outcome as opposed to those in the low-risk category. Multivariate Cox analysis revealed that the risk score calculated based on the prognostic model was an independent prognostic factor for HCC. Analysis of immune mechanisms revealed that the risk score had a positive link to the expression of immune checkpoints, particularly CD274, PDCD1, LAG3, and CTLA4. Differences in immune cells and immune-associated roles were found between the high- and low-risk patients, as determined by single-sample gene set enrichment analysis. The core genes ATF1, CREB1, and CREB3 in the prognostic model were shown to be upregulated in HCC tissues as opposed to adjoining normal tissues, and the 10-year overall survival (OS) rate was worse among patients with elevated expression levels of ATF1, CREB1, and CREB3. Elevated expression levels of ATF1, CREB1, and CREB3 in HCC tissues were confirmed by qRT-PCR and immunohistochemistry studies.Conclusion: According to the results of our training set and test set, the risk model based on the six ATF/CREB gene signatures predicting prognosis has certain predictive accuracy in predicting the survival of HCC patients. This study provides novel insights into the individualized treatment of patients with HCC.Keywords: hepatocellular carcinoma, ATF/CREB transcription factors, immune checkpoints, prognostic model, nomogram

Xiaoli Zhang,1,&ast; Jiao Zeng,1,&ast; Xin Gu,1 Fan Zhang,1 Yongkai Han,1 Ping Zhang,1 Qun Wang,2,3 Renjun Gu1 1Department of Neurology, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renjun Gu, Department of Neurology, The Second Affiliated Hospital of Xinxiang Medical University, Qianjin Road, No. 207, Xinxiang, Henan, People’s Republic of China, Tel +86 0373-3373704, Email gurenjun1961@163.com Qun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Nansihuanxi Road, No. 119, Beijing, People’s Republic of China, Tel +86 010-59975052, Email wangq@ccmu.edu.cnBackground and Study Aims: Antiepileptic drugs are the first choice of treatment for patients with epilepsy. However, the withdrawal of antiepileptic drugs after seizure-free remains a significant focus for the majority of patients with epilepsy and their families. In this study, we evaluated the risk factors associated with relapse after drug withdrawal in patients with seizure free for 2 years. We aimed to guide patients in seizure-free to assess the risk of drug withdrawal.Patients and Methods: Through screening, 452 patients with epilepsy were included in the study.Patients were followed up for at least 2 years or more. Analyzed their clinical data by applying the χ 2-test, Kaplan-Meier survival analysis and multivariate Cox regression analysis.Results: 423 patients completed follow-up, of which 304 cases recurred (71.9%).Related recurrence factors include age of onset, type of seizure, number of AEDs, seizure-free time before withdrawal, and electroencephalogram (EEG) results before drug withdrawal (P< 0.05). The results of correlation analysis showed that age of onset, seizure frequency, seizure type, number of AEDs, the period from AEDs treatment to a seizure-free status, EEG results before drug withdrawal, and pre-medication course, were all significantly related to the recurrence of seizures after drug reduction and withdrawal (P< 0.05). We identified a range of independent risk factors, including onset age, seizure frequency, Multiple AEDs and the period from AEDs treatment to a seizure-free status.Conclusion: The overall recurrence rate of epilepsy in our patient cohort was high, and the peak recurrence period was within one-year of drug withdrawal. Patients with partial seizures, a short seizure-free time before withdrawal, severe EEG abnormalities before drug reduction, and a long course of the disease, are prone to relapse. Patients with an older age at onset and a high frequency of attack, those taking multi-drug combination therapy, and those that take a long time to gain control, should be managed carefully to AEDs withdrawal.Keywords: epilepsy, relapse, antiepileptic drugs, drug withdrawal

Guixuan Wang,1,2 Danyang Zou,2 Xinying Lu,2 Xin Gu,2 Yuanyuan Cheng,2 Tengfei Qi,2 Yanchun Cheng,2 Junjun Yu,2 Meiping Ye,2 Pingyu Zhou1,2 1Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai, People’s Republic of China; 2STD Institute, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Pingyu Zhou, Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai Skin Disease Hospital, 1278 Bao’de Road, Shanghai, 200443, People’s Republic of China, Tel +86-18017336631, Email zpyls@yahoo.comBackground: The gut microbiota plays an important role in the development of neurological disorders such as Parkinson’s disease and Alzheimer’s disease. However, studies on the gut microbiota of patients with neurosyphilis (NS) were rarely reported.Methods: In this study, we collected fecal samples from 62 syphilis patients, including 39 with NS and 23 with non-NS. Among the NS patients, 18 were general paresis (GP). The white blood cell counts, protein concentrations, and Venereal Disease Research Laboratory test positive rates of cerebrospinal fluid from patients in NS or GP group were significantly higher than those from patients in non-NS group. 16S ribosomal RNA sequencing results revealed that the alpha and beta diversities of the gut microbiota were similar between NS and non-NS patients or GP and non-NS patients.Results: Linear discriminant analysis with effect size (LEfSe) analysis showed that some taxa, such as Coprobacter, were increased in both NS group and GP group, compared with non-NS group. Besides, the clade of Akkermansia was also overrepresented in GP Patients. Meanwhile, some taxa such as Clostridia_UCG-014 and SC-I-84 were underrepresented in NS patients. The abundances of class Bacilli and genus Alloprevotella were decreased in GP patients. Among them, the abundances of some taxa such as Coprobacter and Akkermansia have been reported to be associated with other neuropsychiatric disorders.Conclusion: Our findings suggest that the alternation of the gut microbiota in NS patients may contribute to the course of NS, which will deepen our understanding of NS.Keywords: syphilis, neurosyphilis, general paresis, gut microbiota, 16S ribosomal RNA sequencing

