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Zixuan Zhang,1 Jing Bai,1 Siqi Zhang,1 Renzhen Wang,1 Shaobing Zhu,1 Tianyue Li,1 Miao Zhang2 1Graduate Schools, Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2Acupuncture and Moxibustion 10 Departments, The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Miao Zhang, Acupuncture and Moxibustion 10 Departments, The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, Heilongjiang, 150001, People’s Republic of China, Tel +86-13845088833, Fax +86-13114600132, Email hljzmzjzy@163.comAbstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disease caused by multiple causes. The main pathological features of AD are β-amyloid (Aβ) deposition, hyperphosphorylation of Tau protein, and progressive neuronal loss. Pyroptosis is one of the main forms of neuronal death, which is mainly caused by the activation of Gasdermin protein by upstream signals and the release of its N-terminal domain on the cell membrane. Studies have shown that there is a close relationship between Alzheimer’s disease (AD) and pyroptosis. Therefore, this paper summarizes the relationship between pyroptosis and its molecular mechanism and AD, as well as the related research of traditional Chinese medicine in the treatment of AD by regulating pyroptosis, in order to provide a new direction for the study of AD pathogenesis based on pyroptosis pathway.Keywords: Alzheimer’s disease, cell pyroptosis, inflammasome, traditional Chinese medicine

Peng Gao,1 Yanshuo Wu,1 Xinhui Wu,1 Jing Bai,2 Kangkang Shen,1 Yanling Yin1 1Department of Critical Care Medicine, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China; 2Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Yanling Yin, Department of Critical Care Medicine,Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang City, Hebei Province, 050000, People’s Republic of China, Tel +86-13833467312, Email 47400548@hebmu.edu.cnObjective: To explore the effect of the Integrated Management Model of Doctor-Nurse-Pharmacist Collaboration on the Safety of Intravenous Therapy in Critically Ill Patients.Methods: 1587 patients who were hospitalized in the Intensive Care Department of the Fourth Hospital of Hebei Medical University in China from January 2021 to December 2022 were selected. 768 patients before the implementation of the integrated medical, nursing, and drug management model were selected as the control group, and 819 patients who implemented the integrated medical, nursing, and drug management model were selected as the observation group.Results: Compared with the control group, the incidence of drug compatibility contraindications in the observation group decreased from 3.5% to 1.5% (χ2=6.957 P=0.008), the central venous catheter (CVC) blockage rate decreased from 2.5% to 1.0% (χ2=5.249 P=0.022), the daily incidence of catheter related bloodstream infections decreased from (1.84 ± 2.17) to (0.91 ± 1.19)(t=6.988 P=0.015), and the incidence of peripheral venous treatment related complications decreased from 10.3% to 2.9% (χ2=16.663 P=0.000). Among them, the incidence of phlebitis decreased from 5% to 1.6% (χ2=4.817 P=0.028). The incidence of drug exudation decreased from 3.4% to 0.8% (χ 2=0.031 P=0.019). The incidence of extravasation has decreased from 2.5% to 0.4% (χ2=0.044 P=0.027). The differences were statistically significant (P< 0.05).Conclusion: The Integrated Management Model of Doctor-Nurse-Pharmacist Collaboration significantly reduced the incidence of catheter-related bloodstream infections (CRBSI), drug incompatibility, and other intravenous therapy-related complications, thereby enhancing the safety of intravenous therapy in critically ill patients.Keywords: severe patients, integration of doctor-nurse-pharmacist, intravenous treatment safety, complication

Dongdong Zhang,1 Jie Bai2 1Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, 441000, People’s Republic of China; 2Department of Neurology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Xiangyang, People’s Republic of ChinaCorrespondence: Dongdong Zhang, Department of Oncology, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, Jiefang Road No. 15, Xiangyang, Hubei, 441000, People’s Republic of China, Tel +8615072278600, Email zhangdongdong@whu.edu.cnBackground: Vincristine (VCR)-induced peripheral neuropathy (VIPN) is a common adverse reaction during cancer treatment, typically characterized by numbness and paresthesias. This study aimed to report a rare case of VIPN with an atypical genotype, manifesting as grade 3 weakness of the lower limbs.Case Presentation: A 19-year-old man, diagnosed with alveolar rhabdomyosarcoma for 8 months, was transferred to our hospital for further treatment after the failure of first-line treatment. He developed severe long-standing weakness in both lower limbs and could not walk after four sessions of second-line chemotherapy. The diagnosis of VIPN was confirmed based on the patient’s physical examination, imaging studies, electromyogram results, and treatment history. Furthermore, the pharmacogenetic analysis indicated that the patient harbored CYP3A4 rs2740574 TT genotypes.Conclusion: We have reported for the first time a VIPN patient whose main clinical manifestation is severe weakness in both lower limbs, accompanied by the CYP3A4 rs2740574 TT phenotype. This case may provide new information on the phenotypic features of VIPN, and may help to better understand the disease pathogenesis and contributing factors.Keywords: vincristine, vincristine-induced peripheral neuropathy, CYP3A rs2740574 TT genotype

Yudong Miao,1 Ruizhe Ren,1 Zhanlei Shen,1 Yi Li,1 Wanliang Zhang,1 Junwen Bai,1 Dongfang Zhu,1 Jingbao Zhang,1 Dan Guo,1,2 Clifford Silver Tarimo,3 Rongmei Liu,4 Qiuping Zhao,4 Jianping Hu,5 Xue Zhou,6 Wenyong Dong7 1College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania; 4Henan Key Laboratory for Health Management of Chronic Diseases, Central China Fuwai Hospital, Zhengzhou, People’s Republic of China; 5Henan Medical Communication and Project Forward Center, Zhengzhou, People’s Republic of China; 6College of Health Management, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Hypertension, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Rongmei Liu, Assistant research fellow. Fuwai Central China Cardiovascular Hospital, Zhengzhou University Affiliated Central China Fuwai Hospital, &num;1, Fuwai Avenue, Zhengdong New District, Zhengzhou, 450014, People’s Republic of China, Tel +8615038204525, Email liuyongmei0203@163.comObjective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases.Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients’ socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of “persistent health problems after 4 weeks of COVID-19 infection” issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles’ mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases.Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals’ health. After PSM, the non-long COVID cases’ health scores remained higher than that of long COVID cases.Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.Keywords: long COVID, lifestyles, self-reported health status, propensity score matching, effect of mediation

Jie Bai,1 Jinxia Zheng,1 Nafei Guo,2 Yueyan Dong,1 Ke Wang,1 Cheng Cheng,3 Hui Jiang,2 Lin Qian4 1Shanghai Key Laboratory of Maternal-Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Nursing Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3School of Nursing, Fudan University, Shanghai, People’s Republic of China; 4Nursing Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Hui Jiang, Nursing Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel/Fax +86 21-20261221, Email jianghuitest@163.com Lin Qian, Nursing Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Email lc699536@126.comPurpose: Receiving assisted reproductive technology is stressful due to its long-lasting process, which might pose negative impacts on clients’ psychological well-being and quality of life. This study was to investigate coping profiles among couples undergoing assisted reproductive technology and examine their associations with psychological distress and quality of life.Methods: This cross-sectional study was conducted at the IVF center of a specialized hospital in Shanghai, China. Of 502 eligible clients completed a structured, online survey of socio-demographic information, Dyadic Coping Inventory, Kessler Psychological Stress Scale, and Fertility quality of life. Coping profiles were identified using latent profile analysis and differences between identified profiles on psychological distress and quality of life were examined using analyses of covariance.Results: A three-profile solution was supported: low dyadic coping group (n = 168, 33.50%), moderate dyadic coping group (n = 241, 48.00%), and high dyadic coping group (n = 93, 18.50%). Significant differences between those groups were found in psychological distress and quality of life.Conclusion: The findings of this study have revealed dyadic coping profiles in clients undergoing assisted reproductive technology, which are differentially associated with psychological distress and quality of life.Keywords: assisted reproductive technology, coping, latent profile analysis, psychological distress, quality of life

Ying Yin,1 Ke Wang,1,2 Yan Xu,2,3 Xin Huang,1 Jinxia Zheng,1 Yuping Fan,1 Jie Bai1 1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 3School of International Medical Technology, Sanda University, Shanghai, 201206, People’s Republic of ChinaCorrespondence: Ke Wang, Email wangkeyfy@126.comObjective: To analyze the mental health and erectile function status of men using sperm donor during pregnancy after ICSI failure in severe oligoasthenospermia and to provide reference for clinical implementation of more targeted psychological intervention and nursing for this group.Methods: A total of 410 sterile men who received assisted pregnancy treatment in our hospital from December 2020 to December 2022 and met the inclusion and exclusion criteria were collected as the study subjects. Among them, 68 patients with severe oligoasthenospermia who used donor assisted pregnancy after ICSI failure were used as the study group. Sixty-eight patients with severe oligoasthenospermia who continued to receive ICSI assisted pregnancy were matched by propensity score 1:1 as control group. General data questionnaire, self-rating Anxiety Scale (SAS), self-rating Depression Scale (SDS), Chinese version of perceived Stress Scale (CPSS) and International Erectile Function Index Rating Scale (IIEF-5) were used to conduct a cross-sectional investigation to compare the mental health and erectile function status of the two groups.Results: There were statistical differences in age and occupational status between the two groups before PSM (P < 0.05), but there was no statistical significance in social demographic data between the two groups after matching (P > 0.05). The incidence of anxiety, depression, stress and erectile dysfunction (ED) in the study group was higher than that in the control group, and there were statistical differences between the two groups (P < 0.05).Conclusion: The use of donor sperm to assist pregnancy has a great impact on the mental health and erectile function of infertile men. Medical personnel should pay attention to the mental health and erectile function of these men, and formulate targeted measures to help these patients actively cope with infertility, so as to improve the life and marriage quality of this group and improve their mental health status.Keywords: sterile male, supply semen, erectile function, mental health, propensity score

