目的研究40岁及以上农村人群冠心病与认知障碍的相关性。方法2014年10月—2015年3月,选取西安市鄠邑区2个自然村所有40岁及以上的常住村民作为研究对象,收集人口学信息、生活习惯、既往病史、家族史等,完成体格检查及血液生化检查。采...目的研究40岁及以上农村人群冠心病与认知障碍的相关性。方法2014年10月—2015年3月,选取西安市鄠邑区2个自然村所有40岁及以上的常住村民作为研究对象,收集人口学信息、生活习惯、既往病史、家族史等,完成体格检查及血液生化检查。采用简易精神状态量表(Mini-Mental State Examination,MMSE)评估总体认知功能,MMSE评分低于分界值(文盲≤17分;小学≤20分;初中及以上文化程度≤24分)定义为认知障碍。冠心病组和非冠心病组认知障碍的患病率组间比较应用卡方检验;多因素Logistic回归分析冠心病与认知障碍之间的关系。结果共纳入研究对象1833人,其中男性735人(40.1%),冠心病57人(3.1%),符合认知障碍标准234人(13.3%)。单因素分析显示,冠心病组认知功能障碍患病率高于非冠心病组(24.6%vs.12.9%,P=0.016)。未校正混杂因素的二元Logistic分析结果显示,冠心病与认知障碍正相关(OR=2.199,95%CI:1.185~4.084,P=0.013)。校正性别、年龄、受教育年限、高血压、糖尿病、血脂异常、卒中病史、身体质量指数等混杂因素后,冠心病未显著增加认知障碍风险。(OR=1.265,95%CI:0.656~2.441,P=0.483)。分层分析中,糖尿病患者中冠心病和认知障碍显著相关(OR=4.191,95%CI:1.464~12.000,P=0.008)。校正混杂因素后,冠心病合并糖尿病组认知障碍患病率显著增加(OR=4.712,95%CI:1.651~13.449,P=0.004)。结论本研究未确定冠心病和认知障碍的直接关联,但是冠心病合并糖尿病与认知障碍患病风险增加显著相关,应开展更大样本的前瞻性研究以进一步确认两者之间的关联。展开更多
BACKGROUND The atherogenic index of plasma(AIP)has been shown to be positively correlated with cardiovascular disease in previous studies.However,it is unclear whether elderly people with long-term high AIP levels are...BACKGROUND The atherogenic index of plasma(AIP)has been shown to be positively correlated with cardiovascular disease in previous studies.However,it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease(CHD).Therefore,the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people.METHODS 19,194 participants aged≥60 years who had three AIP measurements between 2018 and 2020 were included in this study.AIP was defined as log10(triglyceride/high-density lipoprotein cholesterol).The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020.Cox proportional hazards models were used to estimate the hazard ratio(HR)with 95%CI of CHD events between different trajectory groups from 2020 to 2023.RESULTS Three different trajectory patterns were identified through group-based trajectory model:the low-level group(n=7410,mean AIP:-0.25 to-0.17),the medium-level group(n=9981,mean AIP:0.02-0.08),and the high-level group(n=1803,mean AIP:0.38-0.42).During a mean follow-up of 2.65 years,a total of 1391 participants developed CHD.After adjusting for potential confounders,compared with the participants in the low-level group,the HR with 95%CI of the medium-level group and the high-level group were estimated to be 1.24(1.10-1.40)and 1.43(1.19-1.73),respectively.These findings remained consistent in subgroup analyses and sensitivity analyses.CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly.This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.展开更多
For the past few years,the prevalence of cardiovascular disease has been showing a year-on-year increase,with a death rate of 2/5.Coronary heart disease(CHD)rates have increased 41%since 1990,which is the number one d...For the past few years,the prevalence of cardiovascular disease has been showing a year-on-year increase,with a death rate of 2/5.Coronary heart disease(CHD)rates have increased 41%since 1990,which is the number one disease endangering human health in the world today.The risk indicators of CHD are complicated,so selecting effective methods to screen the risk characteristics can make the risk predictionmore efficient.In this paper,we present a comprehensive analysis ofCHDrisk indicators fromboth data and algorithmic levels,propose a method for CHDrisk indicator identification based on multi-angle integrated measurements and Sequential Backward Selection(SBS),and then build a risk prediction model.In the multi-angle integrated measurements stage,mRMR(Maximum Relevance Minimum Redundancy)is selected from the angle of feature correlation and redundancy of the dataset itself,SHAPRF(SHapley Additive exPlanations-Random Forest)is selected from the angle of interpretation of each feature to the results,and