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Mengyue Sun,1 Yuanyuan Liu,2 Shan Tang,2 Yiming Li,2 Ridong Zhang,2 Li Mao2 1Department of Geratology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of China; 2Department of Endocrinology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of ChinaCorrespondence: Li Mao, Email maoli_mail@126.comAim: This study investigated differences in gut flora between osteoporosis (OP) patients and healthy individuals using 16S rDNA sequencing. The correlation between differential flora abundance and bone mineral density (BMD) was analyzed, and key flora and potential mechanisms associated with OP were explored.Methods: Forty-three OP patients and twenty-four healthy volunteers were recruited. Gender, age, height, weight, and BMD data were collected. DNA from fecal samples was extracted for 16S rDNA sequencing. The Kruskal–Wallis test assessed differences in gut flora composition, while LEfSe analysis identified significant flora. Spearman correlation analysis examined the relationship between differential flora and BMD, and PICRUSt predicted pathways involved in OP.Results: Significant differences in microbial composition were found between the two groups. Klebsiella, Escherichia-Shigella, and Akkermansia were biomarkers in OP patients, with Faecalibacterium in the healthy group. Akkermansia abundance negatively correlated with lumbar BMD, while Klebsiella and Escherichia-Shigella negatively correlated with femoral neck and hip BMD. Faecalibacterium showed a positive correlation with BMD. Functional predictions indicated differences in metabolism-related pathways between the groups.Conclusion: Gut flora differed significantly between OP patients and healthy individuals. Akkermansia, Klebsiella, and Escherichia-Shigella could serve as diagnostic biomarkers for OP, highlighting the potential of gut flora in OP diagnosis and treatment.Keywords: osteoporosis, intestinal flora, 16S rDNA

Mingyue Sun, Weiqiang Xiao, Qingxia Xu Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Qingxia Xu, Department of Clinical Laboratory, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Dongming Road No. 127, Zhengzhou, Henan Province, People’s Republic of China, Tel +860371-65587147, Email qxiaxu@126.comObjective: Klebsiella michiganensis is an emerging pathogen. In this context, we characterised a strain fxq isolated from a cerebrospinal fluid specimen of a patient with tentorial meningioma, and the K. michiganensis isolate produced carbapenemases of KPC and NDM types.Methods: The Phoenix 100 Automated Microbiology System, MALDI-TOF and whole-genome sequencing were used to identify the species. Anti-microbial susceptibility testing was also conducted with the Phoenix 100. The plasmid locations of the blaKPC-2 and blaNDM-1 genes were determined by S1-nuclease pulsed-field gel electrophoresis and Southern blot. The transfer capacity of plasmids carrying blaKPC-2 and blaNDM-1 was investigated by conjugation experiments, and the resistance plasmid stability was evaluated by culture and subculture. K. michiganensis subtypes were identified by multi-locus sequence typing. We performed whole-genome sequencing to confirm species, characterise plasmids and analyse core genes.Results: fxq was originally identified as Klebsiella oxytoca and showed resistance to imipenem and meropenem, but whole-genome sequencing identified it to be K. michiganensis. The strain fxq belonged to the novel sequence type 202 (ST202) and carried the blaKPC-2 and blaNDM-1 genes located on the pB_KPC InFIA and pE_NDM IncU plasmids, respectively. The blaKPC-2-carrying plasmid was successfully transferred to Escherichia coli EC600 by conjugation, whereas the blaNDM-1 gene on the pE_NDM plasmid was not. The pB_KPC and pE_NDM plasmids demonstrated high stability.Conclusion: This work is the first report on a carbapenem-resistant clinical isolate K. michiganensis ST202 harbouring the blaKPC-2 and blaNDM-1 genes encoded by the IncFIA and IncU plasmids, respectively.Keywords: Klebsiella michiganensis, IncU plasmid, carbapenemase gene, NDM, KPC

Mingjun Gong,1 Min Sun,1 Yaqi Sun,2 Lijuan Jin,1 Shen Li3 1Sports Training College, Tianjin University of Sport, Tianjin, People’s Republic of China; 2Mental Health Institute, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Psychoneuromodulation Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Shen Li, Psychoneuromodulation Center, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, No. 13, Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel +86-22-88188875, Email lishen@tmu.edu.cnObjective: Using meta-analysis to comprehensively and quantitatively evaluate the impact of acute sleep deprivation on different sports performance of athletes, this study aims to provide scientific guidance for coaches in optimizing and adjusting training and competition arrangements.Methods: Establishing literature inclusion and exclusion criteria, we conducted searches in both Chinese and English databases. Using stata 14.0, we analyzed 75 indicators from 27 included literature, focusing on three aspects: the impact of acute sleep deprivation on overall athletic performance, the impact on sporting performance across various athletic abilities, and the disparities in athletic performance between morning and afternoon following acute sleep deprivation.Results: The effect size of acute sleep deprivation on overall athletic performance was − 0.56 (P< 0.05). Sub-analyses revealed effect sizes of − 0.23 (P< 0.05) for whole night sleep deprivation, − 1.17 (P< 0.05) for partial sleep deprivation at the end of the night, and − 0.25 (P> 0.05) for partial sleep deprivation in the beginning of the night. The effect sizes of acute sleep deprivation on high intensity intermittent exercise, skill control, speed, aerobic endurance, and explosive power indicators were − 1.57, − 1.06, − 0.67, − 0.54, and − 0.39 respectively (P< 0.05). The effect sizes of acute sleep deprivation on the overall athletic performance in the morning and afternoon were − 0.30, and − 1.11, respectively (P< 0.05).Conclusion: Acute sleep deprivation significantly impairs the overall athletic performance of athletes, with a more pronounced negative impact observed with partial sleep deprivation at the end of the night. Various types of exercise performance are adversely affected by acute sleep deprivation, with magnitude of impact ranking high intensity intermittent, skill control, speed, aerobic endurance, and explosive power. Following acute sleep deprivation, athletes’ overall sporting performance in the afternoon is inferior to that in the morning.Keywords: acute sleep deprivation, athletes, athletic ability, sporting performance, meta-analysis

Weiwei Guan,1,2 Congyue Zhang,1 Tongguo Miao,1 Chen Dong,1 Lu Li,1 Xiwei Yuan,1 Dandan Zhao,1 Rong Ai,1 Xiaoxiao Zhang,1 Mengjiao Sun,1 Haiyan Kang,2,&ast; Yuemin Nan1,&ast; 1Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2Department of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang, Hebei, 050023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuemin Nan, Department of Traditional and Western Medical Hepatology, Hebei Medical University Third Hospital & Hebei International Joint Research Center for Liver Cancer Molecular Diagnosis, Hebei International Science and Technology Cooperation Base, No. 139, Ziqiang Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 18533112266, Email nanyuemin@163.com Haiyan Kang, Department of Liver Disease, The Fifth Hospital of Shijiazhuang, Hebei Medical University, No. 42, Tanan Road, Shijiazhuang, Hebei Province, 050023, People’s Republic of China, Tel +86 13315952782, Email kanghaiyan1976@126.comPurpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC.Materials and Methods: High‐throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated.Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors.Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.Keywords: ADAMTSL4-AS1, AC067931, SOCS2-AS1, HBV-associated HCC, diagnostic biomarkers

Min Sun,1 Guanchi Yan,2 Siming Sun,3 Xiaonan Li,1 Wei Sun,4 Yuehui Wang1 1Department of Geriatrics, The First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, People’s Republic of China; 3Department of Clinical Research, The First Hospital of Jilin University, Changchun, People’s Republic of China; 4Education Department, The First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yuehui Wang, Department of Geriatrics, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130061, People’s Republic of China, Tel +86-13614303457, Email yuehuiwang300@jlu.edu.cn Wei Sun, Education Department, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, 130061, People’s Republic of China, Tel +86-16604302962, Email 18504381676@163.comBackground: Serum trace elements and oxidative stress factors are related to diabetic microvascular complications. The study was to investigate the complex relationship between trace elements, oxidative stress factors, and the severity of microvascular complications of diabetes in older adults.Methods: The present study included patients with or without type 2 diabetes, and blood glucose, blood lipids, trace elements (iron, magnesium, zinc), oxidative stress factors (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC)) were evaluated. Risk factors for the severity of diabetic microvascular complications in older adults with diabetes were also estimated.Results: There were statistically significant differences in fasting blood glucose (FBG), triglycerides (TG), low density lipoprotein (LDL), glycated hemoglobin (HbAlc), MDA, NO, SOD, T-AOC, magnesium, and zinc between the two groups (P< 0.05). Iron (rZinc = 0.147, rSOD = 0.180, rT-AOC = 0.193, P < 0.05) was positively correlated with zinc, SOD and T-AOC. Iron was negatively correlated with MDA (rMDA = − 0.146, P < 0.05). Magnesium was positively correlated with SOD (rMagnesium = 0.147, P < 0.05). Zinc (rSOD = 0.616, rT-AOC = 0.575, P < 0.01) was positively correlated with SOD and T-AOC. Zinc (rMDA =− 0.636, rNO=− 0.616, P< 0.01) was positively correlated with MDA and negatively correlated with NO. The course of disease (18.653, [5.726; 60.764], P < 0.01), FBG (1.265, [1.059; 1.511], P < 0.05), HbAlc (1.545, [1.431; 1.680], P < 0.01), MDA (2.989, [1.900; 4.702], P < 0.01) were risk factor for the severity of diabetic microvascular complications. Zinc (0.680, [0.503; 0.919], P < 0.05) and SOD (0.820, [0.698; 0.964], P < 0.05) were protective factors for the severity of diabetic microvascular complications.Conclusion: Serum trace elements are related to oxidative stress levels in older adults with type 2 diabetes. The more stable trace element in older adults with diabetes, the lower the oxidative stress and the fewer microvascular complications of diabetes.Keywords: type 2 diabetes mellitus, older adults, trace elements, diabetic microvascular complications, oxidative stress

Mingyue Sun, Zhuoyou Chen Department of Neurology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213000, People’s Republic of ChinaCorrespondence: Zhuoyou Chen, Email neuro1972@163.comAbstract: Alzheimer’s disease (AD) is the most common neurodegenerative illness, characterized by memory loss and cognitive decline, accounting for 60– 80% of dementia cases. AD is characterized by senile plaques made up of amyloid β (Aβ) protein, intracellular neurofibrillary tangles caused by hyperphosphorylation of tau protein linked with microtubules, and neuronal loss. Currently, therapeutic treatments and nanotechnological developments are effective in treating the symptoms of AD, but a cure for the illness has not yet been found. Recently, the increased study of extracellular vesicles (EVs) has led to a growing awareness of their significant involvement in neurodegenerative disorders, including AD. Exosomes are small extracellular vesicles that transport various components including messenger RNAs, non-coding RNAs, proteins, lipids, DNA, and other bioactive compounds from one cell to another, facilitating information transmission and material movement. There is growing evidence indicating that exosomes have complex functions in AD. Exosomes may have a dual role in Alzheimer’s disease by contributing to neuronal death and also helping to alleviate the pathological progression of the disease. Therefore, the primary aim of this review is to outline the updated understandings on exosomes biogenesis and many functions of exosomes in the generation, conveyance, distribution, and elimination of hazardous proteins related to Alzheimer’s disease. This review is intended to provide novel insights for understanding the development, specific treatment, and early detection of Alzheimer’s disease.Keywords: Alzheimer’s disease, exosomes, pathogenesis, diagnosis, treatment