John Davidson,1 Xiaolin Gu,2 Michael Breen,2 Raiju J Babu2 1Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA; 2Alcon Vision LLC, Fort Worth, TX, USACorrespondence: John Davidson, Stein Eye Institute, UCLA School of Medicine, Los Angeles, CA, USA, Email doctorjohn@johndavidsonmd.comPurpose: To evaluate absolute prediction errors following phacoemulsification with implantation of a multifocal toric intraocular lens (IOL) using intraoperative aberrometry for IOL power selection and to compare findings with the globally optimized and manufacturer’s recommended lens constants and regression coefficients.Methods: Data from the Optiwave Refractive Analysis (ORA SYSTEM) were analyzed retrospectively. Absolute prediction errors from surgeries performed before and after the first optimization of the manufacturer’s recommended lens constant and non-optimized regression coefficients for the multifocal toric IOL (SND1T3-6) were compared. Optimization was based on outcomes of procedures performed using the ORA SYSTEM and archived in its database (AnalyzOR). Outcome measures included the proportion of eyes with absolute ORA SYSTEM prediction errors ≤ 0.25 D and ≤ 0.5 D and the mean and median absolute prediction errors.Results: The pre-optimization group included 1027 eyes operated on by 184 surgeons, and the optimized group included 419 eyes operated on by 143 surgeons. The proportions of eyes achieving absolute ORA SYSTEM prediction errors ≤ 0.25 D (52.5% vs 35.0%, p < 0.0001) and ≤ 0.50 D (83.1% vs 66.2%, p < 0.0001) were significantly higher in the optimized than in the pre-optimization group. The mean ± standard deviation (0.30 ± 0.25 D vs 0.43 ± 0.32 D, p < 0.0001) and median (0.24 D vs 0.36 D, p < 0.0001) absolute ORA SYSTEM prediction errors were significantly lower after than before optimization. Prediction errors following optimization were reduced more in eyes of average than of long and short axial lengths.Conclusion: Global optimization of the manufacturer’s IOL lens constants and regression coefficients resulted in lower absolute prediction errors when compared with the initial manufacturer labeled lens constants and non-optimized regression coefficients. Reductions in absolute prediction error can result in lower postoperative residual refractive error, which can improve post-operative uncorrected visual acuity and provide the potential for greater patient satisfaction following cataract surgery.Keywords: intraoperative aberrometry, intraocular lens implantation, prediction error, lens constant optimization, refractive error, visual acuity

Rui Wang,1– 4 Wei Zhang,1– 3 Yuanyuan Li,1– 3 Yuting Jiang,1– 3 Hongqi Feng,1– 3 Yang Du,1– 3 Zhe Jiao,1– 3 Li Lan,4 Xiaona Liu,1– 3 Bingyun Li,1– 3 Chang Liu,1– 3 Xingbo Gu,5 Fang Chu,1– 3 Yuncheng Shen,1– 3 Chenpeng Zhu,1– 3 Xinhua Shao,1– 3 Simeng Tong,1– 3 Dianjun Sun1– 3 1Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, People’s Republic of China; 2National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, 150081, People’s Republic of China; 3Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, 150081, People’s Republic of China; 4Harbin Center for Disease Control and Prevention, Harbin, 150056, People’s Republic of China; 5Department of Biostatistics, School of Public Health, Hainan Medical University, Haikou, 571199, People’s Republic of ChinaCorrespondence: Dianjun Sun, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Baojian Road 157, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86-13313685318, Fax +86 45186612695, Email hrbmusdj@163.comPurpose: To investigate the environmental, immune, and inflammatory factors associated with chronic obstructive pulmonary disease (COPD) in middle-aged and older Chinese individuals.Patients and Methods: A community-based case–control study was conducted among 471 patients with COPD and 485 controls. The information on COPD of the participants was collected through face-to-face interviews, and serum samples were measured at the laboratory. The main risk factors for COPD were analyzed using principal component analysis (PCA) and logistic regression.Results: Nine hundred and fifty-six respondents were included in the analysis. The results of the PCA-logistic regression analysis showed significant differences in the environmental factors, medical history, and serum C-reactive protein (CRP) levels between patients and controls. COPD was markedly more usual in those with smoking index > 200 (OR, 1.42; 95% CI, 1.28– 1.57); exposure to outdoor straw burning (OR, 1.64; 95% CI, 1.47– 1.83); use of coal, wood, and straw indoors (OR, 2.31; 95% CI, 1.92– 2.78); history of respiratory disease and coronary heart disease (OR, 3.58; 95% CI, 3.12– 4.10), congestive heart failure (OR, 1.23; 95% CI, 1.09– 1.38), and cerebrovascular disease (OR, 1.15; 95% CI,1.02– 1.31); and higher serum level of CRP (OR, 1.20; 95% CI, 1.11– 1.30). Compared to the logistic regression analysis, PCA logistic regression analysis identified more important risk factors for COPD.Conclusion: PCA-logistic regression analysis was first utilized to explore the influencing factors among rural residents in Northeast China Environmental aged 40 years and above, it was found that environmental factors, medical history, and serum CRP levels mainly affected the prevalence of COPD.Keywords: chronic obstructive pulmonary disease, collinearity, principal component, logistic regression

