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A causal variant rs3769823 in 2q33.1 involved in apoptosis pathway leading to a decreased risk of non-small cell lung cancer

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Cancer Biology & Medicine 2022年第9期19卷 1385-1396页

作者： Xu Zhang Na Qin Jingyi Fan Chang Zhang Qi Sun Yayun Gu Meng Zhu Erbao Zhang Juncheng Dai Guangfu Jin Hongxia Ma Zhibin Hu Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166China Health Management Center The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhou 215008China research units of cohort study on cardiovascular diseases and cancers Chinese Academy of Medical SciencesBeijing 100730China

Objective:Although our previous genome-wide association study(GWAS)has identified chromosome 2q33.1 as a susceptibility locus for non-small cell lung cancer(NSCLC),the causal variants remain *** aims of this study were to identify the causal variants in 2q33.1 and to explore their biological functions in ***:CCK-8,colony formation,EdU incorporation,Transwell,and quantitative real-time polymerase chain reaction assays were applied to examine variant *** tumor xenograft model was used to examine variant function in ***-8 activity assays,flow cytometry analysis,and co-immunoprecipitation assays were used to explore the molecular ***:The missense variant rs3769823(A>G),which caused the substitution of lysine with arginine at amino acid 14 in caspase-8(caspase-8K14R),was identified as a potential causal candidate in *** with the wild type caspase-8(caspase8WT)group,the caspase-8K14R group had higher expression of caspase-8 and cleaved ***-8K14R inhibited the proliferation and metastasis of human lung cancer cell lines in ***,caspase-8K14R repressed lung cancer cell growth in ***,caspase-8K14R was more sensitive than caspase-8WT to tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-mediated apoptosis and showed higher binding of caspase-8 and ***:These results suggested that rs3769823 is the causal variant in chromosome 2q33.1 and is involved in an apoptosis pathway,leading to a decreased risk of NSCLC.

关键词： Non-small cell lung cancer chromosome 2q33.1 risk caspase-8 apoptosis

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Associations Between Active,Passive Smoking and the Risk of Nonalcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 113-118页

作者： Xinyuan Ge Jing Lu Chengxiao Yu Wen Guo Ting Tian Xin Xu Yuqing Ding Jiaxin Gao Wei Zhao Xiaohua Zhou Qingqing Diao Hongxia Ma Qun Zhang Ci Song Hongbing Shen Department of Epidemiology China International Cooperation Center on Environment and Human HealthCenter for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsuChina Health Promotion Center Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChina research units of cohort study on cardiovascular diseases and cancers Chinese Academy of Medical SciencesBeijingChina Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjingJiangsuChina

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease with an estimated worldwide prevalence of 32.4%.1 The multisystem condition is related to an increased risk of liver-related and cardiovascular extrahepatic diseases.2 Smoking is the leading preventable risk factor for premature disability and *** NAFLD and smoking are both associated with the development of metabolic features,there has been increasing interest in testing the relationship between smoking and *** causal relevance of smoking to NAFLD incidence have been implicated in crosssectional and prospective cohort studies.3,4 However,previous studies mainly focused on the effect of active smoking,discussion on the influence of passive smoking on NAFLD will facilitate illustrating the association between smoking and *** conducted a national two-center cross-section study of active,passive smoking and NAFLD risk in Chinese and European *** design allowed us to(1)test for associations between active,passive smoking and NAFLD risk by sex and consolidate evidence for causality by estimating dose-response relationship,(2)identify mediated factors,and(3)resolve their possible interaction with smoking.