Mengjuan Sun,1,&ast; Jun Wei,1,&ast; Yanhui Su,1,&ast; Yangjingwan He,1 Liang Ge,1 Yan Shen,1 Bohui Xu,2 Yanlong Bi,3 Chunli Zheng1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of China; 2School of Pharmacy, Nantong University, Nantong, People’s Republic of China; 3Pediatric Intensive Care Unit, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunli Zheng; Yanlong Bi, Email zhengchunli@cpu.edu.cn; pulong123@163.comPurpose: The purpose of this study is to address the high mortality and poor prognosis associated with Acute Respiratory Distress Syndrome (ARDS), conditions characterized by acute and progressive respiratory failure. The primary goal was to prolong drug circulation time, increase drug accumulation in the lungs, and minimize drug-related side effects.Methods: Simvastatin (SIM) was used as the model drug in this study. Employing a red blood cell surface-loaded nanoparticle drug delivery technique, pH-responsive cationic nanoparticles loaded with SIM were non-covalently adsorbed onto the surface of red blood cells (RBC), creating a novel drug delivery system (RBC@SIM-PEI-PPNPs).Results: The RBC@SIM-PEI-PPNPs delivery system effectively extended the drug’s circulation time, providing an extended therapeutic window. Additionally, this method substantially improved the targeted accumulation of SIM in lung tissues, thereby enhancing the drug’s efficacy in treating ARDS and impeding its progression to ARDS. Crucially, the system showed a reduced risk of adverse drug reactions.Conclusion: RBC@SIM-PEI-PPNPs demonstrates promise in ARDS and ARDS treatment. This innovative approach successfully overcomes the limitations associated with SIM’s poor solubility and low bioavailability, resulting in improved therapeutic outcomes and fewer drug-related side effects. This research holds significant clinical implications and highlights its potential for broader application in drug delivery and lung disease treatment.Keywords: acute lung injury, simvastatin, respiratory distress syndrome, pH response

Ting Yang,1,2 Yanan Du,1 Mingzhen Sun,1 Jingjing Meng,1 Yiyi Li1 1School of Health Services Management, Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 2Intelligent Interconnected Systems Laboratory of Anhui Province (Hefei University of Technology), Hefei, Anhui, 230009, People’s Republic of ChinaCorrespondence: Ting Yang, Email yangting@ahmu.edu.cnAbstract: Over the past decade, the global outbreaks of SARS, influenza A (H1N1), COVID-19, and other major infectious diseases have exposed the insufficient capacity for emergency disposal of medical waste in numerous countries and regions. Particularly during epidemics of major infectious diseases, medical waste exhibits new characteristics such as accelerated growth rate, heightened risk level, and more stringent disposal requirements. Consequently, there is an urgent need for advanced theoretical approaches that can perceive, predict, evaluate, and control risks associated with safe disposal throughout the entire process in a timely, accurate, efficient, and comprehensive manner. This article provides a systematic review of relevant research on collection, storage, transportation, and disposal of medical waste throughout its entirety to illustrate the current state of safe disposal practices. Building upon this foundation and leveraging emerging information technologies like Internet of Things (IoT), cloud computing, big data analytics, and artificial intelligence (AI), we deeply contemplate future research directions with an aim to minimize risks across all stages of medical waste disposal while offering valuable references and decision support to further advance safe disposal practices.Keywords: medical waste, safe disposal, major infectious diseases, progress and challenges

Yaohui Yi, Meng Sun, Jiachen Lu, Xiaofeng Dou, Yingying Yu, Ling Zhou School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of ChinaCorrespondence: Ling Zhou, School of Public Health, Dalian Medical University, Dalian City, Liaoning Province, People’s Republic of China, Tel +86-411-8611-0368, Email zhouling0609@163.comBackground: As future health workers, medical students’ attitudes towards tuberculosis (TB) patients can impact TB control. However, in China, there is a lack of well-quantified assessment regarding the stigma among medical students towards TB patients. Therefore, this study aimed to validate the Chinese version of the Tuberculosis related-Stigma Scale (TSS) in medical students and to apply the scale to measure stigma and its determinants.Methods: A total of 1035 eligible medical students participated in the cross-sectional questionnaire. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were first conducted to test Chinese version of the TSS construct validity, and then internal consistency was assessed using Cronbach’s α. Finally, multiple linear regression analyses were conducted to identify predictors of stigma.Results: EFA extracted two factors (“Social distance” and “Exclusionary sentiments”). The CFA further confirmed the two-factor construct. The internal consistency, convergent and divergent validity of the adapted Chinese version of the TSS was acceptable. Furthermore, Whether one has received TB health education and whether know a person with TB are associated with all dimensions of TB stigma, while differences in sex and place of residence play different roles in influencing the different dimensions of stigma.Conclusion: The adapted Chinese version of the TSS can be used to assess the level of stigma among medical students in China towards tuberculosis patients. When implementing future interventions to reduce stigma associated with TB, special attention should be given to medical students from urban areas, of male gender, who have not received TB health education, and no know a person with TB. However, these two dimensions (“Social distance” and “Exclusionary sentiments”) are impacted by different determinants and should therefore be addressed separately when designing, implementing, and evaluating measures to reduce stigma.Keywords: tuberculosis related-stigma scale, medical student, psychometrics, determinants

Chunyan Yang,&ast; Hao Tian,&ast; Guixing Xu, Qin Luo, Mingsheng Sun, Fanrong Liang Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanrong Liang, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No. 37 Shi’er Qiao Road, Chengdu, Sichuan, 610075, People’s Republic of China, Email acuresearch@126.comPurpose: The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD.Methods: Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence.Results: Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: − 3.25; 95% CI: − 3.73 to − 2.78, P< 0.001) and arterial blood gas (PaCO2: MD: − 1.85; 95% CI: − 2.74 to − 0.95, P< 0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P< 0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: − 0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: − 0.60 to 193.98, P = 0.051), hospitalization duration (MD: − 5.70; 95% CI: − 11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: − 0.19; 95% CI: − 0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in “high” risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in “some concern” and 1 RCT assessing hospitalization duration was in “low” risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported.Conclusion: Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.Keywords: acute exacerbation of chronic obstructive pulmonary disease, acupuncture, systematic review, meta-analysis

Hongjuan Wang,1 Rongzhi Li,1 Lin Ge,2 Fan Xu,1 James Allen Wiley,3 Siyuan Tang,1 Mei Sun1,4 1Xiangya School of Nursing, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Department of Alcohol Addiction and Internet Addiction, Brain Hospital of Hunan Province (The Second People’s Hospital of Hunan Province), Changsha, Hunan Province, People’s Republic of China; 3Department of Family and Community Medicine and Institute for Health Policy Research, University of California, San Francisco, CA, USA; 4School of Nursing, Changsha Medical University, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Siyuan Tang; Mei Sun, Xiangya School of Nursing, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China, Email sytang263@csu.edu.cn; smnjw2008@126.comBackground: Sleep-related outcomes in people with diabetes are poor, which is closely linked to reducing the development of diabetes. Cognitive behavioral therapy (CBT) based intervention presents innovative solutions that can help improve sleep-related outcomes.Aim: This synthesis aims to assess the effectiveness of CBT-based intervention compared to controls in Randomized Controlled Trials (RCTs) for sleep-related outcomes among people with diabetes.Methods: Eight electronic databases were systematically searched: PubMed, EMBASE, Cochrane library, Web of Science, PsycINFO, CINAHL, China National Knowledge Infrastructure (CNKI), and Wan Fang database. We examined CBT-based intervention’s effectiveness on sleep-related outcomes in people with diabetes in RCTs identified in these databases from their inception to 1st November 2023, and updated on 15 January 2024. The risk of bias was assessed using the Cochrane Risk of Bias tool by two reviewers. The meta-analysis of included studies was conducted by RevMan 5.3 software.Results: Seven studies in total (n = 2633 participants) were included in this systematic review based on our inclusion criteria. The systematic review found CBT-based intervention significantly improved sleep quality (Pittsburgh Sleep Quality Index, PSQI scores) at immediate post-intervention [95% CI=(− 1.31 to -0.32), p = 0.001], six months [95% CI=(− 0.75 to − 0.22), p = 0.0003], and 12 months [95% CI=(− 0.72 to − 0.24), < 0.0001], compared to control groups. Furthermore, our findings demonstrated that six sessions [95% CI= (− 0.38 to − 0.13), p < 0.0001] or more than six sessions [95% CI=(− 1.76 to − 0.02), p = 0.05] of CBT-based intervention could improve sleep quality compared to controls (I2=0%). Interestingly, CBT-based intervention improves total sleep time at post-intervention in people with diabetes compared to the control group [95% CI= (− 0.57 to − 0.12), p = 0.003]. However, there was no significant that CBT-based intervention is beneficial to time to fall asleep [95% CI (− 1.89 to 0.43), p = 0.22] and sleep efficiency [95% CI (− 1.27 to 0.27), p = 0.20] after intervention, compared to control group.Conclusion: CBT-based intervention appears to have a beneficial effect on improving sleep quality and total sleep time among people with diabetes. CBT-based intervention could be considered a strategy among healthcare providers to enhance sleep quality and total sleep time for people with diabetes. More RCTs with rigorous designs and long-term follow-up are warranted to provide conclusive evidence of the CBT-based intervention on sleep-related outcomes and to explore the mechanisms by which the CBT-based interventions improve sleep-related outcomes.Keywords: diabetes, cognitive behavioral therapy, sleep, systematic review, meta-analysis

Man Sun,1 Huan Zhang,1 Jiayi Liu,1 Jiayi Chen,1 Yaxin Cui,1 Simiao Wang,1 Xiangyu Zhang,2 Zhaogang Yang1 1School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China; 2Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310020, People’s Republic of ChinaCorrespondence: Xiangyu Zhang; Zhaogang Yang, Tel/Fax +86-431-85155320, Email 3314023@zju.edu.cn; zhaogangyang@jlu.edu.cnAbstract: Recently, gene therapy has become a subject of considerable research and has been widely evaluated in various disease models. Though it is considered as a stand-alone agent for COVID-19 vaccination, gene therapy is still suffering from the following drawbacks during its translation from the bench to the bedside: the high sensitivity of exogenous nucleic acids to enzymatic degradation; the severe side effects induced either by exogenous nucleic acids or components in the formulation; and the difficulty to cross the barriers before reaching the therapeutic target. Therefore, for the successful application of gene therapy, a safe and reliable transport vector is urgently needed. Extracellular vesicles (EVs) are the ideal candidate for the delivery of gene drugs owing to their low immunogenicity, good biocompatibility and low toxicity. To better understand the properties of EVs and their advantages as gene drug delivery vehicles, this review covers from the origin of EVs to the methods of EVs generation, as well as the common methods of isolation and purification in research, with their pros and cons discussed. Meanwhile, the engineering of EVs for gene drugs is also highlighted. In addition, this paper also presents the progress in the EVs-mediated delivery of microRNAs, small interfering RNAs, messenger RNAs, plasmids, and antisense oligonucleotides. We believe this review will provide a theoretical basis for the development of gene drugs.Keywords: extracellular vesicles, gene therapy, drug delivery system, gene drugs

Miaomiao Sun,1– 3,&ast; Fuquan Wang,1– 3,&ast; Haopeng Li,1– 3 Mengyu Li,1– 3 Yu Wang,1– 3 Chenchen Wang,1– 3 Yan Zhang,1– 3 Dingyu Zhang,1– 4 Jianhua Li,5 Shanglong Yao1– 3 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, 430022, People’s Republic of China; 4Wuhan Jinyintan Hospital, Wuhan, 430023, People’s Republic of China; 5Department of Critical Care Medicine, Chongqing University Jiangjin Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanglong Yao; Jianhua Li, Email yaoshanglong@hust.edu.cn; jianhuali2022@cqu.edu.cnBackground: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation.Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay.Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1β and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1β also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1’s protective effects in septic mice.Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.Keywords: Maresin-1, pyroptosis, AMPK/SIRT3, endoplasmic reticulum stress, sepsis-associated acute kidney injury, inflammation