Jiaosheng Li,1 Jiaojiao Bai,2 Xuanxuan Xiang,3 Yifan Guo,3 Haotian Yu4 1Department of Gynecology and Obstetrics, Central People’s Hospital of Zhanjiang, Zhanjiang, People’s Republic of China; 2Department of Gynecology and Obstetrics, Hebei North University, Zhangjiakou, People’s Republic of China; 3Department of Gynecology and Obstetrics, Hainan Hospital of Chinese PLA General Hospital, Sanya, People’s Republic of China; 4Department of Gynecology and Obstetrics, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yifan Guo; Haotian Yu, Email guoyifan301@126.com; yht200725@126.comBackground: To evaluate the dynamically impact of the coronavirus disease 2019 (COVID-19) on the female reproductive system.Methods: An online survey was shared to women of reproductive age who had been infected with COVID-19 and recovered in China between January and March 2023.Results: In total, 610 women of childbearing age completed the menstrual component of the survey and 82.6% (n=504) women self-purchased medications without hospitalization. 254 women were menstruating during COVID-19 infection. 66.9% of them reported changes in menstruation, including cycle length (64.7%), menstrual flow (72.4%), and duration (53%), compared to pre–COVID-19. COVID-19–related chest tightness (OR: 9.5; 95% CI: 1.9– 46.3), COVID-19–related stress (OR: 18.4; 95% CI: 1.4– 249.7), and COVID-19–related low mood (OR: 6.2; 95% CI: 1.4– 28.2) were associated with these menstrual changes. However, over 73% of women who menstruated during and after COVID-19 regained their pre-infection menstrual cycle (73%), duration (79.6%), and flow (75.2%) during their first menstruation after COVID-19 recovery. Compared to pre-infection, 19.7% (n=124) women reported changes in lower reproductive tract during COVID-19, including volume and color of vaginal discharge, vulvar pruritus, and vaginitis. These changes were significantly increased in those with a history of pelvic inflammatory disease (OR: 12.1; 95% CI: 3.1– 48.2), ovarian cysts (OR: 4.9; 95% CI: 1.2– 19.4), and vaginitis (OR: 5.5; 95% CI: 2.1– 14.4) prior to COVID-19. However, 52.4% reported that their lower reproductive tract health had returned to its pre-infection within the first month after recovery from COVID-19, while 73.5% reported a return to the pre-infection within 2 months.Conclusion: Changes in menstruation and lower reproductive tract associated with COVID-19 are transient. Menstruation and lower reproductive tract health will gradually return to pre-COVID-19 status within 2 months of recovery, which can help alleviate excessive concerns about the effects of COVID-19 on the reproductive system.Keywords: COVID-19, menstrual abnormalities, lower reproductive tract health, female reproductive system

Nan Peng,1 Qinghong He,2 Jie Bai,1 Chen Chen,3 Gordon G Liu1,4 1School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, 211198, People’s Republic of China; 2Institute of Economics, Chinese Academy of Social Sciences, Beijing, 100836, People’s Republic of China; 3Department of Global Health, School of Public Health, Wuhan University, Wuhan, 430071, People’s Republic of China; 4Institute for Global Health and Development, Peking University, Beijing, 100080, People’s Republic of ChinaCorrespondence: Gordon G Liu, Institute for Global Health and Development, Peking University, Beijing, 100080, People’s Republic of China, Email gordonliu@nsd.pku.edu.cnPurpose: The aim of this study is to investigate the factors influencing hospitalization costs for patients diagnosed with acute appendicitis in China.Methods: We conducted a cross-sectional study using data from Provincial Health Statistics Support System Database from S Province in China. This dataset contained all hospital’s electronic medical records from January 1, 2015 to December 31, 2018 including both public and private hospitals. The target population was identified based on the principal diagnosis of appendicitis (ICD-10: K35). To examine the impact of various factors on hospitalization costs, we conducted a multivariate linear regression analysis. Furthermore, we employed the Shapley value decomposition method to gain a more comprehensive understanding of the factors that influenced hospitalization costs and their respective levels of importance.Results: Our study comprised 317,200 cases. During the period from 2015 to 2018, the average hospitalization expenses for patients with acute appendicitis were estimated at approximately 7014 RMB (1061 USD), which accounts for a considerable 12% of China’s per capita GDP. The results of this study demonstrate a significant correlation between various factors, such as the patient’s age, gender, marital status, occupation, payment method, number of complications, treatment method, hospital tier, and ownership, and the total hospitalization costs and subcomponents of hospitalization costs. Notably, the treatment method employed had the most substantial impact on hospitalization costs.Conclusion: To the best of knowledge, this is one of the first studies to investigate the hospitalization costs of acute appendicitis incorporating both patient-level and hospital-level covariates, using a large sample size. To reduce the costs associated with acute appendicitis in China, it is recommended to consider suitable treatment options and explore the option of receiving medical care at lower-tier and privately-owned healthcare facilities.Keywords: appendicitis, hospitalization costs, influencing factors, multivariate regression

Kailin Xing,1,&ast; Xinyu Bian,2,&ast; Dongmin Shi,3,&ast; Shuangshuang Dong,1 Hongxin Zhou,1 Shuxiu Xiao,4 Jinjin Bai,4 Weizhong Wu1,4 1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Shanghai, 200032, People’s Republic of China; 2Department of Radiation Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210000, People’s Republic of China; 3Department of Medical Oncology, Shanghai Changzheng Hospital, Shanghai, 200072, People’s Republic of China; 4Clinical Center for Biotherapy, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weizhong Wu, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, 200032, People’s Republic of China, Tel +86-21-60268628, Fax +86-21-64037181, Email wu.weizhong@zs-hospital.sh.cnBackground: MicroRNA-612 (miR-612) has been proven to suppress the formation of invadopodia and inhibit hepatocellular carcinoma (HCC) metastasis by hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA)-mediated lipid reprogramming. However, its biological roles in HCC cell ferroptosis remain unclear.Methods and Results: In this study, we found that HCC cells with high metastatic potential were more resistant to ferroptosis, indicating that ferroptosis is related to HCC metastasis. The levels of lipid reactive oxygen species (ROS) were found to be much lower in HCC cells with high metastatic potential by flow cytometry (FCM). We used HCC cells with miR-612 overexpression/knockout and HADHA overexpression/knockdown to test cell viability after stimulation with RSL3. HCC cells overexpressing miR-612 were more sensitive to ferroptosis, and miR-612 could increase lipid ROS levels. Furthermore, colony formation assays and Transwell assays showed that miR-612 could inhibit the proliferation and metastasis of HCC cells by promoting ferroptosis. We next confirmed that miR-612 influenced HCC cell ferroptosis by regulating HADHA. HADHA could upregulate the expression of key enzymes in the mevalonate (MVA) pathway. HADHA overexpression upregulated the expression of CoQ10 and decreased polyunsaturated fatty acid (PUFA) levels and lipid peroxide abundance. miR-612 also suppressed HCC cell proliferation and metastasis by enhancing RSL3- and lovastatin-induced ferroptosis in vivo.Conclusion: Overall, miR-612 promotes ferroptosis in HCC cells and affects HCC proliferation and metastasis by downregulating CoQ10 and increasing cellular PUFA levels and lipid peroxides via the HADHA-mediated MVA pathway.Keywords: HCC, Ferroptosis, miR-612, HADHA, MVA pathway

Dongfang Yu,1,2,&ast; Jinhua Bai,3,&ast; Yufang Zhao,1,3 Chenzu Yin,4 Fangmei Liang,4 Jun Zhang5 1Center for Studies of Education and Psychology of Ethnic Minorities in Southwest China, Southwest University, Chongqing, Peoples Republic of China; 2Reader Service Department, Guangxi University of Finance and Economics, Nanning, Peoples Republic of China; 3Faculty of Psychology, Southwest University, Chongqing, Peoples Republic of China; 4School of Teacher Education, Hechi University, Hechi, Peoples Republic of China; 5College of International Studies, Southwest University, Chongqing, Peoples Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufang Zhao, Faculty of Psychology, Southwest University, Chongqing, 400715, Peoples Republic of China, Email zhaobee@swu.edu.cnPurpose: Previous studies show that intergroup contact, through common ingroup identity, has impact on intergroup processes such as reducing intergroup bias, improving intergroup relations, etc. The effect of intergroup contact on individual psychological process (through common ingroup identity), however, needs further exploration. Based on the positive effect of both intergroup contact and ingroup identification on mental health and well-being, this article proposes and tests a new model of individual loneliness reduction through intergroup contact by promoting common ingroup identity.Methods: A total of 263 majority ethnic members and 275 minority ethnic members from China participated in the survey. Intergroup contact, common ingroup identity and loneliness were measured at three time-points (T1-T3) over an 8-month period. Longitudinal mediation analysis and parallel process Latent Growth Curve Model for mediation are used for the examination of the indirect effect of common ingroup identity.Results: Longitudinal mediation analysis showed that intergroup contact quality at T1 positively predicted common ingroup identity at T2, and common ingroup identity at T2 alleviated loneliness at T3. Intergroup contact quality at T1 was indirectly linked to loneliness at T3 via common ingroup identity at T2. The parallel process latent growth curve model for mediation confirmed the robustness of the indirect effect of common ingroup identity. In addition, the growth rate of the quality of intergroup contact increased the growth rate of common ingroup identity, but reduced the growth rate of loneliness.Conclusion: The current study revealed the protectiveness of intergroup contact and common ingroup identity on loneliness, viz., intergroup contact reduces individual loneliness by promoting common ingroup identity, the implication being that intergroup contact and common ingroup identity should be taken into account in intervening process of loneliness prevention so that an individual’s physical and mental health could be better safeguarded.Keywords: intergroup contact, common ingroup identity, loneliness, group-based intervention

Jie Bai,1 Jingyu Zhang,1 Li Zhou,2 Yufang Hua1 1Department of Anesthesiology, Lanzhou University Second Hospital, Lanzhou, People’s Republic of China; 2Department of Pediatric Digestive, Gansu Provincial Maternity and Child-Care Hospital/Gansu Provincial Central Hospital, Lanzhou, People’s Republic of ChinaCorrespondence: Yufang Hua, Department of Anesthesiology, Lanzhou University Second Hospital, Lanzhou, 730030, People’s Republic of China, Tel +86 139 1903 2553, Email 40116942@qq.comPurpose: Neuropathic pain (NP) is a chronic pain state with a complex etiology that currently lacks effective treatment in clinical practice. Studies have found that exercise training can alleviate NP hyperalgesia, but the specific mechanism remains unclear. Here, we sought to identify proteins and signaling pathways critical for mediating the effects of treadmill training on NP in a mouse model of spared nerve injury (SNI).Methods: We used Tandem Mass Tag (TMT) technology for proteins and signaling pathways identification. Functional enrichment analyses were conducted using DAVID and Metascape software. Ingenuity pathway analysis was used to conduct functional annotation and analyze alterations in canonical pathways and molecular networks. Reverse transcription quantitative PCR (RT-qPCR) was used to confirm the results of proteomics analysis.Results: A total of 270 differentially expressed proteins were screened in the detrained and trained groups (P ≤ 0.05). Enrichment and ingenuity pathway analysis revealed the effects of treadmill training on autophagy, cAMP-mediated signaling, calcium signaling and NP signaling in dorsal horn nerves. Treadmill training reduced the expression of Akt3, Atf2, Gsk3b, Pik3c3, Ppp2ca, and Sqstm1, and increased the expression of Pik3cb in the autophagic pathway.Conclusion: Our results suggest that treadmill training may alleviate nociceptive hyperalgesia in NP mice by modulating the autophagic pathway, providing unique mechanistic insights into the analgesic effects of exercise.Keywords: proteomic changes, exercise, neuropathic pain, IPA, passway analysis