Zhaojin Lu,1,&ast; Zepeng Zheng,1,&ast; Yufen Xu,1,&ast; Chenlu Wang,1 Yueling Lin,1 Kun Lin,1 LanYan Fu,1 Huazhong Zhou,1 Lei Pi,1 Di Che,1 Xiaoqiong Gu1,2 1Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Di Che, Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076562, Email chedi@gwcmc.org Xiaoqiong Gu, Department of Clinical Biological Resource Bank, Department of Clinical Laboratory, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou, 510623, Guangdong, People’s Republic of China, Tel/Fax +86-20-38076561, Email guxiaoqiong@gwcmc.orgBackground: Kawasaki disease (KD) was one of the most common primary vasculitis. IVIG resistance was associated with an increased risk of coronary artery aneurysm. Accumulating evidences demonstrated that inflammatory gene polymorphisms might play important roles in IVIG resistance, and zinc finger proteins were closely related to immune inflammation regulation, but the effect of ZNF112/rs8113807 and ZNF180/rs2571051 on IVIG resistance in KD patients has not been reported.Methods: A total of 996 KD patients were recruited, and the assay of TaqMan-real-time polymerase chain reaction was used for ZNF112/rs8113807 and ZNF180/rs2571051 genotyping. Odds ratio (OR) and 95% confidence interval (CI) were calculated for estimating the relationship between the polymorphisms of the both SNPs (ZNF112/rs8113807 and ZNF180/rs2571051) and the risk of IVIG resistance.Results: Both of the ZNF112/rs8113807 CC/TC genotype and the ZNF180/rs2571051 TT/CT genotype increased the risk of IVIG resistance in KD (rs8113807: CC vs TT: adjusted OR = 1.83, 95% CI = 1.06– 3.16, p = 0.0293; CC/TC vs TT adjusted: OR = 1.49, 95% CI = 1.10– 2.02, p = 0.0094. rs2571051: TT vs CC adjusted: OR = 2.64, 95% CI = 1.62– 4.29, p < 0.0001; TT/CT vs CC adjusted: OR = 2.14, 95% CI = 1.37– 3.37, p = 0.0009; TT vs CC/CT adjusted: OR = 1.66, 95% CI = 1.22– 2.27, p = 0.0014). Furthermore, the combinative analysis of risk genotypes in ZNF112/rs8113807 and ZNF180/rs2571051 showed that patients with two unfavorable genotypes were more likely to increase risk of IVIG resistance than those who carried with zero or one unfavorable genotypes (adjusted: OR = 1.68, 95% CI = 1.24– 2.27, p = 0.0008).Conclusion: Our findings enriched the genetic background of IVIG resistance risk in the KD development and suggested that the ZNF112/rs8113807 C-carrier and the ZNF180/rs2571051 T-carrier were associated with increased risk of IVIG resistance in KD patients in Chinese southern population.Keywords: Kawasaki disease, ZNF112/rs8113807, ZNF180/rs2571051, IVIG resistance, inflammatory gene, polymorphism

Xuchao Gu,1,2,&ast; Wenhao Wang,1,2,&ast; Yijing Yang,1,2,&ast; Yiming Lei,1,2 Dehua Liu,1,2 Xiaojun Wang,1,2 Tao Wu1,2 1Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Wu; Xiaojun Wang, Department of Traditional Chinese Medicine, Huadong Hospital Affiliated to Fudan University, No. 221 West Yan-An Road, Shanghai, 200040, People’s Republic of China, Tel +86 13641673915 ; +86 13062796919, Email taowuh@hotmail.com; 13681803275@163.comAbstract: Sarcopenia is an age-related systemic disease characterized by skeletal muscle aging that generally severely affects the quality of life of elderly patients. Metabolomics analysis is a powerful tool for qualitatively and quantitatively characterizing the small molecule metabolomics of various biological matrices in order to clarify all key scientific problems concerning cell metabolism. The discovery of optimal therapy requires a thorough understanding of the cellular metabolic mechanism of skeletal muscle aging. In this review, the relationship between skeletal muscle mitochondria, amino acid, vitamin, lipid, adipokines, intestinal microbiota and vascular microenvironment has been separately reviewed from the perspective of metabolomics, and a new therapeutic direction has been suggested.Keywords: sarcopenia, metabolomics, mitochondria, intestinal microbiota, vascular endothelium

Jeffrey D Horn,1 Bret L Fisher,2 Daniel Terveen,3 Helene Fevrier,4 Mohinder Merchea,5 Xiaolin Gu5 1Vision for Life, Nashville, TN, USA; 2Eye Center of North Florida, Panama City, FL, USA; 3Vance Thompson Vision, Sioux Falls, SD, USA; 4Verana Health, San Francisco, CA, USA; 5Alcon Vision LLC, Fort Worth, TX, USACorrespondence: Jeffrey D Horn, Vision for Life, Nashville, TN, USA, Tel +1 615-588-2020, Email jdh@comcast.netPurpose: Academy IRIS® (Intelligent Research in Sight) Registry was used to determine the incidence of postoperative neodymium-doped yttrium aluminum garnet laser capsulotomy (Nd:YAG) and time to posterior capsular opacification (PCO) diagnosis based on intraocular lens (IOL) type and brand.Methods: This retrospective analysis included eyes implanted with 1 of 2 IOL brands, with ≥ 365 days of follow-up available in the IRIS Registry, and ≥ 2 visits within 180 days of surgery. Analyses included Nd:YAG incidence due to PCO within 1 year after surgery by IOL type and brand, mean time to PCO diagnosis, and mean time to Nd:YAG.Results: Of 89,947 eyes after cataract surgery, 24,834 (28%) had PCO diagnosis within 365 days, and 9262 (10%) underwent Nd:YAG; 4.1% of 57,523 eyes with monofocal and 21.2% of 32,424 eyes with diffractive multifocal (MF) or diffractive extended depth of focus (EDOF) IOLs had Nd:YAG. Nd:YAG was 3.2 times more likely in eyes with diffractive MF or diffractive EDOF IOLs versus monofocal. For monofocal IOLs, 3.2% of eyes with AcrySof® and 8.1% of eyes with Tecnis® had Nd:YAG (P< 0.0001). For diffractive MF or diffractive EDOF IOLs, 13.0% of eyes with AcrySof and 21.7% of eyes with Tecnis had Nd:YAG (P< 0.0001). Nd:YAG risk was 2.4 times higher in eyes with Tecnis versus AcrySof IOLs. Overall, mean time to PCO diagnosis and Nd:YAG was 150.7 and 180.7 days. Mean time to PCO for monofocal versus diffractive MF or diffractive EDOF IOLs was 165.3 versus 139.7 days (P< 0.0001). Mean time to Nd:YAG for monofocal versus diffractive MF or diffractive EDOF IOLs was 196.4 versus 175.3 days (P< 0.05).Conclusion: Real-world data for AcrySof and Tecnis IOLs revealed lower Nd:YAG rates and longer time to PCO diagnosis and Nd:YAG after monofocal versus diffractive multifocal or diffractive EDOF implantation. Nd:YAG rates were significantly lower with AcrySof versus Tecnis IOLs.Keywords: monofocal intraocular lenses, diffractive multifocal intraocular lenses, diffractive extended depth of focus intraocular lenses

