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Xueqin Shen,1,2 Xiaoping Niu2 1Department of Clinical Nutrition, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China; 2Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of ChinaCorrespondence: Xiaoping Niu, Department of Gastroenterology, Yijishan Hospital of Wannan Medical College, No. 2 Zheshan West Road, Wuhu, Anhui, 241000, People’s Republic of China, Email niuxiaoping@wnmc.edu.cnBackground: The close association between inflammation and the clinical outcomes of hepatocellular carcinoma (HCC) has been extensively documented. This study aims to analyze the association between a novel inflammatory indicator, the gamma-glutamyl transpeptidase to neutrophil ratio (GNR), and HCC prognosis following curative resection.Methods: A cohort of 204 eligible HCC cases were included. Based on an optimal cut-off value determined utilizing the X-tile software, patients were categorized into low- and high-GNR groups. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using the Kaplan-Meier analysis method with Log rank tests. Multivariate Cox proportional hazard regression was used to investigate the independent association between GNR and HCC prognosis. Restricted cubic splines were used to explore the nonlinear relationship between GNR and the risk of death or recurrence.Results: The low GNR group exhibited significantly higher 3-year OS and RFS rates than the high GNR group. Multivariate Cox analysis indicated that a high GNR level was independently associated with poor OS and RFS. A linear correlation between GNR and the risk of death, as well as a nonlinear inverted “U” shape correlation between GNR and the risk of recurrence, were observed.Conclusion: The findings provide evidence supporting the independent association of GNR with HCC prognosis. These results offer promise for enhancing prognosis assessments and guiding active monitoring strategies for patients with HCC post-curative resection.Keywords: hepatocellular carcinoma, gamma-glutamyl transpeptidase to neutrophil ratio, prognosis, curative resection

Lifen Lu,1 Di Sheng,1 Xiaowei Xia,2 Guanghui Chen,3 Jiali Liang,4 Xiulan Shen,1 Gui Zheng1 1Department of Nursing, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Ministry of Health, the Third Hospital of Ninghai County, Ningbo, Zhejiang, People’s Republic of China; 3Ministry of Health, the Liangzhu Street Community Health Service Center, Yuhang District, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Nursing, the First People’s Hospital of Yuhang District, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiulan Shen; Gui Zheng, Department of Nursing, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China, Email shenxl@zju.edu.cn; zhenggui1119@zju.edu.cnAim: To investigate the emotional response of hospital staff to the Depression Anxiety Stress Scale-21 (DASS-21) over the COVID-19 pandemic and after the relaxation of prevention and control measures in Zhejiang Province, China, and identify influencing factors.Design: Multicenter online cross-sectional design.Methods: From January 10, 2023, to January 20, 2023, 1054 hospital employees in Zhejiang, China, were recruited using WeChat. Data was gathered via online, self-administered surveys. T-tests and one-way analyses of variance, Pearson’s correlation analysis, and multiple linear stepwise regression analyses were used to examine the data.Results: More than 90% of hospital employees were infected with COVID-19. Through regression analysis, the following variables were found to be independent predictors of emotional response to DASS-21: resilience (− 13.346, P < 0.0001), sleep (14.689, P < 0.0001), friend support (− 4.278, P < 0.0001), education level (2.699, P = 0.007), and marriage (− 2.214, P = 0.027). The emotional responses were not as severe as predicted, but they were still well above the Chinese norm. A longitudinal comparison of DASS-21 emotional responses with similar studies showed a parabolic downward trend over time.Conclusion: Our results identified education level, marriage, friend support, resilience, and sleep as independent predictors of emotional responses to the DASS-21 among hospital workers in this outbreak. Improving the mental resilience and sleep status of staff is a key target. Unmarried medical personnel with higher education should be given greater attention and support by management. In addition, there is still room for further improvement in the government and societal responses to similar outbreaks. The study also found a parabolic downward trend in DASS-21 emotional responses among hospital workers during the COVID-19 outbreak over time.Keywords: COVID-19, hospital staff, DASS-21 emotional response, influencing factors, trajectory of change

Xiao Shen,1 Jin-Xing Zhang,1 Jin Liu,2 Sheng Liu,1 Hai-Bin Shi,1 Yuan Cheng,3 Qing-Qiao Zhang,4 Guo-Wen Yin,5 Qing-Quan Zu1 1Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Clinical Medicine Research Institution, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 3Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, People’s Republic of China; 4Department of Interventional Radiology and Vascular Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China; 5Department of Interventional Radiology, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Qing-Quan Zu, Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-13913807470, Fax +86-25-83724440, Email zuqingquan@njmu.edu.cnPurpose: Transarterial chemoembolization (TACE), when used in combination with immunotherapy and antiangiogenic therapy, has been shown to have synergistic anticancer effects. The aim of this study was to further assess the efficacy and safety of TACE combined with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC) in the real world.Methods: Between August 2021 and September 2023, clinical information was collected from consecutive HCC patients who received treatment via TACE-Atezo/Bev at four tertiary institutions. This study evaluated the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as outcomes. Predictors for OS and PFS were also analyzed. Treatment-related adverse events (TRAEs) were recorded and assessed.Results: Ninety-two patients were enrolled in this study, with a median follow-up duration of 14.1 months. The ORRs based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST 1.1 criteria were 54.3% and 41.3%, respectively. The median OS and PFS of the patients were 15.9 months [95% confidence interval (CI), 14.5– 17.2 months] and 9.1 months (95% CI, 7.4– 10.8 months), respectively. Multivariate analyses revealed that the Eastern Cooperative Oncology Group score and neutrophil‒lymphocyte ratio were independent risk factors for OS, whereas tumor size and extrahepatic metastasis were independent risk factors for PFS. Grade 3/4 TRAEs occurred in 16.3% (15/92) of the patients and were controlled conservatively.Conclusion: The combination of Atezo/Bev with TACE demonstrated acceptable synergistic therapeutic effects and manageable safety profiles in patients with unresectable HCC.Keywords: atezolizumab, bevacizumab, efficacy, hepatocellular carcinoma, transarterial chemoembolization

Yun Xiang,1,2,&ast; Dini Lin,1,&ast; Qiang Zhou,1 Hongyu Luo,1 Zixin Zhou,1 Shuyi Wu,2 Keyuan Xu,2 Xiaoting Tang,1 Pingping Ma,2 Chunyuan Cai,1 Xinkun Shen1 1Wenzhou Key Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University (Ruian People’s Hospital), Wenzhou, 325016, People’s Republic of China; 2School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China&ast;These authors contributed equally to this work and share first authorshipCorrespondence: Xinkun Shen; Chunyuan Cai, Wenzhou Key Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University (Ruian People’s Hospital), Wenzhou, Zhejiang Province, 325016, People’s Republic of China, 108&num; Wansong Road, Email shenxinkun123@wmu.edu.cn; caichunyuan123@wmu.edu.cnBackground: Large-diameter titanium dioxide nanotubes (TNTs) have shown promise in preserving osteoblast function under oxidative stress (OS) in vitro. However, their ability to enhance osteogenesis in vivo under OS conditions and the underlying mechanisms remain unclear.Purpose: This study aimed to evaluate the osteogenic potential of 110 nm TNTs (TNT110) compared to 30 nm TNTs (TNT30) in an aging rat model exhibiting OS, and to investigate the mechanisms involved.Methods: Surface properties of TNTs were characterized, and in vitro and in vivo experiments were conducted to assess their osteoinductive effects under OS. Transcriptomic, proteomic analyses, and Western blotting were performed to investigate the protective mechanisms of TNT110 on osteoblasts. Protein adsorption studies focused on the roles of fibronectin (FN) and albumin (BSA) in modulating osteoblast behavior on TNT110.Results: In both in vitro and in vivo experiments, TNT110 significantly improved new bone formation and supported osteoblast survival under OS conditions. Subsequent ribonucleic acid sequencing results indicated that TNT110 tended to attenuate inflammatory responses and reactive oxygen species (ROS) expression while promoting endoplasmic reticulum (ER) stress and extracellular matrix receptor interactions, all of which are crucial for osteoblast survival and functionality. Further confirmation indicated that the cellular behavior changes of osteoblasts in the TNT110 group could only occur in the presence of serum. Moreover, proteomic analysis under OS conditions revealed the pivotal roles of FN and BSA in augmenting TNT110’s resistance to OS. Surface pretreatment of TNT110 with FN/BSA alone could beneficially influence the early adhesion, spreading, ER activity, and ROS expression of osteoblasts, a trend not observed with TNT30.Conclusion: TNT110 effectively protects osteoblast function in the OS microenvironment by modulating protein adsorption, with FN and BSA synergistically enhancing osteogenesis. These findings suggest TNT110’s potential for use in implants for elderly patients.Keywords: osteoporosis, oxidative stress, titania nanotube, protein adsorption, osteogenesis

Jingxian Liao,1 Xiaozhu Shen,1 Zhiqiang Du,2 Xiaojuan Wang,2,&ast; Lei Miao2,&ast; 1Department of Geriatrics, The Second People’s Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of Critical Care Medicine, The Second People’s Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Miao; Xiaojuan Wang, Department of Critical Care Medicine, The Second People’s Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, No. 41, Hailian East Road, Haizhou District, Lianyungang, Jiangsu Province, 222000, People’s Republic of China, Email miaolei061@163.com; 56645221@qq.comPurpose: This study proposes a multiple mediation model to evaluate the association among diminished physical performance, malnutrition, inflammation, and delirium in seniors with community-acquired pneumonia.Patients and Methods: This retrospective cohort study included elderly patients hospitalized for community-acquired pneumonia at the Geriatrics Department of the Second People’s Hospital of Lianyungang from January 1, 2020, to January 1, 2024. Logistic regression analysis was conducted to examine the associations among physical performance, nutritional status, C-reactive protein (CRP) levels, and delirium. Mediation models assessed the effects of nutritional status and CRP on the relationship between physical performance and delirium, with subgroup analyses based on diabetes status.Results: A total of 379 patients were included, with a mean age of 80.0± 7.4 years, and 51.7% were male. The incidence of delirium during hospitalization was 28.5% (n=108). Subgroup analyses revealed significant correlations between physical performance, nutritional status, and CRP (P< 0.001), regardless of diabetes status. After adjusting for confounding variables, CRP was positively associated with delirium, while MNA-SF and SPPB scores showed negative correlations with delirium risk (OR=0.852, 95% CI: 0.730– 0.995; OR=0.580, 95% CI: 0.464– 0.727, P< 0.05). Mediation analyses indicated that MNA-SF scores and CRP significantly mediated the association between SPPB and delirium. Specifically, pathways “SPPB→ MNA-SF→ delirium”, “SPPB→ CRP→ delirium”, and “SPPB→ MNA-SF→ CRP→ delirium” demonstrated significant mediating effects in patients without diabetes, while only the pathway “SPPB→ MNA-SF→ CRP→ delirium” was significant in those with diabetes.Conclusion: Older patients with community-acquired pneumonia and poor physical performance are more susceptible to delirium, with nutritional status and inflammation as key mediators.Keywords: delirium, physical performance, nutritional status, inflammation