Xiaodong Xu,&ast; Yuan Tao,&ast; Yitian Yang, Jiaqiang Zhang, Mingyang Sun Department of Anesthesiology and Perioperative Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, 450003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiaqiang Zhang; Mingyang Sun, Department of Anesthesiology and Perioperative Medicine, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, 450003, People’s Republic of China, Tel +0 371 6558 0728, Email zhangjiq@zzu.edu.cn; mingyangsun1986@163.comPurpose: We investigate the efficacy and safety of butorphanol in multimodal analgesia combined with dexmedetomidine and ketorolac via patient-controlled intravenous analgesia (PCIA) after hepatobiliary surgery, as compared with sufentanil.Patients and Methods: Postoperative follow-up data of hepatobiliary surgery patients in Henan Provincial People’s Hospital from March 2018 to June 2021 were collected retrospectively and divided into butorphanol group (group B) or sufentanil group (group S) according to the postoperative intravenous controlled analgesia scheme. The baseline characteristics and surgical information of the two groups were matched through propensity score matching (PSM).Results: A total of 3437 patients were screened, and PSM yielded 1816 patients after matching, including 908 in the butorphanol group and 908 in the sufentanil group. Compared with group S, the incidence of moderate-to-severe pain on the first postoperative day and the second postoperative day was lower in group B during rest (3.2% vs 10.9%, P< 0.001; 1.2% vs 4.6%, P< 0.001), and during movement (7.0% vs 18.9%, P< 0.001; 2.6% vs 8.7%, P< 0.001). Patients receiving butorphanol had a lower morphine consumption (50mg vs 120mg, P< 0.001). The bolus attempts of an analgesic pump in group B were significantly lower than in group S (1 vs 2, P< 0.001). Postoperative hospital length of stay was shortened in group B (11d vs 12d, P=0.017). The occurrence of postoperative vomiting was lower in group B (1.4% vs 3.0%, P=0.025) than in group S. However, more patients in group B experienced dizziness (0.9% vs 0.1%, P=0.019).Conclusion: Compared with sufentanil, the application of butorphanol in multimodal analgesia combined with dexmedetomidine and ketorolac via PCIA ameliorated postoperative pain after hepatobiliary surgery, with reduced opioid consumption and shorter postoperative hospital length of stay.Keywords: patient controlled intravenous analgesia, butorphanol, sufentanil, propensity score matching

Yue Zhang,1,2,&ast; Meiyan Sun,2,&ast; Hongxiang Zhao,1,2,&ast; Zhengyan Wang,2 Yanan Shi,2 Jianxin Dong,2 Kaifang Wang,3 Xi Wang,4 Xingyue Li,5 Haiyan Qi,6 Xiaoyong Zhao1,2,7 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 3Department of Anesthesia, Tangdu Hospital, Fourth Military Medical University, Xian, Shanxi Province, People’s Republic of China; 4Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 6Department of Anesthesiology, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 7Department of Anesthesiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyong Zhao; Haiyan Qi, Email xyzhao83@163.com; qihy123@163.comAbstract: Dichloroacetate (DCA) is an investigational drug used to treat lactic acidosis and malignant tumours. It works by inhibiting pyruvate dehydrogenase kinase and increasing the rate of glucose oxidation. Some studies have documented the neuroprotective benefits of DCA. By reviewing these studies, this paper shows that DCA has multiple pharmacological activities, including regulating metabolism, ameliorating oxidative stress, attenuating neuroinflammation, inhibiting apoptosis, decreasing autophagy, protecting the blood‒brain barrier, improving the function of endothelial progenitor cells, improving mitochondrial dynamics, and decreasing amyloid β-protein. In addition, DCA inhibits the enzyme that metabolizes it, which leads to peripheral neurotoxicity due to drug accumulation that may be solved by individualized drug delivery and nanovesicle delivery. In summary, in this review, we analyse the mechanisms of neuroprotection by DCA in different diseases and discuss the causes of and solutions to its adverse effects.Keywords: dichloroacetate, neuroprotection, mitochondria, energy metabolism, oxidative stress

Ni Meng, Xiaolong Cheng, Mengyao Sun, Yushan Zhang, Xueke Sun, Xifu Liu, Jing Chen Ministry of Education Key Laboratory of Molecular and Cellular Biology; Hebei Anti-Tumor Molecular Target Technology Innovation Center; Hebei Research Center of the Basic Discipline of Cell Biology; College of Life Science, Hebei Normal University, Shijiazhuang, 050024, People’s Republic of ChinaCorrespondence: Jing Chen; Xifu Liu, Email jingchen@hebtu.edu.cn; xfliu@hebtu.edu.cnIntroduction: The monkeypox (Mpox) virus epidemic presents a significant risk to global public health security. A35R, a crucial constituent of EEV, plays a pivotal role in virus transmission, serves as a vital target for vaccine development, and has potential for serological detection. Currently, there is a dearth of research on nanobodies targeting A35R. The purpose of this study is to identify specific nanobodies target A35R, so as to provide new antibody candidates for Mpox vaccine development and diagnostic kit development.Methods: Three nanobodies specific to the monkeypox virus protein A35R were screened from a naïve phage display library. After four rounds of panning, positive phage clones were identified by enzyme-linked immunosorbent assay (ELISA). Further, the nanobody fusion protein was constructed in pNFCG1-IgG1-Fc vector and expressed in HEK293F cells and purified by affinity chromatography. The specificity and affinity of the nanobodies were identified by ELISA. The binding kinetics of the VHH antibody to A35R were assessed via employment of a bio-layer interferometry (BLI) apparatus, thereby determining the nanobodies affinity.Results: The three purified nanobodies showed specific high-affinity binding MPXV A35R, of them, VHH-1 had the best antigen binding affinity (EC50 = 0.010 ug/mL). In addition, VHH-1 on Protein A biosensor can bind Mpox virus A35R, with an affinity constant of 54 nM as determined in BLI assay.Conclusion: In sum, we has obtained three nanobody strains against Mpox virus A35R with significant affinity and specificity, therefore laying an essential foundation for further research as well as the applications of diagnostic and therapeutic tools of Mpox virus.Keywords: monkeypox virus, A35R, nanobody, phage display library

Xing Zhang,1,&ast; Yuanyuan Song,1,&ast; Hongyang Gong,1,&ast; Chunyan Wu,1 Binquan Wang,1 Wenxuan Chen,2 Jiawei Hu,2 Hanhui Xiang,2 Ke Zhang,1 Mingkuan Sun1 1Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2The Second Clinical Medical School, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingkuan Sun, Department of Toxicology, School of Public Health, Nanjing Medical University, No. 101 Longmian Avenue, Jiangning District, Nanjing, 211166, People’s Republic of China, Email sunmk@njmu.edu.cnAbstract: The increasing use of titanium dioxide nanoparticles (TiO2 NPs) across various fields has led to a growing concern regarding their environmental contamination and inevitable human exposure. Consequently, significant research efforts have been directed toward understanding the effects of TiO2 NPs on both humans and the environment. Notably, TiO2 NPs exposure has been associated with multiple impairments of the nervous system. This review aims to provide an overview of the documented neurotoxic effects of TiO2 NPs in different species and in vitro models. Following exposure, TiO2 NPs can reach the brain, although the specific mechanism and quantity of particles that cross the blood-brain barrier (BBB) remain unclear. Exposure to TiO2 NPs has been shown to induce oxidative stress, promote neuroinflammation, disrupt brain biochemistry, and ultimately impair neuronal function and structure. Subsequent neuronal damage may contribute to various behavioral disorders and play a significant role in the onset and progression of neurodevelopmental or neurodegenerative diseases. Moreover, the neurotoxic potential of TiO2 NPs can be influenced by various factors, including exposure characteristics and the physicochemical properties of the TiO2 NPs. However, a systematic comparison of the neurotoxic effects of TiO2 NPs with different characteristics under various exposure conditions is still lacking. Additionally, our understanding of the underlying neurotoxic mechanisms exerted by TiO2 NPs remains incomplete and fragmented. Given these knowledge gaps, it is imperative to further investigate the neurotoxic hazards and risks associated with exposure to TiO2 NPs. Keywords: TiO2 NPs, neurotoxic effects, oxidative stress, neuronal damage, neurotoxic mechanisms

OBJECTIVES High-need, high-cost (HNHC) patients represent a small proportion of patients in the US, but result in disproportionately higher healthcare utilization. Teaching Internal Medicine (IM) resident trainees to provide high value care for HNHC patients is critical. We sought to improve resident attitudes and increase clinical skills associated with treating HNHC patients by creating a curriculum that leveraged the UCLA Extensivist Program, a patient-centered medical home for HNHC patients. METHODS We developed a curriculum for PGY-2 and PGY-3 IM residents centered on caring for HNHC patients over the course of 6, 4h sessions during 1 academic year. Participants completed pre- and post-intervention surveys assessing self-rated attitudes and skills associated with caring for an HNHC patient population. RESULTS Twenty-one IM residents completed the curriculum and 41 were in the control group. There were no statistically significant differences in assessed attitudes and skills, but there were trends of improvement, including a decrease in participants who agreed or strongly agreed they felt overwhelmed when seeing patients for posthospital discharge follow up (45.0% pre- to 41.7% post-intervention) and an increase in participants who agreed or strongly agreed they have the skills to successfully transition HNHC patients between inpatient and ambulatory settings (20.0% pre- to 33.3% post-intervention). Participants reported better understanding of resources available to HNHC patients, effective coordination of transitions of care, and comprehensive assessment of social determinants of health. CONCLUSION A curriculum to improve resident attitudes and skills associated with caring for HNHC patients was successfully implemented in an IM program at a large academic medical center. The curriculum may be adapted for other training programs; long-term training woven throughout training may be important to significantly improve resident education on how to care for HNHC patients.

Abstract Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late‐stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes‐rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles‐rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early‐stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late‐stage PDAC patients undergoing chemotherapy, lower GPC1 tMV‐mProtein and Exo‐mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Cong Xia,1 Ting Wei,2,3 Qi Tang,2,3 Hongying Zheng,2,3 Mei Sun,2,3 Gang Chen,2,3 Jun Lv2,3 1School of Health Management Anhui Medical University, Hefei, People’s Republic of China; 2School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3China Research Center on Disability, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Gang Chen; Jun Lv, School of Public Health, Fudan University, 130 Dong’an Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86-13661432703 ; +86-13671684324, Email gchen@shmu.edu.cn; lujun@shmu.edu.cnPurpose: To investigate the family support, anxiety, depression, health-related quality of life (HRQoL), and their associations among parents and grandparents of children with disabilities.Methods: This is a cross-sectional study and a total of 327 family caregivers were included. Chi-square test, Mann–Whitney U-test, and two independent t-test were used to identify the intergenerational differences in sociodemographic characteristics, received family support, anxiety, depression, and HRQoL. Eight generalized linear models were developed to examine the associations in both generations.Results: Parents and grandparents were most in need of rehabilitation and financial support, but both populations received the least amount of financial support. 33.6% and 36.1% of family caregivers had the risk of anxiety and depression and found no significant intergenerational differences. As for HRQoL, intergenerational differences were found in the physical component score, but not found in the mental component score. Among parents, childcare support of respite care and household tasks assistance was negatively associated with their depression (p< 0.05), professional support of appropriate surgery for children (p< 0.05) and psychological support from professional psychologists (p< 0.01) were negatively associated with their anxiety and depression, psychological support from relatives and friends was negatively associated with their depression (p< 0.05) whereas was positively associated with their mental HRQoL (p< 0.01). As for grandparents, financial support for daily living expenses was negatively associated with depression (p< 0.05), and psychological support from families was negatively associated with depression (p< 0.05) whereas was positively associated with mental HRQoL (p< 0.05). However, no relationship was found between family support and anxiety among grandparents. Notably, no association was found between family support and physical HRQoL among both populations.Conclusion: Both parents and grandparents had high risks of anxiety, depression and low levels of mental HRQoL. To efficiently improve psychological health, care providers and policymakers may consider intergenerational differences and provide targeted family support.Keywords: mental health, health-related quality of life, family support, children with disabilities, intergenerational differences