Xinran Gu, Guangyi Xu, Chen Qian, Saichao Chang, Dandan Deng School of Business Administration, South China University of Technology, Guangzhou, People’s Republic of ChinaCorrespondence: Chen Qian, School of Business Administration, South China University of Technology, Tianhe District, Guangzhou, People’s Republic of China, Email 201710105492@mail.scut.edu.cnPurpose: Prior work suggests that responsibility is negatively associated with employee procrastination behavior. Based on the conservation of resources (COR) theory, we suggest this view is oversimplified and propose that procrastination can be induced when employees have congruent job and family responsibilities via the mediating effect of emotional exhaustion.Methods: This is a quantitative study of the configurational approach. Survey data were collected from 323 employees at two stages in southern Chinese internet enterprises in September 2020. A randomized cluster sample was used and an anonymous self-assessment questionnaire was distributed to all selected respondents (employees). Samples involved different departments, and the procrastination phenomenon is more significant among them. SPSS20.2 and MPLUS 8.3 software and Response Surface Analysis Strategy were used to test the hypotheses.Results: The data analysis results indicated that: a) employee procrastination behavior is higher when employees’ job responsibility and family responsibility are congruent than the incongruent configurations. b) Procrastination is lower when job-family dyads are congruent at high levels of responsibility compared the low levels. c) Procrastination decreases as employees’ job and family responsibilities become more discrepant (ie, incongruent); employees with low job-high family responsibilities procrastinate more than those with high job-low family responsibilities. d) Additionally, employee-experienced emotional exhaustion mediates the relationship in four configurations between job-family responsibilities congruence and procrastination behavior.Conclusion: Drawing on the conservation of resources theory, we proposed a model clarifying how varying combinations of job and family responsibilities affect employee procrastination behavior. The results showed that there are significant differences in the impact of different job-family responsibility combinations on employee procrastination behavior. Employee procrastination behavior is higher when employees’ job-family responsibility are congruent than the incongruent configurations. Additionally, employee-experienced emotional exhaustion mediates the relationship in four configurations between job-family responsibilities congruence and procrastination behavior.Keywords: job-family responsibilities congruence, emotional exhaustion, employee procrastination behavior, conservation of resources theory, configurational approach

Yating Xu,&ast; Anqi Chen,&ast; Jiehong Wu,&ast; Yan Wan, Mingfeng You, Xinmei Gu, Hongxiu Guo, Sengwei Tan, Quanwei He, Bo Hu Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Hu; Quanwei He, Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +86-27-87542857, Fax +86-27-87547063, Email hubo@mail.hust.edu.cn; hequanwei2008@126.comAbstract: Hemorrhagic stroke is one of the most devastating diseases worldwide due to a high rate of disability and mortality with few effective treatments. Recent advances in nanomedicines to promote hemostasis, drug delivery, neuroprotection, and nerve regeneration may provide insight into hemorrhagic stroke treatment. In this review, we first view the pathophysiology and conventional therapeutics of hemorrhagic stroke. Second, we comprehensively summarize the current nanomedicines applied in hemorrhagic stroke, including inorganic nanomaterials, polymer-based nanomaterials, lipid-based nanomaterials, self-assembling peptide-based hydrogel, exosomes, and gel systems. Finally, the challenges, opportunities, and future perspectives of nanomedicines for hemorrhagic stroke are discussed. Thus, this review promotes greater exploration of effective therapies for hemorrhagic stroke with nanomedicines.Keywords: hemorrhagic stroke, nanomedicine, therapy, subarachnoid hemorrhage, intracerebral hemorrhage

Lijuan Yang, Huihui Deng, Wei Pan, Xiaoyan Huang, Ke Xu, Xingxing Zhang, Xiang Hu, Xuejiang Gu Department of Endocrine and Metabolic Diseases, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaCorrespondence: Xiang Hu; Xuejiang Gu, Department of Endocrine and Metabolic Diseases, the First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou, 325000, People’s Republic of China, Tel/Fax +86-577-55579381, Email huxiang@wmu.edu.cn; guxuejiang@wmu.edu.cnPurpose: Recent studies revealed that high levels of thigh fat were independently associated with better glucose and lipid metabolism, as well as lower risk of hypertension and cardiometabolic disease. Therefore, the purpose of this study was to evaluate the association between leg fat mass (FM) and osteoporosis (OP) in individuals with type 2 diabetes (T2DM).Patients and Methods: In this cross-sectional study, a total of 1,259 individuals aged 50 years or older with T2DM (female 536, male 723) were included. A bioelectrical impedance analyser was used to assess the segment body composition containing FM and lean mass (LM) of arms, legs, and trunk. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry.Results: Leg FM was positively correlated with BMD of all sites in females and BMD of femoral neck and total hip in males after adjusting age, diabetes duration, glucose and lipid metabolism indexes, and lifestyle (all P< 0.05). LM was positively associated with BMD at almost sites (P< 0.001), while leg FM/LM ratio had no relationship with BMD at any skeleton sites (P> 0.05). Compared with the bottom tertile group of leg FM, the risk of OP was significantly lower in the top tertile group both in females (T3 vs T1: OR=0.206, 95% CI=0.098– 0.433, P< 0.001) and males (T3 vs T1: OR=0.385, 95% CI=0.182– 0.815, P< 0.05), even after adjusting for LM.Conclusion: In the present study, higher leg FM was correlated with the lower risk of OP in both men and postmenopausal women with T2DM independently of total LM.Keywords: leg fat mass, bone mineral density, osteoporosis, type 2 diabetes mellitus