关键词： mortality cardiovascular passive

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Association between Fruit and Vegetable Intake and Arterial Stiffness: The China-PAR Project

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Biomedical and Environmental Sciences 2023年第12期36卷 1113-1122页

作者： LIU Shuai LIU Fang Chao LI Jian Xin HUANG Ke Yong YANG Xue Li CHEN Ji Chun CAO Jie CHEN Shu Feng HUANG Jian Feng SHEN Chong LU Xiang Feng GU Dong Feng Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166JiangsuChina Key Laboratory of cardiovascular Epidemiology&Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Tianjin Key Laboratory of Environment Nutrition and Public HealthDepartment of Occupational and Environmental HealthSchool of Public HealthTianjin Medical UniversityTianjin 300070China research units of cohort study on cardiovascular diseases and cancers Chinese Academy of Medical SciencesBeijing 100730China School of Medicine Southern University of Science and TechnologyShenzhen 518055GuangdongChina

Objective This study aimed to investigate the association between fruit and vegetable intake and arterial *** We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic cardiovascular Disease Risk in China(China-PAR)project. A semi-quantitative food-frequency questionnaire was used to assess baseline(2007–2008) and recent(2018–2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from2007–2008 to 2018–2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity–pulse index(AVI) and arterial pressure-volume index(API). Elevated AVI and API values were defined according to diverse age reference *** Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI(B =-0.11;95% confidence interval [CI]:-0.20,-0.02) on average, rather than API(B = 0.02;95% CI:-0.09, 0.13). The risk of elevated AVI(odds ratio [OR] = 0.82;95% CI: 0.70, 0.97) is 18% lower in individuals with high intake(≥ 500 g/d) than in those with low intake(< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up(OR = 0.64;95% CI: 0.49, 0.83).Conclusion Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.

关键词： Fruit Vegetable Arterial stiffness cardiovascular disease

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Beta-blockers and 1-year clinical outcomes in hospitalized heart failure patients with atrial fibrillation

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Journal of Geriatric Cardiology 2021年第9期18卷 728-738页

作者： Fu-Wei XING Li-Hua ZHANG Hai-Bo ZHANG Xue-Ke BAI Dan-Li HU Xin ZHENG Jing LI National Clinical research Center for cardiovascular diseases NHC Key Laboratory of Clinical Research for Cardiovascular MedicationsState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Center for Cardiovascular DiseasesBeijingChina

OBJECTIVE To assess the association between beta-blockers and 1-year clinical outcomes in heart failure(HF)patients with atrial fibrillation(AF),and further explore this association that differs by left ventricular ejection fraction(LVEF)*** We enrolled hospitalized HF patients with AF from China Patient-centered Evaluative Assessment of Cardiac Events Prospective Heart Failure *** proportional hazard regression models were employed to calculate hazard ratio of *** primary outcome was all-cause *** Among 1762 HF patients with AF(756 women[41.4%]),1041(56%)received beta-blockers at discharge and 1272(72.2%)had an LVEF>40%.During one year follow up,all-cause death occurred in 305(17.3%),cardiovascular death occurred in203 patients(11.5%),and rehospitalizations for HF occurred in 622 patients(35.2%).After adjusting for demographic characteristics,social economic status,smoking status,medical history,anthropometric characteristics,and medications used at discharge,the use of beta-blockers at discharge was not associated with all-cause death[hazard ratio(HR):0.86;95%Confidence Interval(CI):0.65-1.12;P=0.256],cardiovascular death(HR:0.76,95%CI:0.52-1.11;P=0.160),or the composite outcome of all-cause death and HF rehospitalization(HR:0.97,95%CI:0.82-1.14;P=0.687)in the entire *** were no significant interactions between use of beta-blockers at discharge and LVEF with respect to all-cause death,cardiovascular death,or composite *** the adjusted models,the use of beta-blockers at discharge was not associated with all-cause death,cardiovascular death,or composite outcome across the different levels of LVEF:reduced(<40%),mid-range(40%-49%),or preserved LVEF(≥50%).CONCLUSION Among HF patients with AF,the use of beta-blockers at discharge was not associated with 1-year clinical outcomes,regardless of LVEF.