ARFS-RF(Algorithmic Randomness Feature Selection Random Forest)is selected from the angle of statistical interpretation of classification algorithm to measure the degree of feature importance.In the SBS stage,the features with low scores are deleted successively,and the accuracy of LightGBM(Light Gradient Boosting Machine)model is used as the evaluation index to select the final feature subset.This new risk assessment method is used to identify important factors affecting CHD,and the CHD dataset from the Kaggle website is used as the study subject.Finally,11 features are retained to construct a risk assessment indicator system for CHD.Using the LightGBM classifier as the core evaluationmetric,ourmethod achieved an accuracy of 0.8656 on the Kaggle CHD dataset(4238 samples,16 initial features),outperforming individual feature selection methods(mRMR,SHAP-RF,ARFS-RF)in both accuracy and feature reduction.This demonstrates the novelty and effectiveness of our multi-angle integrated measurement approach combined with SBS in building a concise yet highly predictive CHD risk model.展开更多
Chromodomain helicase DNA binding protein 7(CHD7),an ATP-dependent chromatin remodeler,plays versatile roles in neurodevelopment.However,the functional significance of its ATPase/nucleosome remodeling activity remains...Chromodomain helicase DNA binding protein 7(CHD7),an ATP-dependent chromatin remodeler,plays versatile roles in neurodevelopment.However,the functional significance of its ATPase/nucleosome remodeling activity remains incompletely understood.Here,we generate genetically engineered mouse embryonic stem cell lines harboring either an inducible Chd7 knockout or an ATPase-deficient missense variant identified in individuals with CHD7-related disorders.Through in vitro neural induction and differentiation assays combined with mouse brain analyses,we demonstrate that CHD7 enzymatic activity is indispensable for gene regulation and neurite development.Mechanistic studies integrating transcriptomic and epigenomic profiling reveal that CHD7 enzymatic activity is essential for establishing a permissive chromatin landscape at target genes,marked by the open chromatin architecture and active histone modifications.Collectively,our findings underscore the pivotal role of CHD7 enzymatic activity in neurodevelopment and provide critical insights into the pathogenic mechanisms of CHD7 missense variants in human diseases.展开更多
Comments Ebstein's Anomaly(EA)is a rare congenital heart disease(CHD)with an incidence of approximately 1 in 20,000.The pathognomonic feature involves apical displacement of the septal and posterior leaflets,resul...Comments Ebstein's Anomaly(EA)is a rare congenital heart disease(CHD)with an incidence of approximately 1 in 20,000.The pathognomonic feature involves apical displacement of the septal and posterior leaflets,resulting in valvular insufficiency and right ventricular(RV)remodeling.Untreated patients exhibit a cumulative mortality rate of up to 25% within the first decade,with heart failure(HF)and arrhythmias constituting the predominant causes of death.Current guidelines suggest that asymptomatic patients with accessory pathways may benefit from prophylactic ablation,though robust evidence specific to EA remains limited[1-3].展开更多