Su Wang, Juan Bai, Jianjun Qiao Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Jianjun Qiao; Juan Bai, Email qiaojianjun@zju.edu.cn; 1515033@zju.edu.cnAbstract: Acute generalized exanthematous pustulosis (AGEP), an uncommon severe cutaneous adverse reaction, is believed to be a T cell-mediated hypersensitivity reaction, of which the most common cause is medication. However, infections have also been reported to be associated with AGEP. Here, we present a case of AGEP possibly related with Staphylococcus pettenkoferi.Keywords: acute generalized exanthematous pustulosis, Staphylococcus pettenkoferi

Ying Yang,1,2 Lingling Li,1,2 Yangyang Zhang,1,2 Hong Yang,1,2 Jia Bai,1,2 Haihong Lv,1,2 Songbo Fu1,2 1Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China; 2The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of ChinaCorrespondence: Haihong Lv; Songbo Fu, Department of Endocrinology, The First Hospital of Lanzhou University, No. 1Donggang West Road, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 13893324091 ; +86 13993122257, Email haihonglv@126.com; 1041685970@qq.comPurpose: The relationship between coronary artery calcification and bone mineral density (BMD) in T2DM is still unclear. The aim of this study is to analyze the association between coronary artery calcium score (CACs) and BMD in T2DM with different visceral fat area (VFA), and further to explore the clinical significance of CACs in predicting osteoporosis in T2DM patients.Patients and Methods: A total of 479 T2DM patients aged ≥ 50 years were included. Agatston was applied to calculate CACs to evaluate the degree of coronary artery calcification. Dual-energy X-ray absorptiometry (DXA) was used to measure BMD. According to VFA, all subjects were divided into VFA < 100cm2 and VFA ≥ 100cm2 group. Adjusted regression analysis was performed to analyze the association between CACs and BMD. ROC curve was used to analyze the optimal cut-off value of CACs for screening osteoporosis.Results: The baseline showed that in VFA ≥ 100cm2 group, CACs increased significantly than that in VFA < 100cm2 group (212.1± 195.9 vs 139.3± 141.8, p< 0.001) and total hip BMD decreased obviously (0.968± 0.19 vs 1.021± 0.184, p=0.01). After multivariable adjustment, CACs was not significantly associated with BMD in all patients (p> 0.05). However, CACs was negatively associated with BMD of total hip and lumbar spine in patients with VFA ≥ 100cm2 (total hip β=− 0.087 p=0.01; lumbar spine β=− 0.052 p=0.005), but not VFA < 100cm2. ROC curve analysis showed that the optimal cut-off value of CACs for screening osteoporosis was 191.505.Conclusion: The present study implied that associations between CACs and BMD varied by the visceral fat deposition. It is critical to evaluate the condition of visceral fat accumulation for exploring the complex interplay of coronary artery calcification and BMD in T2DM patients. It may be of some clinical value for CACs in predicting osteoporosis in T2DM with visceral obesity.Keywords: bone mineral density, coronary artery calcium score, type 2 diabetes mellitus, visceral fat area

Jie Bai,1 Jinxia Zheng,1 Yueyan Dong,1 Ke Wang,1 Cheng Cheng,2 Hui Jiang3 1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2School of Nursing, Fudan University, Shanghai, 200032, People’s Republic of China; 3Nursing Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Hui Jiang, Nursing Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China, Tel +86 021-20261221, Fax +86 021-20261221, Email jianghuitest@163.comPurpose: Infertile clients undergoing assisted reproductive technology (ART) are exposed to a stressful situation and evidence has highlighted the importance of dyadic coping in reducing stress, yet little is known about the associations between psychological distress, dyadic coping, and quality of life in this population.Patients and Methods: A cross-sectional study was conducted at a tertiary hospital in Shanghai, China. A structured questionnaire was administered online to assess psychological distress, dyadic coping, and fertility quality of life. Sociodemographic information was collected. Descriptive statistics, Pearson correlation, and stepwise regression models were used to analyze the data.Results: Of 715 infertile males and females who completed the survey. Results showed that there was a negative association between psychological distress and quality of life. The use of positive dyadic coping was associated with better quality of life, whereas negative dyadic coping might contribute to worse quality of life. Moreover, males reported having a better quality of life in contrast to females.Conclusion: The findings of this study highlighted the significant associations between particular dyadic coping and quality of life in clients undergoing ART. Healthcare professionals should recognize the significance of dyadic coping in the context of ART and consider improving clients’ quality of life through coping-oriented interventions.Keywords: adaptation, infertility, psychological distress, reproductive techniques

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

Chao Li,1,&ast; ZhaoHui Deng,2,3,&ast; GuiXian Zheng,3,&ast; Ting Xie,3 XinYan Wei,3 ZengYu Huo,3 Jing Bai3 1Department of Respiratory Medicine, Hunan Provincial People’s Hospital, Changsha, Hunan, 410219, People’s Republic of China; 2Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Zhuzhou, Hunan, 412000, People’s Republic of China; 3Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Bai, Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, Tel +86-771-5356702, Fax +86-771-5608132, Email bj1312002@aliyun.comObjective: The aim of this study was to investigate the effects of resveratrol (RSV) on cigarette smoke (CS)-induced skeletal muscle atrophy and senescence in mice with emphysema and to explore the underlying mechanisms.Methods: Gastrocnemius muscle weight and lung and muscular morphology were observed in CS-exposed mice with or without RSV treatment. The expression of atrophy-related markers (MURF1 and MAFbx), senescence-related markers (P53, P21 and SMP30) and NF-κB inflammatory pathways was detected by Western blotting and real-time PCR. The levels of IL-1β and TNF-α were also determined by ELISA, and the number of senescent cells was determined by SA-β gal staining. In addition, the expression of HDAC2 and the effect of HDAC2 on CSE-induced skeletal muscle atrophy and senescence by RSV treatment were investigated.Results: RSV prevented emphysema and skeletal muscle atrophy in long-term CS-exposed mice. RSV decreased the expression of MURF1, MAFbx, P53, and P21 and inhibited the NF-κB pathway both in vivo and in vitro. Moreover, RSV reversed CS-induced downregulation of HDAC2 expression both in gastrocnemius and in C2C12 cells. Moreover, knockdown of HDAC2 significantly abolished the inhibitory effect of RSV on the expression of MURF1, MAFbx, P53, P21 and inflammatory factors (IL-1β and TNF-α) in C2C12 cells.Conclusion: RSV prevents CS-induced skeletal muscle atrophy and senescence, and upregulation of HDAC2 expression and suppression of inflammation are involved.Keywords: resveratrol, skeletal muscle, histone deacetylase 2, cigarette smoke, inflammation

Yuqi Chu, Taoming Liu, Juan Bai, Hong Fang, Jianjun Qiao Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Jianjun Qiao, Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, People’s Republic of China, Tel +86 13735542393, Email qiaojianjun@zju.edu.cnAbstract: Pyoderma gangrenosum (PG) is a rare autoinflammatory skin disorder, which is characterised by rapidly developing and tender cutaneous ulcers. The treatment of PG is challenging. Palmoplantar pustulosis (PPP) is also an autoinflammatory dermatosis with sterile pustules on the palms and/or the soles. We demonstrated a 68-year-old patient with coexisting autoinflammatory diseases including PG, 1-year history of plaque psoriasis and PPP, recovered after treatment with adalimumab. We also reviewed published reports of PG-associated autoinflammatory syndromes with adalimumab.Keywords: adalimumab, autoinflammatory syndrome, palmoplantar pustulosis, plaque psoriasis, pyoderma gangrenosum

Zhen Qin,1– 3 Shuai Xu,1– 3 Ruixia Yuan,4 Zeyu Wang,1– 3 Yongzheng Lu,1– 3 Yanyan Xu,1– 3 Yan Lv,1– 3 Fengyi Yu,1– 3 Jing Bai,1– 3 Hui Zhang,1– 3 Li Zhang,1– 3 Jinying Zhang,1– 3 Junnan Tang1– 3 1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan, 450052, People’s Republic of China; 3Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan, 450018, People’s Republic of China; 4Clinical Big Data Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Junnan Tang, Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 15890696166, Email fcctangjn@zzu.edu.cn Jinying Zhang, Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 13503830283, Email jyzhang@zzu.edu.cnObjective: We aimed to investigate the prognostic value of the triglyceride-glucose (TyG) index combined the with Global Registry of Acute Coronary Events (GRACE) score in adult acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) who underwent percutaneous coronary intervention (PCI).Methods: The study enrolled total 899 ACS patients with T2DM who underwent PCI. TyG index and the GRACE risk score were calculated and assessed by median. The correlation was analyzed by Spearman’s rank correlation coefficient. The cumulative major adverse cardiovascular event (MACE) curve was generated using the Kaplan–Meier method. Multivariate Cox regression was used to identify predictors of MACEs. Additionally, the receiver operating characteristic curve (ROC), net reclassification index (NRI) and Integrated Discrimination Improvement (IDI) were applied to analyze the performance of each single factor index and combined multivariate index in predicting MACE.Results: In the ACS patients with T2DM after PCI, there were significant differences in the TyG index and GRACE risk score between the MACE group and the MACE-free group (P < 0.001). Kaplan–Meier analysis showed that the TyG index combined with the GRACE risk score was positively correlated with the occurrence of MACEs (log rank P < 0.001). Multivariate Cox regression analyses showed that the TyG index, the GRACE risk score, and the TyG index combined with the GRACE risk score were independent predictors of long-term MACEs (adjusted HR: 1.805; 95% CI: 1.479– 2.203, P < 0.001; adjusted HR: 1.012; 95% CI: 1.009– 1.016, P < 0.001; and adjusted HR: 2.337; 95% CI: 1.805– 3.025, P < 0.001, respectively). Correlation analysis indicated that the TyG index was positively correlated with the GRACE risk score (R = 0.140, P < 0.001). The analysis of AUC, NRI and IDI revealed that the combined multivariate index performed better prognostic role than each single factor index in predicting the occurrence of MACE.Conclusion: Both the GRACE risk score and the TyG index could be significant and independent predictors of clinical outcomes in ACS patients with T2DM after PCI. A combination of them could be enhanced predictions of clinical outcomes in these patients.Keywords: triglyceride-glucose index, GRACE risk score, predictive biomarker, acute coronary syndrome, type 2 diabetes mellitus, percutaneous coronary intervention

