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Jingdong Xia,1,2 Xiudan Li,1,2 Chunying Bai,2 Xuchen Han1 1Affiliated Hospital of Chifeng University, Chifeng, The Inner Mongol Autonomous Region, Chifeng, People’s Republic of China; 2Key Laboratory of Research on Human Genetic Diseases at Universities of Inner Mongolia Autonomous Region, Chifeng, People’s Republic of ChinaCorrespondence: Xuchen Han; Xiudan Li, Email hanxuchen2004@163.com; 1248337580@qq.comAbstract: Coenzyme Q has garnered significant attention due to its potential role in enhancing cellular energy production and its antioxidant properties. We delve into the therapeutic potential of coenzyme Q in managing diabetes mellitus and its complications, highlighting its capacity to improve mitochondrial function, reduce inflammation and oxidative stress, and correct lipid profiles. Coenzyme Q has shown promise in ameliorating insulin resistance and alleviating complications such as diabetic peripheral neuropathy, kidney disease, retinopathy, and cardiomyopathy. However, its clinical application is limited by poor bio-availability. This review also provides a comprehensive overview of current therapeutic strategies for diabetes complications involving coenzyme Q, including stimulating endogenous synthesis and utilizing carrier transport systems, offering insights into mechanisms for enhancing coenzyme Q bio-availability. These findings suggest that, with improved delivery methods, coenzyme Q could become a valuable adjunct therapy in the management of diabetes mellitus.Keywords: coenzyme Q, diabetes mellitus, diabetic complications

Jing Wang,1 Wenyue Gao,1 Hongbo Yu,1 Yuting Xu,1 Changchuan Bai,2 Qingwei Cong,1 Ying Zhu1 1Infectious Department, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Internal Department of Chinese Medicine, Dalian Hospital of Traditional Chinese Medicine, Dalian, Liaoning, 116013, People’s Republic of ChinaCorrespondence: Ying Zhu, Email zhuyingsh52@126.comAbstract: Hepatocellular carcinoma (HCC) stands as the prevailing form of primary liver cancer, characterized by a poor prognosis and high mortality rate. A pivotal factor in HCC tumorigenesis is epigenetics, specifically the regulation of gene expression through methylation. This process relies significantly on the action of proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These proteins are crucial regulators, orchestrating the methylation process by regulating enzymes and their corresponding binding proteins. This orchestration facilitates the reading, binding, detection, and catalysis of gene methylation sites. Methylation ences the development, prolisignificantly influferation, invasion, and prognosis of HCC. Furthermore, methylation modification and its regulatory mechanisms activate distinct biological characteristics in HCC cancer stem cells, such as inducing cancer-like differentiation of stem cells. They also influence the tumor microenvironment (TME) in HCC, modulate immune responses, affect chemotherapy resistance in HCC patients, and contribute to HCC progression through signaling pathway feedback. Given the essential role of methylation in genetic information, it holds promise as a potential tool for the early detection of HCC and as a target to improve drug resistance and promote apoptosis in HCC cells.Keywords: methylation modifying proteins, biomarkers, methyltransferases, HCC tumorigenesis

Chen Bai, Mingcan Xu, Yan Guo, Yanwu Jin, Xin Zhao Department of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, People’s Republic of ChinaCorrespondence: Yanwu Jin; Xin Zhao, Department of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247, Beiyuan Road, Jinan, Shandong, 250033, People’s Republic of China, Email jinyanwu_aa@163.com; lujnzx@sohu.comAbstract: Remimazolam is a novel ultrashort-acting benzodiazepine that allosterically modulates γ-aminobutyric acid type A (GABAA) receptors to exert sedative effects. Remimazolam has the properties of controllable sedation, rapid onset, and a short duration of action, along with minor depression of circulation and respiration. Remimazolam has been approved for clinical use since 2020 in Japan, and it has been applied for procedural sedation, general anesthesia induction and maintenance, and sedation in ICU patients, and has been proven to be safe and effective. Currently, no consensus has been reached on the clinical application of remimazolam in pediatric patients. This review introduces the clinical research progress and limitations of remimazolam in recent years, aiming to supply scientific guidance and a theoretical reference for the application of remimazolam in pediatric anaesthesia.Keywords: remimazolam, sedation, pediatric patient, clinical anesthesia

Xiudan Li,1,2 Lifeng Gao,2 Xuyang Li,2 Jingdong Xia,1 Yurong Pan,1 Chunying Bai2 1Department of Endocrinology, Affiliated Hospital of Chifeng University, Chifeng, 024000, China; 2Inner Mongolia Key Laboratory of Human Genetic Disease Research, Chifeng University, Chifeng, 024000, ChinaCorrespondence: Chunying Bai, Email baichunying@cfxy.edu.cnAbstract: Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes and can potentially develop into end-stage renal disease. Its pathogenesis is complex and not fully understood. Podocytes, glomerular endothelial cells (GECs), glomerular mesangial cells (GMCs) and renal tubular epithelial cells (TECs) play important roles in the normal function of glomerulus and renal tubules, and their injury is involved in the progression of DN. Although our understanding of the mechanisms leading to DN has substantially improved, we still need to find more effective therapeutic targets. Autophagy, pyroptosis and ferroptosis are programmed cell death processes that are associated with inflammation and are closely related to a variety of diseases. Recently, a growing number of studies have reported that autophagy, pyroptosis and ferroptosis regulate the function of podocytes, GECs, GMCs and TECs. This review highlights the contributions of autophagy, pyroptosis, and ferroptosis to DN injury in these cells, offering potential therapeutic targets for DN treatment.Keywords: diabetic nephropathy, autophagy, pyroptosis, ferroptosis, inflammation

