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Chunxia Yin,1,* Taohua Lan,2,3,* Yunshan Wu,4,5 Jing Cai,1 Haoxiang Li,1 Xiaolan Kuang,1 Lin Jiao,1 Xiaomin Ou,1 Hua Yang,2 Bo Liu,3– 5 Weihui Lu2,6,7 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 3State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 6State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 7Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weihui Lu, Bo Liu, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Email weihui.lu@gzucm.edu.cn; doctliu@gzucm.edu.cnPurpose: This study was designed to evaluate the effect and mechanism of the Qushi Huatan (QSHT) decoction against coronary heart disease (CHD) through network pharmacology and experimental verification.Methods: In the present study, the active ingredients of the QSHT decoction were identified by ultra performance liquid chromatography/tandem mass spectrometry (UPLC/MS), then the potential ingredients and coronary heart disease targets were predicted using the SwissTarget Prediction database and the database of Genecards and OMIM database, respectively. A herb-compound-target network was constructed using Cytoscape. GO and KEGG enrichment analysis were performed using the ClusterProfiler data package of R software. Molecular docking was used to predict the core targets of QSHT against CHD. In addition, we used a myocardial infarction (MI) and high-fat diet ApoE−/− mice model to investigate the cardioprotective effects of QSHT. Western blotting and immunochemistry were used to verify the core targets and the signaling pathway.Results: A total of 68 active ingredients were found in the QSHT decoction. Network pharmacology indicated 28 targets and 147 signal pathways, including AKT1, HIF-1α, GSK-3β, TLR4 and NF-κB, those key targets were also verified by molecular docking. The results of GO and KEGG enrichment analysis showed that the targets of QSHT against CHD were largely associated with inflammatory and oxidative stress, and AKT/HIF-1α and TLR4/NF-κB pathways might be key functional pathways. In vivo, QSHT significantly improved cardiac function and attenuated fibrosis and inflammation. Furthermore, QSHT could significantly inhibit the expression of HIF-1α, TLR4, phosphorylation of AKT1, GSK-3β and NF-κB after MI in ApoE−/− mice.Conclusion: Based on network pharmacology, molecular docking and experimental verification, this study demonstrated that QSHT could improve cardiac function and attenuate cardiac fibrosis by regulating TLR4/NF-κB and AKT/HIF-1α signaling pathway in post- MI and high-fat diet ApoE−/− mice.Keywords: network pharmacology, molecular docking, Qushi Huatan decoction, coronary heart disease

Jingfang Chen,1,2 Linlin Liu,3 Junxiong Huang,1 Youli Jiang,4 Chengliang Yin,1 Lukun Zhang,5 Zhihuan Li,1 Hongzhou Lu1,5 1Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, People’s Republic of China; 2Department of Research and Teaching, The Third People’s Hospital of Shenzhen, Shenzhen, 518112, People’s Republic of China; 3Hengyang Medical School, School of Nursing, University of South China, Hengyang, 421001, People’s Republic of China; 4Department of Neurology, The People’s Hospital of Longhua, Shenzhen, 518109, People’s Republic of China; 5Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The Third People’s Hospital of Shenzhen, Shenzhen, 518112, People’s Republic of ChinaCorrespondence: : Zhihuan Li; Hongzhou Lu, Faculty of Medicine, Macau University of Science and Technology, Macau, 999078, People’s Republic of China, Email baopullon@163.com; luhongzhou@szsy.sustech.edu.cnBackground: Both HIV and TB are chronic infectious diseases requiring long-term treatment and follow-up, resulting in extensive electronic medical records. With the exponential growth of health and medical big data, effectively extracting and analyzing these data has become the research hotspot. As a fundamental aspect of artificial intelligence, machine learning has been extensively applied in medical research, encompassing diagnosis, treatment, patient monitoring, drug development, and epidemiological investigations. This significantly enhances medical information systems and facilitates the interoperability of medical data.Methods: In our study, we analyzed longitudinal data from the electronic health records of 4540 patients, gathered from the National Clinical Research Center for Infectious Diseases in Shenzhen, China, spanning from 2017 to 2021. Initially, we employed the fine-tuned ChatGLM to structure the electronic medical records. Subsequently, we utilized a multi-layer perceptron to classify each patient and determined the presence of tuberculosis in HIV patients. Using machine learning-based natural language processing, we structured these records to build a specialized database for HIV and TB co-infection. We studied the epidemiological characteristics, focusing on incidence patterns, patient characteristics, and influencing factors, to uncover the transmission characteristics of these diseases in Shenzhen. Additionally, we used Long Short-Term Memory to create a predictive model for TB co-infection among HIV patients, based on their medical records. This model predicted the risk of TB co-infection, providing scientific evidence for clinical decision-making and enabling early detection and precise intervention.Results: Based on the refined ChatGLM model tailored for structured electronic health records, the accuracy of symptom extraction consistently surpassed 0.95 precision. Key symptoms such as diarrhea and normal showed precision rates exceeding 0.90. High scores were also achieved in recall and F1 scores. Among 4540 HIV patients, 758 were diagnosed with concurrent tuberculosis, indicating a 16.7% co-infection rate, while syphilis co-infection affected 25.1%, underscoring the prevalence of concurrent infections among HIV patients. Utilizing electronic health records, a Multilayer Perceptron classifier was developed as a benchmark against Long Short-Term Memory to predict high-risk groups for HIV and tuberculosis co-infections. The Multilayer Perceptron classifier demonstrated predictive ability with AUROC values ranging from 0.616 to 0.682 on the test set, suggesting opportunities for further optimization and generalization despite its accuracy in identifying HIV-TB co-infections. In tuberculosis intelligent diagnosis based on laboratory results, the Long Short-Term Memory showed consistent performance across 5-fold cross-validation, with AUROC values ranging from 0.827 to 0.850, indicating reliability and consistency in tuberculosis prediction. Furthermore, by optimizing classification thresholds, the model achieved an overall accuracy of 81.18% in distinguishing HIV co-infected tuberculosis from simple HIV infection.Conclusion: Combining the Multilayer Perceptron classifier with Long Short-Term Memory represented an advanced approach for effectively extracting electronic health records and utilizing it for disease prediction. This underscored the superior performance of deep learning techniques in managing both structured and unstructured medical data. Models leveraging laboratory time-series data demonstrated notably better performance compared to those relying solely on electronic health records for predicting tuberculosis incidence. This emphasized the benefits of deep learning in handling intricate medical data and provided valuable insights for healthcare providers exploring the use of deep learning in disease prediction and management.Keywords: Prediction models, HIV, Tuberculosis, Machine Learning, Artificial Intelligence

Yixian Zeng,1,* Xingfei He,2,* Xinchun Peng,1 Li Zhao,3 Chengqian Yin,4 Shanshan Mao1,* 1School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, 100084, People’s Republic of China; 2Wuxi Huishan District Rehabilitation Hospital, Wuxi, 214001, People’s Republic of China; 3School of Sports Science, Beijing Sport University, Beijing, 100084, People’s Republic of China; 4Department of Interventional Center of Valvular Heart Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shanshan Mao, School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing, 100084, People’s Republic of China, Email ss.mao@bsu.edu.cnObjective: This bibliometric analysis and review aimed to examine the current research status and trends in the combination of nutrition and exercise training for sarcopenia. Additionally, it sought to provide researchers with future research directions in this field.Methods: Relevant publications were obtained from the Web of Science Core Collection (WoSCC) database, covering the period from January 1995 to October 2023. The collected publications were analyzed using CiteSpace, VOSviewer, Bibliometrix, and Review Manager.Results: Out of the 2528 retrieved publications, the United States emerged as the leading contributor in terms of publication volume. The University of Texas System was identified as the most productive institution. Luc J C van Loon emerged as the most published author in this field. Analysis of keywords revealed recent hot topics and emerging areas of interest, such as “gut microbiota” and “mechanisms”. Upon further evaluation, resistance training (RT) and protein supplementation were identified as the most commonly employed and effective methods.Conclusion: RT and protein supplementation are widely recognized as effective strategies. Future research should focus on investigating the molecular aspects of sarcopenia. Moreover, the potential therapeutic role of gut microbiota in sarcopenia requires further comprehensive investigation in human subjects to establish its correlation.Keywords: sarcopenia, nutrition, exercise, bibliometric analysis, review

Yuli Ji,1,2,* Liangyu Mi,1,2,* Miaomiao Zhao,1,2 Xiaoyao He,1,2 Yuting Hu,1,2 Yanan Gao,1,2 Chengliang Yin,3 Ke Xu1,2 1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 2Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 3Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ke Xu, Department of Rheumatology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 Longcheng Street, Taiyuan, Shanxi Province, People’s Republic of China, Email xukesxbqeh@hotmail.comAbstract: Autoimmune diseases refer to a group of conditions where the immune system produces an immune response against self-antigens, resulting in tissue damage. These diseases have profound impacts on the health of patients. In recent years, with the rapid development in the field of biomedicine, engineered exosomes have emerged as a noteworthy class of biogenic nanoparticles. By precisely manipulating the cargo and surface markers of exosomes, engineered exosomes have gained enhanced anti-inflammatory, immunomodulatory, and tissue reparative abilities, providing new prospects for the treatment of autoimmune diseases. Engineered exosomes not only facilitate the efficient delivery of bioactive molecules including nucleic acids, proteins, and cytokines, but also possess the capability to modulate immune cell functions, suppress inflammation, and restore immune homeostasis. This review mainly focuses on the applications of engineered exosomes in several typical autoimmune diseases. Additionally, this article comprehensively summarizes the current approaches for modification and engineering of exosomes and outlines their prospects in clinical applications. In conclusion, engineered exosomes, as an innovative therapeutic approach, hold promise for the management of autoimmune diseases. However, while significant progress has been made, further rigorous research is still needed to address the challenges that engineered exosomes may encounter in the therapeutic intervention process, in order to facilitate their successful translation into clinical practice and ultimately benefit a broader population of patients.Keywords: engineered exosomes, autoimmune diseases, genetic engineering, anti-inflammatory applications

Cong Yin,1,2,* Cen Liufu,3,4,* Tao Zhu,3,4 Shuai Ye,1,2 Jiahao Jiang,1,5 Mingxia Wang,3 Yan Wang,3 Bentao Shi1 1Department of Urology, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 2Shenzhen University Health Science Center, Shenzhen, People’s Republic of China; 3Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen PKU-HKUST Medical Center, Shenzhen, People’s Republic of China; 4Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 5Clinical College of Anhui Medical University, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bentao Shi, Department of Urology, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518035, People’s Republic of China, Email shibentaopku@126.com Yan Wang, Department of Urology, Peking University Shenzhen Hospital, Institute of Urology, Shenzhen PKU-HKUST Medical Center Shenzhen, Shenzhen, 518036, People’s Republic of China, Email wangyan198614@163.comAbstract: Bladder cancer, a prevalent malignant neoplasm of the urinary tract, exhibits escalating morbidity and mortality rates. Current diagnosis standards rely on invasive and costly cystoscopy and histopathology, underscoring the urgency for non-invasive, high-throughput, and cost-effective novel diagnostic techniques to ensure timely detection and standardized treatment. Recent years have witnessed the rise of exosome research in bladder cancer studies. Exosomes contain abundant bioactive molecules that can help elucidate the intricate mechanisms underlying bladder cancer pathogenesis and metastasis. Exosomes hold potential as biomarkers for early bladder cancer diagnosis while also serving as targeted drug delivery vehicles to enhance treatment efficacy and mitigate adverse effects. Furthermore, exosome analyses offer insights into the complex molecular signaling networks implicated in bladder cancer progression, revealing novel therapeutic targets. This review provides a comprehensive overview of prevalent exosome isolation techniques and highlights the promising clinical utility of exosomes in both diagnostic and therapeutic applications in bladder cancer management.Keywords: exosomes, isolation methods, bladder cancer, biomarkers, treatment