关键词： Beta-blockers and 1-year clinical outcomes in hospitalized heart failure patients with atrial fibrillation

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Polygenic risk scores:the future of cancer risk prediction,screening,and precision prevention

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Medical Review 2021年第2期1卷 129-149页

作者： Yuzhuo Wang Meng Zhu Hongxia Ma Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166JiangsuChina Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 211166JiangsuChina research units of cohort study on cardiovascular diseases and cancers Chinese Academy of Medical SciencesBeijing 100010 Department of Medical Informatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjingJiangsuChina

Genome-wide association studies(GWASs)have shown that the genetic architecture of cancers are highly polygenic and enabled researchers to identify genetic risk loci for *** genetic variants associated with a cancer can be combined into a polygenic risk score(PRS),which captures part of an individual’s genetic susceptibility to ***,PRSs have been widely used in cancer risk prediction and are shown to be capable of identifying groups of individuals who could benefit from the knowledge of their probabilistic susceptibility to cancer,which leads to an increased interest in understanding the potential utility of PRSs that might further refine the assessment and management of cancer *** this context,we provide an overview of the major discoveries from cancer *** then review the methodologies used for PRS construction,and describe steps for the development and evaluation of risk prediction models that include PRS and/or conventional risk *** utility of PRSs in cancer risk prediction,screening,and precision prevention are *** and practical considerations relevant to the implementation of PRSs in health care settings are discussed.

关键词： cancer screening genome-wide association study(GWAS) polygenic risk score(PRS) precision prevention risk prediction model.

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Discordance analysis for apolipoprotein and lipid measures for predicting myocardial infarction in statin-treated patients with coronary artery disease:a cohort study

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Journal of Geriatric Cardiology 2023年第12期20卷 845-854页

作者： Tian-Yu LI Pei ZHU Ying SONG Xiao-Fang TANG Zhan GAO Run-Lin GAO Jin-Qing YUAN National Clinical research Center for cardiovascular diseases National Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

BACKGROUND The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease(CAD)at residual cardiovascular risk remain *** study aimed to compare the predictive powers of apolipoprotein B(apoB),non-high-density lipoprotein cholesterol(non-HDL-C),low-density lipoprotein cholesterol(LDL-C),apoB/apolipoprotein A-1(apoA-1)and non-HDL-C/HDL-C for myocardial infarction(MI)in CAD patients treated with statins in the setting of secondary *** The study included 9191 statin-treated CAD patients with a five-year median *** measures were anal-yzed as continuous variables and concordance/discordance groups by *** hazard ratio(HR)with 95%CI was estimated by Cox proportional hazards *** were classified by the clinical presentation of CAD for further *** The high-apoB-low-LDL-C and the high-non-HDL-C-low-LDL-C categories yielded HR of 1.40(95%CI:1.04–1.88)and 1.51(95%CI:1.07–2.13)for MI,respectively,whereas discordant high LDL-C with low apoB or non-HDL-C was not associa-ted with the risk of *** association of MI with discordant apoB versus non-HDL-C,apoB/apoA-1 versus apoB,non-HDL-C/HDL-C versus non-HDL-C,or apoB/apoA-1 versus non-HDL-C/HDL-C was *** patterns were found in patients with acute coronary *** contrast,no association was observed between any concordance/discordance category and the risk of MI in patients with chronic coronary *** ApoB and non-HDL-C better predict MI in statin-treated CAD patients than LDL-C,especially in patients with acute coronary ***/apoA-1 and non-HDL-C/HDL-C show no superiority to apoB and non-HDL-C for predict-ing MI.

关键词： patients coronary infarction

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Disorders of cardiac rhythm in China

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Journal of Geriatric Cardiology 2024年第7期21卷 703-712页

作者： Sheng-Shou HU The Writing Committee of the Report on cardiovascular Health and diseases in China

The Annual Report on cardiovascular Health and diseases in China(2022)intricate landscape of cardiovascular health in *** connection with the previous section,this seventh section of the report offers a comprehensive analysis of dis-orders of heart rhythm in *** 2021,China has achieved significant development and gratifying results in many aspects of the field of *** bundle branch pacing(LBBP),as an emerging pacing technique originating from China,has received widespread *** research results have emerged on its indications,surgical procedures,clinical evaluation,and com-parison with other pacing *** feasibility,effectiveness,and safety have been basically verified,but its long-term pro-gnosis still needs further confirmation from larger samples and longer follow-up time research *** pacemakers have begun to be used in a wider range of clinical applications,and related large sample cohort studies have been *** addi-tion,there are also noteworthy new achievements in the fields of pacemaker remote programming,anticoagulation and radiofre-quency catheter ablation(RFCA)therapy for atrial fibrillation,and implantable cardioverter defibrillator prevention of sudden cardiac *** terms of clinical practice,due to COVID-19 pandemic,the number of RFCA procedures and other device im-plantations in China has fluctuated,but it has gradually recovered since 2020.