Dong Wu,1,&ast; Bingyu Long,1,&ast; Bangxiao Huang,1,&ast; Xiaomei Zhong,1 Xiaoer Chen,1 Xiaoping Shen,1 Qiu Huang,1 Wenchao Zhang,1 Jiayuan Wu,2 Min Chen,1 Dongming Li,1 Bin Wu,1 Dong Lv,3 Dan Huang,1 Xuanna Zhao1 1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Department of Clinical Research, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 3Department of Psychiatry, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanna Zhao; Dan Huang, Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Road, Zhanjiang, Guangdong, 524013, People’s Republic of China, Email 792665234@qq.com; 287538250@qq.comBackground: Education and living environment are related to mental health. But the independent and combined effects of them on mental health among patients with chronic obstructive pulmonary disease (COPD) are uncertain.Methods: The independent and combined effects of education and living environment on mental health were assessed by binary logistic regression in 1064 COPD patients. Additive interaction was assessed with the relative excess risk ratio (RERI), attribution percentage (AP), and synergy index (SI).Results: Our results shown that low education level and urban living environment were independently associated with higher risks for anxiety (odds ratio [OR]: 1.56, 95% confidence interval [CI] 1.06– 2.29 and OR:2.15, 95% CI 1.51– 2.05) or depression (OR:1.62, 95% CI 1.17– 2.27 and OR: 2.01, 95% CI 1.46– 2.75) among COPD patients. The combination effect of them was also associated with higher risks for anxiety (OR: 7.90, 95% CI 3.83– 16.29, P < 0.001) or depression (OR: 11.79, 95% CI 5.77– 24.10, P < 0.001) among these patients. Furthermore, we observed strong synergistic additive interactions between them for anxiety (SI: 11.57, 95% CI 1.41– 95.27; RERI: 6.31, 95% CI 1.60– 11.01; AP: 0.8, 95% CI 0.66– 0.94) and depression (SI: 31.31, 95% CI 1.59– 617.04; RERI: 10.44, 95% CI 2.66– 18.23; AP: 0.89, 95% CI 0.8– 0.97).Conclusion: Low education levels and living in urban areas had an independent and synergistic effects on mental health among COPD patients.Keywords: anxiety, China, COPD, depression, education, living environment

Xiao Shen,1,&ast; Linglin He,2,&ast; Wanru Cai3 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wanru Cai, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, People’s Republic of China, Email caiwanru@aliyun.comAbstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of common critical respiratory conditions characterized by damage and death of alveolar epithelial cells (AECs). Pyroptosis is a form of programmed cell death with inflammatory characteristics, and activation of pyroptosis markers has been observed in AECs of patients with ALI/ARDS. Lipopolysaccharides (LPS) possess strong pro-inflammatory effects and are a crucial pathological factor leading to ALI in patients and animals. In LPS-induced ALI models, AECs undergo pyroptosis. However, physiologically and pathologically relevant concentrations of LPS lead to minor effects on AEC cell viability and minimal induction of cytokine release in vitro and do not induce classical pyroptosis. Nevertheless, LPS can enter the cytoplasm directly and induce non-classical pyroptosis in AECs when assisted by extracellular vesicles from bacteria, HMGB1, and pathogens. In this review, we have explored the effects of LPS on AECs concerning inflammation, cell viability, and pyroptosis, analyzing key factors that influence LPS actions. Notably, we highlight the intricate response of AECs to LPS within the framework of ALI and ARDS, emphasizing the variable induction of pyroptosis. Despite the minimal effects of LPS on AEC viability and cytokine release in vitro, LPS can induce non-classical pyroptosis under specific conditions, presenting potential pathways for therapeutic intervention. Collectively, understanding these mechanisms is crucial for the development of targeted treatments that mitigate the inflammatory responses in ALI/ARDS, thereby enhancing patient outcomes in these severe respiratory conditions.Keywords: alveolar cell death, inflammatory response, programmed cell death, pathological impact, cytokine activation

Junyi Li,1,2,&ast; Zugui Wu,3,&ast; Bin Lu,2,&ast; Congcong Li,1 Shuai Wang,1 Jiahao Zhang,1 Xingxing Shen,1 Ruian Xiang,1 Jiahao Chen,1 Tao Jiang,1 Chuanxi Zhao,1 Wengang Liu,1 Xuemeng Xu1 1Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Osteoarthropathy II, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang, People’s Republic of China; 3Department of Orthopedics and Traumatology, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemeng Xu; Wengang Liu, Department of Orthopedics and Traumatology, The Fifth Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine, Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, No. 60 Hengfu Road, Guangzhou, 510030, People’s Republic of China, Email xuxuemeng@163.com; 914194079@qq.comPurpose: Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults.Methods: The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed.Results: In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030).Conclusion: The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.Keywords: knee osteoarthritis, quadriceps femoris, ultrasound, muscle tone, stiffness

Xinyi Shen,1,2 Ge Guo,1,2 Guoquan Feng,3 Zhongqun Wang1,2 1Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, People’s Republic of China; 2Institute of Cardiovascular Diseases, Jiangsu University, Zhenjiang, 212001, People’s Republic of China; 3Imaging Department, Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, People’s Republic of ChinaCorrespondence: Zhongqun Wang, Email wangtsmc@126.comIntroduction: Vascular calcification is a major cause of cardiovascular accidents in patients with type 2 diabetes mellitus. This study aimed to investigate the impact of carbohydrates on gut microbiota and aortic calcification in diabetic ApoE−/− mice.Methods: The diabetic ApoE−/− mice were randomly divided into 4 groups: ketogenic diet group, low carbohydrate diet group, medium carbohydrate diet group, and high carbohydrate diet group. The mice were fed continuously for 6 months, with blood glucose, blood ketone and body weight monitored monthly. Lipid metabolism indicators and inflammatory factors were detected using ELISA. The intestinal barrier, atherosclerotic lesion areas, and vascular calcifications were analyzed based on their morphology. Gut microbiota was analyzed using 16S rRNA genes.Results: We found that ketogenic diet played some roles improving glucose, lipid metabolism, and inflammation. Ketogenic diet could improve the intestinal barrier to some extent and increase intestinal bacteria. Compared to the other three groups, the relative abundance of genus Allobaculum, species Blautia producta and Clostridium Ramosum in the ketogenic diet group was significantly increased (P < 0.05), which has protective effects in diabetic ApoE−/− mice.Conclusion: Ketogenic diet could delay the onset of aortic atherosclerosis, aortic calcification and improve intestinal barrier function in diabetic ApoE−/− mice. Keywords: diabetes mellitus, atherosclerosis, vascular calcification, gut microbiota, low-carb diet, ketogenic diet, inflammation

Rui Zhang,1,2 Zhengyao Yang,3 Xiaoyong Shen,3 Lu Xia,4 Yun Cheng5 1Department of Nursing, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 2School of Nursing, Fudan University, Shanghai, 200030, People’s Republic of China; 3Department of Chest Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 4Day Surgery Unit, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, People’s Republic of China; 5School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, People’s Republic of ChinaCorrespondence: Lu Xia, Day Surgery Unit, Huadong Hospital Affiliated to Fudan University, No. 221 of Yanan West Road, Jingan District, Shanghai, 200040, People’s Republic of China, Tel +86 21-62483180-530401, Email yihaibeilu@126.com Yun Cheng, School of Medicine, The Chinese University of Hong Kong, Shenzhen, 518172, People’s Republic of China, Tel +86 755-23519000, Email cloud2011930@qq.comObjective: To identify latent classes of preoperative physical dysfunction in elderly patients with early lung cancer. To analyze the differences in demographic characteristics between different classes.Methods: We invited elderly patients with early lung cancer who were scheduled for surgery at Shanghai Elderly Characteristic Hospital to participate in the study using a convenience sampling method. We took latent class analysis to divide elderly patients with early lung cancer into latent classes based on preoperative physical dysfunction features. Furthermore, we used single-factor analysis and multinomial logistic regression to investigate the influence variables of each latent class.Results: The characteristics of preoperative physical dysfunction in elderly patients with early lung cancer can be divided into “Anxiety/depression emotion-poor sleep group” “Frailty of physical function group” “Pulmonary hypofunction-low activity tolerance group”. The distribution of age, chronic disease history, COPD history, smoking history and perceived social support level of elderly patients with early lung cancer in different potential categories were not the same, and the differences were statistically significant (P< 0.05). The elderly lung cancer patients with chronic disease history and age ≥ 75 years were more likely to be classified as “frailty of physical function group”. The elderly lung cancer patients with COPD and smoking history were more likely to be classified into “pulmonary hypofunction-low activity tolerance group”. Elderly lung cancer patients with moderate or low degree of perceived social support were more prone to be grouped into “anxiety/depression emotion-poor sleep group”.Conclusion: The variety of preoperative physical dysfunction seen in elderly patients with early lung cancer can be categorized into three latent classes. Medical professionals should create strategies for intervention for multiple patient populations with the goal of further enhancing their general state of life.Keywords: elderly, lung neoplasm, preoperative physical dysfunction, latent class analysis, influence factors

Nengwen Wu,&ast; Xiaoqing Shen,&ast; Jianwei Li, Miaolian Chen, Guishen Wu, Haiming Niu, Hongkai Liang, Ting Yang Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongkai Liang; Ting Yang, Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, 528400, People’s Republic of China, Email 1019978382@qq.com; 53103334@qq.comAbstract: Septic cardiomyopathy (SCM) is often associated with bacterial infections but also occurs with infections with viruses such as influenza and spirochetes, including syphilis. However, there has been no systematic investigation into whether Aspergillus infections can cause septic cardiomyopathy. We report on such a case for the first time in a patient without immunodeficiency. Therefore, clinicians should be concerned with septic cardiomyopathy caused by some atypical or rare pathogens when admitting such patients.Keywords: septic cardiomyopathy, aspergillus, extracorporeal membrane oxygenation, metagenomic next-generation sequencing