Mei Sun,&ast; Yankai Wei,&ast; Chengyuan Zhang, Hong Nian, Bei Du, Ruihua Wei Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruihua Wei, Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 251 Fukang Road, Nankai District, Tianjin, 300384, People’s Republic of China, Tel/Fax +86 86428862, Email rwei@tmu.edu.cnPurpose: Sjögren’s syndrome-related dry eye (SS-related dry eye) is an intractable autoimmune disease characterized by chronic inflammation of lacrimal glands (LGs), where epigenetic factors are proven to play a crucial role in the pathogenesis of this disease. However, the alteration of DNA methylation in LGs and its role in the pathogenesis of SS-related dry eye is still unknown. Here, we performed an integrated analysis of DNA methylation and RNA-Seq data in LGs to identify novel DNA methylation-regulated differentially expressed genes (MeDEGs) in the pathogenesis of SS-related dry eye.Methods: The DNA methylation and transcription profiles of LGs in NOD mice at different stages of SS-related dry eye (4-, 8-, 12- and 16 weeks old) were generated by reduced representation bisulfite sequencing (RRBS) and RNA-Seq. The differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were analyzed by MethylKit R package and edgeR. Correlation analysis between methylation level and mRNA expression was conducted with R software. The functional correlation of DMGs and DEGs was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, LG tissues from another litter of NOD mice were collected for methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) to validate the methylation and expression levels of key genes. CD4+ cell infiltration of LGs was detected by immunofluorescence staining.Results: Hypermethylation of LGs was identified in NOD mice with the progression of SS-related dry eye and the DMGs were mainly enriched in the GTPases activation and Ras signaling pathway. RNA-seq analysis revealed 1321, 2549, and 3712 DEGs in the 8-, 12- and 16-week-old NOD mice compared with 4-week-old normal control mice. For GO analysis, the DEGs were mainly enriched in T cell immune responses. Further, a total of 140 MeDEGs were obtained by integrated analysis of methylome and transcriptome, which were primarily enriched in T cell activation, proliferation and differentiation. Based on the main GO terms and KEGG pathways of MeDEGs, 8 genes were screened out. The expression levels of these key genes, especially Itgal, Vav1, Irf4 and Icosl, were verified to elevate after the onset of SS-related dry eye in NOD mice and positively correlated with the extent of inflammatory cell infiltration in LGs. Immunofluorescence assay revealed that CD4+ cell infiltration dramatically increased in LGs of SS-related dry eye mice compared with the control mice. And the expression levels of four genes showed significantly positive correlation with the extent of CD4+ cell infiltration in LGs. MSP showed the hypomethylation of the Irf 4 and Itgal promoters in NOD mice with SS-related dry eye compared to control group.Conclusion: Our study revealed the critical role of epigenetic regulation of T cell immunity-related genes in the progression of SS-related dry eye and reminded us that DNA methylation-regulated genes such as Itgal, Vav1, Irf4 and Icosl may be used as new targets for SS-related dry eye therapy.Keywords: Sjögren’s syndrome-related dry eye, lacrimal gland, DNA methylation, RNA-seq, T cell-mediated immune response

Yang Qian, Chenting Cai, Mengqing Sun, Dan Lv, Yun Zhao The First Affiliated Hospital of Ningbo University, Ningbo, People’s Republic of ChinaCorrespondence: Dan Lv, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China, Email fylvdan@nbu.edu.cnAbstract: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is the exacerbation of a range of respiratory symptoms during the stable phase of chronic obstructive pulmonary disease (COPD). AECOPD is thus a dangerous stage and key event in the course of COPD, as its deterioration and frequency seriously affects the quality of life of patients and shortens their survival. Acute exacerbations occur and develop due to many factors such as infection, tobacco smoke inhalation, air pollution, comorbidities, airflow limitation, various biomarkers, history of previous deterioration, natural killer cell abnormalities, immunoglobulin G deficiency, genetics, abnormal muscle and nutritional status, negative psychology, and seasonal temperature changes. There is relatively limited research on the impact of the role of standardized management on the alleviation of AECOPD. However, with the establishment of relevant prevention and management systems and the promotion of artificial intelligence technology and Internet medical approaches, long-term effective and standardized management of COPD patients may help to achieve the quality of life and disease prognosis in COPD patients and reduce the risk of AE.Keywords: chronic obstructive pulmonary disease, acute exacerbation, related risk factors

Meng Sun,1– 3,&ast; Zhouyang Wu,1– 3,&ast; Rong Wang,1– 3 Rui Xia,1– 3 Yi Sun,1– 3 Elham Esmaeili,1– 3 Zhengyuan Xia,4,5 Zhilin Wu,1– 3 Tingting Wang1– 3 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 3Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, People’s Republic of China; 4State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, People’s Republic of China; 5Department of Anesthesiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tingting Wang; Zhilin Wu, Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China, Tel +862785351643, Email wangtt201307@163.com; 840916@qq.comBackground: Erector spinae plane block (ESPB) is an easy and safe method for postoperative analgesia. However its effect lasts only for several hours. This trial was to investigate the effectiveness of different doses of nalbuphine as an adjuvant to ropivacaine in ESPB for patients undergoing percutaneous nephrolithotomy (PCNL).Methods: Patients scheduled for PCNL were randomized into three groups and received ultrasound-guided ESPB at T10 level for postoperative analgesia. Each subject received 28 mL of 100 mg ropivacaine solution mixed with 2 mL of normal saline (Group R), 2 mL of 10 mg nalbuphine (Group RNL), or 2 mL of 20 mg nalbuphine (Group RNH). Primary outcome was the time to first opioid demand. Secondary outcomes were morphine consumption, VAS scores within 24 h postoperatively, rescue analgesic requirements, and length of hospital stay.Results: The median [interquartile range, IQR] time to first opioid demand was significantly longer in group RNH (8.70 [6.90,14.85] h) than that of group R and group RNL (2.90 [2.00,6.30] h and 5.80 [2.95,7.00] h, respectively). VAS scores (either resting or active) within 24 h postoperatively were comparable between the three groups, with the most significant differences especially at 4, 6, 8 h. Morphine consumption at 24 h postoperatively was significant for R group vs RNH group (median difference, 9; 95% confidence interval [CI], 1.57 to 16.43; p = 0.02).Conclusions: Adding 20mg nalbuphine to ropivacaine in ESPB could significantly improve the effect of analgesia and prolong the duration of nerve blocks for PCNL.Keywords: adjuvant, erector spinae plane block, nalbuphine, percutaneous nephrolithotomy, postoperative pain

Meiyan Sun,1,2,&ast; Xiaoyong Zhao,2,&ast; Xingyue Li,2 Chunling Wang,2 Lili Lin,3 Kaifang Wang,2 Yingui Sun,2 Wei Ye,3 Haiyan Li,3 Ye Zhang,1 Chaolu Huang2,4 1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, 261053, People’s Republic of China; 3The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 4Department of Clinical Medicine, Qiandongnan Ethnic Vocational and Technical College, Kaili, 556000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Zhang, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China, Email zhangy@ahmu.edu.cn Chaolu Huang, Department of Clinical Medicine, Qiandongnan Ethnic Vocational and Technical College, Kaili, 556000, People’s Republic of China, Email huangzhaolu2020@163.comObjective: Diabetes mellitus (DM) implicates oxidative stress, apoptosis, and inflammation, all of which may contribute liver injury. Aerobic exercise is assured to positively regulate metabolism in the liver. This project was designed to investigate whether and how aerobic exercise improves DM-induced liver injury.Methods: Seven-week-old male db/db mice and age-matched m/m mice were randomly divided into a rest control group or a group that received 12 weeks of aerobic exercise by treadmill training (10 m/min). Haematoxylin and eosin (HE) staining, electron microscopy, Oil Red O staining and TUNEL assays were used to evaluate the histopathological changes in mouse liver. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TRIG), cholesterol (CHOL) were analyzed by serum biochemical analysis. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed via ELISA. Nuclear factor E2-associated factor-2 (Nrf2), nuclear factor κB (NF-κB) and JAK2/STAT3 pathway-related proteins were measured by immunofluorescence, Western blotting and q-PCR. F4/80 expression in liver tissues was assessed by immunohistochemistry.Results: In diabetic mice, exercise training significantly decreased the levels of serum TRIG, CHOL, IL-6, TNF-α, ALT and AST; prevented weight gain, hyperglycaemia, and impaired glucose and insulin tolerance. Morphologically, exercise mitigated the diabetes-induced increase in liver tissue microvesicles, inflammatory cells, F4/80 (macrophage marker) levels, and TUNEL-positive cells. In addition, exercise reduced the apoptosis index, which is consistent with the results for caspase-3 and Bax. Additionally, exercise significantly increased SOD activity, decreased MDA levels, activated Nrf2 and decreased the expression of NF-kB, phosphorylated JAK2 and STAT3 proteins in the livers of diabetic mice.Conclusion: This study demonstrated that aerobic exercise reversed liver dysfunction in db/db mice with T2DM by reducing oxidative stress, apoptosis and inflammation, possibly by enhancing Nrf2 expression and inhibiting the JAK2/STAT3 cascade response.Keywords: db/db mice, aerobic exercise, inflammation, apoptosis, Nrf2, JAK2/STAT3

Ya Wang,1,&ast; Jiajia Zhang,2,&ast; Xiaoyan Chen,1,&ast; Min Sun,3 Yanqing Li,4 Yanan Wang,5 Yan Gu,6 Yinyin Cai1 1Neurosurgical Intensive Care Unit, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 2Neurosurgery Section Two, Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 3Department of Geriatrics Section Three, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 4Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 5Respiratory and Critical Care Medicine Intensive Care Unit, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 6Infection Management Office, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Chen, Email CXYtdfy@126.comObjective: To develop a predictive model for assessing the risk of multidrug-resistant organisms (MDROs) infection and validate its effectiveness.We conducted a study on a total of 2516 patients admitted to the neurosurgery intensive care unit (NICU) of a Grade-III hospital in Nantong City, Jiangsu Province, China, between January 2014 and February 2022. Patients meeting the inclusion criteria were selected using convenience sampling. The patients were randomly divided into modeling and validation groups in a 7:3 ratio. To address the category imbalance, we employed the Synthetic Minority Over-sampling Technique (SMOTE) to adjust the MDROs infection ratio from 203:1558 to 812:609 in the training set. Univariate analysis and logistic regression analysis were performed to identify risk factors associated with MDROs infection in the NICU. A risk prediction model was developed, and a nomogram was created. Receiver operating characteristic (ROC) analysis was used to assess the predictive performance of the model.Patients and Methods: Results: Logistic regression analysis revealed that sex, hospitalization time, febrile time, invasive operations, postoperative prophylactic use of antibiotics, mechanical ventilator time, central venous catheter indwelling time, urethral catheter indwelling time, ALB, PLT, WBC, and L% were independent predictors of MDROs infection in the NICU. The area under the ROC curve for the training set and validation set were 0.880 (95% CI: 0.857– 0.904) and 0.831 (95% CI: 0.786– 0.876), respectively. The model’s prediction curve closely matched the ideal curve, indicating excellent predictive performance.Conclusion: The prediction model developed in this study demonstrates good accuracy in assessing the risk of MDROs infection. It serves as a valuable tool for neurosurgical intensive care practitioners, providing an objective means to effectively evaluate and target the risk of MDROs infection.Keywords: multidrug-resistant, infection, neurosurgical intensive care unit, nomogram

Miaomiao Sun,1,2 Fahad Alam,3 Cunxiao Ma4 1School of Ethnology and Historiography, Ningxia University, Yinchuan, People’s Republic of China; 2The Party School of the CPC, Ningxia Hui Autonomous Region Party Committee, Ningxia Administration Institute, Yinchuan, People’s Republic of China; 3School of Economics and Management, University of Science and Technology Beijing, Beijing, People’s Republic of China; 4School of Marxism, Shandong Yingcai University, Jinan, People’s Republic of ChinaCorrespondence: Fahad Alam, School of Economics and Management, University of Science and Technology Beijing, Beijing, Email fahadalam@xs.ustb.edu.cnBackground: High turnover rates among nurses are a global concern due to the shortage of skilled professionals and increasing demand for high-quality healthcare. This study aims to enhance understanding of organizational fit by examining the impact of Person-organization fit (P-O fit) on organizational loyalty through the mediating role of organizational support and service quality, and the moderating impact of role ambiguity.Methods: Using a convenience sampling technique, we employed a survey methodology by developing a questionnaire. Data were collected from a sample of 614 nurses in five different healthcare sectors in China. Employing SmartPLS 3.3, we conducted a Structural Equation Modeling (SEM) analysis to examine the relationships among the specified variables.Results: The findings of the structural analysis suggest that the P-O fit influences organizational loyalty in the healthcare sector. Organizational support and service quality were identified as partial mediators of the P-O fit-organizational loyalty link. Additionally, the role of ambiguity represented a negative moderating impact between service quality and organizational loyalty.Discussion: Overall, the study’s findings extend the understanding of person-organization fit, organizational support, service quality, role ambiguity, and organizational loyalty in the context of healthcare sectors and offer implications for medical authorities. Discussions, limitations, practical implications, and suggestions for further research are also provided.Keywords: person-organization fit, organizational support, service quality, role ambiguity, organizational loyalty