Xian Li,1,* Hong Lai,2,* Peng Wang,3 Shuai Feng,4 Xuexin Feng,4 Chao Kong,3 Dewei Wu,5 Chunlin Yin,5 Jianghua Shen,6 Suying Yan,6 Rui Han,7 Jia Liu,7 Xiaoyi Ren,8 Ying Li,8 Lu Tang,9 Dong Xue,9 Ying Zhao,9 Hao Huang,10 Xiaoying Li,10 Yanhong Zhang,10 Xue Wang,11 Chunxiu Wang,12 Ping Jin,13 Shibao Lu,3 Tianlong Wang,4 Guoguang Zhao,14 Chaodong Wang1 On behalf of the APPLE-MDT Research Team, Xuanwu Hospital, Capital Medical University and National Clinical Research Center for Geriatric Diseases1Department of Neurology & Neurobiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, People’s Republic of China; 3Department of Orthopedic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 4Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 5Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 6Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 7Department of Gerontology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 8Department of Nutrition, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 9Department of Oral Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 10Department of Medical Administration, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 11Department of Medical Library, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 12Center for Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 13Center for Medical Information, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 14Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, 100053, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaodong Wang, Department of Neurology, Xuanwu Hospital of Capital Medical University, National Clinical Research Center for Geriatric Diseases, No. 45 Changchun Street, Beijing, 100053, People’s Republic of China, Tel/Fax +86-10-8319-8677, Email cdongwang@xwhosp.orgPurpose: We aimed to identify the risk factors for postoperative cognitive decline (POCD) by evaluating the outcomes from preoperative comprehensive geriatric assessment (CGA) and intraoperative anesthetic interventions.Patients and Methods: Data used in the study were obtained from the Aged Patient Perioperative Longitudinal Evaluation–Multidisciplinary Trial (APPLE-MDT) cohort recruited from the Department of Orthopedics in Xuanwu Hospital, Capital Medical University between March, 2019 and June, 2022. All patients accepted preoperative CGA by the multidisciplinary team using 13 common scales across 15 domains reflecting the multi-organ functions. The variables included demographic data, scales in CGA, comorbidities, laboratory tests and intraoperative anesthetic data. Cognitive function was assessed by Montreal Cognitive Assessment scale within 48 hours after admission and after surgery. Dropping of ≥ 1 point between the preoperative and postoperative scale was defined as POCD.Results: We enrolled 119 patients. The median age was 80.00 years [IQR, 77.00, 82.00] and 68 patients (57.1%) were female. Forty-two patients (35.3%) developed POCD. Three cognitive domains including calculation (P = 0.046), recall (P = 0.047) and attention (P = 0.007) were significantly worsened after surgery. Univariate analysis showed that disability of instrumental activity of daily living, incidence rate of postoperative respiratory failure (PRF) ≥ 4.2%, STOP-Bang scale score, Caprini risk scale score and Sufentanil for maintenance of anesthesia were different between the POCD and non-POCD patients. In the multivariable logistic regression analysis, PRF ≥ 4.2% (odds ratio [OR] = 2.343; 95% confidence interval [CI]: 1.028– 5.551; P = 0.046) and Sufentanil for maintenance of anesthesia (OR = 0.260; 95% CI: 0.057– 0.859; P = 0.044) was independently associated with POCD as risk and protective factors, respectively.Conclusion: Our study suggests that POCD is frequent among older patients undergoing elective orthopedic surgery, in which decline of calculation, recall and attention was predominant. Preoperative comprehensive geriatric assessments are important to identify the high-risk individuals of POCD.Keywords: cognitive dysfunction, postoperative cognitive complications, orthopedic surgery, comprehensive geriatric assessment, risk factors

Qinzhou Zheng,1,* Cuimin Chen,2,* Yong Liu,3 Jie Gao,2,* Luxin Li,1 Chuan Yin,4 Xiaohuan Yuan1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China; 3Center for Comparative Medicine, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 4Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai, 200003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuan Yin, Department of Gastroenterology, Shanghai Changzheng Hospital, Naval Medical, University, Shanghai, 200003, People’s Republic of China, Email ilse1225@163.com Xiaohuan Yuan, College of Life Science, Mudanjiang Medical University, Mudanjiang, 157001, Heilongjiang, People’s Republic of China, Tel/Fax +86-453-6984647, Email yuanxiaohuan@mdjmu.edu.cnAbstract: Diabetic wounds pose a significant challenge to public health, primarily due to insufficient blood vessel supply, bacterial infection, excessive oxidative stress, and impaired antioxidant defenses. The aforementioned condition not only places a significant physical burden on patients’ prognosis, but also amplifies the economic strain on the medical system in treating diabetic wounds. Currently, the effectiveness of available treatments for diabetic wounds is limited. However, there is hope in the potential of metal nanoparticles (MNPs) to address these issues. MNPs exhibit excellent anti-inflammatory, antioxidant, antibacterial and pro-angiogenic properties, making them a promising solution for diabetic wounds. In addition, MNPs stimulate the expression of proteins that promote wound healing and serve as drug delivery systems for small-molecule drugs. By combining MNPs with other biomaterials such as hydrogels and chitosan, novel dressings can be developed and revolutionize the treatment of diabetic wounds. The present article provides a comprehensive overview of the research progress on the utilization of MNPs for treating diabetic wounds. Building upon this foundation, we summarize the underlying mechanisms involved in diabetic wound healing and discuss the potential application of MNPs as biomaterials for drug delivery. Furthermore, we provide an extensive analysis and discussion on the clinical implementation of dressings, while also highlighting future prospects for utilizing MNPs in diabetic wound management. In conclusion, MNPs represent a promising strategy for the treatment of diabetic wound healing. Future directions include combining other biological nanomaterials to synthesize new biological dressings or utilizing the other physicochemical properties of MNPs to promote wound healing. Synthetic biomaterials that contain MNPs not only play a role in all stages of diabetic wound healing, but also provide a stable physiological environment for the wound-healing process.Keywords: metal nanoparticles, wound healing, diabetic wound, drug delivery, antibacterial activity

Jingfang Chen,1– 3 Linlin Liu,3 Shujin Ruan,3 Mengjun Li,3 Chengliang Yin1 1Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China; 2Department of Research and Teaching, the Third People’s Hospital of Shenzhen, Shenzhen, People’s Republic of China; 3Hengyang Medical School, School of Nursing, University of South China, Hengyang, People’s Republic of ChinaCorrespondence: Chengliang Yin, Faculty of Medicine, Macau University of Science and Technology, Macau, People’s Republic of China, Email chengliangyin@163.comObjective: ChatGPT, an advanced language model developed by OpenAI, holds the opportunity to bring about a transformation in the processing of clinical decision-making within the realm of medicine. Despite the growing popularity of research related on ChatGPT, there is a paucity of research assessing its appropriateness for clinical decision support. Our study delved into ChatGPT’s ability to respond in accordance with the diagnoses found in case reports, with the intention of serving as a reference for clinical decision-making.Methods: We included 147 case reports from the Chinese Medical Association Journal Database that generated primary and secondary diagnoses covering various diseases. Each question was independently posed three times to both GPT-3.5 and GPT-4.0, respectively. The results were analyzed regarding ChatGPT’s mean scores and accuracy types.Results: GPT-4.0 displayed moderate accuracy in primary diagnoses. With the increasing number of input, a corresponding enhancement in the accuracy of ChatGPT’s outputs became evident. Notably, autoimmune diseases comprised the largest proportion of case reports, and the mean score for primary diagnosis exhibited statistically significant differences in autoimmune diseases.Conclusion: Our finding suggested that the potential practicality in utilizing ChatGPT for clinical decision-making. To enhance the accuracy of ChatGPT, it is necessary to integrate it with the existing electronic health record system in the future.Keywords: ChatGPT, artificial intelligence, clinical decision support systems, case reports

Jinjie Yu,1,2,* Mengwen Liu,3,* Xiaokaiti Mijiti,4,* Haican Liu,2,* Quan Wang,4 Chunjie Yin,3 Aiketaguli Anwaierjiang,5 Miao Xu,4 Machao Li,2 Lele Deng,2,6 Hui Xiao,3 Xiuqin Zhao,2 Kanglin Wan,2 Guilian Li,2 Xiuqin Yuan1 1School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China; 2State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 3School of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 4The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830049, People’s Republic of China; 5College of Xinjiang Uyghur Medicine, Hetian, 848000, People’s Republic of China; 6National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guilian Li, State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China, Email liguilian@icdc.cn Xiuqin Yuan, School of Public Health, University of South China, Hengyang, 421001, People’s Republic of China, Email wtjysh@126.comBackground: The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphism and tuberculosis susceptibility, as well as the potential interaction of host genetic factors with the heterogeneity of Mycobacterium tuberculosis in the population from Xinjiang, China.Methods: From January 2019 to January 2020, we enrolled 221 tuberculosis patients as the case group and 363 staff with no clinical symptoms as the control group from four designated tuberculosis hospitals in southern Xinjiang, China. The polymorphisms of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in the VDR were detected by sequencing. M. tuberculosis isolates were collected from the case group and identified as Beijing or non-Beijing lineage by multiplex PCR. Propensity score (PS), univariate analysis and multivariable logistic regression models were used to perform the analysis.Results: Our results showed that the allele and genotype frequencies of Fok I, Taq I, Apa I, Bsm I, rs3847987 and rs739837 in VDR were not correlated with tuberculosis susceptibility or lineages of M. tuberculosis. Two out of six loci of the VDR gene formed one haplotype block, and none of the haplotypes was found to correlate with tuberculosis susceptibility or lineages of M. tuberculosis infected.Conclusion: Polymorphisms in the VDR gene may not indicate susceptibility to tuberculosis. There was also no evidence on the interaction between the VDR gene of host and the lineages of M. tuberculosis in the population from Xinjiang, China. Further studies are nonetheless required to prove our conclusions.Keywords: vitamin D receptor, VDR, polymorphism, tuberculosis, Mycobacterium tuberculosis, Beijing lineage

