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Mengyi Shen,1,* Leyu Zhou,1,* Xiaoli Fan,1 Ruiqi Wu,1 Shuyun Liu,2 Qiaoyu Deng,1 Yanyi Zheng,1 Jingping Liu,2 Li Yang1 1Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2NHC Key Laboratory of Transplant Engineering and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Yang; Jingping Liu, Email yangli_hx@scu.edu.cn; liujingping@scu.edu.cnBackground: Autoimmune hepatitis (AIH) is a serious liver disease characterized by immune disorders, particularly effector T-cell overactivation. This study aimed to explore the therapeutic effect and underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment on CD4+ T-cell overactivation and liver injury in AIH.Methods: The metabolic changes of CD4+ T cells were assayed in human AIH and mouse hepatitis models. The liver protective effect of MSC-EVs was evaluated by transaminase levels, liver histopathology and inflammation. The effect of MSC-EVs on the metabolic state of CD4+ T cells was also explored.Results: Enhanced glycolysis (eg, ~1.5-fold increase in hexokinase 2 levels) was detected in the CD4+ T cells of AIH patient samples and mouse hepatitis models, whereas the inhibition of glycolysis decreased CD4+ T-cell activation (~1.8-fold decrease in CD69 levels) and AIH liver injury (~6-fold decrease in aminotransferase levels). MSC-EV treatment reduced CD4+ T-cell activation (~1.5-fold decrease in CD69 levels) and cytokine release (~5-fold decrease in IFN-γ levels) by reducing glycolysis (~3-fold decrease) while enhancing mitochondrial oxidative phosphorylation (~2-fold increase in maximal respiration) in such cells. The degree of liver damage in AIH mice was ameliorated after MSC-EV treatment (~5-fold decrease in aminotransferase levels). MSC-EVs carried abundant mitochondrial proteins and might transfer them to metabolically reprogram CD4+ T cells, whereas disrupting mitochondrial transfer impaired the therapeutic potency of MSC-EVs in activated CD4+ T cells.Conclusion: Disordered glucose metabolism promotes CD4+ T-cell activation and associated inflammatory liver injury in AIH models, which can be reversed by MSC-EV therapy, and this effect is at least partially dependent on EV-mediated mitochondrial protein transfer between cells. This study highlights that MSC-EV therapy may represent a new avenue for treating autoimmune diseases such as AIH.Keywords: autoimmune hepatitis, extracellular vesicles, metabolic reprogramming, mitochondria, inflammation

Xin Huang, Yueying Chen, Fanglu Zhong, Bin Gui, Yugang Hu, Yuxin Guo, Qing Deng, Qing Zhou Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Qing Zhou; Qing Deng, Department of Ultrasound, Renmin Hospital of Wuhan University, 238# Jiefang Road, Wuhan, 430060, People’s Republic of China, Email qingzhou@whu.edu.cn; wudadq@163.comBackground: Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types.Methods: This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs’ impact.Results: The Ce6@aPD-L1 NBs effectively induced reactive oxygen species generation, leading to tumor cells death. In mice, they demonstrated a remarkable enhancement of immune responses compared to control groups. These immune responses encompassed immunogenic cell death induced by sonodynamic therapy and PD-1/PD-L1 blockade, activating dendritic cells maturation and effectively stimulating CD8+T cells.Conclusion: Ce6@aPD-L1 NBs facilitate tumor-targeted delivery, activating anti-tumor effects through direct sonodynamic therapy action and immune system reactivation in the tumor microenvironment. Ce6@aPD-L1 NBs exhibit substantial potential for achieving synergistic anti-cancer effects in PCa.Keywords: Ce6, nanobubbles, ultrasound, sonodynamic therapy, immunotherapy

Dongfang Wang,1,2 Andrew Scherffius,3 Xuan Ouyang,1 Qijian Deng1 1Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2School of Psychology, Centre for Studies of Psychological Applications, Guangdong Key Laboratory of Mental Health and Cognitive Science, Ministry of Education Key Laboratory of Brain Cognition and Educational Science, South China Normal University, Guangzhou, People’s Republic of China; 3Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USACorrespondence: Qijian Deng, Mental Health Institute, The Second Xiangya Hospital of Central South University, Changsha, 410011, People’s Republic of China, Email dengqijian@csu.edu.cnBackground: Depressive symptoms are common among HIV-positive men who have sex with men (MSM). This study aims to explore (1) the relationship between family functioning and depressive symptoms and (2) the mediating roles of stigma and resilience in the relationship among HIV-positive MSM.Methods: We used data from a cross-sectional study of a convenience sample in Hunan Province, China, conducted in 2019. The data analysis included 191 HIV-positive MSM with an average age of 26.98 years. All participants completed self-report questionnaires on demographic variables, family functioning, stigma, resilience, and depressive symptoms.Results: Better family functioning was significantly associated with lower depressive symptoms. Both stigma (Indirect effect = − 0.04, 95% CI, − 0.10 ~ − 0.001) and resilience (Indirect effect = − 0.06, 95% CI, − 0.12 ~ − 0.01) were significant partial mediators in the relationship between family functioning and depressive symptoms. A parallel and chain mediating role of stigma and resilience in the relationship between family functioning and depressive symptoms was also supported (Indirect effect = − 0.03, 95% CI, − 0.08 ~ − 0.01).Conclusion: Improving family functioning is crucial for alleviating depressive symptoms among HIV-positive MSM in China. Depression assessment and reduction should be an integral part of prevention and treatment programs targeting stigma and resilience.Keywords: HIV, men who have sex with men, family functioning, stigma, resilience, depressive symptoms

Yuping Ding,1,2 Guiqiang Wang,3,4 Quanjun Deng,1,2 Mei Yang,1,2 Jinghua Li,5 Zuoyu Wang,1,2 Haiyan Niu,1,2 Shihai Xia1,2 1Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China; 2Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of China; 3Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Infectious Diseases, Peking University International Hospital, Beijing, People’s Republic of China; 5Department of Endocrinology and Hematology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of ChinaCorrespondence: Shihai Xia, Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, 220, Chenglin Road, Dongli, Tianjin, 300162, People’s Republic of China, Email xshhcx@sina.comBackground: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are closely related conditions.Aim: This study investigated a group of individuals with NAFLD to evaluate if liver fibrosis, identified by FibroScan, correlated with T2DM.Methods: 154 NAFLD patients obtained FibroScan, liver ultrasonography (US), and a thorough assessment of clinical implications and chemical biomarkers.Results: In comparison to the NAFLD without T2DM group, the hemoglobin A1c(HBA1c)(mmol/mol%), homeostasis model of assessment for insulin resistance index (HOMA-IR), gamma-glutamyl transferase (GGT), fibrosis indices, and liver stiffness measurement (LSM) values were all considerably higher in the NAFLD with T2DM group. Patients with NAFLD and T2DM had considerably lower serum uric acid(SUA) levels than those with NAFLD alone.Those with severe fibrosis (79.3%, 23/29) in the NAFLD group showed a greater frequency of T2DM than those with mild fibrosis (45.6%, 21/46) or no fibrosis (27.85%, 22/79) (P=0.000). LSM value and elements of the metabolic syndrome (MetS) were independent risk factors for incident T2DM among NAFLD patients (OR=1.466, 95% CI [1.139-1.888], P=0.003; and OR=0.273, 95% CI [0.081-0.916], P=0.036).Conclusion: FibroScan can identify significant fibrosis, which is independently linked to a higher prevalence of T2DM. As a result, it is crucial to make use of this technology to predict T2DM in NAFLD patients.Keywords: liver stiffness measurement, NAFLD, T2DM, risk factors, early warning