Qun Wei, Zilian Wang, Yu He, Xia Hong, Xuling Shen, Songying Zhang Reproductive Medicine Center, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Songying Zhang, Email zhangsongying@zju.deu.cnObjective: This study aims to investigate the phenomenon of sexual intercourse-related fear among women utilizing assisted reproductive technology due to dyspareunia. The primary objective is to offer insights that can inform the development of targeted nursing interventions.Methods: Employing a purposive sampling approach, a cohort of 23 female patients experiencing dyspareunia and undergoing treatment at the Reproductive Medicine Center of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, between July 2022 and December 2022, were selected as participants for this research. Semi-structured, in-depth interviews were conducted to gather qualitative data. The Colaizzi 7-step analysis method was subsequently applied to scrutinize the interview transcripts and identify emergent themes.Results: The analysis yielded five prominent themes: psychological disturbances, incongruent cognitive perceptions, anticipations regarding conception, insufficient adaptive responses, and sexual expectations.Conclusion: It is imperative for medical practitioners to demonstrate reverence for patients’ sexual beliefs and conditions, attune to their apprehensions, and offer efficacious emotional support. Tailored and multifaceted sexual health knowledge should be dispensed based on patients’ individual requirements and their envisioned sexual experiences, thereby fostering spousal and familial harmony. By prioritizing patients’ sexual well-being, cultivating a compassionate medical milieu, and augmenting the quality of assisted reproductive services, comprehensive improvements can be achieved.Keywords: dyspareunia, female, assisted reproductive technology, qualitative research

Hang Li, Xiping Shen, Ji Wu Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Ji Wu, Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, No. 2666, Ludang Road, Wujiang District, Suzhou, Jiangsu Province, People’s Republic of China, Tel +86-0512-82881248, Email 1968232851@qq.com

Ji Wu, Xiping Shen Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Xiping Shen, Department of General Surgery, Suzhou Ninth Hospital Affiliated to Soochow University, Ludang Road, Wujiang District, Suzhou, Jiangsu Province, 2666, People’s Republic of China, Tel +86 0512-82881248, Email shenxiping2022@163.com

Yiyang Li,1,&ast; Jiali Chen,1,&ast; Xingping Quan,1 Ying Chen,2 Yan Han,1 Jinfen Chen,1 Li Yang,1 Youhua Xu,3 Xu Shen,4 Ruibing Wang,1,5 Yonghua Zhao1,5 1Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macau SAR, People’s Republic of China; 2School of Health Economics and Management, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, Macao SAR, People’s Republic of China; 4Jiangsu Key Laboratory of Drug Target and Drug for Degenerative Diseases, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 5Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghua Zhao, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China, Tel +853-88224877, Fax +853-28841358, Email yonghuazhao@um.edu.moBackground: Ischemic stroke (IS) causes tragic death and disability worldwide. However, effective therapeutic interventions are finite. After IS, blood–brain barrier (BBB) integrity is disrupted, resulting in deteriorating neurological function. As a novel therapeutic, extracellular vesicles (EVs) have shown ideal restorative effects on BBB integrity post-stroke; however, the definite mechanisms remain ambiguous. In the present study, we investigated the curative effects and the mechanisms of EVs derived from bone marrow mesenchymal stem cells and brain endothelial cells (BMSC-EVs and BEC-EVs) on BBB integrity after acute IS.Methods: EVs were isolated from BMSCs and BECs, and we investigated the therapeutic effect in vitro oxygen-glucose deprivation (OGD) insulted BECs model and in vivo rat middle cerebral artery occlusion (MCAo) model. The cell monolayer leakage, tight junction expression, and metalloproteinase (MMP) activity were evaluated, and rat brain infarct volume and neurological function were also analyzed.Results: The administration of two kinds of EVs not only enhanced ZO-1 and Occludin expressions but also reduced the permeability and the activity of MMP-2/9 in OGD-insulted BECs. The amelioration of the cerebral infarction, BBB leakage, neurological function deficits, and the increasing ZO-1 and Occludin levels, as well as MMP activity inhibition was observed in MCAo rats. Additionally, the increased levels of Caveolin-1, CD147, vascular endothelial growth factor receptor 2 (VEGFR2), and vascular endothelial growth factor A (VEGFA) in isolated brain microvessels were downregulated after EVs treatment. In vitro, the employment of Caveolin-1 and CD147 siRNA partly suppressed the expressions of VEGFR2, VEGFA and MMP-2/9 activity and reduced the leakage of OGD insulted BECs and enhanced ZO-1 and Occludin expressions.Conclusion: Our study firstly demonstrates that BEC and BMSC-EVs administrations maintain BBB integrity via the suppression of Caveolin-1/CD147/VEGFR2/MMP pathway after IS, and the efficacy of BMSC-EVs is superior to that of BEC-EVs. Keywords: extracellular vesicles, ischemic stroke, Caveolin-1, CD147, matrix metalloproteinase, VEGFR2, blood-brain barrier

Zhiqiang Wang,&ast; Xiaochun Li,&ast; Pengfei Yu,&ast; Yu Zhu, Feng Dai, Zhijia Ma, Xueqiang Shen, Hong Jiang, Jintao Liu Department of Orthopedic Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215009, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jintao Liu, Department of Orthopedic Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, No. 18 Yangsu Road, Canglang New Town, Suzhou, 215009, People’s Republic of China, Email okdoctor2@163.comAbstract: Intervertebral disc degeneration is a chronic degenerative disease caused by the interaction of genetic and environmental factors, mainly manifested as lower back pain. At present, the diagnosis of intervertebral disc degeneration mainly relies on imaging. However, early intervertebral disc degeneration is usually insidious, and there is currently a lack of relevant clinical biomarkers that can reliably reflect early disease progression. Pyroptosis is a regulatory form of cell death triggered by the activation of inflammatory bodies and caspase, which can induce the formation of plasma membrane pores and cell swelling or lysis. Previous studies have shown that during the progression of intervertebral disc degeneration, sustained activation of inflammasomes leads to nuclear cell pyroptosis, which can occur in the early stages of intervertebral disc degeneration. Moreover, intervertebral disc nucleus pulposus cells adapt to the external environment through autophagy and maintain cellular homeostasis and studying the mechanism of autophagy in IDD and intervening in its pathological and physiological processes can provide new ideas for the clinical treatment of IDD. This review analyzes the effects of pyroptosis and autophagy on IDD by reviewing relevant literature in recent years, in order to explore the relationship between pyroptosis, autophagy and IDD.Keywords: intervertebral disc degeneration, pyroptosis, autophagy

Wentao Zhong,1– 3,&ast; Qianyu Wang,2,&ast; Xiaofei Shen,4,&ast; Yuan Lv,2,3 Liang Sun,2 Ran An,5 Hongyan Zhu,5 Huiyun Cai,2 Gang Chen,2,3 Aijun Liu,5 Junfeng Du1– 3 1The Second School of Clinical Medicine, Southern Medical University, Guangdong, 510515, People’s Republic of China; 2Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China; 3Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 4Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of China; 5Department of Pathology, the 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Liu, Department of Pathology, The 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email aliu301@126.com Junfeng Du, Department of General Surgery, the 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email dujf66@126.comPurpose: To demonstrate the intrinsic association of Neutrophil extracellular traps (NETs) with outcome and neoadjuvant therapy response of locally advanced rectal cancer (LARC), and the mechanisms.Patients and Methods: We enrolled 240 patients with LARC who underwent surgery without neoadjuvant therapy in two independent sets (training and validation), and 153 patients who received neoadjuvant therapy with biopsy followed by surgery. Immunohistochemistry, immunofluorescence staining and bioinformatics analysis were performed in formalin-fixed paraffin-embedded sections. NETs were identified by costaining for myeloperoxidase and citrullinated histone H3.Results: NETs were associated with recurrence-free survival in the surgical training and validation sets. High-NET density predicted poor postoperative survival of patients with LARC. Multivariate analysis identified NETs, TNM stage, and neutrophil-to-lymphocyte ratio as independent prognostic factors for recurrence-free survival. Low-NETs LARC demonstrated increased CD8+ T cell and lower T regulatory cell infiltration, which indicated a tumor immune microenvironment with strong antitumor capacity. High-NET density was associated with epithelial–mesenchymal transition, which is considered to contribute to tumor progression. In the neoadjuvant therapy cohort, high-NET density on biopsy was significantly associated with reduced likelihood of complete/near complete response.Conclusion: NET was an independent prognostic factor in LARC that were associated with patients’ survival, and NET density in pretreatment biopsies was an independent predictive biomarker of response to neoadjuvant therapy. This biomarker may be helpful in predicting survival in LARC with improved accuracy and selecting patients who will respond to neoadjuvant therapy.Keywords: NETs, tumor microenvironment, locally advanced rectal cancer, outcome

Shilei Bai,1,&ast; Xiaojing Shen,2,&ast; Jianwei Liu,1,&ast; Caixia Lu,1 Jie Wang,1 Liu Liu,1 Chunyan Wang,1 Huifeng Wang,3 Kai Liu,4 Yanfu Sun,1 Feng Xue1 1Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, People’s Republic of China; 2Department of Pathology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3Department of Hepatic Surgery, the Fifth Clinical Medical College of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Department of Biliary Tract Surgery IV, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Xue; Yanfu Sun, Department of Hepatic Surgery II, the Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), 225 Changhai Road, Shanghai, 200433, People’s Republic of China, Tel +86-21-81875513, Fax +86-21-65562400, Email xuefeng@smmu.edu.cn; sunyanfu@hotmail.comPurpose: When hepatocellular carcinoma (HCC) is closely associated with the left branch of the portal vein, there is still controversy regarding the surgical approach.Methods: This study enrolled 330 HCC patients with tumors adjacent to the left branch of the portal vein. Among them, 85 patients underwent left hemihepatectomy (LH), while the remaining 235 underwent liver lobectomy (LL), which included left medial segmentectomy or left lateral sectionectomy. Perioperative complications, time to recurrence and overall survival (OS) were compared using propensity score matching.Results: LH resulted in a lower 5-year recurrence rate and higher 5-year OS rate than LL (56.5% vs 74.0%, p=0.002; 67.4% vs 53.5%, p=0.029). The LL group showed a higher tendency for early recurrence (ER) and intrahepatic recurrence (IR). The cumulative IR rates at 1- 3-, and 5-years for the LH group and the LL group were 17.0%, 36.7%, 45.1% and 33.8%, 57.1%, 63.7%, respectively, with a p-value of 0.007. There was no statistically significant difference in the cumulative ER rates between the two groups at 1-, 3-, and 5- years. Furthermore, the LH group and the LL group had similar perioperative complications, and no cases of liver failure occurred.Conclusion: LH, compared to LL, reduced the IR rate and ER rate in HCC patients with tumor adjacent to the left branch of the portal vein. It improved the OS outcome of the patients, and there was no significant difference in perioperative complications between the two groups.Keywords: hepatocellular carcinoma, left hemihepatectomy, liver lobectomy, propensity score matching, recurrence, overall survival