Tian-Tian Dong,1– 3 Lan Wang,1– 3 Ming Li,1– 3 Ci Yin,1– 3 Yuan-Yuan Li,1– 3 Fang Nie1– 3 1Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou, 730030, People’s Republic of China; 2Ultrasound Center, Gansu Province Clinical Research Center for Ultrasound, Lanzhou, 730030, People’s Republic of China; 3Intelligence Ultrasound Center, Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou, 730030, People’s Republic of ChinaCorrespondence: Fang Nie, Ultrasound Medical Center, Lanzhou University Second Hospital, Chengguan District, Lanzhou, Gansu, 730030, People’s Republic of China, Tel +86 13993163088, Email ery_nief@lzu.edu.cnAbstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a relatively poor prognosis, especially for advanced HCC. With the availability of a variety of treatment options, the treatment strategies for HCC have become more and more diversified. Microwave ablation (MWA) has gradually been considered as a viable alternative to surgical resection (SR) owing to its comparable long-term survival, reduced complications, and greater preservation of hepatic parenchyma. However, clinical outcomes, tumor progression, and recurrence of HCC after MWA remain major concerns. Here, after reviewing the current therapeutic options for HCC, we focus on MWA, describing the advantages and challenges of MWA and the clinical results after treatment. We then focused on prognostic factors that influence post-ablation clinical outcomes and briefly presented the strategy of MWA for future clinical treatment.Keywords: microwave ablation, hepatocellular carcinoma, clinical outcomes, progression

Dongfang Yu,1,2,* Jinhua Bai,3,* 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*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

Chunjie Yin,1,&ast; Xiaokaiti Mijiti,2,&ast; Haican Liu,3,&ast; Quan Wang,2 Bin Cao,3,4 Aiketaguli Anwaierjiang,5 Machao Li,3 Mengwen Liu,1 Yi Jiang,3 Miao Xu,2 Kanglin Wan,3 Xiuqin Zhao,3 Guilian Li,3 Hui Xiao1 1School of Public Health, Xinjiang Medical University, Urumqi, People’s Republic of China; 2The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 3State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 4School of Public Health, University of South China, Hengyang, People’s Republic of China; 5College of Xinjiang Uyghur Medicine, Hetian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guilian Li; Hui Xiao, Email liguilian@icdc.cn; xh20108262@sina.comBackground: In the last decades, the molecular epidemiological investigation of Mycobacterium tuberculosis has significantly increased our understanding of tuberculosis epidemiology. However, few such studies have been done in southern Xinjiang, China. We aimed to clarify the molecular epidemic characteristics and their association with drug resistance in the M. tuberculosis isolates circulating in this area.Methods: A total of 347 isolates obtained from southern Xinjiang, China between Sep, 2017 and Sep, 2019 were included to characterize using a 15-locus MIRU-VNTR (VNTR-15China) typing and spoligotyping, and test for drug susceptibility profiles. Then the lineages and clustering of the isolates were analyzed, as well as their association with drug resistance.Results: Spoligotyping results showed that 60 spoligotype international types (SITs) containing 35 predefined SITs and 25 Orphan or New patterns, and 12 definite genotypes were found, and the top three prevalent genotypes were Beijing genotype (207, 59.7%), followed by CAS1-Delhi (46, 13.6%), and Ural-2 (30, 8.6%). The prevalence of Beijing genotype infection in the younger age group (≤ 30) was more frequent than the two older groups (30~59 and ≥ 60 years old, both P values < 0.05). The Beijing genotype showed significantly higher prevalence of resistance to isoniazid, rifampicin, ethambutol, multi-drug or at least one drug than the non-Beijing genotype (All P values ≤ 0.05). The estimated proportion of tuberculosis cases due to transmission was 18.4% according to the cluster rate acquired by VNTR-15China typing, and the Beijing genotype was the risk factor for the clustering (OR 9.15, 95% CI: 4.18– 20.05).Conclusion: Our data demonstrated that the Beijing genotype is the dominant lineage, associated with drug resistance, and was more likely to infect young people and contributed to tuberculosis transmission in southern Xinjiang, China. These findings will contribute to a better understanding of tuberculosis epidemiology in this area.Keywords: MIRU-VNTR, spoligotyping, Beijing genotype, drug resistance, genetic diversity, Mycobacterium tuberculosis

Qi Zhou,1 Lili Yu,2 Chunping Yin,1 Qi Zhang,3 Yanlei Tai,1 Lian Zhu,4 Jiangtao Dong,5 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of China; 3Department of Anesthesiology, Hebei Children’s Hospital Affiliated to Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Orthopaedics, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 5Department of Joint Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Qiujun Wang, Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Email wangqiujunsy@163.comPurpose: The aim of this study was to investigate whether transauricular vagus nerve stimulation (taVNS) could reduce the incidence of rebound pain in patients undergoing anterior cruciate ligament reconstruction (ACLR) under general anesthesia combined with preoperative femoral nerve block.Methods: In total, 78 patients were enrolled in this prospective, randomized, double-blind, and sham-controlled study. Patients were randomly assigned to 2 groups (n=39): Group taVNS received taVNS (1h /1time, 6times) within the first 12 h after surgery; Group SS received sham stimulation (SS) in the same manner. Pain scores at 0, 4, 8, 12, 24, 48 h after surgery were assessed with Numeric Pain Rating Scale (NRS). The incidence, duration and onset of rebound pain were recorded. In addition, additional analgesic requirements and side effects in the first 48 h postoperatively, as well as sleep disturbance on the night of surgery, were examined.Results: The incidence and duration of rebound pain were lower in the taVNS group than in the SS group (P=0.025 and P=0.015, respectively). Pain scores at 8 h and 12 h postoperatively were significantly lower in the taVNS group compared with the SS group (P< 0.05). The number of times to press the patient-controlled analgesia (PCA) pump and the number of patients requiring additional analgesic were significantly lower in the taVNS group than in the SS group until 12 h after surgery (P=0.021 and P=0.004, respectively). The number of patients with sleep disturbance in the taVNS group was lower than that in the SS group (P=0.030).Conclusion: The taVNS exerts beneficial effect on rebound pain after femoral nerve block in patients undergoing ACLR, which reduces the incidence and duration of rebound pain, the need for postoperative additional analgesic, and the number of complications.Keywords: rebound pain, transauricular vagus nerve stimulation, femoral nerve block, anterior cruciate ligament reconstruction

Ruoyao Xu,1 Jie Wang,1 Huimin Nie,1 Danyi Zeng,1 Chengyu Yin,1 Yuanyuan Li,1 Huina Wei,1 Boyu Liu,1 Yan Tai,2 Qimiao Hu,1 Xiaomei Shao,1 Jianqiao Fang,1 Boyi Liu1 1Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People’s Republic of China; 2Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Boyi Liu; Jianqiao Fang, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People’s Republic of China, Email boyi.liu@foxmail.com; fangjianqiao7532@163.comBackground: Chronic postsurgical pain (CPSP) is common among patients receiving major surgeries. CPSP produces suffering in patients, both physically and mentally. However, the mechanisms underlying CPSP remain elusive. Here, a genome-wide expression profiling of ipsilateral spinal cord dorsal horn (SCDH) was performed to identify potential genes related with CPSP.Methods: A rat skin/muscle incision and retraction (SMIR) model was established to induce CPSP. Immunostaining was used to study glial cell and neuron activation in ipsilateral SCDH of SMIR model rats. RNA sequencing (RNA-Seq), combined with bioinformatics analysis, was undertaken to explore gene expression profiles. qPCR was applied to validate the expression of some representative genes.Results: The SMIR model rats developed persistent mechanical allodynia in ipsilateral hindpaw for up to 14 days. Ipsilateral SCDH of SMIR rats showed remarkable glial cell and neuron activation. A number of differentially expressed genes (DEGs) were identified in ipsilateral SCDH of SMIR rats by RNA-Seq. qPCR confirmed expression of some representative DEGs. Bioinformatics indicated that chemical synaptic transmission, sensory perception of pain and neuroactive ligand-receptor interaction were predominant functions. We compared our dataset with human pain-related genes and found that several genes exclusively participate in pain modulation and mechanisms.Conclusion: Our study provided novel understandings of the molecular mechanisms possibly contributing to CPSP. These findings may offer new targets for future treatment of CPSP.Keywords: postsurgical pain, spinal cord dorsal horn, RNA-Seq, microglia, genome

Animals are under constant selective pressure from a myriad of diverse pathogens. Microsporidia are ubiquitous animal parasites, but the influence they exert on shaping animal genomes is mostly unknown. Using multiplexed competition assays, we measured the impact of four different species of microsporidia on 22 wild isolates of Caenorhabditis elegans. This resulted in the identification and confirmation of 13 strains with significantly altered population fitness profiles under infection conditions. One of these identified strains, JU1400, is sensitive to an epidermal-infecting species by lacking tolerance to infection. JU1400 is also resistant to an intestinal-infecting species and can specifically recognize and destroy this pathogen. Genetic mapping of JU1400 demonstrates that these two opposing phenotypes are caused by separate loci. Transcriptional analysis reveals the JU1400 sensitivity to epidermal microsporidia infection results in a response pattern that shares similarity to toxin-induced responses. In contrast, we do not observe JU1400 intestinal resistance being regulated at the transcriptional level. The transcriptional response to these four microsporidia species is conserved, with C. elegans strain-specific differences in potential immune genes. Together, our results show that phenotypic differences to microsporidia infection amongst C. elegans are common and that animals can evolve species-specific genetic interactions.

Mengwen Liu,1 Quan Wang,2 Haican Liu,3 Chunjie Yin,1 Xiaokaiti Mijiti,2 Aiketaguli Anwaierjiang,1 Kanglin Wan,3 Miao Xu,2 Machao Li,3 Siqin Nong,4 Guilian Li,3 Hui Xiao1 1School of Public Health, Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 2The Eighth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830001, People’s Republic of China; 3State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China; 4College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, People’s Republic of ChinaCorrespondence: Guilian Li; Hui Xiao, Email liguilian@icdc.cn; xh20108262@sina.comPurpose: Polymorphisms in MBL2 may contribute to the susceptibility to tuberculosis. The aim of the present study was to determine the associations of the polymorphisms of five loci (rs1800450, rs1800451, rs7096206, rs7095891, and rs11003125) in the MBL2 gene with susceptibility to tuberculosis and specific lineages of Mycobacterium tuberculosis causing tuberculosis in the Uyghur population of Xinjiang, China.Methods: From January 2019 to January 2020, we enrolled 170 Uyghur tuberculosis patients as the case group and 147 Uyghur staff with no clinical symptoms as the control group from four designated tuberculosis hospitals in southern Xinjiang, China. The polymorphisms of five loci in MBL2 of human were detected by sequencing. Whole-genome sequencing was applied in 68 M. tuberculosis isolates from the case group and the data were used to perform genealogy analysis.Results: The distributions of allele and genotype frequencies of five loci in MBL2 varied little between the case and control groups and varied little among the groups, including those infected with different lineages of M. tuberculosis and the control (except those of rs11003125), the P values were all > 0.05. The distribution of alleles of rs11003125 was statistically different between patients infected with lineages 3 and 4 M. tuberculosis (χ2=7.037, P=0.008). The C allele and CC genotype of rs11003125 were found to be protective factors against lineage 4 infection when compared to lineage 3 (ORs were 0.190 and 0.158, respectively; 95% confidence intervals were 0.053∼ 0.690 and 0.025∼ 0.999, respectively).Conclusion: Our results suggested that human’s susceptibility to tuberculosis is affected both by the host genetic polymorphisms and the lineage of the M. tuberculosis that people were exposed to. However, due to the limitation of the sample size in the present study, larger sample size and more rigorous design should be guaranteed in future studies.Keywords: mannose-binding lectin 2 gene, polymorphism, tuberculosis, Mycobacterium tuberculosis, lineage