Jing Yang,1,2,* Jinlu Shang,1,2,* Liuxuan Yang,1,2,* Daiqing Wei,3 Xia Wang,1 Qinmin Deng,2 Zhirong Zhong,4 Yun Ye,1 Meiling Zhou1 1Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Clinical Pharmacy, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Meiling Zhou, Email meilzhou@163.comAbstract: Honokiol (HNK) is a small-molecule polyphenol that has garnered considerable attention due to its diverse pharmacological properties, including antitumor, anti-inflammatory, anti-bacterial, and anti-obesity effects. However, its clinical application is restricted by challenges such as low solubility, poor bioavailability, and rapid metabolism. To overcome these limitations, researchers have developed a variety of nano-formulations for HNK delivery. These nano-formulations offer advantages such as enhanced solubility, improved bioavailability, extended circulation time, and targeted drug delivery. However, existing reviews of HNK primarily focus on its clinical and pharmacological features, leaving a gap in the comprehensive evaluation of HNK delivery systems based on nanotechnology. This paper aims to bridge this gap by comprehensively reviewing different types of nanomaterials used for HNK delivery over the past 15 years. These materials encompass vesicle delivery systems, nanoparticles, polymer micelles, nanogels, and various other nanocarriers. The paper details various HNK nano-delivery strategies and summarizes their latest applications, development prospects, and future challenges. To compile this review, we conducted an extensive search using keywords such as “honokiol”, “nanotechnology”, and “drug delivery system” on reputable databases, including PubMed, Scopus, and Web of Science, covering the period from 2008 to 2023. Through this search, we identified and selected approximately 90 articles that met our specific criteria. Keywords: honokiol, nanotechnology, drug delivery, targeting, antitumor, bioavailability

Yuping Ding,1,2 Quanjun Deng,1,2 Mei Yang,1,2 Haiyan Niu,1,2 Zuoyu Wang,1,2 Shihai Xia1,2 1Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force, Tianjin, 300162, People’s Republic of China; 2Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, Tianjin, 300162, People’s Republic of ChinaCorrespondence: Shihai Xia, Department of Gastroenterology and Hepatology, Characteristic Medical Center of the Chinese People’s Armed Police Force; Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis & Treatment, 220, Chenglin Road, Dongli, Tianjin, 300162, People’s Republic of China, Email xshhcx@sina.comAbstract: Obesity,and metabolic dysfunction-associated fatty liver disease (MAFLD) have reached epidemic proportions globally. Obesity and MAFLD frequently coexist and act synergistically to increase the risk of adverse clinical outcomes (both hepatic and extrahepatic). Type 2 diabetes mellitus (T2DM) is the most important risk factor for rapid progression of steatohepatitis and advanced fibrosis. Conversely, the later stages of MAFLD are associated with an increased risk of T2DM incident. According to the proposed criteria, MAFLD is diagnosed in patients with liver steatosis and in at least one in three: overweight or obese, T2DM, or signs of metabolic dysregulation if they are of normal weight. However, the clinical classification and correlation between obesity and MAFLD is more complex than expected. In addition, treatment for obesity and MAFLD are associated with a reduced risk of T2DM, suggesting that liver-based treatments could reduce the risk of developing T2DM. This review describes the clinical classification of obesity and MAFLD, discusses the clinical features of various types of obesity and MAFLD, emphasizes the role of visceral obesity and insulin resistance (IR) in the development of MAFLD,and summarizes the existing treatments for obesity and MAFLD that reduce the risk of developing T2DM.Keywords: obesity, metabolic dysfunction-associated fatty liver disease, phenotypes, type 2 diabetes mellitus, treatment, weight loss

Yingying Lin,1,&ast; Xiaofan Lai,1,&ast; Tianxiang Lei,2,&ast; Yuan Qiu,3 Qiwen Deng,1 Qi Liu,1 Zhongxing Wang,1 Wenqi Huang1 1Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenqi Huang; Zhongxing Wang, Email huangwq@mail.sysu.edu.cn; wzhxing@mail.sysu.edu.cnBackground: Idiopathic pulmonary fibrosis (IPF) is a disease with unclear etiology and a poor prognosis. Although the involvement of neutrophils in IPF pathogenesis has been suggested, the exact nature of this relationship remains unclear.Methods: We analyzed data from the Gene Expression Omnibus (GEO) using immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), and consensus cluster analysis. Neutrophil-related genes and hub genes related to neutrophils were identified and differentially expressed between IPF patients and healthy controls. We also validated the expression differences of hub genes in a bleomycin-induced mice model.Results: Immune infiltration analysis revealed a significantly decreased percentage of neutrophils in the lung tissue of IPF patients compared with healthy controls (P< 0.001) in both the train and validation sets. Neutrophil-related genes in IPF were identified by WGCNA, and functional enrichment analysis showed that these genes were mainly involved in the cytokine-cytokine receptor interaction pathway and correlated with lung disease, consistent with DEGs between IPF and healthy controls. Eight hub genes related to neutrophils were identified, including MMP16, ARG1, IL1R2, PROK2, MS4A2, PIR, and ZNF436. Consensus cluster analysis revealed a low neutrophil-infiltrating cluster that was correlated with IPF (P< 0.001), and a principal component analysis-generated score could distinguish IPF patients from healthy controls, with an area under the curve of 0.930 in the train set and 0.768 in the validation set. We also constructed a diagnostic model using hub genes related to neutrophils, which showed a reliable diagnostic value with an area under the curve of 0.955 in the train set and 0.995 in the validation set.Conclusion: Our findings provide evidence of a low neutrophil-infiltrating characteristic in the IPF microenvironment and identify hub genes related to neutrophils that may serve as diagnostic biomarkers for the disease.Keywords: neutrophils, idiopathic pulmonary fibrosis, immune infiltration analysis, weighted gene co-expression network analysis, consensus cluster analysis, diagnostic model, biomarkers

Xinwei Zhou,1,&ast; Ke Lin,2,&ast; Liangmin Fu,1,&ast; Fei Liu,3,&ast; Hansen Lin,1 Yuhang Chen,1 Bowen Zhuang,2 Hui Liang,4 Qiong Deng,4 Zhu Wang,4 Wei Chen,1 Junhang Luo,1,5 Jiazheng Cao,6 Pengju Li1 1Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Urology, Affiliated Longhua People’s Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6Department of Urology, Jiangmen Central Hospital, Jiangmen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengju Li, Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan Road II, Guangzhou, 510080, People’s Republic of China, Tel +86-20-87618227, Email lipj25@mail.sysu.edu.cn Jiazheng Cao, Department of Urology, Jiangmen Central Hospital, Haibang Street 23, Jiangmen, 529030, People’s Republic of China, Tel +86-750-3165500, Email spotatos@163.comBackground: Triggering receptors expressed by myeloid cells-1 (TREM1) is a receptor belonging to the immunoglobulin superfamily and plays an important role in pro-inflammation in acute and chronic inflammatory disorders. However, the understanding of the immunomodulatory roles of TREM1 in the tumor microenvironment remains incomplete.Methods: The expression patterns of TREM1 mRNA in tumors and adjacent normal tissues were compared by analyzing data obtained from the Genotype-Tissue Expression and The Cancer Genome Atlas datasets. Survival analysis was performed to determine the prognostic value of TREM1. Functional enrichment analysis was applied to decipher the discrepancy in biological processes between high- and low-TREM1 groups across various cancers. The correlation between TREM1 and immune cell infiltration determined by using multiple algorithms was evaluated with the Pearson method. Four independent immunotherapy cohorts were adopted to validate the role of TREM1 as a biomarker.Results: TREM1 was elevated in most cancers as verified with clinical samples. Overexpression of TREM1 was linked with undesirable prognosis in patients. Further analysis revealed that TREM1 was positively correlated with immune response, pro-tumor pathways, and myeloid cell infiltration, while being negatively correlated with CD8+ T cell (including infiltration level and biological processes). Concordantly, tumors with high TREM1 levels were more resistant to immunotherapy. Through connective map analysis, therapeutically potential compounds like tozasertib and TPCA-1 were identified, which can be used synergistically with immunotherapy to improve the poor prognosis of patients with high TREM1 levels.Conclusion: Through a systematic and comprehensive pan-cancer analysis, we demonstrated that overexpression of TREM1 in tumors correlated closely with unfavorable outcome, infiltration of immune-suppressive cells, and immune regulation, which highlights its potential use as a tumor prognostic biomarker and a novel target for immunotherapy.Keywords: triggering receptors expressed by myeloid cells-1, pan-cancer, prognostic biomarker, tumor microenvironment, clear cell renal cell carcinoma, immunotherapy