Jiamiao Dai,1,&ast; Yun Yu,2,&ast; Yuchen Wang,3 Yinying Huang,4 Juan Liu,5 Yumin Lin,4 Xiaoxiao Fan,1 Mingjing Zhang,4 Xiaofang Xu,4 Jinbing Bai,6 Hong Chen,2,&ast; Yanqun Liu1,&ast; 1School of Nursing, Wuhan University, Wuhan, People’s Republic of China; 2Department of Nursing, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Nursing, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4Department of Nursing, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 5Department of Gynaecology and Obstetrics, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, USA&ast;These authors contributed equally to this workCorrespondence: Yanqun Liu, School of Nursing, Wuhan University, Wuhan, People’s Republic of China, Tel +86 27-68758591, Email liuyanqun1984@163.com Hong Chen, Department of Nursing, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China, Tel +86 27-68758591, Email 2077374407@qq.comBackground: CenteringPregnancy Care is a promising group prenatal care innovation that combines assessment, education, and peer support. In China, it is not clear how best to integrate the CenteringPregnancy Care into existing maternal health care models. This qualitative study aimed to explore Chinese pregnant women’s experience in the Internet-based CenteringPregnancy management model.Methods: The Internet-based CenteringPregnancy was applied in a tertiary hospital between 2018 and 2019 in Wuhan, Hubei Province. Through purposive sampling, a total of 9 pregnant women who had experienced Internet-based CenteringPregnancy were recruited. A semi-structured interview was used to collect qualitative data, and Colaizzi’s 7-step method of phenomenological data analysis was used to analyze the collected data.Results: Three themes were extracted from the participants’ interviews, including: 1) empowerment; 2) psychological and social support; 3) challenges of the Internet-based CenteringPregnancy. The Internet-based CenteringPregnancy management model retained advantages of CenteringPregnancy, emphasizing the pregnant woman as the subject of health care and promoting them to participate in health care. Participants believed that they could exchange pregnancy knowledge, help each other, and improve mood both timely and efficiently from the new model. However, it was found that there were challenges in seminar time arrangement, topic selection, and discussion management.Conclusion: The Internet-based CenteringPregnancy management model positively affected pregnant women’s empowerment, psychological, and social support. It is recommended to improve the seminar’s design in future studies.Keywords: CenteringPregnancy, mobile health, health management, prenatal care

Huihui Xu,1,2,&ast; Teng Li,1,2,&ast; Xiaoming Zhang,1,3 Hongqiang Li,4 Diyu Lv,4 Yiyuan Wang,4 Fangjie Huo,5 Jianwen Bai,4,6 Chunmei Wang4,6 1Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, 100000, People’s Republic of China; 3Shanghai Huashen Institute of Microbes and Infections, Shanghai, 200052, People’s Republic of China; 4Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, People’s Republic of China; 5Department of Respiratory Medicine, Xi’an No. 4 hospital, Xi’an, 710004, People’s Republic of China; 6Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunmei Wang; Jianwen Bai, Department of Emergency Medicine and Critical Care, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Shanghai, 200120, People’s Republic of China, Tel +8613761004402 ; +8613386057150, Email wcm1702@163.com; baijianwen1019@163.comPurpose: Sepsis is a condition that derives from a dysregulated host response to infection. Although B lymphocytes play a pivotal role in immune response, little is known about status of their terminally differentiated cells, antibody-secreting cells (ASCs) during immunosuppressive phase of sepsis, especially in elderly patients. Our aim was to extensively characterize the immune functions of ASCs in elderly septic patients.Patients and Methods: Clinical and laboratory data were collected on days 1, 3, and 7 of hospitalization. Circulating ASCs were evaluated by flow cytometry from fresh whole blood in elderly septic patients at the onset of disease. RNA sequencing analyzed ASCs gene expression profile. Receiver operating characteristic (ROC) curve analysis and logistic regression predicted the survival rate of 28-day mortality.Results: A total of 103 septic patients were enrolled. The number and proportion of ASCs among total lymphocytes dramatically increased in septic patients, and RNA sequencing analysis showed that ASCs from septic patients exhibited a different gene expression profile. Furthermore, we found these ASCs could promote the function of T cells. Logistic regression analysis showed ASCs population was an independent outcome predictor in septic shock patients.Conclusion: Our study revealed the complex nature of immune disorders in sepsis and identified circulating ASCs population as a useful biomarker for predicting mortality in elderly septic patients, which provided a novel clue to combat this severe disease.Keywords: biomarker, antibody-secreting cells, prognosis, sepsis, septic shock

Jing Jing Chen,1 Jie Bai2 1Department of Sociology, Faculty of Humanities and Social Sciences, Nanjing Forestry University, Nanjing, 210037, People’s Republic of China; 2School of Psychology, Nanjing Normal University, Nanjing, 210097, People’s Republic of ChinaCorrespondence: Jing Jing Chen, Department of Sociology, Faculty of Humanities and Social Sciences, Nanjing Forestry University, Nanjing, 210037, People’s Republic of China, Email chenjingjing007@126.comPurpose: Given its growing popularity and the richness of its content, the influence of the Internet on the academic achievement of adolescents has attracted increasing attention. However, how Internet use affects adolescents’ academic achievement has not yet been fully discussed in the Chinese context. This study sought to examine the relation between Internet use and adolescents’ academic achievement, as well as the mediating effect of future orientation and the urban-rural differences in this mediating effect.Materials and Methods: Junior high-school students from three schools in Nanjing, China, were recruited to participate in a correlational survey. A total of 1381 participants aged 12– 16 years completed the Internet use questionnaire, the future orientation scale, and reported their scores on the most recent grade unified examination.Results: The analysis results revealed that, after controlling for the variables of grade and gender, (1) the Internet use significantly and positively predicted academic achievement; (2) The future orientation significantly mediated the relation between Internet use and academic achievement; (3) and the effect of Internet use on future orientation was moderated by urban and rural areas. The effect of Internet use in promoting future orientation was only significant among rural adolescents.Conclusion: The results contribute to a better understanding of how Internet use affects adolescents’ academic achievement, revealing that Internet use is of particular significance in the development of rural adolescents.Keywords: internet use, future orientation, academic achievement, urban and rural areas

Lingling Li,1,2 Ying Yang,1,2 Jia Bai,1,2 Yangyang Zhang,1,2 Hong Yang,1,2 Yuqi Zhang,1,2 Haihong Lv1 1Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of China; 2The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, 730000, People’s Republic of ChinaCorrespondence: Haihong Lv, Email haihonglv@126.comPurpose: It is believed that vascular endothelial dysfunction is involved in the occurrence of cardiovascular disease (CVD), and diabetic peripheral neuropathy (DPN) is associated with flow-mediated dilation (FMD), however, the correlation is still unclear. Aims of the present study is to explore the relationship between DPN parameters and FMD, providing a new approach for the prevention of CVD.Patients and Methods: A total of 272 patients with T2DM from the Department of Endocrinology of The First Hospital of Lanzhou University according to the grading criteria were selected. FMD was measured by a new vascular ultrasound system and patients were divided into FMD> 7%, 4%≤FMD≤ 7%, and FMD< 4% groups. The Toronto Clinical Scoring System (TCSS) was used to assess the severity of DPN. The nerve conduction studies (NCS) assessed large fibre neuropathy by nerve conduction velocity (CV), compound muscle action potential (CMAP) amplitude (Amp), and distal motor latency (DML). SPSS 25.0 was used for statistical analysis.Results: TCSS evaluation revealed that the percentage of patients with severe nerve injury was significantly higher in FMD< 4% (70%) compared to FMD> 7% (2%). Among the TCSS indicators of all subjects, the proportion of temperature disturbance was the most (73%), and joint position disturbance was the least (0). TCSS scores were negatively correlated with FMD (r=− 0.756, p< 0.001). More interesting, in FMD< 4% group, CV and Amp were positively correlated with FMD, while DML was negatively correlated (p< 0.05). Linear regression analysis model showed that different systolic blood pressure (SBP), triglyceride (TG), TCSS and CV had statistically different effects on FMD.Conclusion: High TCSS score and decreased CV of common peroneal and tibial nerves are risk factors of FMD injury, which provide potential value for timely prevention and treatment of cardiovascular diseases.Keywords: type 2 diabetes, diabetic peripheral neuropathy, vascular endothelial function, cardiovascular disease, Toronto clinical scoring system

Yujie Liu,1,&ast; Jing Bai,1,&ast; Jianbang Kang,2 Yan Song,2 Donghong Yin,2 Jing Wang,2 Hao Li,3 Jinju Duan2 1Department of Pharmacy, School of Pharmacy, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pharmacy, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Clinical Laboratory, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Li, Department of Clinical Laboratory, First Hospital of Shanxi Medical University, No. 85, Jiefang South Road, Taiyuan, Shanxi, People’s Republic of China, Tel +86 15340705830, Email lihaoasia@163.com Jinju Duan, Department of Pharmacy, Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan, Shanxi, People’s Republic of China, Tel +86 351 3365713, Email duanjinju@163.comBackground: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a significant threat to public health and has already drawn worldwide attention. Hence, we aim to comprehensively analyze the case condition, as well as molecular epidemiology, resistance and virulence of three CRKP isolates with new sequence types (STs).Methods: Three CRKP were collected from November 2019 to April 2021. The three patients’ clinical characteristics were analyzed through His system. In order to screen phenotype of metallo-carbapenemase, the modified Carbapenem Inactivation Method (mCIM) and EDTA-modified Carbapenem Inactivation Method (eCIM) were conducted. Three isolates were subjected to antimicrobial susceptibility testing (AST) using the agar dilution method or minimal broth dilution method. The string test, the sedimentation assay, biofilm formation and the serum resistance assay were performed as phenotypic experiments to assist in evaluating virulence. The presence of resistance and virulence genes were detected by Whole-Genome Sequencing (WGS). Serotypes and new STs were compared and determined by multi-locus sequence typing (MLST).Results: Overall, all Klebsiella pneumoniae isolates were multi-resistant, but sensitive to tigecycline and colistin. Among them, all formed biofilms, strain 1 and strain 2 were classified as moderate-producers, while strain 3 as weak-producer. The results of the serum resistance assay indicated that only strain 2 was resistant. From WGS analysis, it showed that all isolates co-harbored multiple resistance genes, such as carbapenemase genes, sulfonamides, fluoroquinolones, aminoglycosides, and tetracyclines. Meanwhile, several virulence genes were also contained, including siderophores, fimbriae, capsule and lipopolysaccharides-associated genes. The serotypes of strain 1 and strain 2 manifested K35 and KL47, respectively.Conclusion: Three novel ST5365, ST5587, ST5647 were first discovered in North China. Our study suggested that we should pay more attention to their resistance. And the results will help treat CRKP infections caused by these novel STs.Keywords: carbapenem-resistant Klebsiella pneumoniae, CRKP, molecular characteristics, resistance, virulence factors, new sequence types