Dongfang Yu,1,2 Yufang Zhao,1,3 Chenzu Yin,4 Fangmei Liang,4 Wenyu Chen5 1Center for Studies of Education and Psychology of Ethnic Minorities in Southwest China, Southwest University, Chongqing, People’s Republic of China; 2Reader Service Dept, Guangxi University of Finance and Economics, Nanning, People’s Republic of China; 3Faculty of Psychology, Southwest University, Chongqing, People’s Republic of China; 4School of Teacher Education, Hechi University, Hechi, People’s Republic of China; 5College of Computer and Information Science, Southwest University, Chongqing, People’s Republic of ChinaCorrespondence: Yufang ZhaoFaculty of Psychology, Southwest University, Chongqing, 400715, People’s Republic of ChinaEmail zhaobee@swu.edu.cnPurpose: Intergroup contact is an effective strategy to improve intergroup relationships. Although intergroup relationships have been studied extensively, the individual roles of quantity and quality of contact in relationships with cognition, emotion, and intention of behavior toward other ethnic minority groups are not fully understood. This study explores the situation via network analysis among Zhuang and Yao ethnic minorities in Southwest China.Methods: We investigated the quantity and quality of intergroup contact and cognition, emotion, and intention of behavior among a sample of 543 Zhuang and 490 Yao ethnic group members. Data were analyzed using the R-package. Network structures were analyzed via the Qgraph package, and the accuracy and stability of the network were measured via the Bootnet package; communities were detected via the Igraph package; bridge analyses were conducted via the Networktools package; and the network difference was compared via the Network Comparison Test package.Results: The results indicated perceived intimacy is the central node. Quantity of contact constructed a community with “perceived connection,” “sense of community,” “knowledge about out-group,” and “perceived similarity.” Meanwhile, quality of contact constructed a community with “intergroup attitude” and a “feeling thermometer.” The remainder of the nodes constructed two additional communities. The network global connectivity and structure between the two ethnic groups were highly similar.Conclusion: The study examined the quantity and quality of intergroup contact via network analysis for two ethnic minority groups. It was shown that the two groups’ global network structures of intergroup contact and their effects are highly similar. Specifically, quantity and quality of contact produce different effects on intergroup relations. Quantity of contact has proximal effects, including instant cognitive and emotional response without depth cognition, while quality of contact has proximal effects that may change deep-seated cognition and subsequently improve intergroup relations.Keywords: quantity, quality, community analysis, network global connectivity, ethnic minorities, intergroup relationships

Chengchen Yin,1– 3 Xing He,1– 3 Kaili Shen,1– 3 Xingrui Mu,1– 3 Fushan Tang1– 3 1Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, 563006, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563006, People’s Republic of China; 3Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi, 563006, People’s Republic of ChinaCorrespondence: Fushan TangDepartment of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, 563006, People’s Republic of China, Tel +86 851 2864 2337, Fax +86 851 2864 2334, Email fstang@vip.163.comObjective: To investigate the current status of knowledge and behavior about rational drug use in college students in different colleges and universities in a city in southwest China, providing reference for students’ education of rational drug use in colleges and universities.Methods: A questionnaire survey on knowledge and behavior in rational drug use was carried out on the students recruited by occasional sampling method in 6 colleges and universities in Zunyi, China. Statistical analyses on demographic information and answers to questionnaire questions were carried out with SPSS 18.0.Results: A total of 865 valid questionnaires were recovered from 923 questionnaires sent out. Some knowledge and behaviors of the students on drug use were irrational. There was statistically significant difference in some specific questions of the knowledge in rational drug use between medical and non-medical students (P< 0.05); the average score of rational drug use behavior of medical students was lower than that of non-medical students (P< 0.05); the average score of the rational drug use behavior of female students was lower than that of male (P< 0.05); the students’ major types had significantly different influence on their behavior in rational drug use (P< 0.05). The school-carried pharmacy education can effectively improve students’ rational medication; the majority of college students believed that it is necessary to popularize the knowledge of rational drug use on campus; and students’ favorite way to acquire knowledge about rational drug use was to attend related lectures or elective courses.Conclusion: The knowledge and behavior of rational drug use among college students need to be improved. Professional medical education may exert a positive impact on rational drug use among college students. Thus, it is necessary to popularize the knowledge of rational drug use among college students, especially in non-medical colleges and universities.Keywords: college students, rational drug use, knowledge, behavior, ten mistakes in public medication

Huimin Nie,1,&ast; Boyu Liu,1,&ast; Chengyu Yin,1 Ruixiang Chen,1 Jie Wang,1 Danyi Zeng,1 Yan Tai,2 Jingdun Xie,3 Dongwei He,4 Boyi Liu1 1Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People’s Republic of China; 2Academy of Chinese Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 3Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in Southern China, Collaborative Innovation for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 4Laboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Boyi LiuDepartment of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, 310053, People’s Republic of ChinaEmail boyi.liu@zcmu.edu.cnDongwei HeLaboratory of Pathology, Hebei Cancer Institute, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, People’s Republic of ChinaEmail dongweihe@hebmu.edu.cnBackground: Mirror-image pain (MIP), which develops from the healthy body region contralateral to the actual injured site, is a mysterious pain phenomenon accompanying many chronic pain conditions, such as complex regional pain syndrome (CRPS). However, the pathogenesis of MIP still remains largely unknown. The purpose of this study is to perform an expression profiling to identify genes related to MIP in an animal model of CRPS-I.Methods: We established a rat chronic post-ischemic pain (CPIP) model to mimic human CRPS-I. RNA-sequencing (RNA-Seq), bioinformatics, qPCR, immunostaining, and animal behavioral assays were used to screen potential genes in the contralateral dorsal root ganglia (DRG) that may be involved in MIP.Results: The CPIP model rats developed robust and persistent MIP in contralateral hind paws. Bilateral DRG neurons did not exhibit obvious neuronal damage. RNA-Seq of contralateral DRG from CPIP model rats identified a total 527 differentially expressed genes (DEGs) vs sham rats. The expression changes of several representative DEGs were further verified by qPCR. Bioinformatics analysis indicated that the immune system process, innate immune response, and cell adhesion were among the mostly enriched biological processes, which are important processes involved in pain sensitization, neuroinflammation, and chronic pain. We further identified DEGs potentially involved in pain mechanisms or enriched in small- to medium-sized sensory neurons or TRPV1-lineage nociceptors. By comparing with published datasets summarizing genes enriched in pain mechanisms, we sorted out a core set of genes which might contribute to nociception and the pain mechanism in MIP.Conclusion: We provided by far the first study to profile gene expression changes and pathway analysis of contralateral DRG for the studying of MIP mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying MIP.Keywords: RNA-Seq, pain, CRPS-I, dorsal root ganglia, inflammation, cytokine

Aiketaguli Anwaierjiang,1,&ast; Quan Wang,2,&ast; Haican Liu,3,&ast; Chunjie Yin,1 Miao Xu,2 Machao Li,3 Mengwen Liu,1 Yan Liu,2 Xiuqin Zhao,3 Jinbao Liu,1 Guilian Li,3 Xiaokaiti Mijiti,2 Kanglin Wan3 1College of Public Health, Xinjiang Medical University, Wulumuqi, 830011, People’s Republic of China; 2The Eighth Affiliated Hospital of Xinjiang Medical University, Wulumuqi, 830001, People’s Republic of China; 3State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinbao Liu; Guilian Li Email 283474978@qq.com; liguilian@icdc.cnObjective: Drug-resistant tuberculosis is a major public health problem, especially in the southern region of Xinjiang, China; however, there is little information regarding drug resistance profiles and mechanism of Mycobacterium tuberculosis in this area. The aim of this study was to determine the prevalence and molecular characteristics of M. tuberculosis resistant to four anti-tuberculosis drugs from this area.Methods: Three hundred and forty-six isolates from the southern region of Xinjiang, China were included and used to perform phenotypic drug susceptibility testing and whole genome sequencing (WGS). Mutations in seven loci associated with drug resistance, including rpoB for rifampicin (RMP), katG, inhA promoter and oxyR-ahpC for isoniazid (INH), rrs 530 and 912 loops and rpsL for streptomycin (STR), and embB for ethambutol (EMB), were characterized.Results: Among 346 isolates, 106, 60, 70 and 29 were resistant to INH, RMP, STR and EMB, respectively; 132 were resistant to at least one of the four anti-tuberculosis drugs and 51 were multi-drug resistant (MDR). Beijing genotype and retreated patients showed a significantly increased risk for developing MDR tuberculosis. Compared with the phenotypic data, the sensitivity and specificity for WGS to predict resistance were 96.7% and 98.6% for RMP, 75.5% and 97.1% for INH, 68.6% and 99.6% for STR, 93.1% and 93.7% for EMB, respectively. The most common mutations conferring RMP, INH, STR and EMB resistance were Ser450Leu (51.7%) in rpoB, Ser315Thr (44.3%) in katG, Lys43Arg (35.7%) in rpsL and Met306Val (24.1%) in embB.Conclusion: This study provides the first information on the prevalence and molecular characters of drug resistant M. tuberculosis in the southern region of Xinjiang, China, which will be helpful for choosing early detection methods for drug resistance (ig, molecular methods) and subsequently initiation of proper therapy of tuberculosis in this area.Keywords: Mycobacterium tuberculosis, whole-genome sequencing, resistance, prevalence, mutation, isoniazid, rifampicin, streptomycin, ethambutol

Zhigang Wang,1,2 Tianlin Liu,1 Chunping Yin,1 Yanan Li,1 Fang Gao,1 Lili Yu,1 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei, People’s Republic of China; 2Department of Anesthesiology, Handan Central Hospital, Handan, Hebei, People’s Republic of ChinaCorrespondence: Qiujun Wang Tel +86 311 8860 2072Email wangqiujunsy@163.comObjective: Postoperative cognitive dysfunction (POCD) after anesthesia and surgery (AS) is a common complication in the elderly population. A cholinergic-dependent signal, the alpha7-nicotinic acetylcholine receptor (α 7-nAChR), has been suggested to regulate cognitive processes in a variety of neurologic diseases. In the current study, we determined whether electroacupuncture (EA) pretreatment ameliorates AS-induced POCD in aged rats, as well as the underlying mechanism.Methods: Male Sprague-Dawley rats (20 months old) were randomly assigned to the following 5 groups (n=12): vehicle; POCD (tibial fracture surgery); EA plus POCD; EA plus POCD and alpha-bungarotoxin (α-BGT); and POCD plus α-BGT groups. Alpha-bungarotoxin (1 μg/kg), a selective antagonist of α 7-nAChR, was administrated via intraperitoneal injection before EA. Thirty days post-AS, the Morris water maze and a novel objective recognition test were used to evaluate cognitive function. Neuronal amount, apoptosis, microglial activation, percentage of high mobility group box 1 (HMGB1)- and nuclear factor-κB (NF-κB)-positive microglia, and levels of HMGB-1 downstream factors, including NF-κB, interleukin-6 (IL-6), and IL-1β, were detected by Nissl staining, immunofluorescence, and Western blot assays.Results: EA pretreatment significantly increased crossing platform times and elevated the time with a novel object, restored the quantity of neurons, decreased TUNEL-positive neurons, alleviated activation of microglia, downregulated expression of HMGB1 and NF-κB in the microglia, and reduced levels of phosphor-NF-κB, IL-6, and IL-1β 35 days after AS, while α-BGT partially reversed these changes.Conclusion: EA pretreatment improved AS-induced POCD in aged rats, and the underlying mechanism may be associated with inhibition of HMGB1–NF-κB via an α 7-nAChR signal in the microglia.Keywords: electroacupuncture, EA, postoperative cognitive dysfunction, POCD, α 7-nicotinic acetylcholine receptor, α 7-nAChR, microglia, high mobility group box 1, HMGB1