Xiaofeng Chen,1,&ast; Qiyan Deng,1,&ast; Xiaolong Li,1,&ast; Li Xian,2,&ast; Dehai Xian,3 Jianqiao Zhong1 1Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Department of Emergency, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 3Department of Anatomy, Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianqiao Zhong, Email zjq7632@hotmail.com; Dehai Xian, Email xdh969@163.comAbstract: Psoriasis, a chronic immune-mediated inflammatory skin disease, influences approximately 2– 3% of the world’s population. At present, the etiology of psoriasis remains unclear and there is still no causal treatment available. Recent studies indicate that oxidative stress (OS) and T cells dysregulation may participate in the pathogenesis of psoriasis, among which M1-dominant macrophage polarization is a crucial contributor. Macrophages mainly polarize into two different subsets, ie, classically activated macrophage (M1) and alternatively activated macrophage (M2). M1 polarization tends to exacerbate psoriasis via producing substantial reactive oxygen species (ROS) and inflammatory mediators, to encourage OS invasion and T cells dysregulation. Thus, targeting M1 polarization can be a possible therapeutic alternative for psoriasis. Loganin, belonging to iridoid glycosides, is a pharmaceutically active ingredient originated from Cornus officinalis, exerting multiple biological activities, eg, immunomodulation, antioxidation, anti-inflammation, etc. More importantly, it could effectively suppress M1 polarization, thereby arresting OS aggression and T cells’ dysregulation. Numerous studies have confirmed that loganin is quite reliable for diseases treatment via suppressing M1 polarization. Nevertheless, reports about loganin treating psoriasis have seldom appeared so far. Accordingly, we hold a hypothesis that loganin would availably manage psoriasis through preventing M1 polarization. Data from previous studies guarantee the potential of loganin in control of psoriasis.Keywords: loganin, psoriasis, macrophage polarization, oxidative stress, T cells

Zhihong Lu,1,&ast; Ailin Luo,2,&ast; Su Min,3,&ast; Hailong Dong,1 Qiuju Xiong,3 Xinhua Li,2 Qingzhu Deng,2 Tingting Liu,1 Xue Yang,1 Chen Li,4 Qingchuan Zhao,5 Lize Xiong1,6 1Department of Anaesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Department of Anaesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Anaesthesiology, First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Medical Statistics, Fourth Military Medical University, Xi’an, People’s Republic of China; 5Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, People’s Republic of China; 6Translational Research Institute of Brain and Brain-Like Intelligence and Department of Anesthesiology, Shanghai Fourth People’s Hospital Affiliated to Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Lu; Lize Xiong, Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Changle West Road127, Xi’an, Shaanxi, 710032, People’s Republic of China, Tel +86-29-84775337 ; Tel +86-29-84772126, Email deerlu23@163.com; xlzmzk@163.comPurpose: The aim of this study was to evaluate the efficacy of transcutaneous electrical acupoint stimulation (TEAS) in improving bowel function and thus shortening hospital stay after laparoscopic colon surgery within the ERAS pathway.Patients and Methods: From November 2016 to March 2018, 100 patients who underwent elective colon surgery were enrolled and 94 finished study (n = 47 for each) in three university hospitals. Patients in the TEAS group received TEAS 30 min before surgery and once a day for 3 days after surgery, while those in the Control Group received no stimulation. Primary outcome was the time to discharge.Results: Compared with standardized postoperative care, TEAS resulted in a shorter time to first flatus (P=0.03) and time to first defecation (P=0.03), as well as a reduction in the length of hospital stay (P=0.02). Median patient-controlled analgesia (PCA) deliveries and PCA attempts at 24h, 48h and 72h after surgery were less in the TEAS group (P< 0.01). No evidence of significant advantages in postoperative pain intensity, nausea, vomiting, sleeping quality and expenses was found in the TEAS group.Conclusion: Perioperative TEAS further shortens the time to meet discharge criteria after laparoscopic colon surgery in patients under ERAS strategy.Keywords: transcutaneous electrical acupoint stimulation, colon surgery, laparoscopy, ERAS

Zhuoxi Wu,1,&ast; Mi Yang,1,&ast; Peng Zhao,1,2 Feng Zou,1 Jing Peng,1 Qiangting Deng,3 Guangyou Duan,4,&ast; Hong Li1,&ast; 1Department of Anesthesiology, Second Affiliated Hospital of Army Medical University, People’s Liberation Army of China, Chongqing, People’s Republic of China; 2Department of Anesthesiology, Chinese People’s Liberation Army of China (PLA) No. 964 Hospital, Changchun, People’s Republic of China; 3Editorial Office of Journal of Third Military Medical University, Army Medical University, People’s Liberation Army of China, Chongqing, People’s Republic of China; 4Department of Anesthesiology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Li; Guangyou Duan, Email lh78553@163.com; dgy1986anesthesia@126.comBackground: Our previous study found that a long-term diet incorporating spicy foods can reduce the human basal pain threshold. Capsaicin is the pungent ingredient in chili peppers. Transient receptor potential vanilloid type1 is the capsaicin receptor expressed in the oral cavity and is the primary sensory neuron of the “pain” pathway. Few studies have examined the association between long-term spicy diet and chronic postsurgical pain (CPSP). Women who underwent elective cesarean section (eCS) have consistent characteristics of CPSP. This study aimed to investigate the relationship between a long-term spicy diet and the incidence of CPSP after eCS.Methods: Participants were divided into a low frequency group (LF, numerical rating scale (NRS)< 5) for spicy food consumption and a high frequency group (HF, NRS≥ 5) by receiver operator characteristic analysis. The primary outcome was the incidence of CPSP three months after eCS. Propensity score matching (PSM) analysis was performed between the two frequency groups. Stepwise logistic regression analysis was then performed.Results: Of the 1029 enrolled patients, data from 982 were analyzed 3 months after eCS. After PSM, the incidence of CPSP in the HF group (30.1% [108/359]) was higher than that in the LF group (19.8% [71/359]; P = 0.001). Compared with the LF group, the risk of CPSP in the HF group increased 1.61 times by 3 months (95% CI 1.18– 2.20, P = 0.003). PSM results found that 1 year, the incidence of CPSP in the HF group (15.2% [56/369]) was higher than that in the LF group (8.1% [30/369], P = 0.003).Conclusion: With an NRS≥ 5 as a boundary, women who consumed spicy food ≥ 2 days/week were more likely to have CPSP than those who consumed spicy food < 2 days/week.Keywords: long-term spicy diet, chronic postsurgical pain, capsaicin, TRPV1, cesarean section