Yingwu Guo,1,2 Yingrong Du,1 Sanguan Lerkiatbundit,3 Jun Liu,1 Jingsong Bai,1 Yongrui Yang,1 Yin Yang,1 Aihui Wu,1 Virasakdi Chongsuvivatwong2 1Department of Infectious Diseases, Third People’s Hospital of Kunming City, Kunming, People’s Republic of China; 2Department of Epidemiology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand; 3Department of Social and Administrative Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, ThailandCorrespondence: Virasakdi Chongsuvivatwong, Email cvirasak@medicine.psu.ac.thBackground: Survival and quality of life of people living with HIV (PLWH) have been improving. Understanding fertility intention among PLWH is critical in helping them accomplish their pregnancy goals while significantly lowering the risk of HIV transmission. The purpose of this study was to identify factors based on the theory of planned behavior (TPB) that may explain fertility intention among PLWH.Methods: A survey was conducted in face-to-face interviews based on TPB, and the latent variables were devised and tested for their potential influences on fertility intentions in 487 reproductive-aged PLWH at antiretroviral treatment clinics in Kunming, China. Analysis was mainly based on the structural equation model.Results: About 38.4% of the respondents answered that they were likely to have a/another child in the next three years. Our hypothesized factors could explain 53.7% of the total variance of fertility intention. The 20- to 35-year-old group had a higher fertility intention. Perceived partner expectations toward fertility were the strongest predictors of fertility intention followed by beliefs in the support of the two-child policy. In contrast, the three components of attitudes, subjective norm, and perceived behavioral control did not influence fertility intention.Conclusion: In this HIV endemic area of China, fertility intended by PLWH is a matter of the couple that is also influenced by the national population fertility policy.Keywords: people living with HIV, fertility intention, theory of planned behavior

Cheng Cheng,1 Jie Bai2 1School of Nursing, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Cheng Cheng, Tel/Fax +86-21-64431003, Email chengcheng@fudan.edu.cnPurpose: To investigate the association between polypharmacy, anxiety, and depression among Chinese older adults.Patients and Methods: The data used in this study were from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), the 2018 wave. Polypharmacy status was measured by the accumulation of self-reported medications. Anxiety and depression were assessed by the Generalized Anxiety Disorder (GAD-7) scale and the Center for Epidemiologic Studies Depression Scale (CES-D-10), respectively. Logistic regression models were performed.Results: A total of 2484 Chinese older adults (female: 1321, 53.2%) aged from 60 to 117 years old were included in the analysis. Regression analysis showed that polypharmacy was associated with depression after controlling for the covariates. No association was observed between polypharmacy and anxiety.Conclusion: There was a suggestive link between polypharmacy and depression among Chinese older adults. Having polypharmacy might be an indicator for the possible depression among this population, but a comprehensive assessment of polypharmacy is necessary.Keywords: anxiety, depression, multimorbidity, older adults, polypharmacy

Tingting Zhang,1,2,&ast; Qiuyan Li,1– 3,&ast; Bonan Dong,1,2 Xiao Liang,1,2 Mansha Jia,4 Jing Bai,1,2 Jingcui Yu,2,4 Songbin Fu1,2 1Laboratory of Medical Genetics, Harbin Medical University, Harbin, People’s Republic of China; 2Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, People’s Republic of China; 3Editorial Department of International Journal of Genetics, Harbin Medical University, Harbin, People’s Republic of China; 4Scientific Research Centre, The Second Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Songbin Fu; Jingcui Yu Email fusb@ems.hrbmu.edu.cn; yujingcui@ems.hrbmu.edu.cnIntroduction: Genetic variability in genes encoding drug-metabolizing enzymes may contribute to the heterogeneity of drug responses in different populations. Extensive research in pharmacogenomics in major populations around the world provides us with a great deal of information about drug-related genetic polymorphisms.Objective: The purpose of this study was to detect the genetic variation of drug-metabolism-related genes in the five ethnic minorities Daur, Hezhen, Ewenki, Mongolian and Manchu in China, and to analyze the distribution differences among ethnic groups.Methods: We genotyped 32 SNPs of drug metabolism genes in 882 healthy Chinese volunteers from five ethnic groups. The genotype frequency and allele frequency of the five ethnic groups were calculated, and the different variants among the five ethnic groups were compared by chi-square test. Genetic parameters were analyzed using Popgene software. The genetic structure of five ethnic minorities was analyzed by principal component analysis, and compared with 26 populations.Results: We found that SNPs of genes related to drug metabolism existed diversity in different populations. Among them, rs8192766 and rs9419082 in CYP2E1 showed statistical differences between Daur and Manchu, and NAT2 rs1801280 showed statistical differences between Hezhen and Mongolian. In addition, the five populations we studied had the smallest differences with EAS populations. There was haplotype diversity in CHST3, VKORC1, CYP1A2 and CYP2E1 genes in the five ethnic minorities, and these haplotype polymorphisms were related to the use of corresponding drug doses. Cluster analysis shows that the five ethnic minorities in Heilongjiang Province are clustered together with the EAS populations.Conclusion: These results suggest that understanding the diversity of drug-related genetic markers is critical for individualized drug gene therapy programs in ethnic minorities in China as well as in populations highly mixed with these ethnic groups.Keywords: pharmacogenomics, population genetic, single nucleotide polymorphism, Chinese minorities

Xiao Cheng, Zhihui Song, Xin Wang, Shanshan Xu, Liming Dong, Jie Bai, Guangyao Li, Chao Zhang Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Chao ZhangDepartment of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel/Fax +86-10-58267167Email laural.zhang@yahoo.comPurpose: Protocatechualdehyde (PCA) is a phenolic compound found in the roots of Salvia miltiorrhiza with anti-proliferative and antioxidant activities. At present, there are few studies on protocatechualdehyde against diabetic cataract (DC), and there is also lack of systematic research on the mechanism of protocatechualdehyde. Therefore, this study tried to comprehensively clarify the targets and complex mechanisms of PCA against DC from the perspective of network pharmacology.Materials and Methods: Through collecting relevant targets from the databases, GO and KEGG enrichment analysis were performed on the potential targets. Moreover, core genes were identified by topological analysis of protein–protein interaction (PPI) network and gene–phenotype correlation analysis.Results: The results indicated that protocatechualdehyde may be closely related to targets such as AKT1, MAPK3 and HDAC3, as well as signal pathways such as MAPK signaling pathway, PI3K-Akt signaling pathway and AGE-RAGE signaling pathway in diabetic complications.Conclusion: Together, the present study systematically clarified the possible mechanisms of protocatechualdehyde in the treatment of diabetic cataract and provided new ideas for the drug research of this disease.Keywords: protocatechualdehyde, diabetic cataract, network pharmacology, topological analysis, gene–phenotype correlation analysis

Xiaodi Gong,1,&ast; Xin Pu,2,&ast; Jing Wang,1 Linlin Yang,1 Yunxia Cui,1 Lijuan Li,1 Xiao Sun,1 Jichang Liu,2 Jingfeng Bai,3 Yudong Wang1,4 1Department of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2State Key Laboratory of Chemical Engineering, School of Chemical Engineering, East China University of Science and Technology, Shanghai, People’s Republic of China; 3Biomedical Instrument Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Shanghai Municipal Key Clinical Specialty, Female Tumor Reproductive Specialty, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yudong WangDepartment of Gynecologic Oncology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of ChinaTel +86-21-64070434-18602Email wangyudong@shsmu.edu.cnJingfeng BaiBiomedical Instrument Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of ChinaTel +86-21-62933209-601Email Bai_jf@126.comPurpose: Iron-based nanomaterials have recently been developed as excellent and potent Fenton reagents to reactive oxygen species (ROS) during chemodynamic therapy (CDT). The performance of the materials, however, can be impaired by the intrinsic antioxidant defense mechanism in organisms, such as autophagy.Methods: The nanoscale metal-organic frameworks (nMOFs), nMIL-100 (Fe), were exploited and characterized. Also, the Fenton-like catalytic characteristics, anti-endometrial cancer (EC) effects and potential mechanisms of nMIL-100 (Fe) nanoparticles were investigated in vitro.Results: The synthesized nMIL-100 (Fe) nanocatalyst catalyzed hydroxyl radicals (·OH) production in the presence of hydrogen peroxide (H2O2) and simultaneously depleted intracellular glutathione (GSH). Combining with H2O2, nMIL-100 (Fe) nanoparticles exhibited enhanced cytotoxicity for EC cells, especially for progesterone treatment-insensitive KLE cells, probably due to relatively lower expression of the catalase gene. The accumulated ·OH initiated PTEN induced putative kinase 1 (PINK1)/E3 ubiquitin-protein ligase Parkin-mediated cytoprotective mitophagy in turn to partially rescue ·OH-induced cell apoptosis. Furthermore, both pretreatments of EC cells with siRNA-mediated Parkin knockdown and Mdivi-1 (a mitophagy inhibitor) addition were sufficient to ensure nMIL-100 (Fe) synergizing with H2O2-induced oxidative damages.Conclusion: These results suggest that the degree of mitophagy should be taken into consideration to optimize therapeutic efficiency when developing ROS based-CDT for EC cancer therapies. Therefore, a nMIL-100 (Fe)-guided, elevated ROS and overwhelmed mitophagy-mediated therapeutic strategy may have greater promise for EC therapy compared with current treatment modalities.Keywords: mitophagy, chemodynamic therapy, metal-organic frameworks, nanocatalyst, endometrial cancer