Shiqi Sun,1,&ast; Lu Liu,1,&ast; Mengdi Zhou,1 Yi Liu,1 Mingsheng Sun,1 Ling Zhao1,2 1Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Acupuncture and Moxibustion in Prevention and Treatment of Geriatric Diseases (Chengdu University of Traditional Chinese Medicine), Ministry of Education, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Zhao; Mingsheng Sun, Email zhaoling@cdutcm.edu.cn; sunmingsheng@163.comPurpose: To assess the inhibitory effect of acupuncture on pain symptoms in migraine models, and to further summarize the potential mechanisms of acupuncture in regulating hyperalgesia in the treatment of migraine.Materials and Methods: Literature search in databases such as China National Knowledge Infrastructure (CNKI), PubMed, and Web of Science (WOS) etc. The quality was evaluated by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) bias risk assessment tool and Collaborative Approach to Meta-analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Meta-analyses were performed using Stata 17.0 software.Results: Twenty-one studies involving 489 animals were identified. The qualitative score ranged from 3 to 9 points. Facial mechanical withdrawal threshold (FMWT) and paw mechanical withdrawal threshold (PMWT) measured by Von Frey filaments were selected as major outcomes, and serum calcitonin gene-related peptide (CGRP) levels measured by ELISA were selected as secondary outcome. Meta-analysis results revealed that true acupuncture (TA) group significantly increased FMWT, PMWT and CGRP compared to model group. TA group showed superior effect in FMWT, PMWT relative to sham acupuncture (SA) group. Subgroup analysis results showed that high risk of bias scores may be responsible for the high heterogeneity of FMWT; additionally, CGRP analysis suggests that acupoint selection and blood collection sites may be sources of heterogeneity. In the treatment of migraine pain symptoms, the underlying mechanism of acupuncture treatment is either the regulation of hyperalgesia and neurotransmitters, or the reduction of inflammatory factors.Conclusion: The results indicate that TA treatment effectively increased the pain threshold and reduced hyperalgesia in migraine rats. In summary, our study highlights the potential of TA as an effective treatment for migraine, but further investigation is required to fully comprehend its mechanism of action and optimize its clinical application.Keywords: migraine, acupuncture, hyperalgesia, systematic review, meta-analysis

Jianwei Liu,1,&ast; Minmin Sun,2,&ast; Kunpeng Fang,3,&ast; Jie Wang,1 Bowen Ma,1 Li Song,1 Ting Liu,1 Ming Tang,4 Kui Wang,1 Yong Xia4 1Department of Hepatic Surgery II, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 2Department of Hepatic Surgery I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 3Department of Special Treatment I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 4Department of Hepatic Surgery IV, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Xia, Department of Hepatic Surgery (IV), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-2181875005, Fax +86-2165562400, Email xia.yong@126.com Kui Wang, Department of Hepatic Surgery (II), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Email wangkuiykl@163.comPurpose: To investigate the effect of different liver resection modalities on the prognosis of left lateral lobe hepatocellular carcinoma (HCC) patients.Methods: 315 patients with HCC on left lateral lobe were divided into open left lateral lobectomy (LLL) group (n=249) and open left hepatectomy (LH) group (n=66). The differences in long-term prognosis between two groups were compared.Results: The results showed that narrow resection margin (Hazard Ratio (HR):1.457, 95% Confidential Interval (CI): 1.038– 2.047; HR:1.415, 95% CI: 1.061– 1.887), tumor diameter > 5 cm (1.645, 1.161– 2.330; 1.488, 1.123– 1.971), multiple tumors (2.021, 1.330– 3.073; 1.987, 1.380– 2.861), and microvascular invasion (MVI) (1.753, 1.253– 2.452; 1.438, 1.087– 1.902) are independent risk factors for overall survival (OS) and tumor recurrence (TR), while liver resection modality is not. After propensity score matching, liver resection modality is not an independent risk factor for OS and TR. Further analysis revealed that wide resection margins were achieved in all patients in the LH group but only 59.0% patients in the LLL group. The OS and TR rates were not significantly different between wide patients with resection margins in LLL group and LH group (P=0.766 and 0.919, respectively), but significantly different between patients with narrow resection margins in LLL group and LH group (P=0.012 and 0.017, respectively).Conclusion: Liver resection modality is not an independent risk factor for the prognosis of patients with HCC on the left lateral lobe as long as wide margins are obtained. Nevertheless, with narrow margins, patients who underwent LH rather than LLL did better.Keywords: hepatocellular carcinoma, left lateral hepatic lobe, left lateral lobectomy, left hepatectomy, prognosis

Weiqiang Xiao,1,&ast; Xiaokun Wang,1,&ast; Yuanye Qu,1 Mingyue Sun,1 Yanmin Chang,1 Wenjiao Li,1 Yong Shen,1,2 Xiufang Shi,3 Min Jing,1 Qingxia Xu1,4 1Department of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Institute of Biophysics, Chinese Academy of Sciences, Foshan, People’s Republic of China; 3School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 4Zhengzhou Key Laboratory for Diagnosis of Digestive System Tumor Markers, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingxia Xu; Xiufang Shi, Email zlyyxuqingxia0575@zzu.edu.cn; xfshi@zzu.edu.cnBackground: Emergence of blaKPC and blaNDM co-harboring Klebsiella pneumoniae has escalated the threat of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to healthcare. It remains unknown the prevalence and molecular characteristics of CRKP co-producing KPC and NDMs carbapenemases in Henan.Methods and Results: Twenty-seven CRKP strains isolated from different times were selected randomly in affiliated cancer hospital of Zhengzhou University from January 2019 to January 2021, among which one KPC-2 and NDM-5 positive CRKP named K9 was isolated from an abdominal pus sample of a 63-year-old male patient with leukemia. Sequencing of K9 determined that K9 belonged to ST11-KL47, which is resistant to antibiotics such as meropenem, ceftazidime-avibactam and tetracycline. K9 carried two different plasmids that contained blaNDM− 5 and blaKPC− 2. Both plasmids were shown to be novel hybrid plasmids and IS 26 played an important role in generation of two plasmids. Gene blaKPC-2 was flanked by the NTEKPC-Ib-like genetic structure (IS 26-ΔTn 3-ISKpn8-blaKPC-2-ISKpn6-IS 26) and was located on a conjugative IncFII/R/N type hybrid plasmid.Conclusion: The resistance gene blaNDM− 5 located on a region organized as IS 26-blaNDM– 5-ble-trpF-dsbD-ISCR1-sul1-aadA2-dfrA12-IntI1-IS 26 was carried by a phage-plasmid. We described a clinical CRKP co-producing KPC-2 and NDM-5 and emphasized an urgent need to control their further spread.Keywords: carbapenem-resistant Klebsiella pneumoniae, KPC-2, NDM-5, beta-lactamases, hybrid plasmid, IS 26

Min Sun,1,2 Lei Gao,1 Hongmei Bai,1 Weiwei Hu,1 Xiaofang Zhang,1 Jin Xiao,1 Xiangliang Deng,1 Hongmei Tao,1 Ping Ge,2 Yuhong Qin,1,&ast; Dongying Zhang1,&ast; 1Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Health Management Center, The First Branch of the Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongying Zhang; Yuhong Qin, Tel +86-23-13608398395 ; +86-23-13068357151, Email zhangdongying@cqmu.edu.cn; 798213639@qq.comPurpose: To investigate the association of visceral fat with arterial stiffness of heart failure patients with preserved ejection fraction (HFpEF) and to evaluate the extent to which this association is mediated by blood pressure (BP).Patients and Methods: This cross-sectional descriptive study (clinicaltrials.gov identifier: NCT04535726) recruited 94 patients with HFpEF totally from October to December 2020. The obesity-related measurements included visceral fat area (VFA), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist–hip ratio (WC/HC), abdominal circumference (AC), body fat mass and fat percentage. Brachial-ankle pulse wave velocity (baPWV) was used to estimate the degree of arterial stiffness. Mediation analysis was performed to reveal whether the effect of visceral fat area on arterial stiffness can be mediated by BP in patients with HFpEF and the extent to which this association was mediated by BP.Results: About 93.6% of HFpEF patients were accompanied with abdominal obesity. Patients in baPWV ≥ 1800cm/s group were older, with a higher incidence of type 2 diabetes mellitus (T2DM), hypertension and abdominal obesity. VFA, systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) were correlated with baPWV in total group. Adjusted for age ≥ 75 years old, gender, smoking, T2DM, calcium channel blocker and statins, the mediation effect of systolic SBP and PP on the VFA-baPWV association were 53.3% (indirect effect was 2.28, 95% CI 0.62– 4.73) and 48.4% (indirect effect was 2.07, 95% CI 0.51– 4.38), respectively. DBP failed to mediate the association between VFA and baPWV (indirect effect was 0.50, 95% CI − 0.41– 2.14).Conclusion: The association of visceral fat with baPWV in HFpEF patients may be partly accounted for SBP or PP. Elevated SBP and PP might be important potential targets for preventing arterial stiffness in HFpEF patients.Keywords: mediation analysis, blood pressure, visceral fat area, brachial-ankle pulse wave velocity, HFpEF

Jianwei Liu,1,&ast; Minmin Sun,2,&ast; Kunpeng Fang,3,&ast; Jie Wang,1,&ast; Bowen Ma,1 Li Song,1 Ting Liu,1 Ming Tang,4 Kui Wang,1 Yong Xia4 1Department of Hepatic Surgery II, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 2Department of Hepatic Surgery I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 3Department of Special Treatment I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 4Department of Hepatic Surgery IV, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Xia, Department of Hepatic Surgery (IV), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-2181875005, Fax +86-2165562400, Email xia.yong@126.com Kui Wang, Department of Hepatic Surgery (II), Eastern Hepatobiliary Surgery Hospital, Navy Medical University, &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel\Fax +86-2181875514, Email wangkuiykl@163.com

Ziyi Dong,&ast; Qing Zhang,&ast; Changhai Wang, Wenjun Hu, Xianglong Yu, Mingxue Guo, Xinyu Zhang, Meng Sun, Shouying Du, Yang Lu School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shouying Du, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email dumenzidi123@163.com Yang Lu, School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email landocean28@163.comIntroduction: Chemotherapeutic drugs are often ineffective due to the delivery. Local chemotherapy, which has high drug concentration, low systemic toxicity, and long duration, has shown excellent potential. Cationic antimicrobial peptides have been proved to enhance the tumor cells’ uptake of chemotherapeutic drugs through the membrane-breaking effect. In this study, we designed and developed a thermosensitive gel co-loaded with Dermaseptin-PP and paclitaxel liposomes to increase local chemotherapy.Methods: The paclitaxel liposomes were prepared. Then, it was co-loaded with Dermaseptin-PP in a poloxamer-based thermosensitive gel to obtain Dermaseptin-PP/paclitaxel liposomes gel. The thermosensitivity of gels was investigated by test tube inversion method. The rheology was tested by rheometer. The in vitro cytotoxicity and the permeation in tumor of gels were examined by H157 cells and the 3D cell model, respectively. The retention in tumor and antitumor activity of gels were evaluated by H157 tumor-bearing nude mice.Results: The particle size of paclitaxel liposomes was 148.97 ± 0.21 nm. The encapsulation rate was 86.1%, and the drug loading capacity was 19.4%. The gels had slow-release and temperature-sensitive properties. The porous 3D network structure of the gels could ensure that the drug was fixed into the tumor. In vitro and in vivo distribution studies showed that Dermaseptin-PP promoted the permeation of the gels in H157 multicellular tumor spheres and achieved longer retention in tumor. In vitro and in vivo antitumor studies demonstrated that Dermaseptin-PP/paclitaxel liposomes gel significantly inhibited the growth of tumors for local chemotherapy with good biosafety.Conclusion: This study provided a promising nanomedicine platform for combining antimicrobial peptides and chemotherapeutic drugs for local chemotherapy.Keywords: cationic antimicrobial peptides, nanoparticles, temperature-sensitive, membrane-breaking, combination therapy