Huajun Zhao,1 Haigang Wang,1 Yifei Hu,1 Dongqing Xu,1 Chunlai Yin,2 Qiuju Han,1 Jian Zhang1 1Institute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of China; 2Department of Immunology, Dalian Medical University, Dalian, People’s Republic of ChinaCorrespondence: Jian ZhangInstitute of Immunopharmaceutical Sciences, School of Pharmaceutical Sciences, Shandong University, Jinan, People’s Republic of ChinaTel +86-531-8838-3781Fax +86-531-8838-3782Email zhangj65@sdu.edu.cnPurpose: Alum adjuvant in HBV prophylactic vaccines is poor in inducing cellular immunity with the inhibition of IL-12 secretion, and approximately 5– 10% of immunised individuals fail to clear HBV upon infection. IL-12 plasmids (pIL-12) as adjuvants enhance significant humoral and cellular immune response in vaccines. However, finding a novel delivery system to protect pIL-12 from enzymatic degradation and achieve efficient delivery remains a major challenge.Methods: We prepared the chitosan nanovaccine-loaded IL-12 expression plasmid (termed as “Ng(-)pIL-12”) and analysed the physicochemical properties, encapsulation efficiency and safety. Then, we evaluated the efficiency of Ng(-)pIL-12 for prophylactic HBV vaccine. Serum samples were collected and analysed for IL-12, HBsAg, anti-HBs IgG, IgG1 and IgG2b. Liver tissues were collected and analysed for HBV DNA and RNA. BMDCs and lymphocytes were collected and analysed for HBV-specific immune responses. To further confirm the long-term protective immune response against HBV, these immunised mice were challenged with hydrodynamic injection of pAAV/HBV 1.2 plasmid on day 56 after the initiation of immunisation.Results: Chitosan nanovaccine prepared with CS and γ-PGA could load pIL-12 effectively and safely, and IL-12 was efficiently produced in vivo. Interestingly, Ng(-)pIL-12 adjuvant combined with HBsAg induced higher levels of anti-HBs IgG, IgG1 and IgG2b, promoted maturation and presentation capacity of DCs, especially CD8α+/CD103+ DCs. Meanwhile, Ng(-)pIL-12 adjuvant generated robust HBV-specific CD8+ T and CD4+ T cell responses. More importantly, Ng(-)pIL-12 adjuvant triggered terminally differentiated effector memory responses with strong anti-HBV effects.Conclusion: Chitosan nanovaccines as an efficient carrier adjuvant system for pIL-12 combined with HBsAg induced protective anti-HBs IgG and enhanced HBV-specific CD8+ T and CD4+ T cell responses, and achieved long-term memory response against HBV, making it a promising candidate for prophylactic HBV vaccines.Keywords: nanovaccines, hepatitis B, prophylactic vaccine, CD8+ T cells, long-term memory

Tianlin Liu,1,2 Chunping Yin,1 Yanan Li,1 Fang Gao,1 Lili Yu,1,2 Zhigang Wang,1 Qiujun Wang1 1Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei, People’s Republic of China; 2Department of Anesthesiology, Cangzhou Central Hospital, Cangzhou, Hebei, People’s Republic of ChinaCorrespondence: Qiujun Wang Tel +86 311 8860 2072Email wangqiujunsy@163.comBackground: Postoperative cognitive decline (POCD) in the old ages seriously delays the rapid recovery. Here, we aimed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) against POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, as well as the potential mechanism.Methods: A prospective, single-center, parallel-group, randomized trial was designed. A total of 100 patients (age ≥ 65 years) undergoing laparoscopic radical resection of colon cancer were involved and randomly divided into TEAS (Group T) and control (Group C) groups. The patients in Group T were performed with percutaneous acupoint electrical stimulation in bilateral Hegu, Neiguan and Zusanli points from 30 minutes before anesthesia induction to the end of surgery. A Z-score based on Mini-Mental State Exam (MMSE) was used to assess the incidence of POCD. The levels of serum IL-6, hs-CRP, CGRP at 0 min before TEAS (T0), 1 h after beginning of surgery (T1) and the end of surgery (T2) were evaluated.Results: Our data showed that the cumulative duration of POCD on postoperative day 2 and 3 in Group T was significantly decreased compared to Group C (P < 0.05). Compared with T0, the levels of serum IL-6, hs-CRP, and CGRP in both Group T and C were statistically elevated at T1 and T2 (P < 0.05). Moreover, the levels of serum IL-6 and hs-CRP were decreased, but the level of CGRP was increased in Group T compared to Group C at T1 and T2 (P < 0.05).Conclusion: TEAS is associated with a lower cumulative duration of POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, which may be related to the regulation of inflammatory factors and neuropeptides interacted with gut–brain axis.Keywords: cognitive decline, gut–brain axis, transcutaneous electrical acupoint stimulation, colon cancer, elder

Weipeng Wei,1– 3,* Jianhua Tang,4,* Hongfang Li,1– 3 Yongsheng Huang,5 Chengchen Yin,1– 3 Dan Li,6 Fushan Tang1– 3 1Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 3Key Laboratory of Clinical Pharmacy of Zunyi City, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 4Cancer Research UK Manchester Institute, The University of Manchester, Cheshire SK10 4TG, UK; 5Peking Union Medical College, Chinese Academy of Medical Sciences, Institute of Basic Medical Sciences, Beijing 100005, People’s Republic of China; 6State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushan TangDepartment of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Guizhou, People’s Republic of ChinaTel +86851 28642337Fax +86851 28642334Email fstang@vip.163.comDan LiCancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaTel +8610 87787107Email eileenld@gmail.comPurpose: To study the in vitro and in vivo antitumor effects of the colloidal suspension-in situ hydrogel of emodin (EM) constructed with the self-assembling peptide RADA16-I and systematically evaluate the feasibility of the delivery system.Methods: The MTT and colony-formation assays were used to determine the viability of normal cells NCTC 1469 and tumor cells Hepa1-6. The uptake of EM in the RADA16-I-EM in situ hydrogel by tumor cells was analyzed by laser confocal microscope and flow cytometry. Flow cytometry was used to detect the cell apoptosis and cell cycle distribution. Transwell assay was used to detect the migration and invasion of tumor cells. The antitumor efficacy of the RADA16-I-EM in situ hydrogel and its toxic effects was further assessed in vivo on Hepa1-6 tumor-bearing C57 mice.Results: The results showed that the RADA16-I-EM in situ hydrogels could obviously reduce the toxicity of EM to normal cells and the survival of tumor cells. The uptake of EM by the cells from the hydrogels was obviously increased and could significantly induce apoptosis and arrest cell cycle in the G2/M phase, and reduce the migration, invasion and clone-formation ability of the cells. The RADA16-I-EM in situ hydrogel could also effectively inhibit the tumor growth and obviously decrease the toxic effects of EM on normal tissues in vivo.Conclusion: Our results demonstrated that RADA16-I has the potential to be a carrier for the hydrophobic drug EM and can effectively improve the delivery of hydrophobic antitumor drugs with enhanced antitumor effects and reduced toxic effects of the drugs on normal cells and tissues.Keywords: self-assembling peptide, emodin, in situ hydrogels, antitumor, drug delivery system

Hongfang Li,1– 3,* Yunyan Tang,1,4,* Yang Wang,1– 3 Weipeng Wei,1– 3 Chengchen Yin,1– 3 Fushang Tang1– 3 1Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 3Key Laboratory of Clinical Pharmacy of Zunyi City, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 4Department of Pharmacy, Meitan People’s Hospital, Zunyi 564100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushang TangDepartment of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi 563000, People’s Republic of ChinaTel +86 851 2864 2337Fax +86 851 2864 2334Email fstang@vip.163.comBackground: Bupleurum is one of the most important traditional Chinese medicines and an ingredient in many compound preparations. It is widely used together with other drugs in clinical practice, and thus there is great potential for drug–drug interactions. Saikosaponin D (SsD) is a major bioactive triterpenoid saponin extracted from Bupleurum with anti-inflammatory, anticancer, antioxidative, and antihepatic fibrosis effects. Effects of the main components of Bupleurum on cytochromes P450 (CYPs) need to be clarified in the clinical application of combination therapies of formulations containing SsD or Bupleurum.Purpose: This study aimed to investigate the effects of SsD on the CYP1A2 and CYP2D6 mRNAs, protein expression, and relative enzyme activities in HepaRG cells.Methods: HepaRG cells were cultured with SsD at concentrations of 0.5, 1, 5 and 10 μM for 72 hours. mRNA and protein expression of CYP1A2 and CYP2D6 were analyzed with real-time PCR and Western blot analysis. Relative enzyme activities were analyzed with HPLC based on consumption of the specific probe substrate.Results: SsD significantly induced expression of mRNA and increased relative activity of CYP1A2 in HepaRG cells after the cells had been treated with SsD at concentrations of 1, 5 and 10 μM. SsD also induced protein expression of CYP1A2 at concentrations of 5 and 10 μM. SsD exhibited an inductive effect on CYP2D6 mRNA and protein expression, while increasing the relative activity of CYP2D6 at concentrations of 5 and 10 μM.Conclusion: This study is the first to investigate the effect of SsD on CYP1A2 and CYP2D6 in HepaRG cells, and the results may provide some useful information on potential drug–drug interactions related to clinical preparations containing SsD or Bupleurum.Keywords: saikosaponin D, HepaRG cells, drug–drug interactions

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

Zheng Li,* Ci Yin,* Bin Li, Qi-Yao Yu, Wen-Jie Mao, Jie Li, Jun-Ping Lin, Yu-Qi Meng, Hai-Ming Feng, Tao Jing Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, China*These authors contributed equally to this workCorrespondence: Bin LiDepartment of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou 730030, ChinaTel/Fax +86 931 8942073Email dr.leebin@outlook.comPurpose: This study aims to investigate the potential role of DUS4L (dihydrouridine synthase 4 like) in lung adenocarcinoma (LUAD) and explore its associated pathways in human LUAD.Methods: Firstly, we evaluated the relationships between clinicopathological characteristics and DUS4L expression via analysis of TCGA RNA sequencing data and other publicly available databases. Then, DUS4L was effectively silenced in LUAD cell line A549 using the lentiviral shRNA (short-hairpin RNA) transfection to assess its effects on cell proliferation, cycle and apoptosis in LUAD cells. RNA-seq technology was applied to shDUS4L and shCtrl-transfected cells to generate the corresponding gene expression profiles. Differentially expressed genes (DEGs) were identified using the DESeq2 program package. Also, DEGs were subjected to Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis to explore the associated molecular signaling pathways and relevant biological functions.Results: Analysis of TCGA data revealed that DUS4L was highly upregulated in LUAD tissues which was related to clinical T and TNM stages of LUAD. The knockdown of DUS4L effectively inhibited cell proliferation and promoted apoptosis in A549 cells. Furthermore, the DEGs between the shDUS4L and shCtrl A549 cells were mainly enriched in biological processes associated with spliceosome, ribosome, RNA catabolic process, ncRNA (non-coding RNA) processing, and p53 signaling pathway.Conclusion: Altogether, our results suggest that DUS4L is significantly associated with tumorigenesis and could be utilized as a novel biomarker and therapeutic target for LUAD.Keywords: DUS4L, lung adenocarcinoma, proliferation, apoptosis, TCGA