Hao Yang,1– 3,* Guanglin Lei,2,* Zhuoya Deng,1 Fang Sun,1 Yuying Tian,1 Jinxia Cheng,1 Hongyu Yu,1 Cong Li,1 Changqing Bai,4 Shaogeng Zhang,2 Guangwen An,5 Penghui Yang1 1Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Hepatological Surgery, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Surgery, Taian City Central Hospital, Taian, People’s Republic of China; 4Department of Respiratory, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Guangdong, People’s Republic of China; 5Department of Pharmacy, No. 984 Hospital of the PLA, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Penghui Yang; Guangwen An, Email ypenghuiamms@hotmail.com; anchen337722@163.comBackground: Oncolytic virus (OV) therapy has emerged as a promising novel form of immunotherapy. Moreover, an increasing number of studies have shown that the therapeutic efficacy of OV can be further improved by arming OVs with immune-stimulating molecules.Methods: In this study, we used reverse genetics to produce a novel influenza A virus, termed IAV-OX40L, which contained the immune-stimulating molecule OX40L gene in the influenza virus nonstructural (NS1) protein gene. The oncolytic effect of IAV-OX40L was explored on hepatocellular carcinoma (HCC)HCC cells in vitro and in vivo.Results: Hemagglutination titers of the IAV-OX40L virus were stably 27– 28 in specific-pathogen-free chicken embryos. The morphology and size distribution of IAV-OX40L are similar to those of the wild-type influenza. Expression of OX40L protein was confirmed by Western blot and immunofluorescence. MTS assays showed that the cytotoxicity of IAV-OX40L was higher in HCC cells (HepG2 and Huh7) than in normal liver cells (MIHA) in a time- and dose-dependent manner in vitro. We found that intratumoral injection of IAV-OX40L reduced tumor growth and increased the survival rate of mice compared with PR8-treated controls in vivo. In addition, the pathological results showed that IAV-OX40L selectively destroyed tumor tissues without harming liver and lung tissues. CD4+ and CD8+ T cells of the IAV-OX40L group were significantly increased in the splenic lymphocytes of mice. Further validation confirmed that IAV-OX40L enhanced the immune response mainly by activating Th1-dominant immune cells, releasing interferon-γ and interleukin-2.Conclusion: Taken together, our findings demonstrate the novel chimeric influenza OV could provide a potential therapeutic strategy for combating HCC and improve the effectiveness of virotherapy for cancer therapy.Keywords: OVs, OX40L, IAV, HCC

Yuming Shao,1 Wenxiang Wu,2 Fangzhou Fan,2 Haifeng Liu,3 Yongliang Ming,2 Wangwei Liao,2 Chunyu Bai,2 Yuhua Gao2 1Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Forensic Science Center of Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 2Precision Medicine Laboratory for Chronic Non-Communicable Diseases of Shandong Province, Institute of Precision Medicine, Jining Medical University, Jining, Shandong, 272067, People’s Republic of China; 3Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272067, People’s Republic of ChinaCorrespondence: Chunyu Bai; Yuhua Gao, No. 133 Hehua Road, Jining, Shandong, 272067, People’s Republic of China, Tel +86-573-3616565, Email chunyu_bai@hotmail.com; anngyh@126.comAim: Acute pancreatitis is an inflammatory disorder of the pancreas, which causes abnormal activation of immune cells. The macrophages were accumulated in pancreas and infiltrated into islets during the AP process to induce abnormal glucose metabolism. However, the role of macrophages in abnormal glucose metabolism remains understood. Extracellular vesicles act in the regulation of intercellular function, but whether EVs secreted by macrophages contribute to β cell failure and apoptosis in AP is unclear. Based on this, the aim of this study was to reveal the role of macrophages-EVs in AP and develop a treatment for symptoms of hyperglycemia in AP.Methods: The AP model was established and treated by various doses of melatonin to analyze the therapeutic effect. The accumulation and polarization of macrophages in the AP pancreas were observed, and the β cells were incubated with pancreatic derived EVs to analyze the role in β cell failure and apoptosis.Results: The results showed that macrophages were recruited and polarized to M1 phenotype macrophages in the pancreas of AP mice, which obtained inflammatory EVs that contained specific miRNAs to induce β cell failure and apoptosis. Then, the EVs derived from M1 macrophages triggered β cell failure and apoptosis. Melatonin prevented polarization of macrophages to the M1 phenotype in vivo, which reduced the secretion of inflammatory EVs, changed the abundance of miRNAs in EVs, and therefore decreased inflammatory EV-mediated β cell failure and apoptosis.Conclusion: Our results demonstrate that similar to 20S proteasome inhibitor MG132, analyses indicated that melatonin prevented degradation of IκBα through the ubiquitylation pathway to restrict p50 subunits to the cytoplasm of macrophages, inhibited activation of the NF-κB pathway to downregulate the transcription of specific miRNAs, and reduced miRNA transport into EVs.Keywords: acute pancreatitis, diabetes mellitus, macrophages, EVs, melatonin