Background The relationship between glycated hemoglobin(HbA1c) and cognitive impairment in older adults with coronary heart disease(CHD) remains unclear.Methods The present study used a prospective cohort study design...Background The relationship between glycated hemoglobin(HbA1c) and cognitive impairment in older adults with coronary heart disease(CHD) remains unclear.Methods The present study used a prospective cohort study design and included 3244 participants aged ≥ 65 years in Beijing,China. The Mini-Mental State Examination(MMSE) and Montreal Cognitive Assessment(MoCA) were used to assess cognitive function. Serum HbA1c was detected at admission. All patients were divided into high HbA1c group(≥ 6.5 mmol/L) and low HbA1c group(< 6.5 mmol/L) based on their HbA1c levels. Logistic regression analyses were used to evaluate the association between HbA1c and cognitive impairment.Results In this study of 3244 participants, 1201(37.0%) patients were in high HbA1c group and 2045(63.0%) patients were in a state of cognitive impairment. Logistic regression analyses demonstrated that HbA1c was an independent risk factor for cognitive impairment regardless of whether the HbA1c was a continuous or categorical variable(OR = 1.27, 95% CI: 1.15–1.40, P < 0.001;OR = 1.79, 95% CI: 1.41–2.26, P ≤ 0.001, respectively). The restricted cubic spline curve exhibited that the relationship between the HbA1c and cognitive impairment was linear(p for non-linear = 0.323, P < 0.001).Conclusion Elevated levels of HbA1c were associated with an increased risk of cognitive impairment in older patients with CHD. These insights could be used to improve the accuracy and sensitivity of cognitive screening in these patient populations.展开更多
The leaf is a major organ for photosynthesis,and its shape plays an important role in plant development and yield determination in rice(Oryza sativa L.).In this study,an adaxial curled leaf mutant,termed curly leaf 1-...The leaf is a major organ for photosynthesis,and its shape plays an important role in plant development and yield determination in rice(Oryza sativa L.).In this study,an adaxial curled leaf mutant,termed curly leaf 1-1(cul1-1),was obtained by chemical mutagenesis.The leaf rolling index of the cul1-1 mutant was higher than that of the wild-type,which was caused by the abnormal development of bulliform cells(BCs).We cloned the CUL1 gene by map-based cloning.A nonsense mutation was present in the cul1-1 mutant,converting a tryptophan codon into a stop codon.The CUL1 gene encodes a chromodomain,helicase/ATPase and DNA-binding domain containing protein.Genes related to leaf rolling and BC development,such as ADL1,REL1 and ROC5,were activated by the cul1-1 mutation.The trimethylation of lysine 27 in histone 3(H3K27me3),but not H3K4me3,at the ADL1,REL1 and ROC5 loci,was reduced in the cul1-1 mutant.High-throughput mRNA sequencing indicated that the cul1-1 mutation caused genome-wide differential gene expression.The differentially expressed genes were classified into a few gene ontology terms and Kyoto encyclopedia of genes and genomes pathways.In the natural population,22 missense genomic variations in the CUL1 locus were identified,which composed of 7 haplotypes.A haplotype network was also built with haplotype II as the ancestor.The findings revealed that CUL1 is essential for normal leaf development and regulates this process by inhibiting the expression of genes involved in leaf rolling and BC development.展开更多
文摘目的研究40岁及以上农村人群冠心病与认知障碍的相关性。方法2014年10月—2015年3月,选取西安市鄠邑区2个自然村所有40岁及以上的常住村民作为研究对象,收集人口学信息、生活习惯、既往病史、家族史等,完成体格检查及血液生化检查。采用简易精神状态量表(Mini-Mental State Examination,MMSE)评估总体认知功能,MMSE评分低于分界值(文盲≤17分;小学≤20分;初中及以上文化程度≤24分)定义为认知障碍。冠心病组和非冠心病组认知障碍的患病率组间比较应用卡方检验;多因素Logistic回归分析冠心病与认知障碍之间的关系。结果共纳入研究对象1833人,其中男性735人(40.1%),冠心病57人(3.1%),符合认知障碍标准234人(13.3%)。单因素分析显示,冠心病组认知功能障碍患病率高于非冠心病组(24.6%vs.12.9%,P=0.016)。未校正混杂因素的二元Logistic分析结果显示,冠心病与认知障碍正相关(OR=2.199,95%CI:1.185~4.084,P=0.013)。校正性别、年龄、受教育年限、高血压、糖尿病、血脂异常、卒中病史、身体质量指数等混杂因素后,冠心病未显著增加认知障碍风险。(OR=1.265,95%CI:0.656~2.441,P=0.483)。分层分析中,糖尿病患者中冠心病和认知障碍显著相关(OR=4.191,95%CI:1.464~12.000,P=0.008)。校正混杂因素后,冠心病合并糖尿病组认知障碍患病率显著增加(OR=4.712,95%CI:1.651~13.449,P=0.004)。结论本研究未确定冠心病和认知障碍的直接关联,但是冠心病合并糖尿病与认知障碍患病风险增加显著相关,应开展更大样本的前瞻性研究以进一步确认两者之间的关联。
基金supported by the National Key Research and Development Program of China(2017YFC1307705).