Baorui Ma,* Linnuo Pang,* Pingqing Huang, Jie Bai, Zhiqin Zhang, Huimin Wu, Mengru Cai, Jin Yang, Yuchen Xu, Xingbin Yin, Changhai Qu, Jian Ni School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changhai Qu; Jian NiSchool of Chinese Materia Medica, Beijing University of Chinese Medicine, Higher Education Zone, Fangshan District, Beijing, 102488, People’s Republic of ChinaEmail quchanghai@bucm.edu.cn; njtcm@263.netPurpose: To prepare the levocarnitine thermosensitive in situ gel (LCTG) and evaluate its effect on dry eye disease (DED).Methods: Draize eye irritation test and other examinations were used to evaluate the eye irritation after multiple administration of LCTG. The Schirmer test, fluorescein sodium staining, HE staining and TUNEL staining were used to detect the tear secretion, corneal injury, histopathological changes of the cornea and lacrimal gland, and the apoptosis rate of cornea epithelial cells after 3 days of the administration. The conjunctival goblet cell density was detected by PAS staining, and the expression levels of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) of corneal epithelial cells were detected by immunofluorescence staining after 7 days of the administration.Results: LCTG is non-irritating to rabbit eyes and has good biocompatibility. LCTG administration for 3 days can significantly increase the amount of tear secretion in mice with DED, promote corneal epithelial integrity and central corneal epithelium thickness recovery, and improve the pathological morphology and structure of corneal and lacrimal gland tissues, and reduce the apoptosis rate of the corneal epithelial cells. After 7 days of the administration, the preparation can promote the proliferation of conjunctival goblet cells and down-regulate the cornea expression levels of MMP-3 and MMP-9 in epithelial cells.Conclusion: The LCTG has a good curative effect on mice with DED, and the overall curative effect is better than that of levocarnitine solution.Keywords: levocarnitine, cornea, in situ gel, delivery, dry eye disease

Taoming Liu, Juan Bai, Shuni Ying, Sheng Li, Yunlei Pan, Deren Fang, Jianjun Qiao, Hong Fang Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Jianjun Qiao; Hong FangDepartment of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, No.79 Qingchun Road, Hangzhou, People’s Republic of ChinaTel/Fax +86-571-87236706Email qiaojianjun@zju.edu.cn; fanghongzy@zju.edu.cnBackground: Urticarial vasculitis is a small vessel vasculitis characterized by long-lasting wheals. It was suggested omalizumab is well tolerated and effective in patients with hypocomplementaemic urticarial vasculitis.Objective: To evaluate the clinical response and safety of omalizumab for treating patients with normocomplementaemic urticarial vasculitis (NUV) in real-world setting.Methods: We collected data from a single-center. This study included patients with NUV who was received omalizumab therapy. During a 24-week study period, the clinical efficacy was evaluated by patient’s self-assessment instrument urticarial vasculitis activity score and Dermatology Life Quality Index.Results: Five patients with NUV were enrolled. Three patients received 6 doses of 150 or 300 mg omalizumab subcutaneously every 4 weeks. At 24-week follow-up, it was revealed improvement of clinical manifestations and reduction of urticarial vasculitis activity score and Dermatology Life Quality Index. At 24-week visit, mild wheals recurred in one patient who was only administrated with omalizumab for 4 times. One patient did not response to omalizumab therapy. No adverse events were recorded in the 5 patients.Conclusion: Omalizumab may be a potential choice in the treatment of patients with NUV in the real-world life.Keywords: normocomplementemic urticarial vasculitis, omalizumab, real-world, targeted therapy, IgE

Taoming Liu, Juan Bai, Su Wang, Shuni Ying, Sheng Li, Jianjun Qiao, Hong Fang Department of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Jianjun Qiao; Hong FangDepartment of Dermatology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, People’s Republic of ChinaTel/Fax +86-571-87236706Email qiaojianjun@zju.edu.cn; fanghongzy@zju.edu.cnAbstract: Prurigo nodularis (PN) is an intense pruritic skin condition. Treatment of PN is challenging. We described an elderly patient with PN who had contradictions of cyclosporine or methotrexate and achieved significant improvement after treatment with dupilumab. We also reviewed published cases of elderly patients with PN who were refractory to traditional therapy.Keywords: prurigo nodularis, dupilumab, elderly patient, targeted therapy

Xiang Li,1 Jinzhu Bai,2 Yi Hong,2 Junwei Zhang,2 Hehu Tang,2 Zhen Lyu,2 Shujia Liu,2 Shizheng Chen,2 Jiesheng Liu2 1Department of Orthopaedics, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Department of Spine and Spinal Cord Surgery, Beijing Bo’ai Hospital, China Rehabilitation Research Center; School of Rehabilitation, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jinzhu BaiDepartment of Spine and Spinal Cord Surgery, Beijing Bo’ai Hospital, China Rehabilitation Research Center; School of Rehabilitation, Capital Medical University, No. 10 North Jiaomen Road, Fengtai District, Beijing, 100068, People’s Republic of ChinaEmail baijinzhu@126.comPurpose: To investigate the long-term (> 7 years) clinical outcomes of percutaneous endoscopic lumbar discectomy for lumbar degenerative disease to address postoperative problems including postoperative dysesthesia (POD), residual back pain and segmental instability.Methods: Inclusion and exclusion criteria were established. All patients who met the above criteria were treated by PELD using the transforaminal approach. Limited discectomy was performed to preserve the disc material in the intervertebral space as much as possible. The Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score for back pain (VAS-B) and leg pain (VAS-L) and Modified MacNab’s criterion were used for clinical evaluation. Radiographic parameters including height of intervertebral disc and segmental instability were also evaluated.Results: Forty-two patients (24 men and 18 women) who met our inclusion and exclusion criteria were included in our study. The average follow-up period was 95.71± 5.63 months (ranging from 87 to 105 months). There were no neurological complications associated with the operation. POD was found in 14.29% of patients, while only 2 patients (4.76%) complained of mild dysesthesia at final follow-up. Two patients (4.76%) required revision surgery during the follow-up period. The final follow-up ODI, JOA score, VAS-B and VAS-L were significantly better than preoperative values. The average disc-height ratio was 84.52± 5.66% of the preoperative disc height. No instability at the operation level was noted at final follow-up.Conclusion: Our study showed that PELD using the transforaminal approach can provide favorable results after a long-term follow-up period. POD is a common complication at initial prognosis. Limited discectomy can preserve the disc height well and minimize the risk of residual back pain.Keywords: percutaneous endoscopic lumbar discectomy, transforaminal approach, long-term follow-up, back pain

Guixiang Wang,1 Yajun Li,1 Hufei Zhu,1 Guoqiang Huo,1 Jingying Bai,1 Zhiyong Gao2 1Department of Colorectal Surgery, Yan’an People’s Hospital, Yan’an, Shaanxi, People’s Republic of China; 2Department of General Surgery, Yanchuan County People’s Hospital, Yan’an, Shaanxi, People’s Republic of ChinaCorrespondence: Zhiyong Gao Tel +86-911-2888754Email diavze@163.comBackground: Circular RNAs (circRNAs) play a crucial role in a variety of cancers, including colorectal cancer (CRC). This study aimed to explore the role of hsa_circ_0136666 (circ-PRKDC) in CRC and its potential mechanism.Methods: The levels of circ-PRKDC, miR-198 and discoidin domain receptor 1 (DDR1) were measured using quantitative real-time polymerase chain reaction or Western blot. Cell viability was detected using cell counting kit-8 (CCK-8) assay. Cell apoptosis and cycle were evaluated via flow cytometry. Cell migration and invasion were examined using transwell assay. CyclinD1 protein level was determined via Western blot. The interaction among circ-PRKDC, miR-198 and DDR1 was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Xenograft assay was performed to analyze tumor growth in vivo.Results: Circ-PRKDC and DDR1 levels were increased, and miR-198 level was decreased in CRC tissues and cells. Circ-PRKDC depletion inhibited proliferation, migration and invasion, and expedited apoptosis and cell cycle arrest in SW480 and HCT116 cells. Silence of circ-PRKDC impeded CRC progression by sponging miR-198. Overexpression of miR-198 hindered CRC development via targeting DDR1. Moreover, circ-PRKDC silencing suppressed tumor growth in vivo.Conclusion: Knockdown of circ-PRKDC inhibited CRC progression via modulating miR-198/DDR1 pathway.Keywords: colorectal cancer, circ-PRKDC, miR-198, DDR1, cell cycle

Jing Bai,1,* Zhaoguang Xie,1,* Li Sun2 1Department of Maternity, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan 250001, People’s Republic of China; 2Department of Gynecological Oncology, Qingdao Central Hospital, The Second Affiliated Hospital of Medical College of Qingdao University, Qingdao 266042, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Sun Tel +86-18953109686Email sunli766@163.comAbstract: Most multiple primary cancers(MPCs) are double primaries, while quadruple cancer is rare, especially breast cancer and triple genital cancer. Our work is the first report about ametachronous quadruple cancer in the reproductive system, including breast, ovary, fallopian tube and cervix. A54-year-old woman, who underwent modified radical mastectomy and right breast tumor resection 3 years ago, presented with abnormal vaginal discharge for 2 months, and she was subsequently diagnosed with stage IIA2 cervical squamous cell carcinoma. She then underwent radiotherapy and chemotherapy, as well as radical hysterectomy, bilateral salpingo-oophorectomy and bilateral pelvic lymphadenectomy. Postoperative pathological findings revealed that the patient had cervical, ovarian and tubal triple cancers with different histopathology for all lesions, also different from breast cancer, implying that these tumors had separate etiology and were not metastatic tumors. Our work might provide aseries of diagnostic, etiological and therapeutic strategies for MPC patients.Keywords: quadruple cancer, multiple primary carcinoma, metachronous cancer, genital cancer

Lei Duan, Man Li, Fan Wang, Yulun Cai, Huiying Li, Wenli Zhou, Yuerui Li, Qiang Chen, Jing Bai, Hongbin Liu Department of Geriatric Cardiology, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Hongbin Liu Department of Geriatric CardiologyNational Clinical Research Center for Geriatric Diseases, The Second Medical Center of PLA General Hospital, 28 Fuxing Road, Beijing 100853, People’s Republic of ChinaTel +86 010 66876349Email liuhb301@sina.comBackground: It is uncertain whether long-term use of clopidogrel alone can cause gastric mucosal injury. This study aimed to evaluate the relationship between ABCB1 C3435T polymorphisms, which could affect the intestinal absorption of clopidogrel, and gastric mucosal erosion in elderly Chinese men who used clopidogrel alone.Methods: We selected 298 male patients (aged between 68.2 and 89.5 years, average age 78); 201 of them constituted the control group, and 97 constituted the case group. Patients taking clopidogrel alone who had undergone endoscopic screening for gastric erosion were analyzed for ABCB1 C3435T polymorphisms by a TaqMan assay.Results: The proportion of people carrying the ABCB1 3435T allele (n = 63, 64.9% vs n = 97, 48.3%, p = 0.007) was significantly higher in the case group than in the control group. After adjustments for significant factors were made, ABCB1 3435T allele carrier (OR 2.14, 95% CI 1.43– 3.84, p < 0.01) was found to be associated with gastric mucosal erosion in people who used clopidogrel alone.Conclusion: Carrying the ABCB1 3435T allele may be a useful genetic predictor for clopidogrel-induced gastric mucosal erosion in elderly Chinese men.Keywords: clopidogrel, polymorphism, single nucleotide, ABCB1 C3435T, gastric mucosa, risk factor