Tianyu Tan,1 Chao Zhou,1 Rongrong Lu,1 Cheng Chen,2 Chongyang Bai,1 Long Li,1 Guohui Wu1 1Chongqing Center for Disease Control and Prevention, Chongqing, 400042, People’s Republic of China; 2Chongqing Jiulongpo District Center for Disease Control and Prevention, Chongqing, 400039, People’s Republic of ChinaCorrespondence: Guohui Wu, Chongqing Center for Disease Control and Prevention, No. 8, Changjiang 2nd Road, Chongqing, 400042, People’s Republic of China, Tel +8602368801491, Email wgh68803652@163.comPurpose: This study aimed to assess the proportion of depression and its associated factors among men living with HIV/AIDS and aged 50 and over in Chongqing, China.Methods: This cross-sectional study included 774 men diagnosed as HIV/AIDS and aged 50 and over in four regions. Data were collected through face-to-face interviews with a structured questionnaire. Multivariate logistic regression analysis was performed to identify factors associated with depression. A two-tailed P-value less than 0.05 was considered as statistical significance.Results: A total of 293 participants (37.9%) reported depressive symptoms. Results from multivariate logistic regression suggested that individuals aged ≥ 70 (AOR = 1.99, 95% CI: 1.28– 3.08) and those living in rural areas (AOR = 2.79, 95% CI: 1.96– 3.97) were associated with higher odds of depression, while those being employed (AOR = 0.50, 95% CI: 0.32– 0.80) and with monthly income > 3000 CNY (AOR = 0.47, 95% CI: 0.30– 3.74) had lower odds of depression.Conclusion: Our findings indicate a high prevalence of depression among older men living with HIV/AIDS in Chongqing, China. Age, residence, employment, and income have been identified as potential risk factors of depressive symptoms. Mental-health intervention initiatives should be tailored to target adults with a higher risk of depression.Keywords: depression, China, older male, HIV/AIDS, influencing factors

Ke Huang,1,2 Kewu Huang,3 Jianying Xu,4 Lan Yang,5 Jianping Zhao,6 Xiangyan Zhang,7 Chunxue Bai,8 Jian Kang,9 Pixin Ran,10 Huahao Shen,11 Fuqiang Wen,12 Yahong Chen,13 Tieying Sun,14 Guangliang Shan,15 Yingxiang Lin,3 Sinan Wu,2,16 Ting Yang,1,2,17 Chen Wang1,2,17,18 1Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Shanxi Dayi Hospital, Taiyuan, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 8Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 9Department of Pulmonary and Critical Care Medicine, First Hospital of China Medical University, Shenyang, People’s Republic of China; 10State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 11Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 12State Key Laboratory of Biotherapy of China and Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 13Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 14Department of Respiratory and Critical Care Medicine, Beijing Hospital, Beijing, People’s Republic of China; 15Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 16Institute of Clinical Medical Sciences, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 17Department of Respiratory Medicine, Capital Medical University, Beijing, People’s Republic of China; 18Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Chen Wang; Ting YangDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Chaoyang District, Beijing, 100029, People’s Republic of ChinaTel +86 10 65105565; +86 10 84206276Email cyh-birm@263.net; dryangting@qq.comPurpose: Anxiety and depression are often underdiagnosed and affect the prognosis of patients with chronic obstructive pulmonary disease (COPD). We analyzed data from the China Pulmonary Health (CPH) study to assess the prevalence of anxiety and depression in COPD patients and their relationship with disease severity.Patients and Methods: A total of 57,779 subjects aged 20 years or older were recruited in the CPH study. All participants were assessed using a standard questionnaire and underwent pulmonary function tests before and after the use of a bronchodilator in local health centers. The Hospital Anxiety and Depression Scale (HADS) questionnaire with a cutoff score of 8 was used to define anxiety and depression. The prevalence of anxiety and depression in patients of COPD were investigated. Multivariate logistic regression was used to investigate the effects of COPD and lung function on anxiety and depression.Results: A total of 49,053 participants (20,661 men and 28,392 women) completed the questionnaire with reliable post-bronchodilator pulmonary function test results and were included in the final analysis, of which 4686 (9.55%) were diagnosed with COPD. Of the patients with COPD, 10.79% had anxiety, 13.65% had depression, and 7.08% had anxiety and depression concomitantly. In the multivariate logistic regression analysis, COPD was not significantly associated with anxiety, depression, or both. After adjusting for confounders in model 1, patients in the GOLD III–IV group had a significantly higher risk of anxiety, depression, and their coincidence. After further adjusting for respiratory symptoms in model 2, lung function impairment in the GOLD III–IV group was only significantly associated with a higher risk of depression or at least one of anxiety and depression.Conclusion: Anxiety and depression are prevalent in patients with COPD in China. More severe lung function impairment is significantly associated with a higher risk of depression.Keywords: anxiety, COPD, depression, Hospital Anxiety and Depression Scale, HADS