Guohua Dai, Shuzhong Li, Chuqiang Yin, Yuanliang Sun, Derong Xu, Zhongying Wang, Liangrui Luan, Jianwen Hou, Ting Wang Affiliated Hospital of Qingdao University, Qingdao 266003, People’s Republic of ChinaCorrespondence: Ting Wang Tel +86 18661809505Email wangting20@hotmail.comObjective: In the present study, we aimed to describe the clinical features, diagnosis, treatment, and prognosis of spinal epidural abscess (SEA).Methods: The complete clinical data of 11 SEA patients who were treated in our hospital system from January 2015 to June 2018 were retrospectively analyzed. Moreover, the clinical features, diagnosis, treatment, and prognosis of 642 SEA cases collected from the foreign literature from 2010 to 2019 were also investigated.Results: Among our 11 SEA patients, nine cases had purulent inflammation, two cases had tuberculosis, two cases had infection caused by Staphylococcus aureus, one case had infection caused by Streptococcus constellatus, one case had infection caused by Klebsiella pneumoniae, five cases showed negative bacterial culture, and two cases had Mycobacterium tuberculosis. All 11 cases showed focal spinal pain, eight cases exhibited neurological deficits, and six cases experienced fever. Nine of the 11 cases involved the lumbosacral spine, one case involved the thoracic spine, and one case involved the cervical spine. Eight patients had a longer course of disease (> 2 weeks), all 11 patients had vertebral osteomyelitis, and nine patients had intervertebral discitis. One patient had motor dysfunction of arms and legs, one patient had lower limb motor dysfunction, one patient had limb numbness, one patient experienced relapse after the conservative treatment, and one patient experienced relapse after the surgical treatment. The follow-up time was 15– 24 months.Conclusion: The classic diagnosis of triads (focal spine pain, neurological deficit, and fever) was less specific for SEA. MRI examination, blood culture, tissue culture, and biopsy could be used for the diagnosis for SEA. Suppuritis was a common cause of SEA. Early detection, early diagnosis and early treatment, as well as the selection of the most suitable treatment regimen based on comprehensive evaluation, played crucial roles in a better prognosis of SEA. There was no statistically significant difference in terms of the general condition, diagnosis, treatment and prognosis between the patients with negative and positive culture results (P> 0.05). For SEA patient with negative culture, antibiotic treatment should be used empirically.Keywords: epidural abscess, clinical features, diagnosis and treatment, prognosis

Xingrui Mu,1– 3 Chengchen Yin,1– 3 Xing He,1– 3 Hongfang Li,1– 3 Yuansha Gong,4 Weipeng Wei,1– 3 Yan Zhang,1– 3 Fushan Tang1– 3 1Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 2The Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 3Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 4School of Nursing, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaCorrespondence: Fushan TangSchool of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaTel +86 851 2864 2337Fax +86 851 2864 2334Email fstang@vip.163.comObjective: To investigate the correlation between patients’ medication adherence and their psychological contract with hospital pharmacists under the background of the pharmacist–patient relationship, providing a reference for improving the pharmacist–patient relationship and the patients’ medication adherence based on the patients’ psychological contract with the hospital pharmacists.Materials and Methods: Some of the patients who received medication dispensing service at the outpatient pharmacies at the First Affiliated Hospital of Zunyi Medical University and the Second Affiliated Hospital of Zunyi Medical University were included and investigated as follows: 320 patients were included through the convenient sampling method for psychological contract and medication adherence questionnaire survey with the self-designed scales for patients’ psychological contract with the hospital pharmacists and their medication adherence. SPSS 17.0 was used for reliability and validity testing, correlation analysis, and multiple linear regression analysis.Results: The average score of the psychological contract was 3.80± 0.59. The average score of the patients’ medication adherence was 2.93± 0.70. The patients’ psychological contract with the pharmacists and its dimensions (the responsibility of competence, the responsibility of service, and the responsibility of humanistic care) were positively correlated with medication adherence (P< 0.05). The results of the multiple linear regression analysis showed that the effect of patients’ psychological contract with the pharmacists on medication adherence was statistically significant (P< 0.05).Conclusion: Outpatients’ psychological contract with the pharmacists is positively correlated with their medication adherence. Maintaining the patients’ psychological contract with the pharmacists may be an effective way to improve medication adherence.Keywords: psychological contract, medication adherence, the relationship between pharmacists and patients

Mei Jiang1 *,* Qi Chen1 *,* Xiaoting Zhao,1 Yu Teng,1 Chenghong Yin,2 Wentao Yue1 1Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, People’s Republic of China; 2Departments of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wentao YueCentral Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 251, Yaojiayuan Road, Chaoyang District, Beijing 100026, People’s Republic of ChinaEmail yuewt2000@yahoo.comChenghong YinDepartments of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, No. 251, Yaojiayuan Road, Chaoyang District, Beijing 100026, People’s Republic of ChinaEmail modscn@126.comBackground: PFTK1, a novel cyclin-dependent kinase, plays pivotal roles in tumorigenesis. Cell motility and invasiveness could be enhanced by PFTK1 in various tumors. However, the function of PFTK1 in NSCLC metastasis remains unclear. In this study, the potential role of PFTK1 in NSCLC metastasis was determined.Materials and Methods: In this study, the potential function of PFTK1 in lung cancer patients was analyzed with the Kaplan–Meier plotter database. RNA interference-mediated knockdown of PFTK1 was established in two NSCLC cell lines (H1299 and 95C) to explore the role of PFTK1 in NSCLC. The efficacy of downregulation of PFTK1 was examined by Western blot and immunofluorescence. The role of PFTK1 in cell migration and invasion ability was detected by wound healing and transwell assays. The protein levels in lung cancer cells were determined by Western blot. Immunofluorescence analysis was used to evaluate the structure of filamentous actin.Results: Overexpression of PFTK1 was associated with the poor survival prognosis in NSCLC patients. PFTK1 knockdown cells were constructed successfully. Suppression of PFTK1 significantly inhibited the cell migration and invasion in H1299 and 95C cells. Notably, after PFTK1 downregulation, the epithelial–mesenchymal transition (EMT) markers vimentin, ZEB1 and β-catenin were obviously decreased. Additionally, immunofluorescence analysis indicated that PFTK1 downregulation remarkably induced filamentous actin depolymerization.Conclusion: In summary, PFTK1 could significantly promote lung cancer metastasis through changing EMT progress and modulating intracellular cytoskeleton F-actin expression. Taken together, our findings indicated that PFTK1 might serve as a novel therapeutic target for the inhibition of NSCLC progression.Keywords: non-small cell lung cancer, PFTK1, invasion

Waner Wu,1,* Na Xu,1,* Xuan Zhou,1 Liang Liu,1 Yaxian Tan,1 Jie Luo,1 Jixian Huang,2 Jiayue Qin,3 Juan Wang,3 Zhimin Li,3 Changxin Yin,1 Lingling Zhou,1 Xiaoli Liu1 1Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, People’s Republic of China; 2Department of Hematology, Yuebei People’s Hospital, Shantou University, Shaoguan 512025, Guangdong, People’s Republic of China; 3Yiwu Cancer Research Center, Fudan University Shanghai Cancer Center, Yiwu, Zhejiang 322000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoli Liu Email lxl2405@126.comIntroduction: While the acquisition of mutations in the ABL1 kinase domain (KD) has been identified as a common mechanism behind tyrosine kinase inhibitor (TKI) resistance, recent genetic studies have revealed that patients with TKI resistance or intolerance frequently harbor one or more genetic alterations implicated in myeloid malignancies. This suggests that additional mutations other than ABL1 KD mutations might contribute to disease progression.Methods: We performed targeted-capture sequencing of 127 known and putative cancer-related genes of 63 patients with CML using next-generation sequencing (NGS), including 42 patients with TKI resistance and 21 with TKI intolerance.Results: The differences in the number of mutations between groups had no statistical significance. This could be explained in part by not all of the patients having achieved major molecular remission in the early period as expected. Overall, 66 mutations were identified in 96.8% of the patients, most frequently in the KTM2C (31.82%), ABL1 (31.82%), FAT1 (25.76%), and ASXL1 (22.73%) genes. CUX1, KIT, and GATA2 were associated with TKI intolerance, and two of them (CUX1, GATA2) are transcription factors in which mutations were identified in 82.61% of patients with TKI intolerance. ASXL1 mutations were found more frequently in patients with ABL1 KD mutations (38.1% vs 15.21%, P=0.041). Although the number of mutations was low, pairwise interaction between mutated genes showed that ABL1 KD mutations cooccurred with SH2B3 mutations (P< 0.05). In Kaplan–Meier analyses, only TET2 mutations were associated with shorter progression-free survival (P=0.026).Conclusion: Our data suggested that the CUX1, KIT, and GATA2 genes may play important roles in TKI intolerance. ASXL1 and TET2 mutations may be associated with poor patient prognosis. NGS helps improving the clinical risk stratification, which enables the identification of patients with TKI resistance or intolerance in the era of TKI therapy.Keywords: chronic myeloid leukemia, mutations, tyrosine kinase inhibitor, intolerance, resistance

Jing Zhang,1,2,* Chengchen Yin,1,3,4,* Hongfang Li,1,3,4 Weipeng Wei,1,3,4 Yuansha Gong,5 Fushan Tang1,3,4 1Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 2Department of Respiratory Medicine, Central Hospital in Jinchang City (Worker’s Hospital of Jinchuan Group), Jinchang 737102, People’s Republic of China; 3The Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 4Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 5School of Nursing, Zunyi Medical University, Zunyi 563006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushan TangDepartment of Clinical Pharmacy School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaTel +86 851 2864 2337Fax +86 851 2864 2334Email fushantang@qq.comPurpose: Poor medication adherence can negatively affect health outcomes of patients with asthma from medication and significantly increase the healthcare costs. Management of adherence to inhalers remains a challenging topic in the long-term management of patients with asthma. We aim to evaluate the role of asthma control test (ACT) in the management of adherence to inhalers in outpatients with asthma.Patients and Methods: Six hundred twenty-seven outpatients with asthma admitted to the clinic of respiratory medicine in a tertiary hospital in northwestern China during 2016 to 2019 were randomly divided into observation group (n= 315) and control (n= 312) and received standard inhalant therapy for 6 months and lung function test before and after treatment. The patients in the observation group took ACT questionnaires at the end of each month, while the patients in control only took an ACT at the end of the last month. The ‘Test of Adherence to Inhalers’ (TAI) questionnaire was used to evaluate the patients’ adherence to inhalant therapy.Results: All patients completed the study. The ACT scores in the observation group showed a gradual increase month by month. The TAI results indicated that adherence to inhalers of patients in the observation group was significantly better than that in control and the patients’ non-adherence pattern in the observation group, with significantly lower erratic non-adherence, was also different from that in control. After 6 months of treatment, the lung function indexes and their relative improvement and the ACT scores in the observation group were significantly better or higher than those in control.Conclusion: The once-monthly self-reported ACT can effectively improve the adherence to inhalers of outpatients with asthma mainly by addressing erratic non-adherence and improve the treatment effects, and thus deserves widespread use in the treatment adherence management in patients with asthma.Keywords: asthma control test, ACT, medication adherence, Test of Adherence to Inhalers, TAI, self-management, China