Jinjing Zhang,1,* Yunyun Yang,2,* Xue Qiao,1 Liwen Wang,1 Jinyu Bai,1 Tsring Yangchen,1 Pema Chodron1 1School of Medicine, Xizang Minzu University, Xianyang, Shaanxi, People’s Republic of China; 2Department of Pulmonary, The Third People’s Hospital of Tibet Autonomous Region, Lhasa, Tibet, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinjing ZhangSchool of Medicine, Xizang Minzu University, #6 Wenhui East Road, Xianyang 712082, Shaanxi, People’s Republic of ChinaTel +86 186 9100 8710Fax +86 029 3375 5433Email jinjingzhang@xzmu.edu.cnPurpose: Medication nonadherence is one of the most significant obstacles to tuberculosis (TB) control worldwide. Identification of the factors associated with medication nonadherence is important. However, few related studies have been carried out in Tibet. This study aimed to explore factors influencing medication nonadherence to pulmonary TB (PTB) treatment in Tibet, China, from the patient perspective.Patients and Methods: In this qualitative study, seventeen PTB patients in Tibet were recruited by purposive and maximum variation sampling methods. In-depth semistructured interviews were conducted to collect data on factors influencing medication nonadherence, and Colaizzi’s seven-step method was used to analyze the data.Results: The medication nonadherence of PTB patients in Tibet was influenced by one or a combination of the following four factors. First, patient-related factors included a lack of knowledge of PTB treatment, poor self-management capability, poor self-regulation capability and misperception of health condition. Second, a medication-related factor was medication side effects. Third, health service-related factors included the poor treatment skills of doctors in primary hospitals and a lack of directly observed treatment (DOT). Last, sociocultural factors included the effect of traditional Tibetan medicine, lack of family member support and discrimination.Conclusion: Multiple interplaying factors influenced medication nonadherence during PTB treatment in Tibet, and the main influencing factors were a lack of knowledge about PTB treatment, poor self-management capability, and the effect of traditional Tibetan medicine. TB health workers in Tibet should provide permanently viewable PTB treatment knowledge materials to PTB patients when oral health education is conducted, find feasible alternative strategies to DOT and establish links to traditional Tibetan medicine hospitals.Keywords: pulmonary tuberculosis, medication compliance, in-depth interview, influencing factor

Yuan Gao,1 Junping Wen,1 Shaojun Wang,1 Xuebin Xu,2 Zeqiang Zhan,1 Zhengquan Chen,1 Jie Bai,1 Xiaoyun Qu,1 Hongxia Zhang,1 Jianmin Zhang,1 Ming Liao1 1National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Zoonoses, Ministry of Agriculture, Key Laboratory of Animal Vaccine Development, Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Microbiology, Shanghai Municipal Centre for Disease Control and Prevention, Shanghai, People’s Republic of ChinaCorrespondence: Ming Liao; Jianmin ZhangNational and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Zoonoses, Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, Guangdong, People’s Republic of ChinaTel +86 020 85290240; +86 020 85280240Fax +86 020 85290240; +86 020 85285282Email mliao@scau.edu.cn; junfeng-v@163.comPurpose: Carbapenem resistance is rarely reported in Salmonella Typhimurium, especially from a food origin. Here, we report a plasmid-mediated mobile carbapenem-resistant blaNDM-5 gene in Salmonella Typhimurium isolated from pork in Shanghai, China in 2016.Patients and Methods: In July 2016, the S. Typhimurium SH160 strain was recovered from minced pork meat purchased from a supermarket in Yangpu District, Shanghai, China. Antimicrobial susceptibility testing, multi-locus sequence typing, conjugation, S1-PFGE, southern hybridization, whole-genome sequencing and data analysis were performed.Results: This isolate was found to be a ST34 strain and resistant to carbapenems, cephalosporins, and most other commonly used antibiotics. The blaNDM-5 gene was harbored by a 46161-bp IncX3 plasmid which was found to be transferable. The IncX3 plasmid contains a composite cassette, consisting of ISSwil-IS3000-ΔISAba125-IS5-blaNDM-5-bleMBL-trpF-dsbC-IS26-ctuA1-ΔumuD. In addition, this strain was found to harbor an additional 161706-bp IncHI2 plasmid which carries nine resistant genes, such as aadA1, aadA3, aph(3ʹ)-la, sul1, sul2, sul3, floR, cmlA and dfrA12.Conclusion: We reported the S. Typhimurium with transferable IncX3 plasmid harboring blaNDM-5 gene from minced pork. We characterized the complete genetic features of the plasmid, which demonstrated the potential for spreading in different bacterial pathogens. Therefore, extensive surveillance and monitoring for carbapenem-resistant bacterium in the food chain and public health are urgently required.Keywords: S. Typhimurium, pork, blaNDM-5, public health

Yu-Chen Jia,1,* Jia-Yue Fu,2,* Ping Huang,3 Zhan-Pu Zhang,3 Bo Chao,3 Jie Bai3 1Inner Mongolia Key Laboratory of Molecular Biology, School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2Inner Mongolia Medical University, Hohhot, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hospital, Inner Mongolia Medical University, Hohhot, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie BaiDepartment of Neurosurgery, Affiliated Hospital, Inner Mongolia Medical University, No. 1 Tongdao North Road, Hohhot City, Inner Mongolia 010000, People’s Republic of ChinaTel +86-471-6351352Fax +86-471-6351184Email baijie0611@126.comIntroduction: Cerebral arteriovenous malformation (cAVM) is a disease characterized by the angiogenesis and remodeling of veins. However, whether vascular endothelial cells (ECs) exhibit morphological and functional changes during cAVM remains unclear. This study aimed to investigate the role of ECs in the pathogenesis of cAVM.Methods: Rat model of cAVM was established by anastomosing the common carotid artery with the external jugular vein. The digital subtraction angiography (DSA), HE, Masson and immunohistochemical staining were performed to evaluate the model. ECs were isolated from AVM rat model or control rats, and characterized by MTT, cell scratch, and tube formation assays. The secretion of vascular endothelial growth factor (VEGF) was detected by ELISA.Results: AVM rat model showed typical pathological characteristics of cAVM. In addition, the proliferation, migration and tube formation abilities of ECs of arterialized vein (AV-ECs) were significantly better than those of ECs of normal vein (NV-ECs). Moreover, the levels of secreted VEGF were significantly higher in AV-ECs than in NV-ECs.Conclusion: AV-ECs isolated from AVM rat model showed increased proliferation, migration and angiogenesis and may be potential target for the treatment of cAVM.Keywords: cerebral arteriovenous malformation, endothelial cell, angiogenesis, VEGF

Chunjie Liu, 1,* Siyu Tian, 2,* Jiangbo Bai, 2 Kunlun Yu, 2 Lei Liu, 3 Guoli Liu, 4 Ruiyi Dong, 5 Dehu Tian 2 1Department of Orthopedics, Tangshan Workers Hospital, Tangshan, Hebei 063000, People’s Republic of China; 2Department of Hand Surgery, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, People’s Republic of China; 3Department of Orthopedics, Changping District Hospital, Beijing 102200, People’s Republic of China; 4Department of Orthopedics, The Second Hospital of Tangshan, Tangshan, Hebei 063000,People’s Republic of China; 5Department of Orthopedics, Cangzhou Integrated Traditional Chinese and Western Medicine Hospital, Cangzhou, Hebei 061001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dehu TianDepartment of Hand Surgery, The Third Affiliated Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei 050017, People’s Republic of ChinaTel +86-151-3056-6366Fax +86-311-8860-3818Email tiandehu_1961@126.comBackground: Adhesion after tendon injury is a common complication in clinical practice. The lack of effective prevention mechanisms seriously affects the functional rehabilitation of patients. This research aimed to optimise the amniotic membrane and explain the mechanism of tendon–amniotic membrane by imitating the tendon sheath to construct a multilayer electrospun polycaprolactone (PCL) nanofibre membrane.Materials and Methods: Fresh amnions were subjected to freezing and vacuum drying. The two surfaces of freeze-dried amnions were coated with PCL nanofibres by electrospinning, thereby forming a multilayer composite membrane and constructing a growth factor-sustained release system conforming to the tendon-healing cycle. The new materials were characterised, and the biological effects on tenocytes and fibroblasts were evaluated. The tendon injury model of New Zealand rabbits was constructed to observe the effects on tendon adhesion and healing.Results: After freezing and vacuum drying, fresh amnions were found to effectively remove most of the cell components but retained the active components TGF-β 1, bFGF, VEGF, and PDGF, as well as the fibrous reticular structure of the basement membrane. After coating with PCL nanofibres, a composite membrane mimicking the structure of the tendon sheath was constructed, thereby strengthening the tensile strength of the amnion. By up-regulating the phosphorylation of ERK1/2 and SMAD2/3, the adhesion and proliferation of tenocytes and fibroblasts were promoted, and collagen synthesis was enhanced. In the rabbit tendon repair model, the composite membrane effectively isolated the exogenous adhesion tissue and promoted endogenous tendon healing.Conclusion: The composite membrane mimicking the structure of tendon sheath effectively isolated the exogenous adhesion tissue and achieved good tendon slip. By slowly releasing the growth factors TGF-β 1, bFGF, VEGF and PDGF, the ERK1/2 and SMAD2/3 pathways were regulated. Consequently, endogenous tendon healing was promoted. This strategy can alternatively address the clinical problem of tendon adhesion.Keywords: amniotic membrane, electrospinning, nanofibers, composite membrane, tendon adhesion