Yuxia Wang,1,2 Chaoyin Lu,2,3 Mauro Augusto Monteiro Cardoso Lopes,2 Lingqiao Chen,1,2 Yan Luo,1,2 Wenjun Wu,1,2 Xuemei Gu1,2 1Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2The First Clinical School of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Endocrinology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xuemei Gu, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang Road, Wenzhou, 325006, People’s Republic of China, Tel +86-577-55579385, Fax +86-577-88069555, Email guxm@wmu.edu.cnPurpose: To investigate the prevalence, clinical and metabolic characteristics of atherosclerosis (AS) in newly diagnosed patients with ketosis-prone type 2 diabetes (KPT2D) or non-ketotic type 2 diabetes (NKPT2D).Patients and Methods: About 1072 subjects with non-autoimmune new-onset diabetes were included in the cross-sectional study. Patients were classified as non-ketotic type 2 diabetes (NKPT2D, n = 662) or ketosis-prone type 2 diabetes (KPT2D, n = 410). Blood samples were collected to determine the levels of glucose, HbA1c, insulin and C-peptide. Routine liver and kidney function tests were also performed. AS was determined by vascular ultrasonography.Results: The levels of fasting blood glucose and HbA1c were significant higher in the KPT2D group when compared to the NKPT2D group (P< 0.001). The levels of fasting C-peptide, 2 h C-peptide and HOMA-β were lower in the KPT2D group than those in NKPT2D group (P< 0.001). However, no significant difference was observed for HOMA-IR between the two groups. The onset age of the patients with KPT2D was significantly lower compared to NKPT2D patients (38± 13 vs 49± 14, P< 0.001). After adjusting age of the two groups, the KPT2D patients had a higher prevalence of AS compared to the NKPT2D patients (31.4% vs 21.1%, P=0.005). In both groups, age and gender were independent risk factors for AS, whereas estimated glomerular filtration rate (eGFR) was an independent risk factor in the NKPT2D patients and 2-h postprandial plasma glucose (2h-PPG) was an independent risk factor in the KPT2D patients.Conclusion: AS was more prevalent in KPT2D patients compared to the NKPT2D cohort, which was independent of age and gender. These data suggest that KPT2D patients may have a higher risk of macrovascular complications compared to NKPT2D of the same age.Keywords: ketosis, diabetes, atherosclerosis

Qingfei Chu,&ast; Xinyu Gu,&ast; Qiuxian Zheng, Jing Wang, Haihong Zhu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haihong Zhu Tel +86-13656632056Email zhuhh72@zju.edu.cnBackground: PPAT (phosphoribosyl pyrophosphate amido transferase) catalyzes the first committed step of de novo purine biosynthesis and is a key regulatory point in the biosynthesis of nascent purine nucleotides. However, the clinical significance and biologic role of PPAT in hepatocellular carcinoma (HCC) remain unknown.Methods: We compared the expression of PPAT in carcinomatous and precancerous hepatocellular carcinoma tissues by immunohistochemistry in 90 cases of HCC. Correlation analysis was also made on clinical data, survival, classification, and staging.Results: The expression of PPAT in HCC tumor tissues is significantly higher than that in adjacent normal tissues. The results of the Kaplan–Meier analysis showed that HCC patients with high PPAT expression survived shorter than those with low PPAT expression. Moreover, the expression of PPAT was significantly associated with the tumor grade (P=0.014), PD-L1 (P< 0.001), and CTLA4 (P=0.003). The later grade of the tumor, the higher the expression of PPAT. In the PD-L1 high expression group, PPAT is also highly expressed.Conclusion: Our study demonstrated that PPAT expression might be included in the process of carcinogenesis and prognosis. Hence, PPAT could be served as a new prognostic biomarker for patients of HCC.Keywords: PPAT, HCC, prognosis, biomarker, metabolism

Junhui Ji,1,&ast; Xiafang Gu,2,&ast; Chengjiao Xiao1 1Anesthesiology Department, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Anesthesiology Department, The No.2 People’s Hospital of Suzhou Xiangcheng District, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengjiao XiaoAnesthesiology Department, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Gusu District, Suzhou, 215000, Jiangsu, People’s Republic of ChinaTel +86-13962100544Email xiaocj1646@126.comBackground: Whether intraoperative temperature management can help patients recover quickly in the postanesthesia care unit (PACU) still remains to be investigated. This study aimed to investigate the effect of intraoperative temperature management on the quality of postoperative recovery of patients who underwent pulmonary lobectomy in the PACU.Methods: Totally, 98 patients aged 45– 60 years with a body mass index of 20– 25 kg/m2 who underwent elective thoracoscopic lobectomy were enrolled. Patients were categorized into two groups using a random number table: the conventional group received routine intervention to maintain normothermia (Group C, n = 49) and the aggressive group received integrated interventions (Group A, n = 49). In Group C, normothermic fluid was infused intravenously, the heating blanket was turned on when the intraoperative temperature was < 35.0 °C, and the warming was stopped when the temperature reached 36.5 °C. In Group A, the fluid heated to 37 °C was infused intravenously, and the heating blanket was used intraoperatively. When the body temperature was > 37 °C, the heating blanket was turned off, and when the body temperature was < 36.5 °C, the heating blanket was turned on to continue heating.Results: Steward awakening scores at 1 min and 5 min after extubation and PaO2 levels at 15 min after extubation were higher in Group A than in Group C (P < 0.05); incidence of chills, nausea, and vomiting in the PACU was lower in Group A than in Group C (P < 0.05); and length of stay in the PACU was shorter in Group A than in Group C (P < 0.05).Conclusion: Aggressive intraoperative temperature management of patients undergoing thoracoscopic lobectomy can improve the quality of postoperative recovery in the PACU through a safe and smooth transition compared with routine insulation measures.Keywords: hypothermia, recovery room, thoracoscopy, thoracic surgery