Tongtong Zhou,1,2,&ast; Li Tan,1,&ast; Yang Gui,1 Jing Zhang,1 Xueqi Chen,1 Menghua Dai,3 Mengsu Xiao,1 Qing Zhang,1 Xiaoyan Chang,4 Qun Xu,5 Chunmei Bai,6 Yuejuan Cheng,6 Qiang Xu,3 Xue Wang,7 Hua Meng,1 Wanying Jia,1 Ke Lv,1 Yuxin Jiang1 1Department of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Ultrasound, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 3Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Medical Oncology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 7Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Lv; Yuxin JiangDepartment of Ultrasound, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaTel/Fax +86 10-69155493; +86 10-69155491Email lvke@163.com; yuxinjiangxh@163.comObjective: Investigate the CEUS enhancement patterns of PDAC and analyse correlations between the CEUS enhancement pattern and both the degree of tumour tissue differentiation and overall survival (OS).Methods: The study included 56 patients with locally advanced PDAC, performed conventional ultrasound and CEUS, and analysed characteristics of the CEUS enhancement patterns. In addition, clinical data, such as serum level of CA19-9, TNM stage were collected, and patients’ survival times were followed up. TICs of dynamic CEUS images were acquired using image processing software to obtain the peak, TP, sharpness, and AUC. Correlations of the CEUS enhancement patterns of PDAC with the degree of differentiation of tumour tissue and OS were quantitatively analysed, as were the correlations of the TIC parameters and CEUS enhancement patterns with OS.Results: Enhancement in the arterial phase included iso-enhancement (30.3%) and hypo-enhancement (69.6%), and was not significantly correlated with sex, age at disease onset, or lesion size. Also was not significantly correlated with tumour tissue differentiation. Clear survival times were obtained for 50 patients during follow-up, and the median survival time was significantly longer for the patients with iso-enhancement than hypo-enhancement. Among the TIC parameters, peaktumour, sharpnesstumour, AEsharpness, and REsharpness differed significantly between the group with iso-enhancement and hypo-enhancement (p < 0.05).Conclusion: The CEUS enhancement patterns of PDAC in the arterial phase include iso-enhancement and hypo-enhancement. Enhancement pattern was not significantly correlated with the degree of differentiation of tumour tissue, but patient survival time differed significantly between the two enhancement patterns, with longer survival for patients with iso-enhancement.Keywords: contrast-enhanced ultrasound, pancreatic ductal adenocarcinoma, survival time, enhancement pattern, time-intensity curve

Yan Liu,1,* Chi Zhang,2,* Chengyu Li,1 Chunxue Bai,3 Hongcai Shang1 1Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute for Brain Disorders, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongcai ShangKey Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, 5 Haiyuncang, Dongcheng District, Beijing 100700, People’s Republic of ChinaEmail shanghongcai@126.comBackground: There were few studies on the case mortality of severe community-acquired pneumonia (CAP) in elderly people. Improved outcomes with XueBiJing (XBJ) injection vs placebo have been shown in overall trial populations. We investigated the efficacy and safety of XBJ vs placebo in subjects with severe CAP stratified by age (< 65 and ≥ 65 years).Methods: This post hoc analysis of a large randomized trial compared data from elderly and nonelderly patients with XBJ, 100 mL, q 12 h, or a visually indistinguishable placebo for five-to-seven days.Results: Among subjects ≥ 65 years (n=291), 23 (16.0%) XBJ recipients and 41 (27.9%) placebo recipients (P=0.014) died within 28 days. Among subjects < 65 years (n=360), XBJ still had lower mortality (XBJ 15.6% vs placebo 22.8%; P=0.082), without significantly statistical difference. Total duration of ICU stay and the time of mechanical ventilation were similar in both groups (P> 0.05). XBJ also had a favorable safety profile, with no clinically relevant differences between the two groups. The overall incidence of adverse events was similar in both groups.Conclusion: XBJ was safe and effective for reduction in 28-day mortality among elderly patients with severe CAP. Additional confirmatory trials involving elderly patients are needed to further confirm the present results.Trial Registration: http://www.chictr.org.cn/index.aspx. ChiCTR-TRC-13003534.Keywords: severe community-acquired pneumonia, randomized controlled trial, post hoc analysis, 28-day mortality rate, XueBiJing injection

