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Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats

Journal of Geriatric Cardiology 2024年第4期21卷 443-457页

作者： Jing-Yue XU Zheng-Kai XUE Ya-Ru ZHANG Xing LIU Xue ZHANG Xi YANG Tong LIU Kang-Yin CHEN Tianjin Key Laboratory of Ionic-Molecular Function of cardiovascular disease Department of CardiologyTianjin Institute of Cardiologythe Second Hospital of Tianjin Medical UniversityTianjinChina

BACKGROUND Chronic renal failure(CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia(VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this *** A total of 48 rats were randomly divided into sham operation group(Sham group), CRF group, CRF + atorvastatin group(CRF + statin group), and CRF + etanercept group(CRF + rhTNFR-Fcgroup). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43(GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent *** Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay,immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + *** In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept c

关键词： remodeling cardiac inhibited

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Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes

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Science China(Life Sciences) 2024年第2期67卷 301-319页

作者： Xiaoli Tang Hong Liu Rongjia Rao Yafei Huang Mengqi Dong Miaomiao Xu Shanshan Feng Xun Shi Li Wang Zengwu Wang Bingying Zhou State Key Laboratory of cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100037China Department of Epidemiology Cardiovascular Institute and Fuwai HospitalChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100037China Shenzhen Key Laboratory of cardiovascular disease Fuwai Hospital Chinese Academy of Medical SciencesShenzhenShenzhen 518020China

Mitochondrial toxicity induced by therapeutic drugs is a major contributor for cardiotoxicity,posing a serious threat to pharmaceutical industries and patients’***,mitochondrial toxicity testing is not incorporated into routine cardiac safety screening *** accurately model native human cardiomyocytes,we comprehensively evaluated mitochondrial responses of adult human primary cardiomyocytes(h PCMs)to a nucleoside analog,remdesivir(RDV).Comparison of their response to human pluripotent stem cell-derived cardiomyocytes revealed that the latter utilized a mitophagy-based mitochondrial recovery response that was absent in h ***,action potential duration was elongated in h PCMs,reflecting clinical incidences of RDV-induced QT *** a screen for mitochondrial protectants,we identified mitochondrial ROS as a primary mediator of RDV-induced *** study demonstrates the utility of h PCMs in the detection of clinically relevant cardiac toxicities,and offers a framework for h PCM-based high-throughput screening of cardioprotective agents.

关键词： remdesivir mitochondrial toxicity cardiotoxicity human primary cardiomyocytes high-throughput screening

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Direct reprogramming of fibroblasts into functional hepatocytes via CRISPRa activation of endogenous Gata4 and Foxa3

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Chinese Medical Journal 2024年第11期137卷 1351-1359页

作者： Jiacheng Li Ruopu Li Xue Bai Wenlong Zhang Yu Nie Shengshou Hu State Key Laboratory of cardiovascular disease Fuwai Hospital and Cardiovascular InstituteNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Obstetrics and Gynecology Beijing Advanced Innovation Center for GenomicsThird HospitalSchool of Life SciencesPeking UniversityBeijing 100871China

Background:The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease *** regularly interspaced short palindromic repeats(CRISPR)activator(CRISPRa)is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously,providing a new strategy for cell fate *** main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver ***:The differentiation of mouse embryonic fibroblasts(MEFs)into functional induced hepatocyte-like cells(iHeps)was achieved by utilizing the CRISPRa synergistic activation mediator(SAM)system,which drove the combined expression of three endogenous transcription factors-Gata4,Foxa3,and Hnf1a-or alternatively,the expression of two transcription factors,Gata4 and *** vivo,we injected adeno-associated virus serotype 6(AAV6)carrying the CRISPRa SAM system into liver fibrotic Col1a1-Cre^(ER);Cas9^(fl/fl)mice,effectively activating the expression of endogenous Gata4 and Foxa3 in *** endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction(RT-qPCR)and RNA-seq,and the morphology and characteristics of the induced hepatocytes were observed through *** level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining,while the improvement of liver fibrosis is evaluated through Sirius red staining,alpha-smooth muscle actin(α-SMA)immunofluorescence staining,and blood alanine aminotransferase(ALT)***:Activation of only two factors,Gata4 and Foxa3,via CRISPRa was sufficient to successfully induce the transformation of MEFs into *** iHeps could be expanded in vitro and displayed functional characteristics similar to th

关键词： Liver fibrosis CRISPRa Cell reprogramming Transcriptional activation Hepatocytes

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Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model

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Biomedical and Environmental Sciences 2024年第2期37卷 187-195页

作者： LIU Jia Jia SU Qiu Dong YI Yao SHEN Li Ping BI Sheng Li National institute for Viral disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic *** this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer *** Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 *** growth was *** cytometric analysis was performed to evaluate the populations of T cell subsets in the *** The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination *** studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc *** Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