Jingwen Jiang,1– 3,&ast; Na Kong,1– 3,&ast; Qingqing Shi,1– 3,&ast; Yuan Yan,1– 3 Xiaoyue Shen,1– 3 Jie Mei,1– 3 Haixiang Sun,1– 3 Chenyang Huang1– 3 1Center for Reproductive Medicine and Obstetrics and Gynecology, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China; 2Reproductive Medicine Center, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China; 3Center for Molecular Reproductive Medicine, Nanjing University, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixiang Sun; Chenyang Huang, Center for Reproductive Medicine and Obstetrics and Gynecology, Drum Tower Clinic Medical College of Nanjing Medical University, Nanjing, 210008, People’s Republic of China, Tel +8625-8310-6666-70261, Fax +8625-8310-7188, Email stevensunz@163.com; dianshui19901562@126.comBackground: Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear.Methods: We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis.Results: The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day.Conclusion: In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer.Keywords: short-acting GnRHa, elevated progesterone level, hCG trigger day, clinical pregnancy rate, blastocyst transfer

Rongrong Li,1,2 Xuhang Shen,3 Zhengyuan Li,4 Jilong Shen,2 Hao Tang,5 Huaming Xu,6 Jilu Shen,1,7 Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, People’s Republic of China; 3Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Department of Clinical Laboratory, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People’s Republic of China; 7Anhui Public Health Clinical Center, Hefei, People’s Republic of ChinaCorrespondence: Yuanhong Xu, Tel +86 13505694447, Email xyhong1964@163.comBackground: In recent years, carbapenem-resistant Pseudomonas aeruginosa (CRPA) has spread around the world, leading to a high mortality and close attention of medical community. In this study, we aim to find a new strategy of treatment for CRPA infections.Methods: Eight strains of CRPA were collected, and PCR detected the multi-locus sequence typing (MLST). The antimicrobial susceptibility test was conducted using the VITEK@2 compact system. The minimum inhibitory concentration (MIC) for AS101 and mefloquine was determined using the broth dilution method. Antibacterial activity was tested in vitro and in vivo through the chessboard assay, time killing assay, and a mouse model. The mechanism of AS101 combined with mefloquine against CRPA was assessed through the biofilm formation inhibition assay, electron microscopy, and detection of reactive oxygen species (ROS).Results: The results demonstrated that all tested CRPA strains exhibited multidrug resistance. Moreover, our investigation revealed a substantial synergistic antibacterial effect of AS101-mefloquine in vitro. The assay for inhibiting biofilm formation indicated that AS101-mefloquine effectively suppressed the biofilm formation of CRPA-5 and CRPA-6. Furthermore, AS101-mefloquine were observed to disrupt the bacterial cell wall and enhance the permeability of the cell membrane. This effect was achieved by stimulating the production of ROS, which in turn hindered the growth of CRPA-3. To evaluate the therapeutic potential, a murine model of CRPA-3 peritoneal infection was established. Notably, AS101-mefloquine administration resulted in a significant reduction in bacterial load within the liver, kidney, and spleen of mice after 72 hours of treatment.Conclusion: The present study showed that the combination of AS101 and mefloquine yielded a notable synergistic bacteriostatic effect both in vitro and in vivo, suggesting a potential clinical application of this combination in the treatment of CRPA.Keywords: AS101, mefloquine, carbapenem resistance, Pseudomonas aeruginosa, synergy, biofilm

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

Ziyu Jiang,1,2,&ast; Xiaoli Chen,2,3,&ast; Zhaoshen Sun,2,4 Xiaowei Shen,2,3 Yaju Huang,2,3 Jingbing Liu1,2 1Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 2Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 4Department of Dermatology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingbing Liu; Yaju Huang, Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Tel +86 025 85637121 ; +86 025 85639241, Email ljb0427@sina.com; huangyaju1113@163.comAbstract: Immune checkpoint inhibitors such as monoclonal antibodies have been used recently with greater effect for the management of non-small cell lung cancer (NSCLC). Sintilimab, a fully human IgG4 monoclonal antibody is specific for the immune checkpoint protein programmed cell death receptor-1 (PD-1). It is a common medication adopted for treating Hodgkin’s lymphoma and NSCLC. The adverse effects associated with the use of monoclonal antibodies should be closely monitored and in the current report, the use of sintilimab for treating NSCLC led to skin-associated adverse effects such as Stevens-Johnson syndrome and toxic epidermal necrolysis. Genetic testing showed that genes such as KRAS, CREBBP, NTRK1, RAF1, and TP53 were mutated. Initial visible symptom included the formation of a vesicular rash on the skin that had spread to the upper limbs, chest, and dorsum 1 week after the administration of sintilimab. The patient received anti-inflammatory agents to prevent worsening of the rashes and further infections. When the vesicles in back and limbs enlarged and the neck skin began to desquamate, the patient was diagnosed with Stevens-Johnson syndrome and sintilimab-induced toxic epidermal necrolysis. Toxic epidermal necrolysis was diagnosed via clinical symptoms and physical examination. The patient also reported the symptoms of oral mucositis. As soon as the dose of sintilimab was reduced to 20 mg/day, the skin-associated condition of the patient began to improve. Although the lump in the lungs decreased considerably 45 days after initial administration of sintilimab, the medication was stopped from use as soon as the skin-related symptoms improved after its withdrawal. This report suggests that close monitoring, personal care, and proper use of medications such as sintilimab should be implemented to avoid such rare skin-associated toxicities as an adverse effect.Keywords: sintilimab, checkpoint inhibitor, monoclonal antibody, NSCLC, adverse effects

Hui Wang,1,&ast; Xiaonan Zhou,2,&ast; Xingyu Li,1,&ast; Zeng Xu,1,&ast; Qingbing Meng,3 Jianxi Wang,1 Xiaolong Shen,1 Huajiang Chen,1 Wen Yuan,1 Xiaodong Wu1 1Department of Orthopedics, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Anesthesiology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Orthopedics, Shanghai Zhongshan Hospital, Fudan University Shanghai School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huajiang Chen; Xiaodong Wu, Email chenhuajspine@163.com; wuxiaodongspine@163.comIntroduction: Low back pain following transforaminal endoscopic lumbar discectomy (TELD) is prevalent (15– 25% incidence). Modifying TELD techniques to avoid excessive disc removal has been suggested to reduce such pain. Facet injury, re-herniation, and disc space collapse might contribute. This retrospective study aimed to explore factors linked to post-TELD low back pain.Methods: A total of 351 patients with L3/4, L4/5, and L5/S1 intervertebral lumbar disc herniations, who underwent TELD at two spine centers, were included. Patients were followed for one year. Low back and leg pain visual analogue scale (VAS) scores, Oswestry Disability Index (ODI), Pfirrmann grade, and disc height were measured at 3 months and 1 year. Correlation analyses examined links between postoperative low back pain VAS scores, age, sex, disc/vertebrae height ratio (D/V H ratio), Pfirrmann grade, cannula position grade, re-herniation grade, high-intensity zone (HIZ), disc calcification, surgical grade, and other factors. Significant variables were identified using partial least square tests, with variable importance in projection (VIP) values quantifying their impact on low back pain.Results: Univariate analysis indicated that surgical grade correlated with long-term postoperative low back pain (P = 0.023), while re-herniation (P = 0.008, P = 0.000), disc height (P = 0.001, P = 0.034), and sex (P = 0.025, P = 0.003) correlated with both short- and long-term postoperative low back pain. Trephine/cannula position is correlated with short-term low back pain (P = 0.036). Worsening low back pain was associated with female sex, improper trephine/cannula position, re-herniation, and post-surgical disc space collapse. Intradiscal irrigation was linked to decreased low back pain.Discussion: This study highlights factors influencing low back pain after TELD. Loss of disc height, extent of re-herniation, quality of trephine/cannula position, and sex were associated with low back pain at both 3 months and 1-year post-TELD. Proper techniques, like minimizing disc height loss and re-herniation, may help mitigate postoperative low back pain.Keywords: spine, endoscopy, radiology, minimally invasive surgical procedure, postoperative low back pain

Jiawei Qian,1,2 Xiulan Shen,3 Xin Gao,3 Qiuhua Sun2 1Department of Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2School of Nursing, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Emergency and Trauma Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Qiuhua Sun, Email sqh807@163.comBackground: Delirium is common in older patients during the postoperative period, increasing the number of adverse events, and grip strength is associated with delirium. Subsyndromal delirium (SSD) is a prostate of clinical delirium; nevertheless, the relationship between grip strength and SSD has not been elucidated. This study aimed to examine the association between grip strength and SSD in the elderly after arthroplasty.Methods: A total of 181 patients were recruited from two Chinese hospitals. SSD and delirium were evaluated before the surgery and the first week after surgery using the confusion assessment method. The Mini-mental State Examination was used to assess patients’ cognitive function, and their grip strength was evaluated with an electronic hand dynamometer before surgery. Logistic regression and ROC curve analysis were conducted to determine the odds ratio and predictive value of grip strength for SSD.Results: The incidence of SSD and postoperative delirium (POD) was 41.44% and 14.36% for the elderly following arthroplasty respectively, and approximately 1/3 of SSD progressed into POD. Older age, declined cognitive function, fall history, and lower grip strength were risk factors for SSD (P< 0.05). The area under the ROC curve of grip strength was 0.863 and 0.900 for males and females respectively, and the cut-off point of it was determined to be 22.050 kg for men and 18.050 kg for women.Conclusion: SSD and POD are common among older people. Decreased grip strength, advanced age, lower cognitive function, and fall history were independent risk factors for SSD, and grip strength was a significant predictor for SSD in aged patients after the arthroplasty.Keywords: subsyndromal delirium, delirium, grip strength, risk factor, joint replacement