Xuechun Wang,1,&ast; Jia Jia,2,&ast; Xuehong Gu,3 Wei-wei Zhao,4 Caiping Chen,5 Wanxin Wu,6 Jiayuan Wang,1 Midie Xu7 1Department of Laboratory, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 2Shanghai Center for Bioinformation Technology, Shanghai, 201202, People’s Republic of China; 3Department of Nursing, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 4Department of Rehabilitation Medicine, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 5Department of Breast Surgery, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 6Department of Pathology, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 7Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuehong GuDepartment of Nursing, Jiaxing First Hospital, No. 1882 of Central South Road, Jiaxing, 314000, People’s Republic of ChinaTel +86 13957368443Fax +86 573-83599079Email guxuehong145@163.comObjective: Breast cancer has become a fatal disease for women world-wide. Its incidence in China has been increasing yearly, and the identification of early-stage biomarkers is urgently required.Methods: ANOVA was carried out in the case of a primary tumor, adjacent normal tissue, and tumor metastasis of breast cancer, and on pan-cancer samples using the genome-wide methylation data of 31 solid tumor Illumina Methylation 450K chips downloaded from The Cancer Genome Atlas (TCGA) website in September 2018. Methylation sites showing a significant difference (P ≤ 0.05) were screened and compared with the whole-genome methylation data of 31 other solid tumor species in the TCGA database using t-tests in order to screen the methylation sites of breast cancer-specific expression. The expression of the screened methylation sites was confirmed through pyrosequencing in 45 cases of breast cancer, lung cancer, gastric cancer, and colorectal cancer.Results: A total of 10 specific breast cancer methylation sites (cg13683194, cg07996594, cg21646032, cg07671949, cg21185686, cg03625109, cg16429070, cg23601468, cg24818566, and cg01240931) were analyzed; nine genes (C9orf125, RARB, ESR1, RUNX3, PCDHGB7, DBC1, PDGFRB, TIMP3, and APC) were involved. The overall effect was excellent; a total of 4 methylation sites (2 in the DBC1 gene [cg03625109 and cg24818566], 1 in the C9orf125 gene [cg13683194], and 1 in the PDGFRB gene [cg16429070]) could effectively distinguish breast cancer from 31 other cancer species. The pyrosequencing results revealed that 7 screened methylation sites could significantly distinguish between breast cancer, lung cancer, gastric cancer, and colorectal cancer samples; these sites could also specifically distinguish between luminal A, luminal B, HER2, and Basal-like types of breast cancer.Conclusion: The 10 breast cancer methylation sites screened in the present study can effectively distinguish breast cancer from 31 other solid tumors, and they are expected to be used as biomarkers for early screening of breast cancer.Keywords: breast cancer, Basal-like breast cancer, methylation, biomarker, TCGA, ANOVA

Xuetao Zeng,1,&ast; Hongfeng Yang,2,&ast; Yan Yang,1 Xinnan Gu,1 Xiuqin Ma,1 Taofeng Zhu1 1Department of Respiratory and Critical Medicine, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, People’s Republic of China; 2Department of Critical Medicine,The Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuqin Ma; Taofeng ZhuThe Affiliated Yixing Hospital of Jiangsu University, No. 75 Tongzhenguan Road, Yixing, Jiangsu, 214200, People’s Republic of ChinaTel +86-510-879210911; +86-510-87920912Fax +86-510-87921110Email Staff799@yxph.com; Staff1639@yxph.comObjective: Establish a simple predictive model and scoring rule that is suitable for clinical medical staff in respiratory departments to assess intestinal flora imbalance occurrence in stable chronic obstructive pulmonary disease (COPD) patients.Methods: From January 1, 2019, to December 31, 2020, COPD patients (195 cases) – who attended the Outpatient Department, Respiratory and Critical Care, Yixing Hospital, Jiangsu University – were enrolled in a cross-sectional study. Based on stool examination results, patients were divided into experimental (41 cases) and control (154 cases) groups. Single-factor and logistic regression analyses were performed with the baseline data of the two groups to obtain a new predictive model, which was further simplified.Results: Five predictive factors composed the model: body mass index (BMI), serum albumin (ALB), Charlson’s Comorbidity Index (CCI), gastrointestinal symptom score (GSRs), and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The model to predict intestinal flora imbalance in stable COPD patients had an area under the ROC curve (AUC) of 0.953 [95% CI (0.924, 0.982)]. After simplifying the scoring rules, the AUC was 0.767 [95% CI (0.676, 0.858)].Conclusion: In the current study, we obtained a model that could effectively predict intestinal flora imbalance risk in stable COPD patients, being suitable for implementation in early treatments to improve the prognosis. Moreover, all indicators can be easily and simply obtained.Keywords: lung disease, chronic obstruction, early warning score, gastrointestinal tract, flora imbalance, predictive model

