Background Biomarker-assisted diagnosis of acute aortic dissection （AAD） is important for diagnosis and treatment. However, identification of biomarkers for AAD in blood is a challenging task. The aim of this study ...Background Biomarker-assisted diagnosis of acute aortic dissection （AAD） is important for diagnosis and treatment. However, identification of biomarkers for AAD in blood is a challenging task. The aim of this study is to search for new potentially microRNA （miRNAs） biomarkers in AAD. Methods The miRNAs expression profiles in ascending aortic tissue and plasma were examined by microarray analysis in two sets or groups. The tissue group was composed of four patients with AAD and four controls of healthy male organ donors. The plasma group included 20 patients with AAD and 20 controls without cardiovascular disease. Bioinformatics was used to analyze the poten- tial targets of the differentially expressed miRNAs. Results Our study revealed that in AAD patients, the aortic tissue had 30 differentially expressed miRNAs with 13 up-regulated and 17 down-regulated, and plasma had 93 differentially expressed miRNAs, of which 33 were up-regulated and 60 were down-regulated. Four miRNAs were found to be up-regulated in both aortic tissue and plasma in AAD patients. The predicted miRNA targets indicated the four dysregulated miRNAs mainly targeted genes that were associated with cell-cell adhesion, extracellular matrix metabolism, cytoskeleton organization, inflammation, and multiple signaling pathways related to cellular cycles. Con- clusions Four miRNAs, which are up-regulated both in aortic tissue and in plasma in AAD patients, have been identified in this study. These miRNAs might be potential diagnostic biomarkers for AAD. Larger sample investigations are needed for further verification.展开更多
Background:Generic drugs are bioequivalent to their brand-name counterparts;however,concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time i...Background:Generic drugs are bioequivalent to their brand-name counterparts;however,concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies.The purpose of this study was to evaluate the long-term antihypertensive efficacy,cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs.Methods:In a multicenter,community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years,we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2,2176 patients using brand-name drugs and 4352 patients using generic drugs.Results:There were no significant differences between generic drugs and brand-name drugs in blood pressure(BP)-lowering efficacy,BP control rate,and cardiovascular outcomes including coronary heart disease and stroke.The adjusted mean(95%confidence interval[CI])of systolic BP(SBP)-lowering was-7.9 mmHg(95%CI,-9.9 to-5.9)in the brand-name drug group and-7.1 mmHg(95%CI,-9.1 to-5.1)in the generic drug group after adjusting for age,sex,body mass index,number of antihypertensive drugs and traditionally cardiovascular risk factors.Among patients aged<60 years,brand-name drugs had a higher BP control rate(47%vs.41%;P=0.02)and a greater effect in lowering SBP compared with generic drugs,with the between-group difference of 1.5 mmHg(95%CI,0.2-2.8;P=0.03).BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs(46%vs.40%;P=0.01).Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of$315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment.Conclusions:Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits,especially in low-and middle-income areas.展开更多
Objectives Inflammation has been shown to be related with acute aortic dissection （AAD）. The present study aimed to evaluate the association of white blood cell counts （WI3Cc） on admission with both in-hospital an...Objectives Inflammation has been shown to be related with acute aortic dissection （AAD）. The present study aimed to evaluate the association of white blood cell counts （WI3Cc） on admission with both in-hospital and long-term all-cause mortality in patients with uncom- plicated Stanford type B AAD. Methods From 2008 to 2010, a total of 377 consecutive patients with uncomplicated type B AAD were enrolled and then followed up. Clinical data and WBCc on admission were collected. The primary end points were in-hospital death and long-term all-cause death. Results The in-hospital death rate was 4.2%, and the long-term all-cause mortality rate was 6.9% during a median follow-up of 18.9 months. WBCc on admission was identified as a risk factor for in-hospital death by univariate Cox regression analysis as both a continuous variable and a categorical variable using a cut off of 11.0 × 109 cell/L （all P 〈 0.05）. After adjusting for age, sex and other risk factors, elevated admission WBCc was still a significant predictor for in-hospital death as both a continuous variable [hazard ratio （HR）： 1.052, 95% CI： 1.024-1.336, P = 0.002] and a categorical variable using a cut off of 11.0 × 109 cell/L （HR： 2.056, 95% CI： 1.673-5.253, P = 0.034）. No relationship was observed between WBCc on admission and long-term all-cause death. Conclusions Our results indicate that elevated WBCc upon admission might be used as a predictor for increased risk of in-hospital death in uncomplicated type B AAD. There might be no predictive value of WBCc for the long-term survival of type B AAD.展开更多