Jie Gao,1,2,* Junjie Liu,1,3,* Fangyuan Xie,4,* Ying Lu,3 Chuan Yin,5 Xian Shen1 1Department of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 2Scientific Research Center, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, People’s Republic of China; 3Department of Pharmaceutical Sciences, Second Military Medical University, Shanghai, People’s Republic of China; 4Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 5Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Gao; Xian ShenDepartment of Gastrointestinal Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan W Road, Lucheng, Wenzhou, Zhejiang 325000, People’s Republic of ChinaTel +86-0577-88816381; 86-0577-88002709Fax +86-0577-88816381Email gaojiehighclea@163.com; shenxian1963@sina.comPurpose: Conventional chemotherapy is hampered by the presence of breast cancer stem cells (BCSCs). It is crucial to eradicating both the bulky breast cancer cells and BCSCs, using a combination of conventional chemotherapy and anti-CSCs drugs. However, the synergistic ratio of drug combinations cannot be easily maintained in vivo. In our previous studies, we demonstrated that the simultaneous delivery of two drugs via nanoliposomes could maintain the synergistic drug ratio for 12 h in vivo. However, nanoliposomes have the disadvantage of quick drug release, which makes it difficult to maintain the synergistic drug ratio for a long time. Herein, we developed a co-delivery system for docetaxel (DTX)—a first-line chemotherapy drug for breast cancer—and salinomycin (SAL)—an anti-BCSCs drug—in rigid nanoparticles constituted of polylactide-co-glycolide/D-alpha-tocopherol polyethylene glycol 1000 succinate (PLGA/TPGS).Methods: Nanoparticles loaded with SAL and DTX at the optimized ratio (NSD) were prepared by the nanoprecipitation method. The characterization, cellular uptake, and cytotoxicity of nanoparticles were investigated in vitro, and the pharmacokinetics, tissue distribution, antitumor and anti-CSCs activity of nanoparticles were evaluated in vivo.Results: We demonstrated that a SAL/DTX molar ratio of 1:1 was synergistic in MCF-7 cells and MCF-7-MS. Moreover, the enhanced internalization of nanoparticles was observed in MCF-7 cells and MCF-7-MS. Furthermore, the cytotoxicity of NSD against both MCF-7 cells and MCF-7-MS was stronger than the cytotoxicity of any single treatment in vitro. Significantly, NSD could prolong the circulation time and maintain the synergistic ratio of SAL to DTX in vivo for 24 h, thus exhibiting superior tumor targeting and anti-tumor activity compared to other treatments.Conclusion: Co-encapsulation of SAL and DTX in PLGA/TPGS nanoparticles could maintain the synergistic ratio of drugs in vivo in a better manner; thus, providing a promising strategy for synergistic inhibition of breast cancer.Keywords: combined therapy, breast cancer stem cells, docetaxel, salinomycin, nanoparticles

Qi Chen,1,* Quan He,1 Lingling Zhuang,1,* Kunya Wang,2 Chunhua Yin,2 Linsheng He1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, People’s Republic of China; 2Department of Obstetrics and Gynecology, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi 330006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linsheng HeDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Yongwaizheng Street 17, Donghu District, Nanchang, Jiangxi 330006, People’s Republic of ChinaTel/Fax +86 791 8862 3153Email whlsls126@163.comPurpose: This study aimed to explore the effects of interferon-γ inducible protein 10 (IP10) and complementarity-determining region 3 (CDR3) of T cells receptor on ovarian cancer cells and the involved mechanisms.Methods: IP10 and CDR3 were linked with single-chain antibody (scfv) and exotoxin gene muton of Pseudomonas aeruginosa (PE40) to construct IP10-CDR3scfv and IP10-CDR3-PE40scfv. Then, we constructed pcDNA3.1-IP10-CDR3scfv and pcDNA3.1-IP10-CDR3-PE40scfv plasmids which were proved by HindIII/EcoRI digestion. SKOV3 cells and HOSEpiC cells were incubated with fluorescein isothiocyanate (FITC) labeled IP10-CDR3scfv and IP10-CDR3-PE40scfv proteins and protein levels were examined by flow cytometry. After gene transfection, SKOV3 cells were divided into four groups: Control, pcDNA3.1(+) negative control (NC) (pcDNA3.1(+) NC transfection), IP10-CDR3scfv (IP10-CDR3scfv transfection) and IP10-CDR3-PE40scfv (IP10-CDR3-PE40scfv transfection). Levels of IP10, CDR3, Caspase-3, cleaved Caspase-3 and Bcl-2 were determined by RT-PCR and Western blot. Cell viability and apoptosis were investigated by CCK-8 assay and Annexin V-FITC/PI assay, respectively.Results: The levels of FITC-labeled IP10-CDR3scfv and IP10-CDR3-PE40scfv proteins in the SKOV3+IP10-CDR3scfv group and the SKOV3+IP10-CDR3-PE40scfv group were remarkably higher than that in the SKOV3 group (P

Chuntong Yin,1,* Han Zhang,1,* Xin Liu,2 Haiying Zhang,2 Yue Zhang,2 Xue Bai,2 Lei Wang,2 Huimin Li,2 Xia Li,2 Shuqian Zhang,2 Linyou Zhang,1 Yong Zhang2 1Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, People’s Republic of China; 2Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linyou ZhangDepartment of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, People’s Republic of ChinaEmail hmulyzhang@outlook.comYong ZhangDepartment of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, People’s Republic of ChinaEmail hmuzhangyong@hotmail.comObjectives: Autophagy plays various roles in non-small-cell lung cancer (NSCLC). MCOLN1, a reactive oxygen species sensor, can regulate autophagy via lysosomal Ca(2+); however, the role of MCOLN1 in NSCLC is largely unknown. This study aimed to explore the effects of MCOLN1 on proliferation, invasion and migration in NSCLC and the underling mechanisms.Materials and methods: The tissues of NSCLC patients were collected, then MCOLN1 expression in tumor and adjacent tissues was measured and its relationship with pathological staging was analyzed. The Cell Counting Kit-8 (CCK-8) assay, wound healing assay and transwell migration assay were used to evaluate the proliferation, migration and invasion ability, respectively. Live-cell imaging and transmission electron microscopy (TEM) were used to observe autophagic flux and autolysosomes.Results: It was found that MCOLN1 expression was significantly decreased in human NSCLC tissues compared with normal lung tissues while more MCOLN1 in stage III–IV was shown than stage I–II, indicating that MCOLN1 increased along with the progression of NSCLC. Furthermore, CCK-8 assay, wound healing assay and transwell migration assay confirmed that the inhibition of MCOLN1 suppressed NSCLC cells proliferation migration and invasion. Overexpression of MCOLN1 promoted autophagy in A549 and H1299 cells with increased LC3-II/I, lamp1 expression and autolysosomes as well as autophagic flux shown by live-cell imaging and TEM.Conclusion: Our study shows that downregulated MCOLN1 reduced lysosome-autophagy activity contributing to inhibited tumor progression, which reveals a novel role of MCOLN1 in NSCLC, and targeting MCOLN1 may be a therapeutic potential for NSCLC.Keywords: MCOLN1, NSCLC, autophagy, lysosome, progression

Yiping Zhang, Changchang Yin, Xufeng Zhou, Yahua Wu, Lili WangDepartment of Biochemistry and Molecular Biology, Basic Medical College of Jiujiang University, Jiujiang City, Jiangxi Province 332000, People’s Republic of ChinaCorrespondence: Yiping ZhangDepartment of Biochemistry and Molecular Biology, Basic Medical College of Jiujiang University, No. 320, Xunyang East Road, Xunyang District, Jiujiang City, Jiangxi Province 332000, People’s Republic of ChinaTel +86 1 376 727 5087Email zhangyiping109@163.comPurpose: This study aimed to evaluate the specific roles of estrogen receptor β (ERβ) on the invasion and migration of osteosarcoma (OS) cells and explore the regulatory mechanisms relating with Wnt signaling pathway.Methods: The expression of ERβ was detected in human OS tissues by quantitative real-time PCR and immunohistochemistry. U2-OS cells were transfected with siRNA-ERβ (si-ERβ) to downregulate ERβ and treated with FH535 to inhibit Wnt signaling. The migration and invasion ability was detected by scratch and transwell assay, respectively. The expression of β-catenin, MMP-7, and MMP-9 was detected by Western blot. Subcutaneous tumor-bearing model was established by injection of U2-OS cells into mice, and the tumor volumes were measured. Orthotopic transplantation model was established by transplantation of tumor tissues into the liver of mice, and the metastatic tumors were counted.Results: ERβ was downregulated in human OS tissues and U2-OS cells. The transfection of si-ERβ significantly increased the scratch healing rate; the number of invasion cells; and the expression of β-catenin, MMP-7, and MMP-9 in U2-OS cells. The injection of si-ERβ-transfected U2-OS cells into mice significantly increased the subcutaneous tumor volume; the expression of β-catenin, MMP-7, and MMP-9; and the number of metastatic tumors in liver tissues. The promoting effects of si-ERβ on the invasion and migration of U2-OS cells were significantly reversed by FH535 in vitro and in vivo.Conclusion: Silencing of ERβ promotes the invasion and migration of OS cells via activating Wnt signaling pathway.Keywords: estrogen receptor β, osteosarcoma, Wnt signaling pathway, invasion, migration

Qingping Zhao,1,* Rongbo Qu,2,* Lu Teng,1 Changyou Yin,1 Yuan Yuan11Department of Neurosurgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai City, Shandong Province 264000, People’s Republic of China; 2Department of Neurosurgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai City, Shandong Province 264100, People’s Republic of China *These authors contributed equally to this workObjective: This study aimed to investigate the neuroprotective effect of heme oxygenase-1 (HO-1) on the PI3K/AKT signaling pathway in rats with cerebral hemorrhage.Materials and methods: Adult male Sprague-Dawley rats were randomly divided into: a sham group, a model group and an HO-1 inhibitor group (ZnPP group). Functional defects after surgery were scored according to the Longa5 standard. Hemotoxylin and eosin staining was used to detect whether the model was constructed successfully. Superoxide dismutase (SOD) vitality and malondialdehyde (MDA) content were calculated by the xanthine oxidase method and thiobarbituric acid method, respectively. Blood-brain barrier permeability was measured by Evans Blue. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The expression of Bcl-2 and BAX was evaluated by immunohistochemistry and the expression of PI3K, p-PI3K, AKT and p-AKT was tested by Western blotting.Results: The rat intracerebral hemorrhage model was successfully constructed. Compared with the model group, the bleeding in the ZnPP group was more serious, the cell edema and deformation were aggravated, and the neurological deficit score in the rat was significantly increased. In addition, the content of Evans blue, MDA, the number of apoptotic cells, the water content of brain tissue and the expression of BAX were significantly increased, while the SOD activity and the expressions of Bcl-2, p-PI3K and p-AKT protein were decreased.Conclusion: HO-1 could protect the nerves of rats with cerebral hemorrhage by regulating the PI3K/AKT signaling pathway.Keywords: PI3K/AKT signaling pathway, HO-1, neuroprotection, hemorrhage