Cui Shao,1,&ast; Mengxue Sun,2,&ast; Wanwen Liu,2 Shaoyang Zhao,1 Yang Liu,2 Yuna Chen,1 Shu-Nung Liang,2 Haoyu Yuan,2 Huacheng Sui,2 Baohua Wang,1 Saimei Li1 1Department of Endocrinology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baohua Wang; Saimei Li, Department of Endocrinology, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China, Tel +8613580515855 ; +8615818159018, Fax +86 20-36588726, Email wangbaohua@gzucm.edu.cn; lsm@gzucm.edu.cnPurpose: We aimed to assess the efficacy of the Jiang Tang San Huang (JTSH) tablet for the treatment of patients with type 2 diabetes mellitus (T2DM).Methods: All data for this retrospective cohort study were acquired from the outpatient clinic database of our institution, and all enrolled patients received JTSH tablet for at least two months. Overall, 147 patients were included in the analysis. The primary outcome was patient-reported outcomes on the efficacy of the JTSH tablets using a questionnaire survey. Correlation analysis evaluated the duration of JTSH tablet administration and glycemic control in patients with T2DM. The secondary outcome measures included: changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-hour postprandial blood glucose, homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) after 2 months of treatment with JTSH tablets.Results: Overall,120 patients (81.63%) reported a JTSH tablet treatment satisfaction score of ≥ 60 points, and believed that JTSH tablets had satisfactory hypoglycemic effects and could improve symptoms. The average duration of JTSH tablet treatment was 2.57± 1.45 years. Overall, 111 patients achieved good blood glucose control, while 36 patients had poor glycemic control. Multivariate logistic regression model analysis showed that taking JTSH tablets for 1 year might reduce the risk of poor hypoglycemic effect by 17.00% (Risk ratio=0.830, 95% confidence interval:0.578, 1.021, P=0.066). Compared with the baseline data, the levels of HbA1c, FPG and HOMA-IR decreased significantly and HOMA-β levels increased significantly (P< 0.05).Conclusion: Good blood glucose control may be positively correlated with the duration of JTSH tablets administration. Patients with T2DM were satisfied with the anti-diabetic effects of JTSH tablets, which can significantly reduce blood glucose and insulin resistance, and improve the function of islet cells.Keywords: type 2 diabetes mellitus, Jiang Tang San Huang tablet, patient-reported outcomes, blood glucose control, multiple logistic regression

Zhuo Zhou,1 Guixing Xu,1 Liuyang Huang,1 Yunjie Shu,1 Hao Tian,1 Fengyuan Huang,1 Yilin Liu,1 Fanrong Liang,2 Mingsheng Sun1 1Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 2Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine/Clinical Research Center for Acupuncture and Moxibustion in Sichuan Province, Chengdu, People’s Republic of ChinaCorrespondence: Fanrong Liang, Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine/Clinical Research Center for Acupuncture and Moxibustion in Sichuan Province, Chengdu, People’s Republic of China, Tel +86 136 0805 8216, Fax +86-28-87683962, Email acuresearch@126.comIntroduction: Chronic pain is one of the major health problems worldwide in recent years, and acupuncture-related therapies have been reported to have definite analgesic effects. However, it is still unclear which treatment is the most effective. Our systematic review and network meta-analysis protocol aims to summarize the evidence and determine the most effective method to treat the chronic musculoskeletal pain.Methods and Analysis: Our literature search will be performed in five electronic databases—the Cochrane Library, EMBASE, and PubMed, AMED, CINAHL, until May 20, 2022. All randomized controlled trials of acupuncture-related therapies for chronic musculoskeletal pain will be included. The primary outcomes will be common pain-related scales, and the secondary outcomes will include quality of life and incidence of adverse events. Excel 2019 will be used for data extraction, RoB2 will be used for bias risk assessment. R 3.6.2 and WinBUGS V.1.4.3 software will be used for network data synthesis and to produce related plots. During the study, literature selection, data extraction, quality assessment and bias risk assessment will be independently completed by two reviewers, and differences will be judged by the third reviewer. Finally, the risk of bias and sources of heterogeneity in the study will be analyzed and explained in order to obtain reliable results.Results: Our study will evaluate the effectiveness and safety of acupuncture-related therapies for the treatment of chronic musculoskeletal pain, and we will rank all methods to recommend the best appropriate treatment option.Conclusion: This study will provide a good foundation for complementary and alternative medicine to treat chronic musculoskeletal pain. It will be also helpful to promote the clinical practice by providing evidence-based medical evidence.Keywords: systematic review, network meta-analysis, acupuncture-related therapies, chronic musculoskeletal pain

Meixue Yao,1,&ast; Mengda Liu,2,&ast; Xia Chen,3 Jianjun Li,4 Yan Li,5 Yu Run Wei,2 Yong Liu,3 Kang Long Yang,3 Xiaoxiao Duan,5 Weixing Shao,2 Xiangxiang Sun,2 Xiaoxu Fan,2 Shufang Sun,2 Lili Tian,2 Dehui Yin,1 Mingjun Sun2 1Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Laboratory of Zoonoses, China Animal Health and Epidemiology Center, Qingdao, 266032, People’s Republic of China; 3Yubei Animal Husbandry and Aquatic Products Station, Chongqing, 401120, People’s Republic of China; 4School of Animal Science and Veterinary Medicine, Tianjin Agriculture College, Tianjin, 300384, People’s Republic of China; 5Qingdao Animal Disease Prevention and Control Center, Qingdao, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingjun Sun, Laboratory of Zoonoses, China Animal Health and Epidemiology Center, No. 369 Nanjing Road, Qingdao, 266032, People’s Republic of China, Email sunmingjun@cahec.cn Dehui Yin, Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China, Email yindh16@xzhmu.edu.cnBackground: Brucellosis is one of the most important zoonotic diseases in the world. Canine brucellosis, caused mainly by Brucella canis, is seriously neglected, and there is a lack of accurate diagnostic tools.Methods: In this study, to compare BP26, Omp25, Omp31 and a multiepitope-based fusion protein in the serological detection of canine brucellosis, using 34 brucellosis-positive dog sera and 62 negative control sera, the Brucella outer membrane proteins Omp31, BP26, Omp25 and a multiepitope-based fusion protein were evaluated by iELISA for their potential use as antigens in the serological diagnosis of canine brucellosis.Results: The results showed that the multiepitope-based fusion protein performed best in distinguishing brucellosis-positive and brucellosis-negative dog sera, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 98.41%. BP26 and Omp31 showed excellent sensitivity in detecting brucellosis-positive dog sera, but their cross reaction to sera infected with Vibrio parahaemolyticus and Listeria monocytogenes may hinder their application as diagnostic reagents. Omp25 lacked sufficient sensitivity and showed limited ability in distinguishing positive and negative dog sera.Conclusion: The multiepitope-based fusion protein can be used as an ideal antigen for serologically diagnosing canine brucellosis currently prevalent worldwide.Keywords: Brucella, outer membrane protein, multiepitope, canine brucellosis

Rongrong Sun,1 Zhixin Yan,2 Wenxia Yi,2 Wenqiu Tian,2 Mei Sun,2 Jing Zhang1 1Children’s Ward, Cangzhou Central Hospital, Cangzhou, Hebei Province, People’s Republic of China; 2Cangzhou Central Hospital, Cangzhou, Hebei Province, People’s Republic of ChinaCorrespondence: Jing Zhang, Children’s Ward, Cangzhou Central Hospital, Cangzhou City, Hebei Province, 061001, People’s Republic of China, Tel +86 15031730097, Email wuwo681230754@163.comObjective: To study serum levels of vitamins A, D and E in children with recurrent respiratory tract infections of different ages and the correlation.Methods: The clinical data of two groups of children of different ages were collected. The serum levels and deficiencies of vitamins A, D and E in children were statistically analyzed.Results: The proportions of premature infants, low body weight infants, special physique, hospitalization history, hypocalcemia, living in a bungalow, and daily outdoor activities in less than 30 minutes in the case group were higher than those in the control group (χ2=4.507, 5.165, 7.040, 14.907, 4.267, 33.800, 4.507, 8.571, P < 0.05). The serum levels of vitamins A, D and E of children aged 0– 1, 2– 5, and 6– 12 in the case group were lower than those in the control group (P < 0.05). Compared with the control group, the serum vitamin A level of children in the case group was lower (t = 2.631, P < 0.05), and the deficiency rate was higher (χ2=24.200, P < 0.05).Conclusion: Serum levels of vitamins A, D and E, which are related to birth mode, physical fitness, hospitalization history, hypocalcemia, vitamin deficiency, living environment, and daily outdoor activity time, vary in children with recurrent respiratory tract infections of different ages, and are lower in children with recurrent respiratory tract infections than in healthy children.Keywords: different age groups, recurrent respiratory tract infections, children, serum vitamins A, D and E levels, correlation

Meixue Yao,1,2,&ast; Xiaohan Guo,1,2,&ast; Xiling Wu,1,2 Qiongqiong Bai,1,2 Mingjun Sun,3 Dehui Yin1,2 1Center for Medical Statistics and Data Analysis, School of Public Health, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Laboratory of Zoonoses, China Animal Health and Epidemiology Center, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dehui Yin, Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, No. 129 Tongshan Road, Xuzhou, 221004, People’s Republic of China, Email yindh16@xzhmu.edu.cnBackground: Brucellosis is a zoonotic disease that causes substantial public health problems and endangers the development of animal husbandry in endemic areas. Early diagnosis of infected animals and humans is a crucial step in reducing the incidence of brucellosis. In this study, we designed different combinations of Brucella major outer membrane proteins (omps) including omp10, omp16, omp19, omp25, omp31 and BP26 as antigens and evaluated their efficiency in serodiagnosis for brucellosis. The efficiency assay was conducted using the method of indirect enzyme-linked immunosorbent assay (iELISA) together with a collection of brucellosis-positive sera and healthy sera from multiple species (161 from human, 120 from goat and 144 from cattle). The diagnostic effectiveness of each omp combination was analyzed by receiver operating characteristic (ROC) curve with the software GraphPad Prism version 6.05.Results: The omp25/omp31/BP26 combination showed the best efficiency in diagnosis for human brucellosis. The area under the ROC curve (AUC) was 0.995 and, compared with the serum tube agglutination test (SAT) and the Rose Bengal plate agglutination test (RBPT), the positive and negative diagnostic accuracies of iELISA were 94.59% (105/111) and 100.0% (50/50), respectively. Evaluation of the 120 goat and 144 cattle serum samples showed that the best combination for diagnosing both omp31/BP26, the AUC was 0.9262 in goat and 0.9344 in cattle, and compared with those of SAT and RBPT, the positive and negative diagnostic accuracies in goat were 72.73% (48/66) and 100.0% (54/54), respectively. The positive and negative diagnostic accuracies in cattle were 79.79% (75/94) and 100.0% (50/50), respectively. Cross-reaction assays showed that omp25/omp31/BP26 and omp31/BP26 do not cross with other common pathogens.Conclusion: The results indicated that combinations of omps, as protein antigens, can be used to diagnose brucellosis with high accuracy in human, goat and cattle.Keywords: brucellosis, diagnosis, outer membrane proteins, iELISA