Haixia Wang, Chenxiao Bai, Mo Yi, Yuanmin Jia, Yizhang Li, Di Jiang, Ou Chen School of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People’s Republic of ChinaCorrespondence: Ou ChenSchool of Nursing, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, People’s Republic of ChinaTel +8615990991181Email chenou@sdu.edu.cnBackground: Although metabolic syndrome is awell-known risk factor for many non-communicable diseases, its contribution to asthma remains controversial.Objective: The aim of this study was to explore the associations of metabolic syndrome and its components with incident asthma in Chinese adults.Methods: We conducted an open cohort study of participants who were asthma-free at baseline (n=42,304) in the Shandong multi-center health check-up longitudinal study from 2004 to 2015. Participants aged ≥ 20 years and had regular physical examination (once ayear) more than three times during follow-up.Results: Ninety subjects (38 women and 52 men) developed incident asthma over 12 years of follow-up. Our study suggested that metabolic syndrome itself was not significantly associated with incident asthma in either women or men (P> 0.050). Interestingly, we found that overweight and/or obesity was arisk factor for incident asthma among women but not men in the Cox proportional hazards model after adjusting covariates (adjusted incidence rate ratio (IRR)= 2.940, 95% confidence interval (CI): 1.467– 5.894, P=0.002). The result was consistent with the Poisson regression model (hazard ratio (HR)= 2.241, 95% CI: 1.135– 4.988, P=0.026). After stratifying according to overweight and/or obesity, we found that female subjects with overweight and obesity were associated with the occurrence of incident asthma (P< 0.050). However, we did not find this result among men. Conclusion: Metabolic syndrome was not significantly associated with incident asthma in both women and men; however, overweight and/or obesity was shown to be asignificant risk factor for incident asthma but only in women, not in men.Keywords: overweight and/or obesity, metabolic syndrome, risk factor, incident asthma

Jing-Tao Zhou,1,* Jiang-Hao Liu,2,* Ting-Ting Song,2 Bo Ma,3 Nuermaimait Amidula,1 Chao Bai4 1General Surgery, The Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2General Surgery, Xinjiang Uygur Autonomous Region Eighth People’s Hospital, Urumqi, People’s Republic of China; 3General Surgery, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 4Department of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao BaiDepartment of Vascular and Thyroid Surgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137 South Liyushan Road, New District, Urumqi 830000, People’s Republic of ChinaTel +86 991-4364657Email baichao1981yww@163.comObjective: To investigate the anti-tumor effects of programmed cell death protein 1 (PD-1) scFv-secreting EGFR-chimeric antigen receptor-modified (CAR)-T cells against gastric cancer.Methods: Second-generation EGFR-CAR-T cells and fourth-generation PD-1 scFv-secreting EGFR-CAR-T cells were engineered. The anti-tumor activities of chimeric antigen receptor-modified (CAR)-T cells were analyzed in vitro by long-term co-culture with gastric cancer cells. The tumor scavenging capacity in vivo was evaluated in xenograft and PDX mouse models.Results: EGFR-CAR-T cells secreting PD-1 scFv showed enhanced long-term tumor cell killing capacity in vitro. These cells also showed significant anti-tumor effect in the subcutaneous xenograft model of gastric cancer as well as in the PDX model, and autocrine PD-1 antibody secretion significantly increased tumor infiltration of the CAR-T cells.Conclusion: EGFR-CAR-T cells secreting PD-1 scFv are highly effective against gastric cancer and offer new insights into anti-cancer immunotherapy.Keywords: EGLIF-CAR-T cells, PD-1 blocking antibodies, elimination, gastric cancer

Yinxian Chen, Sicheng Zhang, Chuanqing Bai, Zhiye Guan, Wenjian Chen Department of Orthopedic, Children’s Hospital of Anhui Medical University, Hefei, Anhui 230032, People’s Republic of ChinaCorrespondence: Wenjian ChenDepartment of Orthopedic, Children’s Hospital of Anhui Medical University, Baohe District, Hefei, Anhui 230032, People’s Republic of ChinaTel +86-13721021060Email vfpacs@163.comBackground: As a malignant tumor, the progression of osteosarcoma (OS) is mediated by multiple regulators, including circular RNAs (circRNAs). However, the role of circ_0000885 in OS is unclear.Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ_0000885, miR-1294 and fibroblast growth factor receptor 1 (FGFR1). Cell proliferation was evaluated using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Flow cytometry and transwell assay were employed to determine the cell cycle distribution, cell migration and invasion, respectively. Moreover, the relationship between miR-1294 and circ_0000885 or FGFR1 was confirmed by dual-luciferase reporter assay. The protein level of FGFR1 was assessed via Western blot (WB) analysis. Animal experiments were used to verify the effect of circ_0000885 silencing on OS tumor growth in vivo.Results: Circ_0000885 level was increased in OS tissues and cells. Knockdown of circ_0000885 repressed the proliferation, migration, invasion and induced cell cycle arrest in OS cells. There was a binding relationship between miR-1294 and circ_0000885, and miR-1294 inhibitor could reverse the inhibitory effect of silenced circ_0000885 on OS progression. MiR-1294 could target FGFR1, and overexpressed FGFR1 could invert the suppression effect of miR-1294 mimic on OS progression. Silencing of circ_0000885 hindered FGFR1 expression, while this effect could be recovered by miR-1294 inhibitor. In addition, circ_0000885 knockdown reduced OS tumor growth via regulating the FGFR1 expression by sponging miR-1294 in vivo.Conclusion: Circ_0000885 played an active role in OS progression, indicating that it might be a potential target for OS therapy.Keywords: OS, progression, circ_0000885, miR-1294, FGFR1