Jingwen Lyu,1,2,&ast; Qianyun Deng,2,&ast; Rongqing Li,3 Benshun Tian,1,2 Yunhu Zhao,2 Xuejiao Hu,2 Maohua Zhou,2 Bing Gu2 1Xuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510000, People’s Republic of China; 3Jiangsu Province Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maohua Zhou; Bing Gu, Laboratory Medicine, Guangdong Provincial People’s Hospital, 106 Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong, 510000, People’s Republic of China, Tel +86-20-83827812-62462, Email zhoumaohua@gdph.org.cn; gb20031129@163.comBackground: Pneumonia produced by coinfection with Pneumocystis jirovecii (PJ) and cytomegalovirus (CMV) in infants and young children without timely diagnosis and treatment is often fatal due to the limitations of traditional tests. More accurate and rapid diagnostic methods for multiple infections are urgently needed.Case Presentation: Here, we report a case of a 2-month-old boy with pneumonia caused by Pneumocystis jirovecii (PJ) and cytomegalovirus (CMV) without HIV infection. Chest computed tomography (CT) showed massive exudative consolidation in both lungs. Microscopic examination of stained sputum and smear specimens and bacterial and fungal culture tests were all negative, and CMV nucleic acid and antibody tests were positive. After a period of antiviral and anti-infective therapy, pulmonary inflammation was not relieved. Subsequently, sputum and venous blood samples were analysed by metagenomic next-generation sequencing (mNGS), and the sequences of PJ and CMV were acquired. The patient was finally diagnosed with pneumonia caused by PJ and CMV coinfection. Anti-fungal combined with anti-viral therapy was given immediately. mNGS re-examination of bronchoalveolar lavage fluid (BALF) also revealed the same primary pathogen. Therapy was stopped due to the request of the patient’s guardian. Hence, the child was discharged from the hospital and eventually died.Conclusion: This case emphasizes the combined use of mNGS and traditional tests in the clinical diagnosis of mixed lung infections in infants without HIV infection. mNGS is a new adjunctive diagnostic method that can rapidly discriminate multiple causes of pneumonia.Keywords: metagenomic next-generation sequencing, Pneumocystis jirovecii, cytomegalovirus, pneumonitis, HIV-negative

Qingwen Deng,1,2 Wenbin Liu1 1Department of Health Management, School of Public Health, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Wenbin Liu, Tel +86 13799983766, Email wenbinliu126@126.comBackground: Liver cancer is a globally acknowledged threat to public health, and there is a critical and urgent need to determine factors associated with the use of liver cancer screening and to further promote its use.Purpose: To examine whether the extended theory of planned behavior (TPB) incorporating social norms predicts physicians’ intentions to use liver cancer screening and to identify the associated factors quantitatively, using contrast-enhanced ultrasound (CEUS) as an example.Methods: A research framework was established by adding social norms to the TPB, based on which the questionnaire for this study was developed. Through multistage random sampling, a cross-sectional questionnaire survey was conducted among 292 physicians in Fujian and Jiangxi provinces. Due to the multicollinearity problem of the data, ridge regression was applied to determine the influencing factors of physicians’ intentions to use CEUS.Results: Most participants (87.30%) reported that they were willing to use liver cancer screening in their clinical practice. The scores of TPB variables were generally higher than those of social norms variables. Ridge regression results indicated that the proposed model was explanatory, which has accounted for 73.5% of the total variance in physicians’ intentions. Analyses also illustrated the significant role of TPB variables (attitude and perceived behavioral control) and social norms variables (personal norms, organizational norms, and industrial norms) on physicians’ intentions to use CEUS.Conclusion: The study extended the TPB by including the concepts of social norms, which is not only conducive to expanding the knowledge of factors associated with physicians’ intentions to use liver cancer screening, but also provides implications for developing strategies to promote the use of certain health services or products, such as playing the role of core members, holding panel meetings, and establishing information push systems.Keywords: social norms, intention, liver cancer, screening, physicians

Juan Pan,1,2,&ast; Rui Tong,1,&ast; Qing Deng,3 Yanni Tian,1 Ning Wang,1 Yanqi Peng,1 Sijia Fei,1 Wei Zhang,4 Jiaqi Cui,1 Chaoying Guo,1 Juanchuan Yao,1 Cui Wei,1 Jing Xu1 1Department of Geriatric Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of China; 2Department of Endocrinology, Xianyang Central Hospital, Xianyang, 712000, Shaanxi, People’s Republic of China; 3Department of Endocrinology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, 712000, Shaanxi, People’s Republic of China; 4Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cui Wei; Jing XuDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University, #277 West Yanta Road, Xi’an, 710061, Shaanxi, People’s Republic of China, Tel +86 18991232462; Tel +86 18991232462Email doctorweiwei.cui@126.com; 254309205@qq.comBackground: SOCS2 is downregulated in diabetes, which might be related to diabetes. We explored the effect of SOCS2 polymorphisms on the development of type 2 diabetes mellitus (T2DM) and diabetic complications.Methods: The subjects consisted of 500 patients with T2DM and 501 healthy controls. Five variants in SOCS2 were genotyped by Agena MassARRAY system. RT-qPCR profiling was performed to detect the expression of SOCS2 mRNA. Logistic regression analysis was utilized to calculate odds ratio (OR) and 95% confidence intervals (95% CIs).Results: Rs3825199 (OR = 1.44, p = 0.007), rs11107116 (OR = 1.39, p = 0.014) and rs10492321 (OR = 1.48, p = 0.004) had an increased T2DM risk of T2DM. Moreover, the contribution of SOCS2 polymorphisms to T2DM risk was associated with age, gender, smoking, drinking, and BMI. SOCS2 variants also had a reduced risk for T2DM patients with diabetic nephropathy, diabetic retinopathy and coronary heart disease. SOCS2 rs10492321 was the best single locus model. SOCS2 mRNA was downregulated in patients with T2DM compared to healthy controls (p = 0.029).Conclusion: This study firstly reported that rs3825199, rs11107116 and rs10492321 in SOCS2 conferred to an increased risk for the occurrence of T2DM in the Chinese Han population. Moreover, SOCS2 mRNA was downregulated in patients with T2DM, suggesting that SOCS2 might have an important role in the occurrence of T2DM.Keywords: type 2 diabetes mellitus, SOCS2 variants, diabetic complications, life style

Haopeng Luan, Qiang Deng, Weibin Sheng, Mardan Mamat, Hailong Guo, Huaqiang Li Department of Spine Surgery, XinJiang Medical University Affiliated First Hosptial, Urumqi, XinJiang, People’s Republic of ChinaCorrespondence: Qiang DengDepartment of Spine Surgery, Xinjiang Medical University Affiliated First Hospital, Urumqi, XinJiang, People’s Republic of ChinaTel +86 13325636562Email dengqiang_abc@163.comObjective: The present study aimed to investigate the surgical efficacy of staged posterior–anterior combined surgery for the treatment of cervicothoracic segmental tuberculosis (TB) with kyphosis in pediatric patients.Methods: The clinical data of 15 pediatric patients admitted to our hospital from January 2010 to December 2017 who underwent staged posterior–anterior combined surgery for cervicothoracic segmental TB with kyphosis were collected. A posterior median incision was made for patients after general anesthesia. Autologous bone particles or allogeneic bone particles were taken, trimmed, and placed in the articular eminence of the diseased vertebral body. Fifteen pediatric patients underwent second-stage lesion removal using the anterior approach. The left sternocleidomastoid muscle was selected as the medial oblique incision approach. The abscess and caseous necrotic material were removed and sent for pathological examination. The sagittal and coronal parameters (including the local Cobb angle, the sagittal vertical axis [SVA], and the coronal balance distance [CBD]) were measured at three time points: preoperatively, postoperatively, and at the final follow-up. The American Spinal Injury Association’s spinal-cord injury classification, the Japanese Orthopaedic Association’s (JOA) cervical spine function score, the neck disability index (NDI), and the visual analogue score (VAS) for cervicothoracic segment pain were adopted for the assessment of functional improvement and quality of life.Results: All 15 pediatric patients completed the surgery successfully, with an operation duration of 3.56 ± 0.68 h, an intraoperative hemorrhage of 289.7 ± 84.3 mL, an average fixation of 7.3 ± 1.8 segments, and a follow-up duration of 28.1 ± 9.7 months. The preoperative and postoperative sagittal local Cobb angle was 67.06 ± 17.54° vs 19.48 ± 2.32° (P < 0.01), the SVA was 35.19 ± 10.69 mm vs 7.67 ± 1.40 mm (P < 0.01), and CBD was 22.58 ± 7.59 mm vs 8.99 ± 1.25 mm (P < 0.01). The levels of the postoperative erythrocyte sedimentation rate and C-reactive protein were significantly lower in all patients. The preoperative and postoperative JOA scores were 8.93 ± 3.51 and 14.67 ± 1.34, respectively, the preoperative and postoperative VAS was 7.40 ± 1.35 and 2.67 ± 0.62, respectively, and the preoperative and postoperative NDI was 32.67 ± 4.83 and 13.73 ± 2.08, respectively. There were statistically significant differences in the above indicators before and after surgery (P < 0.05).Conclusion: In the surgical treatment of cervicothoracic TB with kyphosis in pediatric patients, staged posterior–anterior combined surgery significantly corrects deformity, achieves the safe and effective neurological decompression of the spinal cord, and obtains good neurological recovery and bone-graft fusion according to the extent of the involved segments of kyphosis, the characteristics of the lesion, and the degree of neurospinal injury.Keywords: spinal tuberculosis, cervicothoracic segment, posterior and anterior combined surgery, pediatric patient, therapeutic effect