关键词： cardiac prevention landscape

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Lifestyle improvement and the reduced risk of cardiovascular disease:the China-PAR project

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Journal of Geriatric Cardiology 2023年第11期20卷 779-787页

作者： Ying-Ying JIANG Fang-Chao LIU Chong SHEN Jian-Xin LI Ke-Yong HUANG Xue-Li YANG Ji-Chun CHEN Xiao-Qing LIU Jie CAO Shu-Feng CHEN Ling YU Ying-Xin ZHAO Xian-Ping WU Lian-Cheng ZHAO Ying LI Dong-Sheng HU Jian-Feng HUANG Xiang-Feng LU Dong-Feng GU Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingChina Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Key Laboratory of cardiovascular Epidemiology Chinese Academy of Medical SciencesBeijingChina research units of cohort study on cardiovascular diseases and cancers Chinese Academy of Medical SciencesBeijingChina Tianjin Key Laboratory of Environment Nutrition and Public HealthDepartment of Occupational and Environmental HealthSchool of Public HealthTianjin Medical UniversityTianjinChina Division of Epidemiology Guangdong Provincial People's Hospital and Cardiovascular InstituteGuangzhouChina Department of Cardiology Fujian Provincial HospitalFuzhouChina Cardio-Cerebrovascular Control and research Center Institute of Basic MedicineShandong Academy of Medical SciencesJinanChina Sichuan Center for Disease Control and Prevention ChengduChina Department of Epidemiology and Health Statistics College of Public HealthZhengzhou UniversityZhengzhouChina Department of Epidemiology and Health Statistics School of Public HealthShenzhen University Health Science CenterShenzhenChina School of Medicine Southern University of Science and TechnologyShenzhenChina

BACKGROUND The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease(CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project(Prediction for Atherosclerotic cardiovascular Disease Risk in China).METHODS A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors(LFs)(smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios(HRs) and corresponding 95% confidence intervals(CIs). The risk advancement periods(RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage(PAR%) were also *** A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1healthy LFs, maintaining 3–4 healthy LFs was associated with a 40% risk reduction of incident CVD(HR = 0.60, 95% CI: 0.45–0.79)and delayed CVD risk by 6.31 years(RAP:-6.31 [-9.92,-2.70] years). The PAR% of maintaining 3–4 unhealthy LFs was 22.0%compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2to 3–4 was associated with a 23% lower risk of CVD(HR = 0.77, 95% CI: 0.60–0.98).CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

关键词： hazard maintaining alcohol

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Prolonging dual antiplatelet therapy improves the long-term prognosis in patients with diabetes mellitus undergoing complex percutaneous coronary intervention

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Journal of Geriatric Cardiology 2023年第8期20卷 586-595页

作者： Jing-Jing XU Si-Da JIA Pei ZHU Ying SONG De-Shan YUAN Xue-Yan ZHAO Yi YAO Lin JIANG Jian-Xin LI Yin ZHANG Lei SONG Run-Lin GAO Ya-Ling HAN Jin-Qing YUAN Department of Cardiology National Clinical Research Center for Cardiovascular DiseasesNational Center for Cardiovascular DiseasesState Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Cardiology General Hospital of Northern Theater CommandShenyangChina