关键词： Anti-OX40 antibody Hepatitis B core virus-like particles Tumor Combination therapy

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Genetically predicted waist circumference and risk of atrial fibrillation

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Chinese Medical Journal 2024年第1期137卷 82-86页

作者： Wenting Wang Jiang-shan Tan Jingyang Wang Wei Xu Liting Bai Yu Jin Peng Gao Peiyao Zhang Yixuan Li Yanmin Yang Jinping Liu Department of Cardiopulmonary Bypass State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Anaesthesiology Second Affiliated HospitalHainan Medical CollegeHaikouHainan 570311China State Key Laboratory of cardiovascular disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Introduction:Observational studies have revealed an association between waist circumference(WC)and atrial fibrillation(AF).However,it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk ***,the causal role of WC in AF is *** study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization(MR)***:In our two-sample MR analysis,the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study(GWAS)of WC(42 single nucleotide polymorphisms with a genetic significance of Pinstitute database,containing 55,114 AF cases and 482,295 controls)were used to assess the causal role of WC on *** different approaches(inverse variance weighted[IVW],MR-Egger,and weighted median regression)were used to ensure that our results more ***:All three MR analyses provided evidence of a positive causal association between high WC and *** WC was suggested to increase the risk of AF based on the IVW method(odds ratio[OR]=1.43,95%confidence interval[CI],1.30-1.58,P=2.51×10^(-13)).The results of MR-Egger and weighted median regression exhibited similar trends(MR-Egger OR=1.40[95%CI,1.08-1.81],P=1.61×10^(-2);weighted median OR=1.39[95%CI,1.21-1.61],P=1.62×10^(-6)).MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and ***:Our findings suggest that greater WC is associated with an increased risk of *** measures to reduce WC may help prevent the occurrence of AF.

关键词： Genetically predicted Waist circumference Atrial fibrillation Mendelian randomization

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Genomic Surveillance for SARS-CoV-2 Variants: Dominance of XBB Replacement — China, January–June 2023

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China CDC weekly 2024年第15期6卷 324-331页

作者： Yenan Feng Qiudong Su Lili Li Xiaozhou He Peihua Niu Xiaojuan Guo Xiang Zhao Jing Tang Zhiyuan Jia Ji Wang Changcheng Wu Baicheng Xia Zhixiao Chen Yuchao Wu Jing Yang Songqi Chen Cao Chen Shiwen Wang Xiaoping Dong National Key Laboratory of Intelligent Tracking and Forecasting for Infectious diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina NHC Key Laboratory of Medical Virology and Viral diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina

Introduction:In the first half of 2023,a global shift was observed towards the predominance of XBB *** faced a significant epidemic between late 2022 and early 2023 due to Omicron subvariants BA.5.2 and *** study aims to depict the evolving variant distribution among provincial-level administrative divisions(PLADs)in China and explore the factors driving the predominance of XBB ***:Sequences from local and imported coronavirus disease 2019(COVID-19)cases recorded between January 1 and June 30,2023,were *** study analyzed the changing distribution of viral variants and assessed how the prior dominance of specific variants,XBB subvariants,and imported cases influenced the prevalence of the XBB replacement ***:A total of 56,486 sequences were obtained from local cases,and 8,669 sequences were from imported *** in April,there was a shift in the prevalence of XBB from imported to local cases,with varying dominance among *** PLADs previously high in BF.7,the rise of XBB was delayed.A positive correlation was found between XBB proportions in imported cases from January to March and local cases in *** distribution pattern of XBB subvariants differed between local and imported cases within the same *** significant differences were noted in the replacement rates of XBB ***:The timing of XBB dominance differed among various PLADs in China in the first half of 2023,correlating closely with the prevalence of XBB variants among imported cases.

关键词： dominance imported distribution

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Protein C deficiency with venous and arterial thromboembolic events

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World Journal of Clinical Cases 2024年第12期12卷 2000-2003页

作者： Nan Zhang Dong-Kun Sun Xu Tian Xin-Yu Zheng Tong Liu Department of Cardiology Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular DiseaseTianjin Institute of CardiologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China

Protein C(PC)is a key component of the vitamin K-dependent coagulation *** exerts anticoagulant effects by inactivating factors V and *** or inherited PC deficiency results in a prothrombotic state,with presentations varying from asymptomatic to venous ***,there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events,such as myocardial infarction and ischemic *** editorial focuses on the association between PC deficiency and thromboembolism,which may provide some insights for treatment strategy and scientific research.