Shuting Yu,1 Yingying Zhu,1 Xiaohua Shi,2 Ke Hu,3 Chunmei Bai,4 Wenwen Diao,1 Xiaoli Zhu,1 Zhiqiang Gao,1 Xingming Chen1 1Department of Otolaryngology-Head and Neck Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Radiotherapy, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Oncology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Xingming Chen Tel +86 13901077778Email xingming.chen@hotmail.comPurpose: To date, no guidelines have been proposed for the ideal treatment of postoperative larynx squamous cell carcinoma (LSCC) patients with lymphovascular invasion due to a lack of similar studies. The present study was conducted to compare the survival and toxicity in LSCC patients with lymphovascular invasion receiving either postoperative radiotherapy (PORT) or postoperative chemoradiotherapy (POCRT). The results can be applied for more appropriate treatment of these patients.Patients and Methods: Three hundred eighty-eight eligible LSCC patients with lymphovascular invasion were enrolled in this retrospective study. Survival and treatment-related toxicities were compared in the POCRT and PORT group using propensity score matching (PSM) methodology (1:1).Results: Five-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of all patients were 48.7%, 58.2%, and 56.0%, respectively. Significantly, higher RFS rates (P=0.040) were found in the POCRT group than the PORT group in the PSM cohort. In the multivariate analysis, higher OS, DSS, and RFS rates were observed in the POCRT group than the PORT group (P=0.049, 0.024, and 0.011 respectively). Patients in the POCRT group presented more acute toxicities than those in the PORT group such as hematological toxicities (25.0% vs 0.9%, P< 0.001) and mucositis (35.0% vs 19.1%, P=0.002).Conclusion: In the context of no ideal treatment for LSCC patients with lymphovascular invasion, the present study proposes POCRT as a preferable modality compared with PORT, as POCRT was associated with higher RFS rates. Higher RFS, DFS, and OS rates were also observed in the POCRT group in the multivariate analysis.Keywords: head and neck carcinoma, larynx carcinoma, lymphovascular invasion, propensity score, chemoradiotherapy, survival

Xicheng Wang,1 Jianfeng Zhou,2 Yan Li,1 Yuping Ge,2 Yanping Zhou,2 Chunmei Bai,2 Lin Shen1 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 2Department of Oncology, Peking Union Medical College Hospital, Beijing 100032, People’s Republic of ChinaCorrespondence: Lin ShenKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, No. 52, Fu Cheng Road, Hai Dian District, Beijing, People’s Republic of ChinaTel +86-010-88156175Fax +86-010-88196561Email linshenpku@163.comChunmei BaiDepartment of Oncology, Peking Union Medical College Hospital, No. 41, Da Mu Cang Hutong, Xi Cheng District, Beijing, People’s Republic of ChinaTel/ Fax +86-010-69158315Email baichunmei1964@163.comPurpose: Trifluridine/tipiracil (FTD/TPI) is approved in Japan, the United States (US), and Europe for metastatic colorectal cancer (mCRC) refractory to standard therapies. This Phase 1b open-label study focused on the pharmacokinetic (PK) and toxicity profiles of FTD/TPI in Chinese patients with solid tumors.Methods: Patients with definitive histologically or cytologically confirmed advanced/metastatic solid tumors refractory to standard treatments were enrolled. FTD/TPI (35 mg/m2) was administered orally twice daily for five consecutive days, followed by a 2-day recovery. Treatment was repeated for five consecutive days, followed by a 16-day recovery. The primary objective was to assess PK characteristics of FTD, 5-trifluoromethyl-2,4 (1H,3H)-pyrimidinedione (FTY; an inactive form of FTD), and TPI, calculated from plasma concentrations. Additionally, these PK values were compared with those from similar Phase 1 studies in patients from Japan and the US, using Tukey–Kramer’s honestly significant difference (HSD) multiple comparison tests. Safety and preliminary efficacy of FTD/TPI were assessed.Results: Fifteen patients (12 males, three females) were enrolled, most with CRC (87%). Geometric mean analysis showed that maximum plasma concentration (Cmax) of FTD increased after multiple administration (from day 1 [3019.5 ng/mL] to day 12 [3693.1 ng/mL]), and the exposure (AUC0-t) increased 2.4-fold (day 1:7796.6 ng/mL•h; day 12:18,181.3 ng/mL•h). There was no meaningful change in the exposure to FTY and TPI throughout the study. HSD tests showed comparable PK for FTD, FTY, and TPI between Chinese and Japanese patients, and comparable exposure to FTD between Chinese and US patients. Eight patients (53.3%) experienced Grade 3 treatment-emergent adverse events, most frequently anemia and fatigue (13.3%, two events each). Median progression-free survival was 1.9 months.Conclusion: FTD/TPI had an acceptable safety and efficacy profile and PK characteristics were comparable between Chinese, Japanese, and US patients, suggesting that this treatment may be suitable for Chinese patients with refractory mCRC.Trial Registration: This trial was registered at clinicaltrials.gov as NCT02261532.Keywords: Chinese, colorectal cancer, pharmacokinetics, safety, trifluridine/tipiracil