Xiaodan Jiang,1,2,&ast; Yu Wan,1,2,&ast; Hao Yuan,1,2,&ast; Liming Zhao,3,&ast; Min Sun,4,&ast; Yanhui Xu,5,&ast; Xiangyang Xin,6,&ast; Jing Dong,7,&ast; Die Hu,8,&ast; Dongmei Chen,9,&ast; Xuemin Li1,2 1Department of Ophthalmology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, Beijing, People’s Republic of China; 3Department of Ophthalmology, Beijing Fengtai Hospital, Beijing, People’s Republic of China; 4Department of Ophthalmology, Huabei Petroleum General Hospital, Renqiu, Hebei, People’s Republic of China; 5Department of Ophthalmology; Hebei Provincial Eye Hospital, Xingtai, Hebei, People’s Republic of China; 6Department of Ophthalmology, Inner Mongolia Baogang Hospital, Baotou, Inner Mongolia, People’s Republic of China; 7Department of Ophthalmology, the First Affiliated Hospital of Baotou Medical College, Baotou, Inner Mongolia, People’s Republic of China; 8Department of Ophthalmology, Baoding Zhuozhou GEM Flower Hospital, Zhuozhou, Hebei, People’s Republic of China; 9Department of Ophthalmology, Baoding GEM Flower Eastern Hospital, Zhuozhou, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemin Li, Department of Ophthalmology, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Peking University Third Hospital, No. 49 Huayuan North Road, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86 10 8226 6312, Fax +86 10 8208 9951, Email lxmlxm66@sina.comObjective: To investigate the incidence of acute postoperative endophthalmitis (POE) after cataract surgery in Northern China from 2013 to 2019, evaluate the efficacy of prophylaxis and analyze the predictors of visual prognosis among POE patients.Methods: The study was conducted as a retrospective multi-center research, with seven hospitals in Northern China enrolled. The diagnosis of acute-onset POE was made on the basis of clinical manifestations within six weeks after initial surgery. By reviewing electronic medical system, the number of cataract surgeries and acute POE cases were recorded to estimate the overall incidence and incidences by different years and hospitals. Perioperative measures for preventing infection in different hospitals were collected. The correlations between unfavorable final vision and potential factors including basic information and clinical characteristics were examined to determine the predictive factors for final visual prognosis.Results: Of 72,255 cataract surgeries performed during seven years in the seven hospitals, 19 cases developed acute POE, yielding an overall incidence of 0.026%. The average incidence of acute POE among seven hospitals significantly declined annually during the past 7 years (p = 0.021). In Hospital-D, the incidence of acute POE significantly decreased after the application of 0.5% povidone-iodine (PVP-I) for conjunctival washing (p = 0.003). Two hospitals adopting tobramycin in the irrigation solution achieved a significant lower incidence of POE than the other hospitals (p = 0.044). The positive rate of pathogen culture was just 17.6% (3/19). Patients with presenting BCVA of CF or better were more likely to present with unfavorable final vision than those with worse presenting BCVA (p = 0.003).Conclusion: The overall incidence of acute POE after cataract surgery from 2013 to 2019 in Northern China was 0.026%, and the incidence declined annually over the period. Presenting BCVA could be a significant prognosis factor for predicting the final visual outcomes of acute POE patients.Keywords: endophthalmitis, cataract surgery, infection prophylaxis, prognosis predictors

Lectins are non-enzymatic carbohydrate binding proteins important to human cellular functions. Here, the authors characterize a lectin produced by a human associated bacterium, and show that interacts with myeloid cells in the blood and intestine, suggesting commensal microbiota lectins as a diverse and widespread mechanism to interact with host physiology.

Mengfei Sun,1,&ast; Qianqian Yang,2,&ast; Chunling Hu,1 Hengchao Zhang,2 Lihua Xing1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Department of Erythrocyte Biology Laboratory, School of Life Sciences, Zhengzhou University, Zhengzhou, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lihua Xing, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshedong Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel/Fax +8613838095088, Email xinglihua95088@163.comPurpose: Autophagy-related genes (ARGs) play an important role in the pathophysiology processes of sepsis-induced acute respiratory distress syndrome (ARDS). However, expression profiles of ARGs have rarely been used to explore the relationship between autophagy and sepsis-induced ARDS. Therefore, we aim to identify and validate the potential ARGs of sepsis-induced ARDS through bioinformatics analysis and experiment validation.Methods: We downloaded GSE32707 data from the Gene Expression Omnibus (GEO) database. The potential differentially expressed genes (DEGs) and differentially expressed ARGs (DEARGs) of sepsis-induced ARDS were screened by R software. Then, we performed functional enrichment analyses to explore the potential biological functions of DEARGs and constructed protein–protein interaction (PPI) networks. Subsequently, correlation analysis and receiver operating characteristic (ROC) curve were used for the DEARGs. In addition, we estimated the proportions of 22 immune cell subsets by using CIBERSORT algorithm. Finally, RNA expression of seven DEARGs were validated by qRT-PCR in blood samples from sepsis-induced ARDS and healthy controls.Results: We identified 28 DEARGs, including 11 up-regulated genes and 17 down-regulated genes, which were primarily involved in autophagy and apoptosis. Seven genes (BAG3, CTSD, ERBB2, MYC, PEA15, RAB24 and SIRT1) with AUC > 0.70 were considered possible to be sepsis-induced ARDS hub genes for ROC curve analysis. CIBERSORT results shown that sepsis-induced ARDS contained a higher proportion of naive CD4+ T cells, gamma delta T cells, monocytes, and neutrophils, and lower levels of CD8+ T cells, memory resting CD4+ T cells, follicular helper T cells were relatively lower. The results of qRT-PCR also demonstrated that the expression levels of BAG3, CTSD, ERBB2, MYC and SIRT1 in sepsis-induced ARDS patients and healthy controls had differences.Conclusion: We identified an association between DEGs and immune infiltration in sepsis-induced ARDS and validated BAG3, CTSD, ERBB2, MYC and SIRT1 that may be have excellent diagnostic performance.Keywords: autophagy, sepsis-induced ARDS, immune infiltration, bioinformatics analysis, Gene Expression Omnibus dataset

Ling Wang, Mengzi Sun, Yinpei Guo, Shoumeng Yan, Xiaotong Li, Xuhan Wang, Wenyu Hu, Yixue Yang, Jing Li, Bo Li Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, People’s Republic of ChinaCorrespondence: Bo Li, Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 1163 Xinmin Avenue, Changchun, 130021, People’s Republic of China, Email li_bo@jlu.edu.cnObjective: People with poor sleep quality have higher risk of cardiovascular disease (CVD), and one potential mechanism of CVD is chronic inflammation. The aim of this study was to investigate the role of dietary inflammation in the relationship between sleep quality and CVD risk.Methods: This study involved 5594 participants from the National Health and Nutrition Examination Survey (NHANES) in 2005– 2008. Sleep quality, dietary inflammation, and 10-year CVD risk were evaluated via the Pittsburgh Sleep Quality Index (PSQI), the Energy-adjusted Dietary Inflammatory Index (E-DII), and the Framingham Risk Score (FRS), respectively. We used generalized additive model (GAM) and mediation analysis to investigate the relationship among sleep quality, 10-year CVD risk, and E-DII.Results: PSQI had a non-linear relationship with 10-year CVD risk (P < 0.001). Meanwhile, among the participants with poor sleep quality, PSQI was positively associated with increased 10-year CVD risk (P < 0.001) and E-DII (P < 0.001). Furthermore, the association between sleep quality and CVD risk was partially mediated by E-DII, and the mediated proportion was 14.6%, and the mediating effect of E-DII varied in different gender and age groups. However, in the subjects with good sleep quality, the association among PSQI, E-DII, and 10-year CVD risk was not existed.Conclusion: Ten-year CVD risk could be reduced by controlling the intake of inflammatory food, especially for whom with sleep disorders. In general, the reduction of inflammatory diet could weaken the effect of sleep disorders on the CVD risk.Keywords: inflammatory diet, sleep quality, cardiovascular disease, NHANES, mediation

Qiyun Jiang,1,2 Dan Gong,1,2 Huiqi Li,3 Donglan Zhang,4 Suzhen Hu,5 Qinghua Xia,6 Hong Yuan,7 Peng Zhou,6 Yiying Zhang,7 Xing Liu,8 Mei Sun,1,2 Jun Lv,1,2 Chengyue Li1,2 1Department of Health Policy and Management, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Research Institute of Health Development Strategies, Fudan University, Shanghai, People’s Republic of China; 3School of Public Health and Community Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Department of Health Policy and Management, College of Public Health, University of Georgia, Athens, GA, USA; 5Department of Medical Affairs, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 6Department of Chronic Disease Prevention and Control, Changning District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 7Department of Chronic Disease Prevention and Control, Jiading District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 8Department of Epidemiology, School of Public Health, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Chengyue Li; Jun Lv, Department of Health Policy and Management, School of Public Health, Fudan University, P.O. Box 177, 130 Dong’an Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-33561022 ; +86-21-33563953, Fax +86-21-33563380, Email lichengyue@fudan.edu.cn; lujun@shmu.edu.cnPurpose: This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China.Methods: A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance.Results: Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797– 0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance.Conclusion: We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.Keywords: Eastern China, high-risk population, hypertension, risk scoring method, screening tool

Honglin Li,1,&ast; Chunzheng Ma,1,&ast; Sisi Chang,2 Yutan Xi,2 Shuai Shao,2 Mengli Chen,2 Juan Ren,2 Mingyue Sun,1 Liang Dong1 1Oncology Department, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 2Oncology Department, Henan Provincial University of Traditional Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Honglin Li, Oncology Department, Henan Provincial Hospital of Traditional Chinese Medicine, No. 6 Dongfeng Road, Zhengzhou, 450002, People’s Republic of China, Email 46991701@qq.com Chunzheng Ma, Oncology Department, Henan Provincial Hospital of Traditional Chinese Medicine, No. 6 Dongfeng Road, Zhengzhou, 450002, People’s Republic of China, Email mchzh666@126.comObjective: Traditional Chinese medicine (TCM) is an ancient form of personalized medicine and may improve morbidity and mortality in patients with esophageal cancer. This retrospective study aimed to evaluate the utility of TCM in the treatment of stage IV esophageal squamous cell carcinoma (SCC).Methods: We collected the medical records of patients with stage IV SCC admitted to Henan Provincial Hospital of Traditional Chinese Medicine and Linzhou Hospital of Traditional Chinese Medicine between July 2017 and June 2020. We used univariate and multivariate analyses to determine if the use of TCM improved patient prognosis. Moreover, cluster analysis was used to classify the patients according to TCM syndrome type and identify the most frequently used combinations of remedies.Results: After that 402 patients were included in PSM, of which 196 (48.8%) were treated with traditional Chinese medicine. TCM prolonged the survival time of patients with stage IV esophageal SCC (P=0.084), and was an independently associated with prognosis as demonstrated by Cox multivariate regression analysis [risk ratio (RR) =0.543, 95% confidence interval (CI): 0.390– 0.755, P< 0.001]. Association analysis revealed 75 cases (38.26%) had obstruction of phlegm and qi syndrome, 53 cases (27.04%) had phlegm and blood stasis syndrome, 38 cases (19.39%) had yang-qi deficiency syndrome, and 30 cases (15.31%) had heat retention and fluid consumption syndrome.Conclusion: Treatment with TCM derived therapies may increase the survival time of patients with stage IV esophageal SCC. Since these patients were diagnosed with different TCM syndromes, individualized TCM therapy is essential for improving symptoms and survival.Keywords: esophageal cancer, survival time, traditional Chinese medicine syndrome type, syndrome differentiation, syndrome treatment

Yongmei Lv, Yamei Gao, Na Lan, Minghui Sun, Chenchen Zhang, Jing Gao, Na Wang, Xingyu Yang Departments of Dermatology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of ChinaCorrespondence: Yongmei Lv, Department of Dermatology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei Economic and Technological Development Zone, Hefei, Anhui Province, 230601, People’s Republic of China, Email yongmei_lv830@163.comPurpose: To understand the distribution characteristics of onset time, onset age and gender of pityriasis alba (PA) patients in the dermatology clinic of our hospital and to further explore the pathogenesis of the disease to provide a scientific basis for the prevention and treatment of this disease.Patients and Methods: The clinical data of 2726 outpatients with PA diagnosed for the first time from January 2016 to December 2020 were collected and descriptively analyzed.Results: The number of patients with PA was less from January to March. The peak was reached in July and August. The number of cases affected by the COVID-19 epidemic in 2020 was significantly lower than that in previous years. Furthermore, the onset age of the patients ranged from 0 to 64 years old, and the median age of the total population was 7 (3, 13) years old, including 1566 males (57.45%) and 1160 females (42.55%). The ratio of male to female was 1.35:1. The number of male patients before 18 years old was higher than that of female patients, especially in the high paroxysmal age group.Conclusion: PA can be seen all the year round, and the onset peak of the disease is from July to August every year. It occurs frequently at the age of 1 to 14 before puberty. In the season of high incidence of PA, the protection from sun and moisture retention should be strengthened for infants and adolescents.Keywords: pityriasis alba, epidemic characteristics, pathogenic factors