Wenwei Nong,1,* Liping Ma,2,* Biyang Lan,1 Ning Liu,1 Hongzhi Yang,1 Xiaoxia Lao,2 Qiaomei Deng,2 Zhihu Huang2 1Department of General Surgery, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Clinical Laboratory, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhihu HuangAffiliated Minzu Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaEmail hoftiger@126.comBackground: Hepatitis B virus infection co-occurs in 33% of individuals with hepatocellular carcinoma worldwide. However, the molecular link between hepatitis B virus and hepatocellular carcinoma is unknown. Thus, we aimed to elucidate molecular linkages underlying pathogenesis through in-depth data mining analysis.Materials and Methods: Differentially expressed genes were identified from patients with chronic hepatitis B virus infection, hepatocellular carcinoma, or both. Gene set enrichment analysis revealed signaling pathways involving differentially expressed genes. Protein-protein interaction networks, protein crosstalk, and enrichment were analyzed to determine whether differentially expressed gene products might serve as a bridge from hepatitis B virus infection to hepatocellular carcinoma pathogenesis. Prognostic potential and transcriptional and post-transcriptional regulators of bridge genes were also examined.Results: We identified vital bridge factors in hepatitis B virus infection-associated hepatocellular carcinoma. Differentially expressed genes were clustered into modules based on relative protein function. Signaling pathways associated with cancer, inflammation, immune system, and microenvironment showed significant crosstalk between modules. Thirty-two genes were dysregulated in hepatitis B virus infection-mediated hepatocellular carcinoma. CPEB3, RAB26, SLCO1B1, ST3GAL6 and XK had higher connectivity in the modular network, suggesting significant associations with survival. CDC20 and NUP107 were identified as driver genes as well as markers of poor prognosis.Conclusion: Our results suggest that the sustained inflammatory environment created by hepatitis B virus infection is a risk factor for hepatocellular carcinoma. The identification of hepatitis B virus infection-related hepatocellular carcinoma bridge genes provides testable hypotheses about the pathogenesis of hepatocellular carcinoma.Keywords: signaling pathways, molecular processes, protein-protein interactions, chronic hepatitis B virus infection, hepatocellular carcinoma

Hui Zhang,1,* Yi Zhao,2,* Ping Zou,3 Shuanghong Lin,2 Shaoyu Mu,4 Qiansu Deng,5 Chunxue Du,1 Guanglan Zhou,1 Jiang Wu,2 Lu Gan2 1Department of Cardiology, Guizhou Provincial People’s Hospital, Guiyang, 550002, Guizhou, People’s Republic of China; 2Department of Nursing, Hubei NO.3 People’s Hospital of Jianghan University, Wuhan, People’s Republic of China; 3Department of Scholar Practitioner Program, School of Nursing, Nipissing University, Toronto, M6J 3S3, Ontario, Canada; 4Department of Nursing, Nursing College of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 5Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuanghong LinDepartment of Nursing, Hubei NO.3 People’s Hospital of Jianghan University, Wuhan, People’s Republic of ChinaTel +8618771059373Email 18771059373@163.comBackground: Little is known about the associated factors with organizational citizenship behavior among Chinese nurses combating COVID-19. The aim of the present study was to investigate the relationships between autonomy, optimism, role conflict, work engagement, and organizational citizenship behavior based on moderated mediation models among Chinese nurses combating COVID-19.Methods: This cross-sectional study was performed on a sample of 368 nurses supporting the COVID-19 epidemic in Wuhan Leishenshan Hospital, China. According to the Job Demands-Resources model, two moderated mediation models were tested, in which autonomy/optimism was associated with organizational citizenship behavior through work engagement, when role conflict served as a moderator.Results: This current study found the mediating effect of work engagement and the moderating effect of role conflict on the relationship between autonomy/optimism and organizational citizenship behavior among nurses. Of note, nurses working in the COVID-19 epidemic viewed role conflict as challenge job demands rather than hindrance job demands.Conclusion: Based on the findings, organizational citizenship behavior can be affected by work engagement and role conflict. Nursing management is suggested to put emphasis on work engagement and role conflict among nurses supporting the COVID-19 epidemic.Keywords: the job demands-resources model, autonomy, optimism, organizational citizenship behavior, nurses, COVID-19

Peng-Chao Zhang, Qiang Deng, Wei-Bin Sheng, Hai-Long Guo, Mardan Mamat, Yun-Xiao Luo, Shu-Tao Gao Department of Spine Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of ChinaCorrespondence: Qiang DengDepartment of Spine Surgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137 of Liyushan South Road, Xinshi District, Urumqi, 830054, People’s Republic of ChinaTel +86 13325636562Email dengqiang_abc@163.comObjective: This study aimed to compare the changes in sagittal parameters and the efficacy of pedicle subtraction osteotomy (PSO) in patients with ankylosing spondylitis (AS) and kyphosis under different lumbar sagittal morphologies and to explore the effect of sagittal morphology on the selection of PSO levels.Methods: A total of 24 patients with AS and thoracolumbar kyphosis (TK) who were admitted to the First Affiliated Hospital of Xinjiang Medical University between 2008 and 2019 were enrolled in this study. They were divided into two groups: a lumbar lordosis group (n = 14) and a lumbar kyphosis group (n = 10). Changes in sagittal parameters, lumbar Japanese Orthopaedic Association (JOA) scores, and visual analog scale (VAS) scores for lumbar pain before and after operation were compared between the two groups to evaluate postoperative efficacy.Results: The preoperative lumbar lordosis (LL) was − 29.29 ± 5.40 (lordosis) and 13.50 ± 3.65 (kyphosis) (P < 0.01), and the preoperative sagittal vertical axis (SVA) was 171.35 ± 25.46 (lordosis) and 223.58 ± 21.87 (kyphosis) (P < 0.01). Preoperative global kyphosis (GK) was 75.71 ± 5.26 (lordosis) and 86.30 ± 10.32 (kyphosis) (P < 0.05). All patients in the lordosis group underwent PSO surgery at the twelfth thoracic vertebra (T12) or the first lumbar spinal vertebra (L1), while all patients in the kyphosis group underwent the surgery at the second or third lumbar spinal vertebra (L2 or L3). The differences in postoperative GK, LL, and SVA between the two groups were not significant (P > 0.05). The JOA scores of the two groups increased from 13.00 ± 0.83 (lordosis) and 11.30 ± 0.93 (kyphosis) before surgery to 21.00 ± 0.67 and 19.70 ± 0.60 after surgery (P < 0.05).Conclusion: Preoperative lumbar sagittal morphology needs to be considered when selecting the optimal osteotomy plane. An osteotomy can achieve the greatest success in patients with lumbar kyphosis at L2/L3; for patients with lumbar lordosis, it can achieve satisfactory outcomes at T12/L1.Keywords: ankylosing spondylitis, kyphosis, sagittal parameters, PSO, osteotomy