关键词： Protein C deficiency Venous thromboembolism Myocardial infarction Editorial Arterial thromboembolism

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Probiotics intervention in colorectal cancer:From traditional approaches to novel strategies

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Chinese Medical Journal 2024年第1期137卷 8-20页

作者： Suki Ha Xiang Zhang Jun Yu institute of Digestive disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong SARChina

The intestine harbors a large population of microorganisms that interact with epithelial cells to maintain host healthy physiological *** intestinal microbiota engage in the fermentation of non-digestible nutrients and produce beneficial metabolites to regulate host homeostasis,metabolism,and immune *** disruption of microbiota,known as dysbiosis,has been implicated in many intestinal diseases,including colorectal cancer(CRC).As the third most common cancer and the second leading cause of cancer-related death worldwide,CRC poses a significant health *** is an urgent need for novel interventions to reduce CRC incidence and improve clinical *** the intestinal microbiota has emerged as a promising approach for CRC prevention and *** research efforts in CRC probiotics primarily focus on reducing the incidence of CRC,alleviating treatment-related side effects,and potentiating the efficacy of anticancer therapy,which is the key to successful translation to clinical *** paper aims to review the traditional probiotics and new interventions,such as next-generation probiotics and postbiotics,in the context of *** underlying mechanisms of probiotic anti-cancer effects are also discussed,including the restoration of microbial composition,reinforcement of gut barrier integrity,induction of cancer cell apoptosis,inactivation of carcinogens,and modulation of host immune *** paper further evaluates the novel strategy of probiotics as an adjuvant therapy in boosting the efficacy of chemotherapy and *** all the promising findings presented in studies,the evaluation of potential risks,optimization of delivery methods,and consideration of intra-patient variability of gut microbial baseline must be thoroughly interpreted before bench-to-bedside translation.

关键词： colorectal cancer probiotics gut microbiota dysbiosis adjuvant therapy immune modulation gut barrrier

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Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

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Biomedical and Environmental Sciences 2024年第2期37卷 178-186页

作者： SONG Yun HE Ying LU Xue Xin ZHANG Xiao Mei JIANG XIAO Lin SONG Qing HUANG Xue Yong MA Hong Xia YU Peng Cheng ZHU Wu Yang Henan Provincial Center for disease Control and Prevention Infectious Disease Prevention and Control InstituteHenan Provincial Key Laboratory of Infectious Disease PathogensZhengzhou 450000HenanChina National institute for Viral disease Control and Prevention China CDCKey Laboratory of BiosafetyNational Health CommissionBeijing 102206China Shandong Provincial Center for disease Control and Prevention Jinan 250014ShandongChina Qingdao Chengyang District Center for disease Control and Prevention Qingdao 266108ShandongChina

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and *** Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first ***,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death *** a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first *** A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P0.05)in RVNAs levels at any time *** post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

关键词： Rabies Post-exposure immunization Essen regimen RVNAs

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Association of psychological stress with wives’hypertension across over 10 million Chinese married female population aged 20-49 years

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Chinese Medical Journal 2024年第13期137卷 1583-1591页

作者： Zhenyan Zhao Jiajing Jia Xinyi Lyu Lihua Zhang Yuanyuan Wang Yuan He Zuoqi Peng Ya Zhang Hongguang Zhang Qiaomei Wang Haiping Shen Yiping Zhang Donghai Yan Xu Ma Ying Yang State Key Laboratory of cardiovascular disease Department of CardiologyFuwai HospitalNational Center for Cardiovascular DiseaseChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100037China National Research institute for Family Planning Beijing 100081China National Human Genetic Resources Center Beijing 102206China Graduate School of Peking Union Medical College Beijing 100730China Department of Maternal and Child Health National Health and Family Planning Commission of the PRCBeijing 100044China

Background:Psychological stress has been reported to be a potential risk factor for hypertension among females,but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among *** examined the associations between stress within the family and hypertension among married ***:Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects(NFPCP)across 31 provinces in China in 2016 and *** stress of wives or husbands was measured with a 5-point Likert-type scale,and assessed from three domains:work/life-related stress,economic stress,and overall ***-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of ***:Of 10,027,644 couples,261,098(2.60%)women had *** results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women(P_(for trend)<0.001).Compared with non-stressed participants,female participants with the highest stress themselves were at a greater risk of hypertension,with adjusted odds ratio(OR)of 1.31(95%confidence interval[CI]:1.25-1.37);and compared with participants whose husbands had no stress,those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24(95%CI:1.20-1.29).Moreover,compared with non-stressed status for both couples,only-wife-stressed,only-husband-stressed,and both-stressed couples were found to be significantly associated with increased risks of wives’hypertension,with adjusted ORs of 1.28(95%CI:1.25-1.31),1.19(95%CI:1.17-1.21),and 1.28(95%CI:1.26-1.31),***:Moderate to severe stress in both spouses might be associated with female hypertension prevalence,which highlights the importance of paying attention to the psychological stresses of couples within the f

关键词： Psychological stress Hypertension Occupational stress Life stress Financial stress

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