Lei Wu,1,* Siyuan Wang,2,* Yanting Wang,1 Kan Zhang,1 Jie Bai,1 Jijian Zheng1,3 1Department of Anesthesiology, Shanghai Children’s Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Pudong, Shanghai, People’s Republic of China; 2Department of Anesthesiology, 3201 Hospital, Hanzhong City, Shaanxi, People’s Republic of China; 3Pediatric Clinical Pharmacology Laboratory, Shanghai Children’s Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Pudong, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jijian ZhengDepartment of Anesthesiology, Shanghai Children’s Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, 1678 Dongfang Road, Pudong, Shanghai 200127, People’s Republic of ChinaTel +86 21 38626161Fax +86 21 58393915Email zhengjijian626@sina.comPurpose: The pain threshold index (PTI) is a novel measure of nociception based on integrated electroencephalogram parameters during general anesthesia. The wavelet index (WLI) reflects the depth of sedation. This study aims to evaluate the ability of the PTI and WLI to predict hemodynamic reactivity after tracheal intubation and skin incision in pediatric patients.Patients and methods: Pediatric patients (n=134) undergoing elective general surgery or urinary surgery were analyzed. Measurements at predefined time-points during tracheal intubation and skin incision included the PTI, WLI, heart rate (HR), and mean blood pressure (MBP). Receiver-operating characteristic (ROC) curves were computed to evaluate the predictive performance of the PTI and WLI in measuring hemodynamic reactivity (an increase of more than 20% in either MBP or HR) during general anesthesia.Results: Of the 134 patients evaluated, positive reactivity of HR and MBP was observed in 95 (70.9%) and 61 (45.5%) patients induced by intubation, respectively, and 19 (14.2%) and 24 (17.9%) patients induced by skin incision, respectively. Using either HR or MBP reactivity induced by intubation as a dichotomous variable, the areas under the curves (AUCs) [95% CI] of PTI and WLI were 0.81[0.73–0.87] and 0.58[0.49–0.67] with the best cutoff values of 62 and 49. The AUCs [95% CI] of PTI and WLI were 0.82[0.75–0.88] and 0.61[0.52–0.69] after skin incision. The best cutoff values of PTI and WLI were 60 and 46, respectively.Conclusion: The PTI can predict hemodynamic reactivity with the best cutoff values of 62 and 60 after tracheal intubation and skin incision in pediatric patients during general anesthesia. The WLI failed in predicting hemodynamic changes.Keywords: pain threshold index, wavelet index, hemodynamic reactivity, pediatric patients

Jinbo Bai,1,* Fen Zhao,2,* Shuang Pan3 1Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People Republic of China; 2Department of Stomatology, Qilu Children’s Hospital of Shandong University, Jinan, Shandong 250022, People Republic of China; 3Department of Orthodontics, Jinan Stomatological Hospital, Jinan, Shandong 250001, People Republic of China*These authors contributed equally to this workCorrespondence: Shuang PanDepartment of Orthodontics, Jinan Stomatological Hospital, 101 Jingliu Road, Jinan, Shandong 250001, People’s Republic of ChinaEmail pansoral@163.comBackground: Small cell carcinoma (SmCC) of the salivary gland is rare, and the characteristics and survival are not well defined due to only case reports or case series being reported. The present study aimed to describe the clinicopathological characteristics and determine the factors associated with survival of this rare cancer.Materials and methods: A population-based study was carried out to investigate clinical characteristics and prognosis of SmCC of the salivary gland using prospectively extracted data from the Surveillance, Epidemiology and End Results (SEER) database between 1988 and 2016.Results: Totally, 198 patients with SmCC of the salivary gland were identified with an average age of 72.6±12.4 and a male to female ratio of 3.4:1. The lesions of most patients (167/198) were located in the parotid gland. The median overall survival (mOS) of all patients is 25.0 months. The 1-, 3-, 5- and 10-year survival rate was 65.7%, 40.9%, 33.0% and 22.7%, respectively. Surgery could prolong significantly the mOS by almost 17.0 months (28.0 months vs 11.0 months; P72 years), lymph node (N3) and distant metastases were independent factors for poor survival, whereas radiotherapy was an independent factor for favorable survival.Conclusion: Small cell carcinoma of the salivary gland is a rare disease, and old age, lymph node and distant metastases, and radiotherapy were significantly associated with prognosis. In order to understand this disease more thoroughly, more cases with adequate information are required.Keywords: small cell carcinoma, salivary gland, outcomes, SEER database

Cheng Cheng,1 Jie Bai2 1School of Nursing, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 2Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Cheng Cheng, Email chengcheng@fudan.edu.cn View the original paper by Dr Cheng and colleagues This is in response to the Letter to the Editor

Long Long,1,* Xue Zhang,1,* Jian Bai,2,3 Yizhou Li,4 Xiaolong Wang,5 Yunfeng Zhou11Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China; 2Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, Wuhan, 430071, People’s Republic of China; 4Department of Orthopaedics, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China; 5Department of Urology, Research Lab/LIFE-Zentrum, University of Munich (LMU), München, Germany*These authors contributed equally to this workAbstract: Lung cancer is the most prevalent and deadly malignancy. Radiotherapy is a major treatment modality for lung cancer. Nevertheless, radioresistance poses a daunting challenge that largely limits the efficacy of radiotherapy. There is a pressing need for deciphering molecular mechanisms underlying radioresistance and elucidating novel therapeutic targets for individualized radiotherapy. MicroRNAs are categorized as small noncoding RNAs that modulate target-gene expression posttranscriptionally and are implicated in carcinogenesis and cancer resistance to treatment. Overwhelming evidence has unraveled that tissue-specific miRNAs are essential for regulation of the radiosensitivity in lung cancer cells through a complex interaction with multiple biological processes and radiation-induced pathways. Moreover, exosome-derived miRNAs are a novel horizon in lung cancer treatment in which exosomal miRNAs act as potential diagnostic and therapeutic biomarkers of radiotherapy. In the present review, we discuss the mediation of key biological processes and signaling pathways by tissue-specific miRNAs in lung cancer radiotherapy. Additionally, we provide new insight into the potential significance of exosomal miRNAs in radiation response. Lastly, we highlight miRNAs as promising predictors and therapeutic targets to tailor personalized lung cancer radiotherapy.Keywords: lung cancer, microRNAs, exosome, radioresistance, personalized radiotherapy

Jian Lu,1,* Changjun Sun,2,* Jiangbo Bai,1,* Siyu Tian,1,* Bing Zhang,1 Dehu Tian,1 Lingde Kong1 1Department of Orthopedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, China; 2Department of Emergency, The Second Hospital of Tangshan City, Tangshan, Hebei 063000, China *These authors contributed equally to this work Background: This study was conducted to determine whether sagittal lordotic alignment and clinical outcomes could be improved by the correction of segmental kyphosis after single-level anterior cervical discectomy and fusion (ACDF) surgery.Patients and methods: We retrospectively reviewed patients who underwent single-level ACDF surgery in our hospital between January 2014 and February 2017. Basic characteristics of patients included age at surgery, gender, diagnosis, duration of symptoms, and location of target level. Pre- and postoperative radiographs at the 6-month follow-up were used to evaluate the following parameters, such as segmental angle, C2–C7 angle, T1 slope, and C2–C7 sagittal vertical axis (SVA). Postoperative clinical outcomes were assessed by the Neck Disability Index and VAS. According to the segmental angle of postoperative radiographs, patients were divided into noncorrection group and correction group.Results: A total of 181 patients (99 males and 82 females) were analyzed in our study. There were 32 patients in the noncorrection group and 149 patients in the correction group. There was no significant difference in demographic and clinical data between the two groups before surgery. However, patients in the correction group showed larger C2–C7 angle and lower C2–C7 SVA after surgery in comparison with those in the noncorrection group. Besides, changes in the segmental angle were positively correlated with changes in C2–C7 angle and negatively correlated with changes in C2–C7 SVA.Conclusion: Surgical correction of segmental kyphosis in single-level cervical surgery contributed to balanced cervical alignment in comparison with those without satisfactory correction. However, we could not demonstrate that the correction of segmental alignment is associated with a better recovery in clinical outcomes. Keywords: segmental kyphosis, sagittal alignment, single level, cervical spine, anterior cervical discectomy and fusion

Meng-meng Lu,1,2 Yuran Ge,1,2 Jing Qiu,1,2 Dan Shao,3 Yue Zhang,4 Jing Bai,4 Xiao Zheng,5 Zhi-min Chang,3 Zheng Wang,3 Wen-fei Dong,3 Chun-bo Tang1,2 1Department of Oral Implantology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, China; 2Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China; 3CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China; 4School of Materials Science and Engineering, Southeast University, Nanjing, 211189, China; 5Department of Pharmacology, Nanomedicine Engineering Laboratory of Jilin Province, College of Basic Medical Sciences, Jilin University, Changchun, 130021, China Background: Oral plaque biofilms pose a threat to periodontal health and are challenging to eradicate. There is a growing belief that a combination of silver nanoparticles and chlorhexidine (CHX) is a promising strategy against oral biofilms.Purpose: To overcome the side effects of this strategy and to exert maximum efficiency, we fabricated biodegradable disulfide-bridged mesoporous silica nanoparticles (MSNs) to co-deliver silver nanoparticles and CHX for biofilm inhibition.Materials and methods: CHX-loaded, silver-decorated mesoporous silica nanoparticles (Ag-MSNs@CHX) were fabricated after CHX loading, and the pH- and glutathione-responsive release profiles of CHX and silver ions along with their mechanism of degradation were systematically investigated. Then, the efficacy of Ag-MSNs@CHX against Streptococcus mutans and its biofilm was comprehensively assessed by determining the minimum inhibitory concentration, minimum bactericidal concentration, minimal biofilm inhibitory concentration, and the inhibitory effect on S. mutans biofilm formation. In addition, the biosafety of nanocarriers was evaluated by oral epithelial cells and a mouse model.Results: The obtained Ag-MSNs@CHX possessed redox/pH-responsive release properties of CHX and silver ions, which may be attributed to the redox-triggered matrix degradation mechanism of exposure to biofilm-mimetic microenvironments. Ag-MSNs@CHX displayed dose-dependent antibacterial activity against planktonic and clone formation of S. mutans. Importantly, Ag-MSNs@CHX had an increased and long-term ability to restrict the growth of S. mutans biofilms compared to free CHX. Moreover, Ag-MSNs@CHX showed less cytotoxicity to oral epithelial cells, whereas orally administered Ag-MSNs exhibited no obvious toxic effects in mice.Conclusion: Our findings constitute a highly effective and safe strategy against biofilms that has a good potential as an oral biofilm therapy. Keywords: biodegradable mesoporous silica nanoparticles, silver nanoparticles, chlorhexidine, GSH, pH-responsive release, biofilm, biocompatibility