Lu Yang,1 Zhen’an He,2 Xuan Gu,3 Hao Cheng,4 Lin Li5 1Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital City, Hangzhou, Zhejiang Province, People’s Republic of China; 2Shaanxi Institute of Medical Device Quality Supervision and Inspection, Xi’an City, Shaanxi Province, People’s Republic of China; 3Xi’an Hospital of Civil Aviation, Xi’an City, Shaanxi Province, People’s Republic of China; 4Department of Ultrasonography, Shaanxi Cancer Hospital Affiliated to Xi’an Jiaotong University, Xi’an City, Shaanxi Province, People’s Republic of China; 5Shaanxi Cancer Hospital Affiliated to Xi’an Jiaotong University, Xi’an City, Shaanxi Province, People’s Republic of ChinaCorrespondence: Hao Cheng; Lin Li Email uschenghao@163.com; lloyd_115599@sina.comObjective: The purpose of the current study is to explore the demographic characteristics of hyperuricemia in China.Study Design: The cross-sectional study was conducted, and the CHARLS dataset in 2011 was used.Methods: Logistic regression model was used to assess the association between BMI and hyperuricemia. We also used restricted cubic spline with three knots to assess the dose–response relationship. To investigate the differences in dose–response relationships in various groups, stratification analysis was conducted.Results: Of the 9408 middle and older participants, those who were overweight or obese had higher risk for hyperuricemia (OR=1.26, 95% CI=1.01– 1.57; OR=1.90, 95% CI=1.46– 2.47). In the subgroup, the effect of obesity on hyperuricemia was robust in varying gender and age. However, among overweight group, those with being male and aged over 60 years had higher risk for hyperuricemia (male: OR=1.42, 95% CI=1.07– 1.90; over 60 years: OR=1.28, 95% CI=1.03– 1.60). A dose-response relationship was examined between BMI and the risk of hyperuricemia. The result showed that the odds ratio of hyperuricemia and BMI displayed U-shaped nonlinear relationship (Ptrend< 0.001, non-linear P< 0.001).Conclusion: The association between BMI and hyperuricemia showed positive relationship. Specifically, the group with male and age over 60 years had higher risk of hyperuricemia along with increased weight.Keywords: body mass index, hyperuricemia, CHARLS, middle and older people

Sijie Tang,1,2 Xueqi Lian,1 Huiying Cheng,1 Jiaqian Guo,1 Daguang Ni,1 Can Huang,1 Xiang Gu,2 Hong Meng,3 Jiajia Jiang,1 Xiaohua Li1,4,5 1The Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 2Department of Urology, the Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, 215600, People’s Republic of China; 3Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Detroit, MI, 48201, USA; 4The Laboratory of Clinical Genomics, Hefei KingMed Diagnostics Ltd, Hefei, 230088, People’s Republic of China; 5National Center for Gene Testing Technology Application & Demonstration (Anhui), Hefei, 230088, People’s Republic of ChinaCorrespondence: Xiaohua Li; Jiajia JiangThe Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, 279 Jingang Blvd., Zhangjiagang, Suzhou, 215600, People’s Republic of ChinaEmail joshua28li@163.com; 2111913004@stmail.ujs.edu.cnPurpose: To study bacterial lipopolysaccharide (LPS)-induced cancer stem-like transformation and to investigate the inhibitory effect of Trichostatin A (TSA) on the malignant transformation through targeting p-Stat3 signaling.Methods: 2D, 3D, and serum-free suspension culture system were used to study LPS-induced malignant transformation in series malignant grade of prostate cancer (PCa) epithelial cells. Flow cytometry assay and RT-PCR were utilized to evaluate the CD44+CD133+ stem cell population, the expression of inflammatory cytokines and series tumor stemness biomarkers. Meanwhile, Western blot was used to analyze the alteration of cell signaling associated-molecules by treatment with TSA, an original antifungal antibiotic and a panel inhibitor of histone deacetylase.Results: Our study found that LPS promoted the migration, invasion and stem-like tumoroshpere forming in multiple PCa cell lines including DU145, PC3, 22RV1, LNCaP. LPS also enriched CD44+CD133+ stem cell population and increased the expression of series tumor stemness biomarkers (e.g., CD44, CD133, SOX-2, α-intergrin, Nestin, etc.). TSA was found to prevent tumor cell migration, invasion and tumorosphere forming in DU145 and PC3 cells with increasing tumor suppressive Maspin and reducing both phosphorylation of Stat3 (p-Stat3) and pro-oncogene c-Myc expression in LPS-treated DU145 cells. Furthermore, blocking Stat3 signaling pathway by treatment with TSA and/or small molecule compound Stattic of an p-Stat3 inhibitor effectively abrogated LPS-induced tumorosphere forming with decrease of IL-6, IL-8 and stemness biomarkers CD44, SOX-2 expression.Conclusion: Our data demonstrated that the inflammatory agent of bacterial LPS augmented malignant transformation and promoted the cancerous stemness in PCa epithelial cells. TSA could prevent, at least in part, the LPS-induced malignant transformation by targeting p-Stat3/c-Myc signaling pathway and reducing inflammatory IL-6, IL-8. In addition, the assay of LPS-induced tumorosphere forming could serve as a simple and an easy handling method for targeting cancer stem cells drug screening in vitro in clinical practice.Keywords: tumorosphere forming, prostate cancer, bacterial lipopolysaccharide, epithelial malignant transformation, cancer stemness