Weiwei Liu,&ast; Yiru Wang,&ast; Kaizheng Chen,&ast; Min Ye, Weisha Lu, Keyu Chen, Xia Shen Department of Anesthesiology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Shen, Department of Anesthesiology, Eye & ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email shenxiash@fudan.edu.cnPurpose: To examine whether intraoperative dexmedetomidine reduces postoperative delirium (POD) in elderly patients who underwent a laryngectomy.Methods: Patients were randomly assigned to receive dexmedetomidine or a saline placebo infused during surgery. The study period was July 2020 to January 2022. Participants were elderly individuals (≥ 65 years) who underwent a laryngectomy. Immediately after induction of anesthesia, a 0.5 μg.kg− 1 bolus of study solution was administered for 10 min, followed by a maintenance infusion of 0.2 μg.kg− 1.hr− 1 until the end of surgery. Patients were assessed daily for POD (primary outcome). Plasma inflammatory factors were measured at baseline, on the first postoperative day, and on the third postoperative day.Results: In total, 304 male patients were randomized; 299 patients [median (interquartile range) age, 69.0 (67.0– 73.0) years] completed in-hospital delirium assessments. There was no difference in the incidence of POD between the dexmedetomidine and control groups (21.3% [32 of 150] vs 24.2% [36 of 149], P=0.560). However, dexmedetomidine reduced POD in patients with laryngeal cancer and a higher tumor stage (21.6% vs 38.5%; OR, 0.441; 95% CI, 0.209– 0.979; P=0.039). Dexmedetomidine reduced levels of C-reactive protein (CRP) (P=0.0056) and interleukin 6 (IL-6) (P< 0.001) on the first and third postoperative days, respectively. More patients had intraoperative hypotension in the dexmedetomidine group (29.3% [44 of 150] vs 17.4% [26 of 149], P=0.015).Conclusion: Intraoperative dexmedetomidine administration did not prevent POD in patients with laryngeal cancer. Dexmedetomidine reduced serum CRP and IL-6 levels postoperatively but caused a higher occurrence of intraoperative hypotension in elderly patients after a laryngectomy.Keywords: dexmedetomidine, laryngectomy, postoperative delirium, inflammatory factors, surgery complication

Xiaoqing Shen,&ast; Hongkai Liang,&ast; Guishen Wu, Miaolian Chen, Jianwei Li Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianwei Li, Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, 528400, People’s Republic of China, Email lijwprof2005@163.comAbstract: Streptococcus dysgalactiae subspecies equlsimilis (SDSE) is considered an important bacterial pathogen, and attention has also increased with the increasing number of invasive SDSE infections. Here, we report a patient with S. dysgalactiae toxic shock syndrome complicated by symmetrical peripheral gangrene (SPG). Despite surviving active treatment, amputation severely impacts the quality of life of patients. Therefore, we should pay attention to the early treatment of SDSE infection and the prevention and treatment of related complications.Keywords: Streptococcus dysgalactiae subspecies equlsimilis, streptococcal poisoning shock syndrome, symmetric peripheral gangrene

Xin Shen,1,&ast; Hai Shi,1,&ast; Xinli Chen,1 Junwei Han,1 Haiwang Liu,1 Jie Yang,1 Yuan Shi,2 Jiajia Ma2 1Department of Gastrointestinal Surgery, Xi’an Daxing Hospital, Xi’an, 710016, People’s Republic of China; 2Department of Gynecology and Obstetrics, Xijing Hospital, Air Force Military Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiajia Ma, Xijing Hospital, Air Force Military Medical University, No. 15 Changle Western Road, Xincheng District, Xi’an, Shaanxi, 710032, People’s Republic of China, Email majiajia69_11122@163.comAim: Intestinal ischemia/reperfusion (I/R) injury is a challenging pathological phenomenon accountable for significant mortality in clinical scenarios. Substantial evidence has supported the protective role of esculetin in myocardial I/R injury. This study is designed to reveal the specific impacts of esculetin on intestinal I/R injury and disclose the underlying mechanism.Methods: First, intestinal I/R injury model and intestinal epithelial cell line hypoxia/reoxygenation (H/R) model were established. Pathologic damages to intestinal tissues were observed through H&E staining. Serum diamine oxidase (DAO) levels were examined. RT-qPCR and Western blot examined the expression of inflammatory mediators. Commercial kits were used for detecting the levels of oxidative stress markers. TUNEL assay and caspase 3 activity assay measured cell apoptosis. Immunofluorescence (IF) staining measured autophagy levels. Western blot analyzed the expression of apoptosis-, Sirtuin 3 (SIRT3)/AMP activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling- and autophagy-related proteins. Molecular docking verified the interaction of esculetin with SIRT3. Cell viability was explored via CCK-8 assay.Results: The experimental results revealed that esculetin treatment mitigated pathological damage of intestinal tissues, reduced serum DAO level, ameliorated inflammation, oxidative stress and apoptosis and promoted autophagy in intestinal I/R rats. Moreover, esculetin bond to SIRT3 and activated SIRT3/AMPK/mTOR signaling both in vitro and in vivo. Furthermore, esculetin treatment enhanced cell viability and SIRT3 silencing reversed the impacts of esculetin on autophagy, inflammation, oxidative stress and apoptosis in H/R cell model.Conclusion: In a word, esculetin activated SIRT3/AMPK/mTOR signaling and autophagy to protect against inflammation, oxidative stress and apoptosis in intestinal I/R injury.Keywords: intestinal I/R injury, autophagy, esculetin, SIRT3/AMPK/mTOR signaling

Jing Nie, Xue Shen, Yan Li, Wenju Wang Department of Dermatology, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610000, People’s Republic of ChinaCorrespondence: Jing Nie, Department of dermatology, Chengdu Second People’s Hospital, 165 Caoshi Street, Qingyang District, Chengdu, Sichuan, 610000, People’s Republic of China, Tel +86-15902687253, Email niejing122402@163.comAbstract: Pediculosis has been reported in all countries and socio-economic classes. Due to the small size and translucent nature of their nits, patients with Pthirus pubis may be misdiagnosed. Here, we report three cases of Pthirus pubis infection involving different body sites, including the eyelashes, axillary region and head, respectively. This case series have discussed their clinical features and corresponding responses. A large number of eggs and adult pubic lice were observed under dermoscopic observation, which can be considered an effective tool for diagnosing Pthirus pubis and reducing the misdiagnosis rate.Keywords: Phthirus pubis, eyelashes, axillary region, head, dermoscopy

Zeling Huang,&ast; Binjie Lu,&ast; Xianda Zhang,&ast; Jiangping Wang, Xuefeng Cai, Yujiang Liu, Jianxiong Mo, Yuwei Li, Bo Xu, Xiaofeng Shen Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Xu; Xiaofeng Shen, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215008, People’s Republic of China, Tel +86 18359146790, Email xubo12080@163.com; 29240818@qq.comPurpose: The aim of this study was to investigate the effect of Zhiqiao Gancao decoction (ZQGCD) on hyperalgesia in lumbar disc herniation (LDH) and its mechanism.Methods: The potential mechanism of ZQGCD’s therapeutic effect on LDH was investigated through network pharmacology, which involved screening the targets of eight components that were absorbed into the bloodstream. The effects of CCR2 inhibitors and ZQGCD-containing serum on the excitability of the CCL2/CCR2 signaling pathway and dorsal root ganglion neurons (DRGn) were investigated in vitro. The effects of CCR2 inhibitors and ZQGCD on the expression of the CCL2/CCR2 signaling pathway and ASIC3 in the rat intervertebral disc and dorsal root ganglion (DRG), the degree of disc degeneration, the threshold of foot retreat, and the latency of foot retreat in LDH rats were examined in vivo. The binding affinities and interaction modes between CCR2 and the components absorbed into the blood were analyzed using the AutodockVina 1.2.2 software.Results: Network pharmacology revealed that ZQGCD could treat LDH through a mechanism involving the chemokine signaling pathway. It was observed that the CCR2 inhibitor and ZQGCD-containing serum downregulated CCR2 and ASIC3 expression and decreased cell excitability in DRGn. The CCL2/CCR2 signaling pathway was activated in the degenerated intervertebral disc and DRG of LDH rats, increased the expression of ASIC3, and decreased the mechanical allodynia domain and thermal hyperalgesia domain. However, a CCR2 inhibitor or ZQGCD could ameliorate the above changes in LDH rats. The target proteins, CCL2 and CCR2, exhibited a robust affinity for the eight components that were absorbed into the bloodstream.Conclusion: The CCL2/CCR2 pathway was activated in the intervertebral disc and DRG of LDH rats. This was accompanied by upregulation of ASIC3 expression, increased excitability of DRGn, and the occurrence of hyperalgesia. ZQGCD improves hyperalgesia in LDH rats by inhibiting the CCL2/CCR2 pathway and downregulating ASIC3 expression.Keywords: lumbar disc herniation, dorsal root ganglion neurons, hyperalgesia, traditional Chinese medicine, molecular docking

Yuelong Liang,1,&ast; Zhengze Huang,1,&ast; Xuqiu Shen,1,&ast; Yiyin Zhang,1 Yihan Chai,1 Kexin Jiang,1 Qi Chen,2 Feng Zhao3 1Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of General Surgery, Hangzhou Fuyang Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuelong Liang; Feng Zhao, Email yuelongliang@zju.edu.cn; fengzhao3901@zju.edu.cnBackground: Antimicrobial peptides (AMPs) can act on the bacterial cell membrane to play an antibacterial role in types of drug-resistant bacteria. Therefore, AMPs have attracted more and more attention in the treatment of drug-resistant bacteria.Methods: Bibliometric analysis was employed to sort out the development and trends in the research of AMPs in the treatment of drug-resistant bacteria and map the knowledge structure for scholars.Results: Since 2010, the publications and citations in this field have exploded, indicating a growing global interest in the field of AMPs for the treatment of drug-resistant bacteria. And as major countries in this field, China and the USA had conducted very in-depth exchanges and cooperation, which had injected a steady stream of impetus into this field. Both old and new scholars have made efforts, and related fields have developed rapidly, especially in the synthesis and improvement of novel AMPs. In recent years, research directions in the field of AMPs for the treatment of drug-resistant bacteria gradually focused on the practical application, optimization of drug delivery mode, optimization of synthesis mode, screening of new AMPs and other fields, indicating that the relevant research results of AMPs for the treatment of drug-resistant bacteria had entered the actual clinical stage, with higher practical significance.Conclusion: The research history, global research status, future research hotspots, and trends of the research of AMPs in the treatment of drug-resistant bacteria were discussed in depth in this study, which can provide research references and inspiration for researchers inside and outside the related field.Keywords: antimicrobial peptides, AMP, drug-resistant bacteria, bibliometric