Jialing Lin,1 Jianping Liang,2 Ting Zhang,1 Chan Bai,1 Jiaping Ye,1 Zhenjiang Yao1 1Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, China; 2Department of Health Education, Guangzhou Primary and Secondary School Health Promotion Center, Guangzhou, China Background: Methicillin-resistant Staphylococcus aureus (MRSA) can cause serious infections in elementary students. Therefore, we aimed to elucidate the quantitative associations of school environmental contamination with nasal carriage of MRSA by students in a dose-response manner. Phenotypic and molecular characterizations were performed to further assess the associations. Materials and methods: A cross-sectional study was conducted from March to August 2016 in eight elementary schools in Guangzhou, China. A multistage stratified cluster sampling design was used to include Chinese students and selected classes. Nasal swabs from students and environmental swabs from the schools were collected. The dose-response relationship was examined using multivariate logistic regression modeling with cluster-correlated robust variance estimates to account for correlations of isolates between the environment and the students. Results: The prevalence rates of MRSA among 1705 students and 1240 environment samples were 10.15% and 3.87%, respectively. There were positive prevalence associations of school (odds ratio 1.09, 95% confidence interval [CI] 1.05–1.13) and class (odds ratio 1.03, 95% CI 1.01–1.06) environmental contamination with nasal carriage of MRSA isolates by students.Conclusions: Comparisons of MRSA isolates between the environment and the students in terms of phenotypic and molecular characterization were mostly insignificant. School environmental contamination with MRSA was positively associated with MRSA nasal carriage by elementary students. Disinfection measures and education regarding hand hygiene should be considered to decrease the prevalence of MRSA nasal carriage among students. Keywords: methicillin-resistant Staphylococcus aureus, school environment, contamination, elementary students, nasal carriage

Chunxue Bai,1 Masakazu Ichinose,2 Sang Haak Lee,3 Kwan Ho Lee,4 Olaf Jöns,5 Ulrich Bothner,6 Yihua Zhao,7 Roland Buhl8 1Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China; 2Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 3Department of Internal Medicine, St Paul’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 4Department of Internal Medicine, Yeungnam University Medical Center, Daegu, South Korea; 5Department of Medicine TA Respiratory Diseases, 6Department of Pharmacovigilance, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 7Department of Biostatistics and Data Sciences, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 8Pulmonary Department, Mainz University Hospital, Mainz, Germany Background and purpose: While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO® trials.Materials and methods: In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tiotropium/olodaterol, tiotropium, or olodaterol. We assessed the forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 3 hours (AUC0–3) response and trough FEV1 response at 24 weeks for the approved doses, tiotropium/olodaterol 5/5 µg, tiotropium 5 µg, and olodaterol 5 µg. Treatment-emergent adverse events were recorded throughout treatment and ≤21 days after study medication.Results: In the East Asian population, 1,152 patients were randomized (5,163 overall). After 24 weeks, FEV1 AUC0–3 and trough FEV1 responses were greater (P

Xixin Yan,1 Yuanlin Song,2,3 Ce Shen,4 Wenbing Xu,5 Liangan Chen,6 Jian Zhang,7 Huiguo Liu,8 Mao Huang,9 Guoxiang Lai,10 Guishen Qian,11 Jing Wang,12 Xianwei Ye,13 Jinping Zheng,14 Chunxue Bai21Department of Pulmonary and Critical Care Medicine, Second Hospital Affiliated to Hebei Medical University, Hebei, 2Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 3Shanghai Respiratory Research Institute, 4Department of Pulmonary Medicine, Shanghai 6th People’s Hospital, Jiaotong University, 5Department of Respiratory Disease, Peking Union Hospital, Beijing, 6Department of Pulmonary and Critical Care Medicine, Beijing 301 Military Hospital, Beijing, 7Department of Pulmonary Medicine, Xijing Hospital, The Affiliated Hospital of Fourth Military Medical University, 8Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, 9Department of Pulmonary Medicine, Jiangsu Province Hospital, First Affiliated Hospital of Nanjing Medical University, Nanjing, 10Department of Pulmonary and Critical Care Medicine, General Hospital of Fuzhou Military Region, Fuzhou, 11Department of Respiratory Medicine, Xinqiao Hospital, Third Military Medical University, Chongqing, 12Department of Respiratory Medicine, First Hospital Affiliated to Zhengzhou University, Zhengzhou, 13Department of Respiratory Medicine, People’s Hospital of Guizhou Province, Guizhou, 14Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaAbstract: Airway mucus hypersecretion is a frequent symptom associated with acute and chronic airway disease. Inhibition of mucus production or promotion of mucolysis not only relieved symptoms but also improved disease outcomes. There are numerous available mucoactive medicines for prescription, and how to select them properly for different diseases is important for clinical practice. So far, there is no one consensus or guideline reported. A group of Chinese pulmonary physicians worked together to complete this consensus based on literature review, summarized mechanism and usage of each classical mucoactive medicine. In general, antioxidant mucoactive medicines play an important role in chronic airway disease, including but not limited to airway mucus clearance, reduced acute exacerbation and improved pulmonary function.Keywords: sputum, chronic bronchitis, mucolysis