文摘BACKGROUND The atherogenic index of plasma(AIP)has been shown to be positively correlated with cardiovascular disease in previous studies.However,it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease(CHD).Therefore,the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people.METHODS 19,194 participants aged≥60 years who had three AIP measurements between 2018 and 2020 were included in this study.AIP was defined as log10(triglyceride/high-density lipoprotein cholesterol).The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020.Cox proportional hazards models were used to estimate the hazard ratio(HR)with 95%CI of CHD events between different trajectory groups from 2020 to 2023.RESULTS Three different trajectory patterns were identified through group-based trajectory model:the low-level group(n=7410,mean AIP:-0.25 to-0.17),the medium-level group(n=9981,mean AIP:0.02-0.08),and the high-level group(n=1803,mean AIP:0.38-0.42).During a mean follow-up of 2.65 years,a total of 1391 participants developed CHD.After adjusting for potential confounders,compared with the participants in the low-level group,the HR with 95%CI of the medium-level group and the high-level group were estimated to be 1.24(1.10-1.40)and 1.43(1.19-1.73),respectively.These findings remained consistent in subgroup analyses and sensitivity analyses.CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly.This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.
基金supported by the National Natural Science Foundation of China(No.72071150)the Fujian Provincial Natural Science Foundation of China(Nos.2024J01903,2025J01393).
文摘For the past few years,the prevalence of cardiovascular disease has been showing a year-on-year increase,with a death rate of 2/5.Coronary heart disease(CHD)rates have increased 41%since 1990,which is the number one disease endangering human health in the world today.The risk indicators of CHD are complicated,so selecting effective methods to screen the risk characteristics can make the risk predictionmore efficient.In this paper,we present a comprehensive analysis ofCHDrisk indicators fromboth data and algorithmic levels,propose a method for CHDrisk indicator identification based on multi-angle integrated measurements and Sequential Backward Selection(SBS),and then build a risk prediction model.In the multi-angle integrated measurements stage,mRMR(Maximum Relevance Minimum Redundancy)is selected from the angle of feature correlation and redundancy of the dataset itself,SHAPRF(SHapley Additive exPlanations-Random Forest)is selected from the angle of interpretation of each feature to the results,and ARFS-RF(Algorithmic Randomness Feature Selection Random Forest)is selected from the angle of statistical interpretation of classification algorithm to measure the degree of feature importance.In the SBS stage,the features with low scores are deleted successively,and the accuracy of LightGBM(Light Gradient Boosting Machine)model is used as the evaluation index to select the final feature subset.This new risk assessment method is used to identify important factors affecting CHD,and the CHD dataset from the Kaggle website is used as the study subject.Finally,11 features are retained to construct a risk assessment indicator system for CHD.Using the LightGBM classifier as the core evaluationmetric,ourmethod achieved an accuracy of 0.8656 on the Kaggle CHD dataset(4238 samples,16 initial features),outperforming individual feature selection methods(mRMR,SHAP-RF,ARFS-RF)in both accuracy and feature reduction.This demonstrates the novelty and effectiveness of our multi-angle integrated measurement approach combined with SBS in building a concise yet highly predictive CHD risk model.
基金supported by the Medical Science Data Center at Shanghai Medical College of Fudan Universitysupported by grants from National Natural Science Foundation of China (81974229and 82171167 to W.F.,82330049 to W.Z.)+2 种基金Xiamen Municipal Major Project of High-Quality Development of Health and Wellness Technology Program (2024-GZL-GD06 to W.F.)National Key R&D Program of China (2022YFA0806603 to W.F.)Science and Technology Program of Guangzhou,China (2024A04J4924 to C.H.)
文摘Chromodomain helicase DNA binding protein 7(CHD7),an ATP-dependent chromatin remodeler,plays versatile roles in neurodevelopment.However,the functional significance of its ATPase/nucleosome remodeling activity remains incompletely understood.Here,we generate genetically engineered mouse embryonic stem cell lines harboring either an inducible Chd7 knockout or an ATPase-deficient missense variant identified in individuals with CHD7-related disorders.Through in vitro neural induction and differentiation assays combined with mouse brain analyses,we demonstrate that CHD7 enzymatic activity is indispensable for gene regulation and neurite development.Mechanistic studies integrating transcriptomic and epigenomic profiling reveal that CHD7 enzymatic activity is essential for establishing a permissive chromatin landscape at target genes,marked by the open chromatin architecture and active histone modifications.Collectively,our findings underscore the pivotal role of CHD7 enzymatic activity in neurodevelopment and provide critical insights into the pathogenic mechanisms of CHD7 missense variants in human diseases.