Jingjing Huang,1,2,&ast; Minju Qin,3,&ast; Weisha Lu,3 Xia Shen3 1ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital of Fudan University, Shanghai, People’s Republic of China; 2Shanghai Municipal Key Clinical Specialty, Eye & ENT Hospital of Fudan University, Shanghai, People’s Republic of China; 3Department of Anesthesiology, Eye & ENT Hospital of Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Shen, Department of Anesthesiology, Eye & ENT Hospital of Fudan University, Fenyang Road No. 83, Xuhui District, Shanghai, People’s Republic of China, Tel +86-13611874118, Fax +86-21-64373416, Email zlsx@yahoo.comPurpose: To examine whether nighttime dexmedetomidine infusion improved sleep quality in patients after laryngectomy.Patients and Methods: Thirty-five post-laryngectomy patients admitted to the intensive care unit (ICU) were randomly assigned to a 9-h (from 2100 h on surgery day to 0600 h the morning after laryngectomy) dexmedetomidine (0.3 μg/kg/h continuous infusion) or placebo group. Polysomnography results were monitored during the dexmedetomidine infusion period. The percentage of stage 2 non-rapid eye movement (stage N2) sleep was the primary outcome measure.Results: Thirty-five patients (18 placebo group; 17 dexmedetomidine group) had complete polysomnogram recordings. The percentage of stage N3 sleep was significantly increased in the dexmedetomidine infusion group (from median 0% (0 to 0) in placebo group to 0% (interquartile range, 0 to 4) in dexmedetomidine group (difference, − 2.32%; 95% CI, − 4.19 to − 0.443; P = 0.0167)). Infusion had no effect on total sleep time, stage N1 or N2 sleep percentages, or sleep efficiency. It decreased muscle tensity and snore non-rapid eye movement. Subjective sleep quality improved. Hypotension incidence increased in the dexmedetomidine group, but significant intervention was not required.Conclusion: Dexmedetomidine infusion improved overall patient sleep quality in the ICU after laryngectomy.Keywords: dexmedetomidine infusion, postoperative, polysomnography, sleep disordered

Xuwei Shen,1,&ast; Chenggong Wang,1,&ast; Caiyan Chen,1 Yifan Wang,2 Zinuo Wang,1 Yanpei Zheng,1 Hanyue Liu3 1College of Science and Technology, Ningbo University, Ningbo, People’s Republic of China; 2Mental Health Education Center, Zhengzhou University, Zhengzhou, People’s Republic of China; 3School of Health Management, XiHua University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hanyue Liu, School of Health Management, XiHua University, No. 999 Hongguang Road, Jinniu District, Chengdu, CD, 610039, People’s Republic of China, Email psyhanyueliu@163.comBackground: The link between stress and Internet addiction (IA) has been confirmed. However, the mechanism underlying the correlation is poorly understood. Thus, the current study proposed a moderated mediation model to test the mediating role of anxiety and the moderating role of self-control (SC) in the link between stress and IA.Methods: Eight hundred and sixty-one Chinese college students (Mage = 20.62 years; SD = 1.58; male = 47.7%) were required to complete an online questionnaire package, including a depression-anxiety-stress scale, a self-control scale, and an Internet addiction test. The PROCESS macro developed based on SPSS was used to test the moderated mediation model.Results: When controlling for gender and age, the results revealed that anxiety partially mediated the link between stress and IA. Specifically, the more stressed college students are, the higher their anxiety level is, and the more likely they are to become addicted to the Internet. Additionally, the direct and indirect links between stress and IA were all moderated by SC. SC buffered the effect of stress on anxiety and anxiety on IA but enhanced stress on IA.Conclusion: These findings emphasized the predictor role of stress on IA and provided insights on intervening in college students’ excessive Internet use behaviors for educators, such as reducing anxiety levels and improving self-control abilities.Keywords: stress, internet addiction, anxiety, self-control, college students

Lang Wang,1,2,&ast; Zhiqi Zhang,1,3,&ast; Xingxiang Chen,1 Fang Yu,4 Hai Huang,4 Xue Shen,4 Yujie Tan,4 Qingqing Wu4 1Department of Microbiology and Immunology, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, People’s Republic of China; 2Hunan University of Medicine, Huaihua, People’s Republic of China; 3Taian City Central Hospital Affiliated to Qingdao University, Taian, People’s Republic of China; 4Center of Clinical Laboratory, the Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingqing Wu, Center of Clinical Laboratory, the Affiliated Hospital of Guizhou Medical University, Guiyang, People’s Republic of China, Email wuqingqing@gmc.edu.cnPurpose: The study aimed to investigate the relationship between the expression of PD-1 and CTLA-4 on the surface of peripheral blood T lymphocyte subsets in patients with sepsis and the severity and prognosis of the disease.Patients and Methods: The study included patients with sepsis who were admitted to the intensive care unit. The expression of PD-1 and CTLA-4 on T lymphocyte subsets was detected by flow cytometry, and the severity of sepsis was assessed using the SOFA score.Results: The expression of PD-1 on CD4+T cells, PD-1 on Tregs, and CTLA-4 on Tregs increased with the severity of the disease (P< 0.05). Multivariate logistic regression analysis showed that PD-1 expression on CD4+T cells, CTLA-4 expression on Tregs, and the SOFA score were independent risk factors for 28-day mortality in patients with sepsis (P< 0.05). The area under the curve of the SOFA score combined with the expression of PD-1 on CD4+T cells and CTLA-4 on Treg cells was significantly higher than any single indicator (P< 0.05). Patients with high expression of PD-1 on CD4+T cells (> 31.25%) and CTLA-4 on Tregs (> 12.64%) had a lower 28-day survival rate (P< 0.05).Conclusion: The increased expression of PD-1 and CTLA-4 on CD4+T cells and Tregs is significantly associated with the severity and prognosis of sepsis patients. The combination of the SOFA score and the expression of PD-1 on CD4+T cells and CTLA-4 on Tregs can further improve the prognostic predictive value. These findings may be promising biomarkers for prognostic assessment, risk stratification, and identification of immunosuppression in patients with sepsis.Keywords: sepsis, T lymphocyte subsets, programmed cell death receptor-1, cytotoxic T lymphocyte antigen-4, prognosis

Ying Hu,1,&ast; Wei Zhang,1,&ast; Xiufen Shen,1,&ast; Qiaoli Qu,1 Xiao Li,2 Rucai Chen,3 Zhuo Wang,1 Run Ma,1 Zaikun Xiong,3 Yuming Wang,1 Pengfei Wang3 1Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, and Key Laboratory for Southwest Microbial Diversity of the Ministry of Education, Yunnan University, Kunming, People’s Republic of China; 3Department of Key Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuming Wang, Department of Clinical Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China, Tel +86 13708406058, Fax +86-0871-65334416, Email wangym992011@163.com Pengfei Wang, Department of Key Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China, Tel +86 15288453604, Email 196545723@qq.comIntroduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has been widespread in coastal cities of eastern China since 2009. However, how CRKP spreads and evolves in southwest China is unclear.Aim: We investigated the genetic characteristics and dissemination mechanisms of carbapenemase genes in forty-one non-repetitive CRKP isolates collected from a southwest hospital, Kunming, Yunnan, during 2010– 2013.Methodology: Drug susceptibilities were analyzed by using VITEK 2 compact system. Genetic relationships were ascertained based on multilocus sequence typing (MLST) and Pulsed-field gel electrophoresis (PFGE) analysis. Genetic backgrounds of blaKPC-2 and blaNDM-1 were revealed by DNA walking and high-throughput sequencing.Results: All isolates were highly resistant to common antibiotics except for tigecycline. In total, 34 blaKPC-2, 3 blaNDM-1, 1 blaIMP-4 and 3 blaIMP-26 genes were identified and KP67 plasmid 1 co-harbored blaNDM-1 and blaIMP-26. Five sequence types, namely ST11, ST290, ST340, ST395 and ST437, were recognized by MLST. Surprisingly, blaKPC-2 was only detected in ST11 strains. We described a clonal dissemination of fosA3-positive IncR-IncF33:A-:B- multireplicon plasmid carrying the gene cassettes IS 26-ΔTn 3-ISKpn27-blaKPC-2-ΔISKpn6-korC-klcA-ΔrepB-Tn 1721 in all ST11 isolates. Three blaNDM-1 positive isolates belonged to three different ST types and their blaNDM-1 genetic backgrounds were also distinct. Interestingly, the flanking regions of blaNDM-1 in KP67 and KP72 were duplicated into one to five copies in a form of tandem repeat by the transposition of IS 91 like element. The blaNDM-1 of KP82 was carried on a common IncX3 plasmid.Conclusion: This study described the early epidemiological characteristics of blaKPC-2/blaNDM-1-carrying CRKP, and reported a new tandem repeat pattern of blaNDM-1 cluster in Yunnan. These findings extend our knowledge on the carbapenemase gene evolutions.Keywords: carbapenem-resistant Klebsiella pneumoniae, clonal dissemination, genetic backgrounds, IS 91 transposons, blaNDM-1 duplication