Qingwen Deng, Junhong Lu, Zhichao Zeng, Yuhang Zheng, Wenbin Liu Department of Health Management, School of Public Health, Fujian Medical University, Fuzhou 350122, People’s Republic of ChinaCorrespondence: Wenbin LiuDepartment of Health Management, School of Public Health, Fujian Medical University, Room 108 in the Building for School of Public Health, No. 1 Xuefubei Road, Minhou District, Fuzhou 350122, People’s Republic of ChinaTel + 86 13799983766Email wenbinliu126@126.comBackground: Limited diffusion of health technology has greatly halted the improvement of resource integration and healthcare outcomes. The importance of understanding the dynamics of health technology diffusion is increasingly highlighted. However, the dynamic mechanism of health technology diffusion in the context of the integrated care system (ICS) remained largely unknown.Purpose: To develop and validate the scale on Dynamics of Health Technology Diffusion in Integrated Care System (DHTDICS) for providing an instrument to investigate the health technology diffusion in the ICS in China, by taking the Des-gamma-Carboxy Prothrombin (DCP) test as an example.Methods: Based on previous classical theories such as the theory of planned behavior (TPB), technology acceptance model (TAM), and technology-organization-environment framework (TOE), the scale with 34 items was initially developed. It was tested in a cross-sectional questionnaire survey including 246 participants from February to August 2019 in China. Cronbach’s alpha, corrected item-total correlation, and factor loadings were used to assess reliability. Exploratory factor analysis and confirmatory factor analysis were applied to evaluate the validity by assessing factor structures and correlations.Results: Reliability analysis revealed excellent internal consistency. Acceptable validity was confirmed through tests of convergent validity and discriminant validity. Regarding the domains that DHTDICS contributes, the results highlighted 4 domains: personal beliefs (including dimensions of attitudes, subjective norms and perceived behavioral control), technical drivers (including dimensions of ease of use and price rationality), organizational readiness (including dimensions of organizational culture, technology absorptive willingness and technology sharing willingness), and external environment (dimension of industry competition pressure).Conclusion: The findings confirmed the reliability and validity of the scale on DHTDICS. The scale will be not only a scientific tool in determining the dynamics of health technology diffusion in the ICS, but also a helpful reference for developing future interventions to promote health technology diffusion.Keywords: health technology diffusion, dynamics, scale development, integrated care system, validity, reliability, China

Qiuyang Deng,1,* Jinyong Zhang,2,* Min Zhang,1 Zhou Liu,3 Yuxin Zhong,1 Shiyi Liu,1 Ruiqin Cui,1 Yun Shi,2 Hao Zeng,2 Xiyao Yang,3 Chuchu Lin,4 Yutian Luo,5 Huaisheng Chen,5 Weiyuan Wu,6 Jinsong Wu,6 Tianle Zhang,7 Yuemei Lu,6 Xueyan Liu,5 Quanming Zou,2 Wei Huang1 1Bacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 2National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, People’s Republic of China; 3Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Nosocomial Infection Control, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 5Intensive Care Unit, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 6Department of Clinical Microbiology, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of China; 7Guangdong Medical University, Dongguan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HuangBacteriology & Antibacterial Resistance Surveillance Laboratory, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong 518020, People’s Republic of ChinaTel +86 7522942513Fax +86 7522942514Email whuang_sz@163.comQuanming Zou National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical PharmacyCollege of Pharmacy, Army Medical University, Chongqing 400038, People’s Republic of ChinaTel/Fax +86 2368752316Email qmzou2007@163.comObjective: We aimed to establish a tool for rapid identification of KL49 Acinetobacter baumannii.Methods: Based on the capsular polysaccharide (CPS) synthesis genes database, we investigated the distribution of K locus type 49 (KL49) genes in other KL types and established a rapid identification method for KL49. We collected 61 clinical carbapenem-resistant A. baumannii (CRAB) strains, identified KL49 by gtr100 detection, and used whole genome sequencing (WGS) for verification. A mouse pneumonia model was used to confirm the hypervirulence phenotype. We tested the presence of gtr100 gene in 165 CRAB strains from three provinces in China and evaluated the correlation of gtr100 carrying CRAB infection with mortality.Results: The gtr100 gene is the CPS synthesis gene found only in KL49. We screened out nine WGS-validated KL49 strains from 61 CRAB clinical strains using polymerase chain reaction (PCR) to detect the gtr100 gene. The survival rates of KL49 strains were significantly lower than nonKL49 strains in a mouse pneumonia model. The survival rates of LAC-4 gtr100 knockout strain decreased significantly. Analysis of phylogenetics showed the worldwide spread of KL49 A. baumannii. Infection of gtr100 carrying CRAB is an independent risk for mortality (OR, 10.76; 95%CI: 3.08– 37.55; p< 0.001).Conclusion: The hypervirulence phenotype of KL49 CRAB and the association with mortality highlight the urgent need for implementing control measures. The rapid identification assay has the potential to facilitate early medical intervention and worldwide surveillance.Keywords: Acinetobacter baumannii, hypervirulent, K locus, Kaptive, mortality

Qing Deng1,2 ,* Shu-ping Zhang1,2 ,* Yu-Xuan Deng,1,2 Fang-fen Liu,1,2 Wei Shi,1– 3 Hong-fu Xie,1– 4 Yi Xiao,1,2 Ying-Xue Huang,1,2 Ji Li1– 4 1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China; 3Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan, People’s Republic of China; 4Key Laboratory of Molecular Radiation Oncology Hunan Province, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying-Xue Huang; Ji LiDepartment of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, People’s Republic of ChinaTel +86 186 2755 6448; +86 139 7512 3658Fax +86 0731 8432 8888Email 29103866@qq.com; liji_xy@csu.edu.cnBackground: Intense pulsed light (IPL), as a therapeutic approach for rosacea, had advantage in removing erythema and telangiectasia and was gradually accepted by rosacea patients, but there have been few studies on economic evaluation of this therapy.Purpose: This study aimed to detect willingness-to-pay (WTP) of IPL treatment for rosacea and to conduct a benefit–cost analysis (BCA) among the Chinese population, so as to provide an economic reference for doctors to make treatment decisions.Materials and Methods: An observational, cross-sectional study assessed respondent’s demographic characteristics and willingness-to-pay (WTP) of IPL and rosacea patients’ clinical data and Dermatology Life Quality Index (DLQI). WTP was obtained by contingent valuation (CV) method. In brief, contrast figures of three cases treated with IPL (Case1, Case2, and Case3 represented the increasing severity of rosacea) were showed and WTP was inquired. The costs were obtained according the market and compared with WTP (benefits) to get a benefit–cost ratio (BCR). Predictors of cost-effective WTP were identified using the multivariable logistic regression model.Results: A total of 303 rosacea patients and 202 controls were included in the study. The average cost of a single IPL treatment for rosacea was USD 208.04 in Changsha, China. The mean WTP for Case 1, Case 2, and Case 3 was USD 201.57, 214.64, and 221.74, respectively. WTP was statistically lower for Case 1 than that for Case 2 or Case 3 (P< 0.05). The BCRs were 0.85, 1.03, and 1.06 for Case 1, Case 2, and Case 3, respectively. WTP is significantly associated with household monthly income, previous treatment cost, and DLQI after adjustments for demographic characteristics (P< 0.05).Conclusion: IPL is an acceptable treatment for rosacea with moderate to severe erythema. For patients with relatively high income or severely impaired quality of life, IPL is an economically feasible therapy and deserves to be recommended.Keywords: benefit-cost analysis, intense pulsed light, rosacea, willingness-to-pay, economic evaluation