Kai Guo,1 Lijuan Qiu,1 Yufen Xu,2 Xiaoqiong Gu,2 Linyuan Zhang,3 Kun Lin,3 Xiaohuan Wang,1 Shanshan Song,1 Yu Liu,1 Zijian Niu,1 Shuxuan Ma1 1Department of Transfusion Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Clinical Lab, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shuxuan MaDepartment of Transfusion Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health No. 56 Nan Lishi Road, Xi Cheng District, Beijing, 100045, People’s Republic of ChinaTel +86 10 59616422Email masxfwyy@sina.comBackground: Kawasaki disease (KD) is a multisystem vasculitis in infants and young children and involved in the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation. Genetic factors may increase the risk of KD. To assess the association between rs7248320 in long noncoding RNA (lncRNA) AC008392.1 located in the upstream region of CARD8 and the risk of KD, a case–control study was conducted in the Han Chinese population.Methods: This study genotyped the polymorphism rs7248320 in the lncRNA AC008392.1 gene using the TaqMan real-time polymerase chain reaction assay. The genetic contribution of rs7248320 was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. The association between rs7248320 and KD susceptibility was analyzed by performing a hospital-based case–control study including 559 KD patients and 1055 non-KD controls.Results: In this study, a significant relationship between rs7248320 and KD risk was observed in the genotype/allele frequency distribution. The rs7248320 polymorphism was associated with a significantly decreased risk of KD after adjustment for age and sex (AG vs AA: adjusted OR = 0.80, 95% CI: 0.64– 0.99, P = 0.0421; GG vs AA: adjusted OR = 0.71, 95% CI: 0.51– 1.00, P = 0.0492; AG/GG vs AA: adjusted OR = 0.78, 95% CI: 0.63– 0.96, P = 0.0186). Moreover, the rs7248320 G allele also exhibited a decreased risk for KD (adjusted OR = 0.83, 95% CI: 0.72– 0.97, P = 0.0193) compared with the A allele. In the stratification analysis, compared to the rs7248320 AA genotype, AG/GG genotypes were more protective for males (OR = 0.71, 95% CI: 0.55– 0.93, P = 0.0122).Conclusion: This study suggests for the first time that the lncRNA AC008392.1 rs7248320 polymorphism may be involved in KD susceptibility in the Han Chinese population.Keywords: Kawasaki disease, rs7248320, AC008392.1, CARD8, lncRNA, single-nucleotide polymorphism

Zhiyuan Wu,1,&ast; Yufeng Liang,1,&ast; Yunlong Zuo,1,&ast; Yufen Xu,2 Hanran Mai,2 Lei Pi,2 Di Che,2 Xiaoqiong Gu2 1Pediatric Intensive Care Unit. Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqiong Gu; Di CheDepartment of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, 510623, People’s Republic of ChinaTel/Fax +86-20-38076561; +86-20-38076562Email guxiaoqiong@gwcmc.org; chedi@gwcmc.orgPurpose: Accumulating evidence demonstrates that genetic susceptibility genes can be used as biomarkers to assess sepsis susceptibility, and genetic variation is associated with susceptibility and clinical outcomes in patients with sepsis and inflammatory disease. Although studies have shown that the lncRNA CCAT2 is involved in inflammatory diseases, it remains unclear whether CCAT2 gene polymorphisms are associated with susceptibility to inflammatory diseases, such as sepsis, in children.Methods: We genotyped the rs6983267 CCAT2 polymorphism in 474 cases (pediatric sepsis) and 678 controls using TaqMan methods, and odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of associations.Results: Our results indicate that the rs6983267 T > G polymorphism is significantly associated with an increased risk of sepsis in children (TG and TT: adjusted OR = 1.311, 95% CI = 1.016– 1.743, GG and TT: adjusted OR = 1.444, 95% CI = 1.025– 2.034 dominant model: GG/TG vs TT adjusted OR = 1.362, 95% CI = 1.055– 1.756). Furthermore, the risk effect was more pronounced in children younger than 60 months who were male and who had sepsis.Conclusion: We found that the CCAT2 gene polymorphism rs6983267 T > G may be associated with an increased risk of pediatric sepsis in southern China. A larger multicenter study should be performed to confirm these results.Keywords: lncRNA CCAT2, sepsis, susceptibility, polymorphism

Wenfeng Li,&ast; Yuanshen Mao,&ast; Yufei Gu, Chao Lu, Xin Gu, Bao Hua, Weixin Pan, Qinghong Xi, Bin Xu Department of Urology, The Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Xu; Qinghong XiDepartment of Urology, The Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaTel +862156691101Email kuangfeng0612@126.com; 13611829161@163.comBackground: Effective pain management is limited for patients during prostate biopsy (PBx). Touch support, such as hand holding, has stress-buffering benefits and effective analgesic effects. We conducted a prospective, single-center randomized clinical trial to assess whether hand holding can reduce patient anxiety, pain, and dissatisfaction during PBx.Methods: Between April 2020 and October 2020, 120 male patients were randomized into three groups: a hand holding with relatives (HR) group, a hand holding with strangers (HS) group and a control group. A visual analog scale (VAS) was used for self-assessments of pain and satisfaction. Anxiety levels were quantified according to the State-Trait Anxiety Inventory (STAI). Hemodynamic changes were also measured.Results: The degree of pain and anxiety in the hand-holding groups was significantly better than that in the control group (P< 0.001), and the patients were more willing to undergo repeat PBx (P=0.017). The anxiety levels in the HR group were significantly lower than those in the HS group (P=0.019). During PBx, the changes in systolic blood pressure and heart rate in the hand-holding groups were more stable than those in the control group (P< 0.01), and the fluctuations in heart rate in the HR group were smaller than those in the HS group (P< 0.01).Conclusion: Hand holding, especially with relatives, can promote incremental reductions in anxiety, pain and dissatisfaction in patients during PBx. Hence, we recommend hand holding with relatives as an effective adjunct during PBx.Keywords: anxiety, transrectal prostate biopsy, hand holding, pain, satisfaction