Sheng-Yan Wang,1 Qing Qiu,2 Xu Shen1 1Medical Center for Anesthesia and Pain, First Hospital of Jiaxing, Jiaxing City, People’s Republic of China; 2Anesthesia Medicine, Zhejiang Chinese Medical University, Hangzhou City, People’s Republic of ChinaCorrespondence: Xu Shen, Email 00181787@zjxu.edu.cnPurpose: Bladder spasm (BS) and catheter-related bladder discomfort (CRBD) are complications after transurethral holmium laser enucleation of the prostate (HoLEP). The pudendal nerve (PN) innervates the perineum. Therefore, we evaluated whether PN block (PNB) can reduce the incidence of BS and CRBD in patients undergoing HoLEP.Methods: In this randomized, parallel, single-blind prospective study, we enrolled 110 patients who were scheduled to undergo HoLEP under general anesthesia. Patients were randomly allocated to the PNB group (ultrasound-guided PNB at the entrance of the pudendal [Alcock’s] canal bilaterally; n = 55) or the control group (general anesthesia only; n = 55). The primary outcome was the incidence of BS and CRBD at 0.5, 1, 2, 4, 6, 12, and 24 hours postoperatively. The CRBD severity, postoperative pain, and analgesic drug use were also assessed. A P value of < 0.05 was considered statistically significant.Results: A significantly lower incidence of BS (P = 0.023) and CRBD (P < 0.001) was reported within the first 24 hours postoperatively in the PNB group. The incidence of CRBD above a moderate grade at 0.5 (P < 0.001), 1 (P < 0.001), 2 (P < 0.001), and 4 (P = 0.019) hours postoperatively was significantly lower in the PNB group. Additionally, postoperative pain scores and analgesic drug use were significantly lower in the PNB group. No PNB-related complications were observed.Conclusion: PNB at the entrance of the pudendal canal bilaterally resulted in a lower incidence of BS and CRBD, less postoperative pain, and less analgesic drug use in patients undergoing HoLEP without PNB-related side effects.Implication Statement: Bladder spasm and catheter-related bladder discomfort can occur in older individuals undergoing transurethral holmium laser enucleation of the prostate. They often result in severe pain and prolonging the hospital stay. We performed a bilateral ultrasound-guided pudendal nerve block at the entrance of the pudendal (Alcock’s) canal and found that the block reduced bladder spasm, catheter-related bladder discomfort, postoperative pain, and use of anesthetics. Besides, pudendal nerve block also decreased the severity of catheter-related bladder discomfort and helped older individuals achieve rapid recovery.Keywords: transurethral holmium laser enucleation of the prostate, pudendal nerve block, bladder spasm, catheter-related bladder discomfort, pudendal (Alcock’s) canal

Shuaishuai Li,1 Zeyu Chen,1 Rui Chen,1 Ning Xue,1 Xihao Shen,2 Haitao Zhu,1 Yunpeng Peng1 1Department of Urology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 2The First Clinical Medical College of Nanjing Medical University, NanJing, People’s Republic of ChinaCorrespondence: Haitao Zhu; Yunpeng Peng, Department of Urology, The Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Quanshan District, Xuzhou, 221100, People’s Republic of China, Tel +8615055521680 ; +8617826444501, Email xyfyuro1096@163.com; pyunp1984@163.comPurpose: This study aimed to assess the relationship between the preoperative reactive oxygen species and free ferrous protoporphyrin (ROS and FH) combined test and the risk of recurrence in a pathologically confirmed non-muscular invasive bladder cancer (NMIBC) patients.Patients and Methods: The retrospective study included 218 patients, newly diagnosed with NMIBC between January 2019 and February 2022. According to the results of FH and ROS combined test of voided urine, all patients were classified as FH(-)/ROS(-), FH(+)/ROS(-), or FH(+) /ROS(+). We reviewed demographic information, pathological results, and the FH and ROS combined test status. The clinicopathological characteristics were evaluated, and the survival rates of each group were compared. Finally, we also analyzed the association between preoperative free ferrous protoporphyrin and reactive oxygen species status and the tumor stage and grade.Results: This study included 218 NMIBC patients with a median age of 68 years (interquartile range [IQR] 60– 76 years). The number and proportion of patients in FH(-)/ROS(-), FH(+)/ROS(-) and FH(+) /ROS(+) were 95(43.6%), 79(36.2%) and 44(20.2%), respectively. And the pathological stages for those with FH(+) and ROS(+), FH(+) and ROS(-), FH(-) and ROS(-) at diagnosis were 0.5% Tis, 6.4% Ta, 13.3% T1; 2.3% Tis, 20.6% Ta, 13.3% T1; 5.5% Tis, 28.9% Ta, 9.2% T1, respectively. After adjusting for clinical factors, including tumor grade, tumor stage and FH/ROS status were independent risk factors for RFS In the multivariate Cox regression analysis. Through logistics regression analysis, FH(+)/ROS(+) were found to be corelated with high grade and more high stage (T1). Kaplan–Meier analysis showed that 1-year RFS of FH(+)/ROS(+), FH(+)/ROS(-) and FH(-)/ROS(-) were 46.0%, 87.8% and 93.4%, respectively (P=0.000).Conclusion: In newly diagnosed NMIBC patients, the status of FH(+)/ROS(+) has an association with a higher risk in recurrence. Furthermore, FH(+)/ROS(+) at diagnosis was correlated with high grade and higher stage (T1). Hence, the FH/ROS combined test can help specify treatment options for patients diagnosed with NMIBC.Keywords: non-muscular invasive bladder cancer, free ferrous protoporphyrin, reactive oxygen species, recurrence-free survival, stage, grade

Ao-lin Yuan,1 Xin Shen,2 Bin Chen1 1Minimally Invasive Spine Surgery, Chengde Medical University Affiliated Hospital, Chengde, Hebei Province, People’s Republic of China; 2Breast and Thyroid Surgical Oncology, Hebei Medical University Second Affiliated Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Bin Chen, Minimally Invasive Spine Surgery, Chengde Medical University Affiliated Hospital, Chengde, Hebei Province, People’s Republic of China, Email drchenbin@vip.sina.comPurpose: This study aimed to investigate the use of the percutaneous intervertebral foramen lens technology for secondary molding of the intervertebral foramen in the treatment of calcified lumbar discs.Methods: The study included 104 patients who were divided into two groups. Group A comprised 50 patients with calcified lumbar disc herniation and group B comprised 54 patients with non-calcified lumbar disc herniation diagnosed by computed tomography and magnetic resonance imaging. Patients underwent a percutaneous endoscopic lumbar discectomy at our hospital from January 1, 2017, to December 31, 2019. Demographic characteristics before the surgery and perioperative outcomes were retrospectively reviewed. The treatment outcome was analyzed using the numerical rating scale (NRS) score, Oswestry Disability Index (ODI) score, and modified Macnab criteria.Results: Patients in groups A and B showed significant improvement in both the NRS and ODI scores after the surgery and maintained relatively low ODI and NRS scores during subsequent follow-ups. According to the evaluation under the modified MacNab standard, the good–excellent rate of clinical efficacy was 94% in group A and 92.6% in group B at the 3 month follow-up. In group A, one patient developed neck pain during the surgery, which was diagnosed as spinal hypertension syndrome, and the surgery was suspended until the patient’s condition improved. No similar complications occurred in group B. In both the groups, no patient reported any dural leak, infection, or other related complications.Conclusion: The use of transforaminal remolding technology can significantly improve the symptoms and dysfunction of patients with calcified and non calcified lumbar disc herniation. There are few intraoperative and postoperative complications and have little impact on vertebral stability. It can provide a reference for the treatment of special types of lumbar disc herniation.Keywords: lumbar disc herniation, calcification, percutaneous transforaminal endoscopic surgery, nerve root compression, visual analog scale, Oswestry, disability index, Macnab criteria

Qineng Xue,&ast; Junming Xia,&ast; Jin Lu, Xia Shen Department of Anesthesiology, Eye & and ENT Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Shen, Department of Anesthesiology, Eye & and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Tel +86-21-64377134, Fax +86-21-64373416, Email zlsx@yahoo.comPurpose: To investigate the tolerability of midazolam intravenous (IV) solution by masking its bitter taste through the addition of syrup.Methods: In the waiting area before surgery at our institution, Eye and ENT Hospital, from May to November of 2021, pediatric patients scheduled for anterior ear fistula removal or eardrum catheterization were randomly assigned to receive a mixture of IV midazolam and water (Group C) or IV midazolam and syrup (Group S) in equal volumes. We measured the difference between the groups in terms of drug tolerability with a 5-point facial hedonic scale given to every patient, parent, and nurse involved in the study. Secondary outcomes included sedation and anxiety levels, which were assessed at separation from the parents and general anesthesia induction via a mask.Results: In total, 180 patients were enrolled. The facial hedonic scales were higher in Group S as evaluated by the children (p=0.046), parents (p=0.020), and nurses (p=0.026). More patients were willing to take the same solution again in Group S than in Group C (p=0.024). The levels of sedation and anxiety at two timepoints were similar between the groups (all p> 0.05). No adverse events were noted preoperatively.Conclusion: The tolerability of IV midazolam administered orally was increased in a pediatric population by adding syrup. The sedative and anxiolytic effects were comparable for both midazolam mixtures.Trial Registry Number: China Clinical Research Information Service, ChiCTR2000040229.Keywords: oral midazolam, pediatric preoperative sedation, pediatric preoperative anxiety

Fangzheng Zhao,1 Nienie Qi,1 Xihao Shen,2 Zhuang Xiong,1 Ning Xue,1 Yang Xu,1 Junqi Wang,1 Haitao Zhu1 1Department of Urology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 2The First Clinical Medical College of Nanjing Medical University, NanJing, People’s Republic of ChinaCorrespondence: Junqi Wang; Haitao Zhu, Department of Urology, the Affiliated Hospital of Xuzhou Medical University, No. 99 Huaihai West Road, Quanshan District, Xuzhou, 221100, People’s Republic of China, Tel +86-18761389113, Fax +86051685609999, Email 595851028@qq.com; xyfy1096@163.comPurpose: This study was conducted to evaluate the correlation between the free ferrous protoporphyrin and reactive oxygen species (FH and ROS) combined test and the tumor grade and stage in a pathologically confirmed uroepithelial carcinoma (UC) patient population.Patients and Methods: In this retrospective study, we enrolled patients newly diagnosed with UC between May 2020 and June 2021. All patients were classified as FH(+) and ROS(+), FH(+) and ROS(-), or FH(-) and ROS(-), based on the FH and ROS combined test of voided urine. Demographic information, pathological results, and status of the FH and ROS combined test were reviewed retrospectively. The relationship between FH and ROS combined test status and tumor stage and grade was evaluated using logistic regression.Results: This study included 120 UC patients with a median age of 69 years (interquartile range [IQR] 62– 77 years). Eighteen patients (15%) were diagnosed with upper tract urothelial carcinoma, and the others (85%) were diagnosed with bladder cancer. The pathological stages for those with FH(+) and ROS(+) at diagnosis were 25.0% Ta, 45.8% T1, and 29.2% ≥T2. The pathological stages for those with FH(+) and ROS(-) at diagnosis were 23.5% Ta, 35.3% T1, and 41.2% ≥T2. The pathological stages for those with FH(-) and ROS(-) at diagnosis were 52.6% Ta, 26.3% T1, and 21.1% ≥T2. After adjusting for clinical factors, including age, sex, and smoking history, FH(+) and ROS(-) were independent risk factors for muscle-invasive UC (≥T2 stage) at diagnosis (odds ratio [OR] 3.379; 95% confidence interval [CI] 1.103– 10.355; P=0.033) in the univariate and multivariate logistic regression analyses.Conclusion: Among patients with newly diagnosed UC, FH(+) and ROS(-) might have an association with a more advanced pathological stage. This finding may help differentiate between patients with aggressive diseases and those who may benefit from organ-sparing surgery.Keywords: urothelial carcinoma, free ferrous protoporphyrin, reactive oxygen species, stage, grade