YongLi Hou,1 Ting Yan,2 Hui Cao,1 Peng Liu,1 Kang Zheng,1 Zhenyu Li,1 Qing Deng,1 SiHai Hu11Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Institution of Pathogenic Biology, Hengyang Medical College, University of South China, Hengyang 421001, People’s Republic of China; 2Department of Health Services, Air Force Medical University, Xi’an, Shaanxi 710032, People’s Republic of ChinaCorrespondence: SiHai HuInstitution of Pathogenic Biology, Hengyang Medical College, University of South China, 28 West Changsheng Road, Hengyang 421001, Hunan, People’s Republic of ChinaTel +86 1 397 340 7567Fax +86 734 828 2907Email hhsshh_518@163.comPurpose: The primary goal of the present study was to explore and evaluate the highly conserved Neisserial surface protein A (NspA) molecule, fused with truncated HBV virus-like particles (VLPs), as a candidate vaccine against the virulent Neisseria meningitidis serogroup B (NMB).Methods: NspA was inserted into the major immunodominant region of the truncated hepatitis B virus core protein (HBc; amino acids 1–144). The chimeric protein, HBc-N144-NspA, was expressed from a prokaryotic vector and generated HBc-like particles, as determined by transmission electron microscopy. Further, the chimeric protein and control proteins were used to immunize mice and the resulting immune responses evaluated by flow cytometry, enzyme-linked immunosorbent assay, and analysis of serum bactericidal activity (SBA) titer.Results: Evaluation of the immunogenicity of the recombinant HBc-N144-NspA protein showed that it elicited the production of high levels of NspA-specific total IgG. The SBA titer of HBc-N144-NspA/F reached 1:16 2 weeks after the last immunization in BALB/c mice, when human serum complement was included in the vaccine. Immunization of HBc-N144-NspA, even without adjuvant, induced high levels of IL-4 and a high IgG1 to IgG2a ratio, confirming induction of an intense Th2 immune response. Levels of IL-17A increased rapidly in mice after the first immunization with HBc-N144-NspA, indicating the potential for this vaccine to induce a mucosal immune response. Meanwhile, the immunization of HBc-N144-NspA without adjuvant induced only mild inflammatory infiltration into the mouse muscle tissue.Conclusion: This study demonstrates that modification using HBc renders NspA a candidate vaccine, which can trigger protective immunity against NMB.Keywords: hepatitis B core protein, Neisserial surface protein A, virus-like particles, recombinant protein vaccine, Neisseria meningitidis serogroup B

Kankan Gao,1 Xiaoshan Guan,1 Lanlan Zeng,1 Jiabi Qian,2 Sufei Zhu,1 Qiulian Deng,1 Huamin Zhong,1 Shuying Pang,1 Fei Gao,1 Jielin Wang,1 Yan Long,1 Chien-Yi Chang,3 Haiying Liu1 1Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 2Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, China; 3School of Chemistry and Biosciences, University of Bradford, Bradford, BD7 1DP, UK Background: A multidrug-resistant (MDR) RR2 gene cluster was identified by whole-genome sequencing in several highly virulent (ST-17) Group B streptococcus (GBS) isolates, which caused neonatal invasive infections in southern China in 2016. Tracing the transmission and distribution of MDR isolates in this area is important for the effective management of future infections. The aim of this study was to obtain longitudinal data of MDR isolates to monitor epidemiological trends of general common isolates in southern China, and provide evidence for future characterization of antimicrobial resistance mechanisms.Methods: Clinical information and antimicrobial susceptibility of GBS isolates were acquired from electronic information management system databases of the hospital under study between January 2011 and December 2017. To confirm the presence of intact RR2, the tetO, ant6, lnuB, and ant9 genes located upstream, midstream, and downstream of RR2 were detected by PCR and DNA sequencing.Results: A total of 149 cases of neonatal invasive GBS infection were identified during the period 2011–2017. Among them, 119 cases (79.9%) were caused by MDR isolates, with a general increasing trend over the past 7 years. Further characterization of 11 isolates showed that six isolates causing late-onset disease (LOD) carry the tetO, ant6, and lnuB genes, which are located on RR2. Moreover, lnuB and ant9 consistently co-occurred in GBS isolates, which suggests their close proximity to one another in the RR2 gene cluster.Conclusion: The MDR GBS is responsible for a large number of neonatal invasive infections and occurs with increasing frequency over time. Particularly, the MDR GBS isolates that cause LOD are more likely to carry the RR2 gene cluster, compared with those that cause early-onset disease. The rise in number of MDR GBS isolates emphasizes the pressing need for continuous surveillance to monitor their antibiotic susceptibility and epidemiology. Keywords: invasive infection, gene cluster, neonates, multidrug-resistance

Yuquan Tao,1,* Yesheng Li,2,* Xing Liu,1 Qing Deng,1 Yongchun Yu,1 Zongguo Yang1,3 1Department of Central Laboratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China; 2Department of Hepatobiliary Surgery, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; 3Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China *These authors contributed equally to this work Objective: The roles of nonsteroidal anti-inflammatory drugs (NSAIDs) in the occurrence and prognosis of hepatocellular carcinoma (HCC) remain controversial. This analysis aimed to summarize the relationships between NSAIDs and HCC development. Methods: Studies published prior to October 1, 2017, in the PubMed, Embase, Ovid, Web of Science, and Cochrane Library databases were systematically searched and analyzed. Results: Eleven studies were included in this analysis. A meta-analysis of five studies revealed that aspirin use could significantly decrease the risk of HCC occurrence (hazards ratio [HR] = 0.64, 95% confidence interval [CI] = 0.45–0.91, P = 0.014). No significant difference was found for the use of NSAIDs (six studies) and non-aspirin NSAIDs (three studies) in HCC occurrence (HR = 0.74, 95%CI = 0.53–1.02, P = 0.064 and HR = 0.98, 95%CI = 0.87–1.12, P = 0.81, respectively). However, subgroup analysis of cohort studies demonstrated that NSAIDs significantly decreased the risk of HCC occurrence (HR = 0.58, 95%CI = 0.43–0.78, P < 0.001). HCC patients who received NSAIDs achieved better disease-free survival and overall survival compared with the non-NSAID users (HR = 0.79, 95%CI = 0.74–0.84, P

Jie Ruan,1,* Peipei Xu,2,3,* Wei Fan,4 Qiaoling Deng,3 Mingxia Yu3 1Key Laboratory for Medical Molecular Diagnostics of Guangdong, Guangdong Medical University, Dongguan, Guangdong, 523808, China; 2Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450072, China; 3Department of Clinical Laboratory, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China; 4Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China *These authors contributed equally to this work Abstract: Epigenetic alteration of P16INK4a is conventionally thought to induce the initiation of carcinoma. However, the role of P16INK4a methylation in ovarian cancer still remains controversial. Therefore, we performed a meta-analysis to further elucidate the relationship between P16INK4a promoter methylation and ovarian cancer. A total of 24 studies, including 20 on risk, 10 on clinicopathological features, and 3 on prognosis, were included in our meta-analysis. Our results indicated that the frequency of P16INK4a methylation in cancer tissues was significantly higher than normal tissues and low malignant potential tumor tissues (odds ratio [OR] =5.01, 95% CI=1.55–16.14; OR =1.88, 95% CI=1.10–3.19, respectively), but similar to benign tissues (OR =1.18, 95% CI=0.52–2.65). Furthermore, P16INK4a promoter methylation was not strongly correlated with age, clinical stage, tumor differentiation, or histological subtype in patients with ovarian cancer. Additionally, survival analysis showed that patients with P16INK4a promoter methylation had a shorter progression-free survival in univariate and multivariate Cox regression models (hazard ratio =1.68, 95% CI=1.26–2.24; hazard ratio =1.55, 95% CI=1.15–2.08; respectively). In The Cancer Genome Atlas datasets, the methylation levels of seven out of nine CpG sites were significantly increased in the ovarian tumor tissues compared with the normal tissues. In conclusion, the present meta-analysis suggests that P16INK4a promoter methylation may be useful in distinguishing malignant cancer from healthy ovarian tissues, and it may be a potential predictive marker for prognosis in patients with ovarian cancer. Keywords: ovarian cancer, P16INK4a promoter methylation, TCGA datasets, meta-analysis