基金funded by E Fund Congenital Heart Disease Medical Talent Cultivation and Education Fund,grant number 2023QT0009the Science and Technology Planning Project of Guangdong Province,grant number 2023B03J1255.
文摘Comments Ebstein's Anomaly(EA)is a rare congenital heart disease(CHD)with an incidence of approximately 1 in 20,000.The pathognomonic feature involves apical displacement of the septal and posterior leaflets,resulting in valvular insufficiency and right ventricular(RV)remodeling.Untreated patients exhibit a cumulative mortality rate of up to 25% within the first decade,with heart failure(HF)and arrhythmias constituting the predominant causes of death.Current guidelines suggest that asymptomatic patients with accessory pathways may benefit from prophylactic ablation,though robust evidence specific to EA remains limited[1-3].
基金funded by National Natural Science Foundation of China (grant numbers 82270258,82100260)National Key Research&Development Prog ram of China (grant number 2020YFC2004800)。
文摘Background The relationship between glycated hemoglobin(HbA1c) and cognitive impairment in older adults with coronary heart disease(CHD) remains unclear.Methods The present study used a prospective cohort study design and included 3244 participants aged ≥ 65 years in Beijing,China. The Mini-Mental State Examination(MMSE) and Montreal Cognitive Assessment(MoCA) were used to assess cognitive function. Serum HbA1c was detected at admission. All patients were divided into high HbA1c group(≥ 6.5 mmol/L) and low HbA1c group(< 6.5 mmol/L) based on their HbA1c levels. Logistic regression analyses were used to evaluate the association between HbA1c and cognitive impairment.Results In this study of 3244 participants, 1201(37.0%) patients were in high HbA1c group and 2045(63.0%) patients were in a state of cognitive impairment. Logistic regression analyses demonstrated that HbA1c was an independent risk factor for cognitive impairment regardless of whether the HbA1c was a continuous or categorical variable(OR = 1.27, 95% CI: 1.15–1.40, P < 0.001;OR = 1.79, 95% CI: 1.41–2.26, P ≤ 0.001, respectively). The restricted cubic spline curve exhibited that the relationship between the HbA1c and cognitive impairment was linear(p for non-linear = 0.323, P < 0.001).Conclusion Elevated levels of HbA1c were associated with an increased risk of cognitive impairment in older patients with CHD. These insights could be used to improve the accuracy and sensitivity of cognitive screening in these patient populations.
基金supported by the National Natural Science Foundation of China(32070642 and 31371222 to Dr.Xiaoxue Wang)the National Key Research and Development Program from the Ministry of Science and Technology of China(2016YFD0100406 and 2017YFD0300107 to Dr.Xiaoxue Wang)the Science and Technology Department of Liaoning province(2022JH6/100100039 to Dr.Xiaoxue Wang)。
文摘The leaf is a major organ for photosynthesis,and its shape plays an important role in plant development and yield determination in rice(Oryza sativa L.).In this study,an adaxial curled leaf mutant,termed curly leaf 1-1(cul1-1),was obtained by chemical mutagenesis.The leaf rolling index of the cul1-1 mutant was higher than that of the wild-type,which was caused by the abnormal development of bulliform cells(BCs).We cloned the CUL1 gene by map-based cloning.A nonsense mutation was present in the cul1-1 mutant,converting a tryptophan codon into a stop codon.The CUL1 gene encodes a chromodomain,helicase/ATPase and DNA-binding domain containing protein.Genes related to leaf rolling and BC development,such as ADL1,REL1 and ROC5,were activated by the cul1-1 mutation.The trimethylation of lysine 27 in histone 3(H3K27me3),but not H3K4me3,at the ADL1,REL1 and ROC5 loci,was reduced in the cul1-1 mutant.High-throughput mRNA sequencing indicated that the cul1-1 mutation caused genome-wide differential gene expression.The differentially expressed genes were classified into a few gene ontology terms and Kyoto encyclopedia of genes and genomes pathways.In the natural population,22 missense genomic variations in the CUL1 locus were identified,which composed of 7 haplotypes.A haplotype network was also built with haplotype II as the ancestor.The findings revealed that CUL1 is essential for normal leaf development and regulates this process by inhibiting the expression of genes involved in leaf rolling and BC development.