Long-term changes of soil nematode diversity and distribution patterns in replant peach orchard (RPO) and continuous-planting peach orchard (CPPO) were assessed to evaluate different effects on nematode community and function by RPO and CPPO, in relation to peach replant problem from the point of soil fauna. Observations were conducted on a silt loam soil, and soil sampling was performed four times through the growing season of peach trees in the period from 2006 to 2008 in Pinggu, Beijing. The result showed that RPO differed from CPPO by its higher abundance of plant feeding nematodes but lower abundance of bacterivore nematodes, as well as significantly higher values of plant parasite index but lower nematode biodiversity. Obviously, the absolute abundance of Paratylenchus in RPO was higher than that in CPPO, which could be a key factor for the peach replant problems from the part of soil nematode. Nematode function indices and weighted nematode fauna profile analysis were no significantly different in the two peach ecosystems, but they represented an indication of high disturbance, N-enriched, bacterial decomposition pathway.

In order to improve the energy utilization of rotary hearth furnace (RHF), some methods were raised to solve the problem. Through changing the inlet angle of the nozzle, a higher and more uniform temperature field can be got. Thus, the burden in the furnace can be heated to the reduction temperature in a relatively shorter time. By using multilayer pellets technology, the energy can be utilized as much as possible. However, the top layer pellets would be reoxidized when the middle and bottom layer pellets were reduced. The average metallization of the reduced pellets get the maximum value at 25 min, which is consistent with the reality operation.

Physic-chemical properties of slag at high temperature were very important for the production of ferronickel alloy by pyrometallurgical process. It determines the operation efficiency, metal recovery ratio, energy consumption and the distribution of elements (like S and P) between the slag and metal. In the present work, the effect of slag basicity on melting features and viscosity of the slag was investigated. The basicity of the SiO2-CaO-MgO-Al2O3-FeO quinary slag system varied from 0.76 to 0.99. The results showed that: 1) all the slag samples began to soften at the same temperature; 2) the softening temperature, melting temperature and flowing temperature decreased with the increase of basicity from 0.76 to 0.92, after that, the temperatures would increase sharply. 3) the inflection point temperature of viscosity-temperature curve became larger and larger with the increase of basicity within 0.76 ~ 0.99.

The granulation process, which is determined by many factors like properties of the mixture and the operating parameters, is of very importance for getting a good permeability of the burden in the sintering strand. The prediction of the size distribution of the granules and the permeability of its bed by the artificial neural network was studied in this paper. It was found by the experiments that the order of significance in the granulation process is water content added into the mixture, the mass fraction of the particles of 0.7-3 mm, and the moisture capacity. The water content added in the mixture and the mass fractions of the particles of 0.7-3 mm have the positive relation to the permeability of granulation, While, the moisture capacity has the negative relation to the permeability of granulation. Both the moisture capacity and the water content added were used as the inputs in the model of artificial neural network, which can give a good prediction on the permeability and mass fraction of the granules of 3-8 mm, as well as the tendency of the samples under instable raw materials conditions. These two models can be used for optimization the granulation.

The ferrotitanium alloy was prepared in the molten CaCl2 system, in which resolidified ilmenite and the graphite crucible were used as cathode and anode. In this study, the electrolytic voltage was fixed at 3.1V, and three different temperatures were applied: 850oC, 875oC and 900ºC. Finally, the product was examined by SEM and XRD to determine the phase transformation after the electrolysis. The results show that the ilmenite was firstly reduced to Fe, and finally the TiFe alloy was formed. The intermediate products include CaTiO3, TiO2, Ti2O3, TiO, Fe, TiFe2, and Ti. Different product and structure can be obtained by changing temperature. According to thermodynamic calculation, the principal electroreduction products are Ti and TiFe2 and then Ti and TiFe2 are formed by interdiffusion which is governed by temperature.

An investigation into the deoxidization mechanism of the electrochemical reduction of ilmenite concentrate to FeTi alloy in molten calcium chloride has been performed. The results show that deoxidization proceeds through a number of individual stages some of which involve reduction of iron, formation and desposition of calcium titanates(CaTiO3), reduction of the various low value titanium oxides and formation of Fe2Ti and FeTi. CaTiO3 is formed because Ca2+ contained in electrolyte take part in the deoxidization process.