Wei Du,1,* Jun Liu,2,* Jianlong Zhou,1,* Dan Ye,3 Yan OuYang,4 Qingnan Deng11Respiratory Diseases Group, the 6th Unit, Department of Internal Medicine, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China; 2Department of Gerontology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China; 3Luopu Street Community Health Service Centre, Guangzhou 511431, China; 4Department of Respiratory Medicine, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China *These authors contributed equally to this workObjective: The aim of this study was to investigate the role of obstructive sleep apnea (OSA) on all-cause mortality in patients with COPD.Methods: Data for this cross-sectional study were obtained from the National Health and Nutrition Examination Survey (NHANES) data (year 2005–2008). Eligible subjects were ≥20 years who had no COPD or OSA (n=9,237), had only OSA (n=366), had only COPD (n=695), and had OSA/COPD overlap syndrome (n=90). Univariate and multivariate analyses were used to evaluate factors associated with overall mortality.Results: Multivariate analysis found that the COPD and OSA/COPD overlap syndrome groups had significantly higher chance of all-cause mortality than the group of subjects who did not have OSA or COPD (adjusted hazard ratio [HR] =1.5 for the COPD group and 2.4 for the overlap syndrome group) (P≤0.007). Although not significant, having OSA/COPD overlap syndrome was associated with higher likelihood of death than COPD alone (HR =1.5; P=0.160). Other factors associated with higher overall mortality were aging, poorer family status, current smoker, serum vitamin D deficiency, cardiovascular disease, history of cancer, diabetes, and impaired renal function.Conclusion: The present study found that COPD and OSA/COPD overlap syndrome were associated with higher all-cause mortality compared with patients without either disease and that OSA did not significantly increase mortality in patients with COPD.Keywords: OSA, COPD, overlap syndrome, mortality

Christoph Sarrazin,1 Francesco Castelli,2 Pietro Andreone,3 Maria Buti,4 Massimo Colombo,5 Stanislas Pol,6 Filipe Calinas,7 Massimo Puoti,8 Antonio Olveira,9 Mitchell Shiffman,10 Jerry O Stern,11 George Kukolj,12 Michael Roehrle,13 Stella Aslanyan,11 Qiqi Deng,11 Richard Vinisko,11 Federico J Mensa,11 David R Nelson,14 on behalf of the HCVerso1 and 2 study groups 1Department of Internal Medicine 1, JW Goethe University Hospital, Frankfurt, Germany; 2Department of Infectious and Tropical Diseases, University of Brescia, Brescia, 3Department of Medical and Surgical Sciences, Università di Bologna and Azienda Ospedaliero-Universitaria, Policlinico Sant‘Orsola-Malpighi, Bologna, Italy; 4Department of Internal Medicine, Hospital Universitari Vall d’Hebron and CIBERehd del Instituto Carlos III, Barcelona, Spain; 5Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy; 6University Paris Descartes, Department of Hepatology, Hospital Cochin, APHP and INSERM UMS-20, Institut Pasteur, Paris, France; 7Department of Gastroenterology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal; 8Department of Infectious Diseases, AO Ospedale Niguarda Cà Granda, Milan, Italy; 9Liver Unit, Hospital Universitario La Paz, CIBERehd, Madrid, Spain; 10Liver Institute of Virginia, Bon Secours Health System, Richmond, VA, USA; 11Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 12Boehringer Ingelheim Ltd/Ltée, Burlington, ON, Canada; 13Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany; 14Clinical and Translational Science Institute, University of Florida, Gainesville, FL, USA Abstract: The interferon-free combination of once-daily faldaprevir 120 mg, twice-daily deleobuvir 600 mg, and weight-based ribavirin was evaluated in two Phase III studies (HCVerso1, HCVerso2) in hepatitis C virus genotype-1b-infected, treatment-naïve patients, including those ineligible for peginterferon (HCVerso2). Patients without cirrhosis were randomized to 16 weeks (Arm 1; n=208 HCVerso1, n=213 HCVerso2) or 24 weeks (Arm 2; n=211 in both studies) of faldaprevir + deleobuvir + ribavirin. Patients with compensated cirrhosis received open-label faldaprevir + deleobuvir + ribavirin for 24 weeks (Arm 3; n=51, n=72). Primary endpoints were comparisons of adjusted sustained virologic response (SVR) rates with historical rates: 71% (HCVerso1) and 68% (HCVerso2). Adjusted SVR12 rates were significantly greater than historical controls for Arms 1 and 2 in HCVerso2 (76%, 95% confidence interval [CI] 71–81, P=0.002; 81%, 95% CI 76–86, P

Gao K, Guan X, Zeng L, et al. Infect Drug Resist. 2018;11:2561–2569.In this article both Wenjing Ji and David J McIver were erroneously listed in the acknowledgements but should have been included as coauthors. A communication error at the manuscript submission stage led to both authors being left off the original authorship list. Both Wenjing Ji and David J McIver were originally acknowledged for their assistance with formatting and proofreading and language editing, respectively. However, it was shown both authors also assisted with the interpretation of data and analysis, as well as assisting in drafting the manuscript, extensive editing, recommendations for analysis and the interpretation of findings. The authors wish to apologize for this error. The correct author list and affiliations are shown below.Read the original article

C48H40BCuF4N4OP2, triclinic, P1 (no. 2), a = 11.909(2) Å, b = 13.046(2) Å, c = 15.144(3) Å, α = 99.617(4)°, β = 96.925(4)°, γ = 96.039(3)°, V = 2283.9 Å3, Z = 2, Rgt(F) = 0.048, wRref(F2) = 0.123, T = 293 K.

Modified activated carbon was prepared by thermal treatment at high temperature under nitrogen flow. The surface properties of the activated carbon were characterized by Boehm titration, BET and point of zero charge determination. The adsorption mechanism of phenol on modified activated carbon was explained and the adsorption capacity of modified activated carbon for phenol when compared to plain activated carbon was evaluated through the analysis of adsorption isotherms, thermodynamic and kinetic properties. Results shows that after modification the surface alkaline property and pHpzc value of the activated carbon increase and the surface oxygen-containing functional groups decrease. The adsorption processes of the plain and modified carbon fit with Langmuir isotherm equation well, and the maximum adsorption capacity increase from 123.46, 111.11, 103.09mg/g to 192.31, 178.57, 163,93mg/g under 15, 25 and 35°C after modification, respectively. Thermodynamic parameters show that the adsorption of phenol on activated carbon is a spontaneously exothermic process of entropy reduction, implying that the adsorption is a physical adsorption. The adsorption of phenol on activated carbon follows the pseudo-second-order kinetics (R2>0.99). The optimum pH of adsorption is 6~8.

C18H18N2O6Zn, triclinic, P1̅ (no. 2), a = 9.2816(7) Å, b = 10.5205(8) Å, c = 11.0378(7) Å, α = 103.144(4)°, β = 99.428(4)°, γ = 111.743(3)°, V = 937.6 Å3, Z = 2, Rgt(F) = 0.029, wRref(F2) = 0.080, T = 293 K.

C18H15CdN2O5, monoclinic, P121/n1 (no. 14), a = 9.9973(5) Å, b = 9.0433(4) Å, c = 19.4849(8) Å, β = 101.235(2)°, V = 1727.9 Å3, Z = 4, Rgt(F) = 0.025, wRref(F2) = 0.065, T = 273 K.

C12H10CuMoN2O5, monoclinic, P121/n1 (no. 14), a = 14.147(3) Å, b = 5.890(1) Å, c = 16.221(3) Å, β = 103.27(1)°, V = 1315.5 Å3, Z = 4, Rgt(F) = 0.023, wRref(F2) = 0.061, T = 298 K.

The modified strain gradient theory (MSGT) with flexoelectric and micro-inertia effects is developed to study the free vibration of tube made of elastic centrosymmetric materials. Within this theory, the internal energy density is the function of the strain tensor, deviatoric part of stretch gradient and rotation gradient tensors, dilatation gradient, polarization vector, and electric quadrupoles. The linear coupled governing equations and boundary conditions are derived from the Hamilton variation principle. The torsional vibration problem is analytically solved for non-piezoelectric nanotube with fixed edges. The effect of the nanotube geometry, flexoelectric coefficient, micro-inertia, and micro-stiffness parameters on the natural frequency is studied. [ABSTRACT FROM AUTHOR]