Jiao Peng,1– 3,&ast; Xi Li,4,&ast; Lin Zheng,3,5 Lifang Duan,1 Zhengxian Gao,2,5 Die Hu,1 Jie Li,6 Xiaofeng Li,6 Xiangchun Shen,5 Haitao Xiao2 1Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 3Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, People’s Republic of China; 4Department of Gastroenterology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 5School of Pharmacy, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haitao Xiao, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xhaitao@szu.edu.cn Xiangchun Shen, School of Pharmacy, Guizhou Medical University, Guizhou, 550004, People’s Republic of China, Email shenxiangchun@126.comPurpose: GLP-1 based therapy represents a new treatment option for inflammatory bowel disease. Ban-Lan-Gen (BLG) granule, a known anti-viral TCM formulation, exhibits potential anti-inflammatory activities in treating various kinds of inflammation. However, its anti-inflammatory effect on colitis and the underlying mechanisms remain unknown.Methods: Dextran sulfate sodium (DSS)-induced chronic relapsing colitis in mice was established. The disease activity index, histological sign of damage, and levels of proinflammatory cytokines were performed to assess the protective effects of BLG. Serum GLP-1 level and colonic Gcg, GPR41 and GRP43 expression, the community compositions of gut microbiota, the levels of SCFAs in the feces and GLP-1 release from primary murine colon epithelial cells were performed to characterize the effects of BLG on gut microbiota and gut SCFA derived-GLP-1 production.Results: BLG treatment significantly alleviated body weight loss, DAI, colon shortening, colon tissue damage, and pro-inflammatory cytokine levels of TNF-α, IL-1β and IL-6 in the colon tissues. Moreover, BLG treatment could observably restore colonic Gcg, GPR41 and GRP43 expression and serum GLP-1 level of colitic mice, as well as correct the alteration of gut microbiota in colitic mice by increasing the abundances of SCFA-producing bacteria, eg, Akkermansia and Prevotellaceae_UCG-001, and decreasing the abundances of bacteria, eg, Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas, and Oscillibacter. Furthermore, BLG treatment could markedly increase the levels of SCFAs in feces of colitic mice. In parallel, ex vivo assay also showed that and the extract of feces from BLG-treatment mice could greatly stimulate the secretion of GLP-1 from primary murine colon epithelial cells.Conclusion: These findings suggest that the anti-colitis effects of BLG are achieved at least partly by regulating gut microbiota and restoring gut SCFA derived-GLP-1 production, and BLG has the potential to be developed as a promising agent for the treatment of chronic relapsing colitis.Keywords: colitis, Ban-Lan-Gen granule, gut microbiota, short-chain fatty acids, GLP-1

Xue Gao,1,&ast; Mohammed A Al-Baadani,2,&ast; Minjie Wu,1 Ningyang Tong,1 Xinkun Shen,2 Xi Ding,1 Jinsong Liu2 1Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325016, People’s Republic of China; 2School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinkun ShenSchool and Hospital of Stomatology, Wenzhou Medical University, 268# Xueyuan West Road, Lucheng District, Wenzhou City, 325000, People’s Republic of ChinaTel +86-577-88066010Email 20111902015@cqu.edu.cnXi DingDepartment of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Ouhai District, Wenzhou City, 325016, People’s Republic of ChinaTel +86-577-55579913Email dingxi@wzhospital.cnBackground: Compared with the healthy condition, osteoporotic bone defects are often accompanied by poor osteogenesis and excessive reactive oxygen species (ROS), which pose serious challenges to bone augmentation and repair by normal resorbable guided bone regeneration (GBR) membrane.Purpose: Polaprezinc (PZ) was loaded into polycaprolactone/gelatin (PG) hybrid electrospun nanofibers to fabricate a GBR membrane with antioxidant and osteogenesis ability.Methods: A series of physicochemical characterization were performed by scanning electron microscopy, Fourier-transform infrared spectroscopy, and water contact angle measurement. In addition to membrane degradation and PZ release detection, membranes were tested for cell viability, differentiation, and protein expression in MC3T3-E1 cells by CCK8, alkaline phosphatase activity, mineralization, and Western blotting assays. The membrane osteogenic capacity in cranial bone defects was studied by micro-CT in vivo.Results: PZ was successfully doped into the PCL/GEL nanofibers to form a hydrophilic GBR membrane. The cumulative release of PZ was closely related to the membrane degradation behavior. PG/0.4%PZ membranes produced the best protective effect on cell proliferation/differentiation under oxidative stress microenvironment; however, the PG/0.8%PZ membrane was cytotoxic. Western blotting demonstrated that the PZ-loaded membrane upregulated the Nrf2/HO-1/SOD1 signaling molecules in a concentration-dependent manner. In addition, micro-CT results showed an abundant formation of new bones in the PG/0.4%PZ group compared to the PG group.Conclusion: PZ-loaded degradable PG membranes (especially PG/0.4%PZ) have great potential to accelerate bone regeneration in oxidative stress-related diseases.Keywords: electrospun membrane, polaprezinc, antioxidant, osteogenesis, osteoporosis

Kai Fang,&ast; Yiding Shen,&ast; Kendrick Hii Ru Yie, Zixin Zhou, Lei Cai, Shuyi Wu, Abdullrahman M Al-Bishari, Mohammed A Al-Baadani, Xinkun Shen, Pingping Ma, Jinsong Liu School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinkun Shen; Pingping MaSchool and Hospital of Stomatology, Wenzhou Medical University, 268#Xueyuan West Road, Lucheng District, Wenzhou City, 325000, People’s Republic of ChinaTel +86-577-88066010; +86-577-88066085Email 20111902015@cqu.edu.cn; ppma2012@sina.comBackground: Sandblasted/acid-etched titanium (SLA-Ti) implants are widely used for dental implant restoration in edentulous patients. However, the poor osteoinductivity and the large amount of Ti particles/ions released due to friction or corrosion will affect its long-term success rate.Purpose: Various zirconium hydrogen phosphate (ZrP) coatings were prepared on SLA-Ti surface to enhance its friction/corrosion resistance and osteoinduction.Methods: The mixture of ZrCl4 and H3PO4 was first coated on SLA-Ti and then calcined at 450°C for 5 min to form ZrP coatings. In addition to a series of physiochemical characterization such as morphology, roughness, wettability, and chemical composition, their capability of anti-friction and anti-corrosion were further evaluated by friction-wear test and by potential scanning. The viability and osteogenic differentiation of MC3T3-E1 cells on different substrates were investigated via MTT, mineralization and PCR assays.Results: The characterization results showed that there were no significant changes in the morphology, roughness and wettability of ZrP-modified samples (SLA-ZrP0.5 and SLA-ZrP0.7) compared with SLA group. The results of electrochemical corrosion displayed that both SLA-ZrP0.5 and SLA-ZrP0.7 (especially the latter) had better corrosion resistance than SLA in normal saline and serum-containing medium. SLA-ZrP0.7 also exhibited the best friction resistance and great potential to enhance the spreading, proliferation and osteogenic differentiation of MC3T3-E1 cells.Conclusion: We determined that SLA-ZrP0.7 had excellent comprehensive properties including anti-corrosion, anti-friction and osteoinduction, which made it have a promising clinical application in dental implant restoration.Keywords: titanium, zirconium hydrogen phosphate, anti-corrosion, anti-friction, osteoinduction

Jieluan Lu,1 Hanbing Xia,2 Wenzhou Li,2 Xianhuan Shen,1 Huijuan Guo,2 Jianping Zhang,1 Xiaomei Fan2 1Department of Clinical Pharmacology, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Pharmacy, Baoan Women’s and Children’s Hospital, Jinan University, Shenzhen, 518102, People’s Republic of ChinaCorrespondence: Jianping ZhangDepartment of Clinical Pharmacology, College of Pharmacy, Jinan University, 601 W. Huangpu Avenue, Guangzhou, 510632, People’s Republic of ChinaTel +86 20 85220261Email tzhangjp@jnu.edu.cnXiaomei FanDepartment of Pharmacy, Baoan Women’s and Children’s Hospital, Jinan University, 56# Yulv Road, Baoan District, Shenzhen, 518102, People’s Republic of ChinaTel +86 755 27863999Email xmfane@163.comBackground: Valproic acid (VPA) is recommended as a first-line treatment for children with epilepsy. GABRG2 polymorphism is found to be associated with epilepsy susceptibility and therapeutic response of anti-seizure medications (ASM); however, the role of GABRG2 in VPA treatment still remains unknown.Objective: The purpose of this study was to explore the association of GABRG2 gene polymorphism with the drug response and adverse drug reactions (ADRs) related to VPA.Methods: A retrospective study including 96 Chinese children with epilepsy treated by VPA was carried out. The ADRs were collected during VPA therapy and GABRG2 rs211037 in enrolled patients was genotyped using Sequenom MassArray system. A network pharmacological analysis involved protein–protein interaction and enrichment analysis was constructed to investigate the potential targets and pathways of GABRG2 on VPA-related ADRs.Results: Among 96 patients, 41 individuals were defined as seizure together with 49 patients with seizure-free and 6 patients unclassified. Carriers of homozygote GABRG2 rs211037 CC genotype exhibited seizure-free to VPA (P = 0.042), whereas those with CT genotype showed seizure. Furthermore, CC genotype had predisposition to digestive ADRs (P = 0.037) but was a protective factor for VPA-associated weight gain (P = 0.013). Ten key genes related to digestive ADRs and weight gain induced by VPA were identified by network pharmacological analysis and mainly involved in “GABAergic synaptic signaling”, “GABA receptor signaling”, and “taste transduction” pathways/processes through enrichment analysis.Conclusion: This study revealed that GABRG2 variation exerted a predictable role in the efficacy and safety of VPA treatment for Chinese children with epilepsy.Keywords: children with epilepsy, GABRG2, gene polymorphism, valproic acid, therapeutic response, adverse drug reactions