OBJECTIVE To investigate the optimal duration of dual antiplatelet therapy(DAPT)in patients with diabetes mellitus(DM)requiring complex percutaneous coronary intervention(PCI).METHODS A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group(11-13 months,n=689)and two prolonged groups(13-24 months,n=1133;>24 months,n=581).RESULTS Baseline characteristics,angiographic findings,and complexity of PCI were comparable regardless of DAPT *** incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or>24 months(4.6%vs.8.1%vs.6.0%,P=0.008),as was the incidence of all-cause death(1.9%vs.4.6%vs.2.2%,P=0.002)and cardiac death(1.0%vs.3.0%vs.1.2%,P=0.002).After adjustment for confounders,DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event[hazard ratio(HR)=0.544,95%CI:0.373-0.795]and all-cause death(HR=0.605,95%CI:0.387-0.944).DAPT for>24 months was associated with a lower risk of all-cause death(HR=0.681,95%CI:0.493-0.942)and cardiac death(HR=0.620,95%CI:0.403-0.952).The risk of major bleeding was not increased by prolonging DAPT to 13-24 months(HR=1.356,95%CI:0.766-2.401)or>24 months(HR=0.967,95%CI:0.682-1.371).CONCLUSIONS For patients with DM undergoing complex PCI,prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

关键词： patients coronary mellitus

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Integrating polygenic and clinical risks to improve stroke risk stratification in prospective Chinese cohorts

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Science China(Life Sciences) 2023年第7期66卷 1626-1635页

作者： Qingmei Cui Fangchao Liu Jianxin Li Xiaoge Niu Zhongying Liu Chong Shen Dongsheng Hu Keyong Huang Shufeng Chen Jie Cao Xiaoqing Liu Ling Yu Fanghong Lu Xianping Wu Liancheng Zhao Jianfeng Huang Ying Li Zhibin Hu Hongbing Shen Dongfeng Gu Xiangfeng Lu Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100037China Key Laboratory of cardiovascular Epidemiology Chinese Academy of Medical SciencesBeijing100037China Department of Nephrology Henan Provincial Key Laboratory of Kidney Disease and ImmunologyHenan Provincial Clinical Research Center for Kidney DiseaseHenan Provincial People’s Hospital and People’s Hospital of Zhengzhou UniversityZhengzhou450053China Department of Epidemiology and Biostatistics Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing211166China Department of Epidemiology and Health Statistics College of Public HealthZhengzhou UniversityZhengzhou450001China Department of Prevention Medicine Shenzhen University School of MedicineShenzhen518060China Division of Epidemiology Guangdong Provincial People’s Hospital and Cardiovascular InstituteGuangzhou510080China Department of Cardiology Fujian Provincial People’s HospitalFuzhou350014China Cardio-Cerebrovascular Control and research Center Institute of Basic MedicineShandong Academy of Medical SciencesJinan250062China Sichuan Center for Disease Control and Prevention Chengdu610041China research units of cohort study on cardiovascular diseases and cancers Chinese Academy of Medical SciencesBeijing100730China School of Medicine Southern University of Science and TechnologyShenzhen518055China

The utility of the polygenic risk score(PRS)to identify individuals at higher risk of stroke beyond clinical risk remains unclear,and we clarified this using Chinese population-based prospective *** proportional hazards models were used to estimate the 10-year risk,and Fine and Gray’s models were used for hazard ratios(HRs),their 95%confidence intervals(CIs),and the lifetime risk according to PRS and clinical risk categories.A total of 41,006 individuals aged 30–75 years with a mean follow-up of 9.0 years were *** the top versus bottom 5%of the PRS,the HR was 3.01(95%CI 2.03–4.45)in the total population,and similar findings were observed within clinical risk *** gradients in the 10-year and lifetime risk across PRS categories were also found within clinical risk ***,among individuals with intermediate clinical risk,the 10-year risk for those in the top 5%of the PRS(7.3%,95%CI 7.1%–7.5%)reached the threshold of high clinical risk(≥7.0%)for initiating preventive treatment,and this effect of the PRS on refining risk stratification was evident for ischemic *** among those in the top 10%and 20%of the PRS,the 10-year risk would also exceed this level when aged≥50 and≥60 years,***,the combination of the PRS with the clinical risk score improved the risk stratification within clinical risk strata and distinguished actual high-risk individuals with intermediate clinical risk.

关键词： stroke polygenic risk score clinical risk score utility stratification

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