Hua Ye,1 Mengxia Sun,2 Shiliang Huang,1 Feng Xu,1 Jian Wang,3 Huiwei Liu,1 Liangshun Zhang,1 Wenjing Luo,1 Wenying Guo,1 Zhe Wu,1 Jie Zhu,4 Hong Li4 1Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of China; 2Department of Clinical Medicine, Medical School of Ningbo University, Ningbo, Zhejiang, 315211, People’s Republic of China; 3Department of Dermatology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of China; 4Department of Hepatobiliary Surgery, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaCorrespondence: Hua YeDepartment of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaTel/Fax +86 57483023687Email yh-med@163.comHong LiDepartment of Hepatobiliary Surgery, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaEmail lancet2017@163.comBackground: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. HCC transcriptome has been extensively studied; however, the progress in disease mechanisms, prognosis, and treatment is still slow.Methods: A rank-based module-centric workflow was introduced to analyze important modules associated with HCC development, prognosis, and drug resistance. The currently largest HCC cell line RNA-Seq dataset from the LIMORE database was used to construct the reference modules by weighted gene co-expression network analysis.Results: Thirteen reference modules were identified with validated reproducibility. These modules were all associated with specific biological functions. Differentially expressed module analysis revealed the crucial modules during HCC development. Modules and hub genes are indicative of patient survival. Modules can differentiate patients in different HCC stages. Furthermore, drug resistance was revealed by drug-module association analysis. Based on differentially expressed modules and hub genes, six candidate drugs were screened. The hub genes of those modules merit further investigation.Conclusion: We proposed a reference module-based analysis of the HCC transcriptome. The identified modules are associated with HCC development, survival, and drug resistance. M3 and M6 may play important roles during HCV to HCC development. M1, M3, M5, and M7 are associated with HCC survival. High M4, high M9, low M1, and low M3 may be associated with dasatinib, doxorubicin, CD532, and simvastatin resistance. Our analysis provides useful information for HCC diagnosis and treatment.Keywords: HCV, IC50, microarray, module preservation, WGCNA

Liuyang Huang,1 Guixing Xu,1 Jiamei He,1 Hao Tian,1 Zhuo Zhou,1 Fengyuan Huang,1 Yilin Liu,1 Mingsheng Sun,1 Fanrong Liang2 1Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Acupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine/Clinical Research Center for Acupuncture and Moxibustion in Sichuan Province, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Fanrong LiangAcupuncture and Tuina School/The 3rd Teaching Hospital, Chengdu University of Traditional Chinese Medicine/Clinical Research Center for Acupuncture and Moxibustion in Sichuan Province, Chengdu, Sichuan, People’s Republic of ChinaTel +86 136 0805 8216Fax +86-28-87683962Email acuresearch@126.comBackground: Researches on the central mechanisms of acupuncture analgesia have been widely conducted worldwide. However, there is no bibliometric analysis of functional magnetic resonance imaging (fMRI) studies on acupuncture analgesia. This study visualized the current status, hot spots and frontiers of fMRI studies on acupuncture analgesia in the past 20 years to provide a theoretical basis for its clinical application.Methods: All publications were obtained from Science Citation Index-Expanded (SCI-E) of Web of Science (WOS). We used CiteSpace to analyze publications, journals, cited journals, authors, cited authors, institutions, countries, references, and keywords. We also analyzed collaborative network maps and co-occurrence network maps.Results: We retrieved a total of 797 articles. Regarding the volume of publications, the total number of annual publications showed a fluctuating but overall increasing trend. Evidence-based Complementary and Alternative Medicine (21 articles) was the most productive journal, and Pain (225 articles) was the most cited journal. The most productive author was Qin W (16 articles), and the most co-cited author was Hui KKS (111). The most prolific institution and country were Massachusetts General Hospital (34 articles) and USA (212 articles). “Pain” was the top-ranked for keyword frequency and centrality. “Functional connectivity” was the frontier hotspot for 2018– 2021.Conclusion: First, fMRI researches on acupuncture analgesia involved several countries (regions) and institutions, mainly located in the USA, China and Korea, and most of them were universities. In addition, the USA was a major contributor in this field. Second, in terms of disciplinary distribution, the literatures were mainly from clinical neurology, neuroscience, and radiology nuclear medicine medical imaging. Third, the keyword co-occurrence analysis showed that the hot keywords included pain, fMRI, and lower back pain. Fourth, through keyword clustering analysis, the hot disease was found to be lower back pain, and the hot contents were acupuncture specificity and frequency specificity. Fifth, a timeline analysis of the references identified that chronic low back pain and specificity will remain a hot topic for future research.Keywords: acupuncture analgesia, functional magnetic resonance imaging, CiteSpace, bibliometric analysis

Haoqiang Ji,1 Jia Xu,1 Ruiheng Wu,1 Xu Chen,1 Xintong Lv,2 Hongyu Liu,2 Yuxin Duan,1 Meng Sun,1 Yuanping Pan,1 Yunting Chen,1 Xiwei Lu,2 Ling Zhou1 1School of Public Health, Dalian Medical University, Dalian, 116044, People’s Republic of China; 2Office of Epidemic Surveillance, Dalian Tuberculosis Hospital, Dalian, Liaoning, People’s Republic of ChinaCorrespondence: Xiwei Lu; Ling Zhou 9 West Section, Lvshun South Road, Dalian, Liaoning Province, People’s Republic of ChinaTel +86 411 8611 0368Email yiluxiwei@126.com; zhouling0609@163.comPurpose: Despite increasing literature on the association between treatment delay and outcomes, cut-off point (1 month or median) selection in almost all studies for treatment delay is too subjective. This study explored more scientific cut-off points of treatment delay for poor treatment outcomes and death at the clinical level.Patients and Methods: A total of 18,100 newly confirmed pulmonary tuberculosis (TB) cases in Dalian, China were used in the final analysis. A 3-knotted restricted cubic spline (RCS) fitted for Cox proportional hazard regression models is used to analyse the effects of cut-off points of treatment delay on incident poor treatment outcomes. To explore the moderating effects of age, gender and diabetes, we added the interaction terms of these moderating variables and treatment delay to Cox proportional hazard regression models.Results: The median time of treatment initiation was 30 days (IQR: 14– 59 days). The risk of incident poor treatment outcomes increased when the time was greater than cut-off point 1 (53 days; adjusted HR: 1.26; 95% CI: 1.00– 1.60) of treatment delay, and the risk of incident death events increased when the time was greater than cut-off point 2 (103 days; adjusted HR: 1.56; 95% CI: 1.00– 2.44) of delay. In addition, treatment delay was associated with an increased risk of incident poor treatment outcomes and death, and older age, male sex, and diabetes may increase the risk of treatment delay for poor outcomes.Conclusion: This study is the first to identify scientific cut-off points of treatment delay for poor treatment outcomes and death, and this method of exploration should be popularized. In addition, the knowledge of tuberculosis must be spread to every adult. Moreover, the tuberculosis diagnosis level of community level health workers should be enhanced.Keywords: new pulmonary tuberculosis patients, poor treatment outcomes, treatment delay, cut-off points, restricted cubic spline

Manman Sun,1 Ke Huang,1 Xueshi Luo,2,3 Hong Li1 1Department of Materials Science and Engineering, College of Chemistry and Materials Science, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 2The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, Guangdong, People’s Republic of China; 3Department of Chemistry, College of Chemistry and Materials Science, Jinan University, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Xueshi Luo; Hong Li Tel +86 020 85223062Fax +86 020 85223271Email 1254914942@qq.com; tlihong@jnu.edu.cnPurpose: Bone metastasis is one of the common causes of death relative to breast cancer. However, the evolvement of bone niche in cancer progression remains poorly understood. A three-dimensional (3D) engineered bone matrix was developed as an effective biomimetic model to explore the mechanism relative to bone cancer metastasis.Methods: In the study, a 3D engineered bone matrix was developed via cell biomineralization templated by a biomimetic collagen template. The process of bone metastasis relative to breast cancer was investigated by co-culturing breast cancer MDA-MB-231-GFP cells with pre-osteogenic MC3T3-E1 cells on the 3D bone matrix.Results: A typical bone matrix was obtained, where mineralized collagen fibers were packed into the bundle to form a 3D engineered bone matrix. As the cancer cells were invading along the way vertical to the alignment of mineralized collagen fiber, the bone matrix gradually became thinner, accompanied with the erosion of Col I and the loss of calcium and phosphorus. As a result, the disassembled structure of mineralized collagen fiber was observed, which may be attributed to osteolytic bone metastasis.Conclusion: An engineered 3D bone-like matrix was successfully prepared via cell mineralization, which can act as a model for bone metastasis process. The study revealed mineralized collagen fiber disassembled at nanoscale relative to breast cancer cells.Keywords: biomimetic models, breast cancer, MDA-MB-231-GFP cells, bone metastasis

Dongfang Wang,1,2,&ast; Liang Zhou,1,&ast; Jiali Wang,3 Meng Sun1 1Department of Social Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, 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; 3Xiangya School of Public Health, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meng SunDepartment of Social Psychiatry, the Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), 36 Mingxin Road, Fangcun, Liwan District, Guangzhou, Guangdong, 510370, People’s Republic of ChinaEmail sunmengjw0701@163.comStudy Objectives: Previous literature supports that insomnia is predictive of subsequent psychotic-like experiences (PLEs) in the general population. However, there is a lack of empirical data on the reverse causality between the two variables and on the correlation between the symptom severity of insomnia and PLEs. This study aimed to explore the bidirectional associations between insomnia and PLEs before and during the COVID-19 pandemic.Methods: A total of 938 students aged 14– 25 years completed both waves of the survey before and during the pandemic (the first wave: October 2019 to November 2019; the second wave: April 2020 to May 2020). PLEs were assessed using the 15-item positive subscale of the community assessment of psychic experiences (CAPE-P15), and insomnia was assessed using three questions on difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening.Results: Students with baseline insomnia were more likely to exhibit new-onset PLEs during the pandemic (OR: 5.13, 95% CI: 2.54– 10.38), while no significant predictive effect of insomnia was found for the persistence and severity of PLEs. Meanwhile, baseline PLEs not only predicted the presence of insomnia during the pandemic (OR: 2.14, 95% CI: 1.25– 3.65) but also correlated with its severity (B: 0.89, 95% CI: 0.47– 1.31).Conclusion: The study provides the first piece of evidence for the bidirectional association between insomnia and PLEs in the general population. However, although insomnia has an important predictive role in the occurrence of PLEs, it does not predict the persistence and development of PLEs, suggesting that there is a more complex mechanism underlying the process.Keywords: insomnia, psychotic-like experiences, COVID-19

Mingyue Sun, Weiqiang Xiao, Qingxia Xu Department of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Qingxia XuDepartment of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Dongming Road No.127, Zhengzhou, Henan Province, People’s Republic of ChinaTel +860371-65587147Email qxiaxu@126.comPurpose: Klebsiella oxytoca is an opportunistic pathogen causing nosocomial infections. This study was designed to characterize the genomic features of a carbapenem-resistant K. oxytoca strain and analyze its molecular characteristics.Materials and Methods: The strain wzx-IMP was isolated from the blood of a 2-year-old girl diagnosed with acute myeloid leukemia-M7. Species identification was performed, and the minimal inhibitory concentration of the strain was measured. Multilocus sequence typing was performed to identify the subtypes of K. oxytoca. The transfer capacity of the blaIMP-4-harboring plasmid was investigated by conjugation experiments, and the genome characteristics of the strain were examined using whole-genome sequencing.Results: wzx-IMP belongs to the ST85 type and is resistant to imipenem and meropenem, which harbored the blaIMP-4 gene. The blaIMP-4 gene was located in an IS26-associated class 1 integron of pwzx_IMP, which contains conserved IncN1-type backbone regions with a replication gene and its accessory structure for plasmid replication. The blaIMP-4-carrying plasmid in wzx-IMP was successfully transferred to Escherichia coli EC600 by conjugation. Whole-genome sequencing showed that the wzx-IMP isolate included the blaOXY-1-1 gene, accompanied by OmpK36 absence.Conclusion: We report an ST85-type carbapenem-resistant K. oxytoca strain, which produces blaIMP-4 located in an IncN1-type plasmid and accompanied by OmpK36 porin deficiency.Keywords: Klebsiella oxytoca, blaIMP-4, ST85, IncN1, OmpK36