Chengyu Yin,1,2,* Qimiao Hu,1,* Boyu Liu,1,* Yan Tai,3 Xiaoli Zheng,1 Yuanyuan Li,1 Xuaner Xiang,1 Ping Wang,4 Boyi Liu11Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Hangzhou, People’s Republic of China; 2College of Life Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3Academy of Chinese Medicine Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Pathology, School of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China*These authors contributed equally to this workPurpose: Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition, which remains clinically challenging. The mechanisms of CRPS-I still remain largely unknown. We aim to identify transcriptome profiles of genes relevant to pain mechanisms and major pathways involved in CRPS-I.Methods: A rat model of chronic post-ischemia pain (CPIP) was established to mimic CRPS-I. RNA-sequencing (RNA-Seq) was used to profile transcriptome of L4-6 dorsal root ganglia (DRGs) of a rat model of CRPS-I.Results: CPIP model rats developed persistent mechanical/thermal hyperalgesia in ipsilateral hind paw. RNA-Seq identified a total of 295 differentially expressed genes (DEGs), including 195 up- and 100 downregulated, in ipsilateral DRGs of CPIP rats compared with sham rats. The expression of several representative genes was confirmed by qPCR. Functional analysis of DEGs revealed that the most significant enriched biological processes of upregulated genes include response to lipopolysaccharide, inflammatory response and cytokine activity, which are all important mechanisms mediating pain. We further screened DEGs implicated in pain progress, genes enriched in small- to medium-sized sensory neurons and enriched in TRPV1-lineage nociceptors. By comparing our dataset with other published datasets of neuropathic or inflammatory pain models, we identified a core set of genes and pathways that extensively participate in CPIP and other neuropathic pain states.Conclusion: Our study identified transcriptome gene changes in DRGs of an animal model of CRPS-I and could provide insights into identifying promising genes or pathways that can be potentially targeted to ameliorate CRPS-I.Keywords: RNA-Seq, pain, CRPS-I, dorsal root ganglion, neuropathic pain

Dazhong Chen,1–3,* Xiaoli Pan,4,* Fangyuan Xie,5,* Ying Lu,2 Hao Zou,2 Chuan Yin,6 Yu Zhang,7 Jie Gao1,2 1Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China; 2Department of Pharmaceutical Sciences, Second Military Medical University, Shanghai 200433, China; 3Department of Planning, Kunming General Hospital of Chengdu Military Command, Yunnan 650032, China; 4Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 5Department of Pharmacy, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China; 6Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China; 7Department of Oncology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Hubei 441000, China *These authors contributed equally to this work Purpose: Liver cancer is the third leading cause of cancer-related deaths worldwide. Liver cancer stem cells (LCSCs) are a subpopulation of cancer cells that are responsible for the initiation, progression, drug resistance, recurrence, and metastasis of liver cancer. Recent studies have suggested that the eradication of both LCSCs and liver cancer cells is necessary because the conversion of cancer stem cells (CSCs) to cancer cells occasionally occurs. As ATP-binding cassette (ABC) transporters are overexpressed in both CSCs and cancer cells, combined therapies using ABC transporter inhibitors and chemotherapy drugs could show superior therapeutic efficacy in liver cancer. In this study, we developed poly(lactide-co-glycolide)/d-alpha-tocopherol polyethylene glycol 1000 succinate nanoparticles to accomplish the simultaneous delivery of an optimized ratio of doxorubicin (DOX) and elacridar (ELC) to target both LCSCs and liver cancer cells.Methods: Median-effect analysis was used for screening of DOX and ELC for synergy in liver cancer cells (HepG2 cells) and LCSCs (HepG2 tumor sphere [HepG2-TS]). Then, nanoparticles loaded with DOX and ELC at the optimized ratio (NDEs) were prepared by nanoprecipitation method. The cytotoxicity and colony and tumor sphere formation ability of nanoparticles were investigated in vitro, and the tissue distribution and antitumor activity of nanoparticles were evaluated in vivo.Results: We demonstrated that a DOX/ELC molar ratio of 1:1 was synergistic in HepG2 cells and HepG2-TS. NDEs were shown to exhibit significantly increased cytotoxic effects against both HepG2 and HepG2-TS compared with DOX-loaded nanoparticles (NDs) or ELC-loaded nanoparticles (NEs) in vitro. In vivo studies demonstrated that the nanoparticles exhibited better tumor targeting, with NDE showing the strongest antitumor activity with lower systemic toxicity.Conclusion: These results suggested that NDE represented a promising combination therapy against liver cancer by targeting both liver cancer cells and CSCs. Keywords: combined therapy, cancer stem cells, liver cancer, doxorubicin, elacridar, nanoparticles

Jin Ma,1,* Chunxia Yin,1,* Shiyu Ma,2 Huiliang Qiu,1 Chaoyang Zheng,1 Qiuxiong Chen,1 Chunhua Ding,1,3 Weihui Lv1 1Heart Center, Guangdong Provincial Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; 2Department of Critical-Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China; 3Cardiac Department, Aerospace Center Hospital, Peking University Aerospace Clinical College of Medicine, Beijing 100049, China *These authors contributed equally to this work Purpose: Shensong Yangxin (SSYX) capsule is a traditional Chinese medicine that has been used widely to treat cardiac arrhythmia. This study aimed to assess whether SSYX prevents atrial fibrillation (AF) after chronic myocardial infarction (MI)-induced heart failure and to determine the underlying mechanisms.Materials and methods: The study included 45 male Sprague Dawley rats. The rats underwent MI induction or sham surgery. One week after MI induction surgery, we performed serial echocardiography and administered SSYX capsule to some rats that experienced MI. After 4 weeks of treatment, AF inducibility was assessed with transesophageal programmed electrical stimulation technology. Additionally, multielectrode array assessment, histological analysis, and Western blot analysis were performed.Results: AF inducibility was significantly lower in SSYX rats than in MI rats (33.3% vs 73.3%, P

Epithelial–mesenchymal transition (EMT) and its reversal, mesenchymal–epithelial transition (MET) drive tissue reorganization critical for early development. In carcinomas, processing through EMT, MET, or partial states promotes migration, invasion, dormancy, and metastatic colonization. As a reversible process, EMT is inherently regulated at epigenetic and epigenomic levels. To understand the epigenomic nature of reversible EMT and its partial states, we characterized chromatin accessibility dynamics, transcriptomic output, protein expression, and cellular phenotypes during stepwise reversible EMT. We find that the chromatin insulating protein machinery, including CTCF, is suppressed and re-expressed, coincident with broad alterations in chromatin accessibility, during EMT/MET, and is lower in triple-negative breast cancer cell lines with EMT features. Through an analysis of chromatin accessibility using ATAC-seq, we identify that early phases of EMT are characterized by enrichment for AP-1 family member binding motifs, but also by a diminished enrichment for CTCF binding motifs. Through a loss-of-function analysis, we demonstrate that the suppression of CTCF alters cellular plasticity, strengthening the epithelial phenotype via the upregulation of epithelial markers E-cadherin/CDH1 and downregulation of N-cadherin/CDH2. Conversely, the upregulation of CTCF leads to the upregulation of EMT gene expression and an increase in mesenchymal traits. These findings are indicative of a role of CTCF in regulating epithelial–mesenchymal plasticity and gene expression.

Xuanxuan Dai,1,* Junru Zhang,2,* Guilong Guo,1 Yuepiao Cai,3 Ri Cui,3 Changtian Yin,1 Weidong Liu,3 Rajamanickam Vinothkumar,3 Tingting Zhang,3 Guang Liang,3 Xiaohua Zhang1 1Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; 2College of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, China; 3Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China *These authors contributed equally to this work Introduction: Targeted therapies using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC) patients harboring EGFR mutations, leading to the approval of gefitinib and erlotinib as standard first-line clinical treatment. Inevitably, a considerable proportion of patients develop resistance to EGFR-TKIs due to the acquisition of secondary mutations within EGFR. Therefore, alternative strategies to target NSCLC are desperately needed. Materials and methods: In this study, we have evaluated the effect of a reactive oxygen species (ROS)-inducing agent WZ35, a mono-carbonyl analog of curcumin, to target an inherent biological property of cancer cells, increased oxidative stress. To study whether WZ35 can inhibit NSCLC tumorigenesis, we used gefitinib- and erlotinib-resistant cell line H1975.Results: In this study, we show that WZ35 treatment dramatically decreases cell viability and induces apoptosis in H1975 cells through the generation of ROS. We also found that the ­antitumor activity of WZ35 involved ROS-mediated activation of the endoplasmic reticulum stress pathway and mitochondrial dysfunction. Furthermore, WZ35 significantly inhibited H1975 xenograft tumor growth through the inhibition of cell proliferation and induction of apoptosis. Discussion: These findings show that WZ35 may be a promising candidate for the treatment of EGFR-TKI-resistant NSCLC. Keywords: epidermal growth factor receptor, reactive oxygen species, mono-carbonyl analog of curcumin, ER stress, mitochondrial dysfunction, apoptosis, NSCLC

Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P

Fangxin Liao,1,2,* Wenzhuo He,1,2,* Chang Jiang,1,2 Chenxi Yin,1,2 Guifang Guo,1,2 Xuxian Chen,1,2 Huijuan Qiu,1,2 Yuming Rong,1,2 Bei Zhang,1,2 Dazhi Xu,1,3 Liangping Xia1,21State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 2VIP Region, 3Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China*These authors contributed equally to this workAbstract: Although lipid disequilibrium has been documented for several types of cancer including colorectal cancer (CRC), it remains unknown whether lipid parameters are associated with the outcome of metastatic CRC (mCRC) patients. Here, we retrospectively examined the lipid profiles of 453 mCRC patients and investigated whether any of the lipid parameters correlated with the outcome of mCRC patients. Pretreatment serum lipids, including triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were collected in 453 initially mCRC patients. The LDL-C to HDL-C ratio (LHR) was calculated and divided into the first, second, and third tertiles. Univariate and multivariate analyses were performed to evaluate the impact of lipids on overall survival (OS) and progression-free survival (PFS). Nearly two-fifths of the patients (41.3%) exhibited elevations in LDL-C while most patients (88.3%) showed normal HDL-C levels. Decreased HDL-C (P=0.542) and increased LDL-C (P=0.023) were prognostic factors for poor OS, while triglyceride (P=0.542) and cholesterol (P=0.215) were not. Multivariate analysis revealed that LDL-C (P=0.031) was an independent prognostic factor. Triglyceride, cholesterol, HDL-C, and LDL-C did not correlate with PFS. Among patients with elevations in LDL-C levels, patients in the third tertile of the LHR had a markedly shorter median OS compared to those in the first or second tertile (P=0.012). Thus, increased LDL-C level is an independent prognostic factor for poor prognosis in mCRC patients, and a high LHR predicts poor prognosis for initially mCRC patients with elevations in LDL-C.Keywords: high low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, metastatic colorectal cancer

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).