Background： Takayasu arteritis （TA） is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. Methods： Four single ...Background： Takayasu arteritis （TA） is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. Methods： Four single nucleotide polymorphisms （SNPs） those locate in the IL12B region （rs56167332）, the MLX region （rs665268）, the FCGR2A/FCGR3A locus （rsi0919543）, and the HLA-B/M1CA locus （rs12524487）, associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. Results： Among the four SNPs, rs 10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs 10919543 at the FCGR2A/FCGR3A locus is a high risk factor （odds ratio [OR] = 6.532, 95% confidence interval [C1] = 2.402 - 17.763, P 〈 0.001 ） for TA. Among TA patients, the level of eosinophil granulocytes （Eos） in the peripheral blood was observed to be higher in the GG group of rs 10919543 （n = 23, Eos = 0. I 1 [0.08, 0.17] x 109/L） than the GA ＋ AA group （n = 100, Eos = 0.08 [0.05, 0.13] 10/L, P = 0.028）. No correlation between the genotypes of the other three SNPs and TA patients was observed. Conclusions： Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.展开更多
Gene diagnosis refers to the use of genetic testing in the diagnosis of inheritable conditions,which has gradually been applied in clinical practice with the completion of the gene sequencing efforts of the Human Geno...Gene diagnosis refers to the use of genetic testing in the diagnosis of inheritable conditions,which has gradually been applied in clinical practice with the completion of the gene sequencing efforts of the Human Genome Project and the advancement of gene detection technology.In the specialty field of cardiology,monogenic cardiovascular diseases are defined as monogenic inherited diseases with cardiovascular damage as the only phenotype,or accompanied by cardiovascular damage.Although the incidence of such diseases is relatively low,in the country of China with its vast population of 1.33 billion,the sheer volume of patients with monogenic cardiovascular diseases is alarming.With early onset,severe symptoms,and poor prognosis,delays in diagnosis and treatment of monogenic cardiovascular diseases often have serious consequences.Gene testing is perfectly suited for early diagnosis of monogenic cardiovascular diseases,especially for“pre-symptomatic”diagnosis.In this article,we generally review the characteristics of common monogenic cardiovascular diseases,summarize the progress of the standardized application of gene testing technology in clinical practice,describe the applicable population and condition of genetic testing for different monogenic cardiovascular diseases,analyze the practicality of genetic diagnosis of these inheritable conditions,and provide guidance on identifying suitable candidates for gene diagnosis.In conclusion,gene diagnosis provides new insights into the way physicians diagnose diseases,and is well-positioned to guide clinical decision making and treatment,especially in cardiology.展开更多
BACKGROUND Three-vessel disease(TVD)with a SYNergy between PCI with TAXus and cardiac surgery(SYNTAX)score of≥23 is one of the most severe types of coronary artery disease.We aimed to take advantage of machine learni...BACKGROUND Three-vessel disease(TVD)with a SYNergy between PCI with TAXus and cardiac surgery(SYNTAX)score of≥23 is one of the most severe types of coronary artery disease.We aimed to take advantage of machine learning to help in de-cision-making and prognostic evaluation in such patients.METHODS We analyzed 3786 patients who had TVD with a SYNTAX score of≥23,had no history of previous revascularization,and underwent either coronary artery bypass grafting(CABG)or percutaneous coronary intervention(PCI)after enrollment.The patients were randomly assigned to a training group and testing group.The C4.5 decision tree algorithm was applied in the training group,and all-cause death after a median follow-up of 6.6 years was regarded as the class label.RESULTS The decision tree algorithm selected age and left ventricular end-diastolic diameter(LVEDD)as splitting features and divided the patients into three subgroups:subgroup 1(age of≤67 years and LVEDD of≤53 mm),subgroup 2(age of≤67 years and LVEDD of>53 mm),and subgroup 3(age of>67 years).PCI conferred a patient survival benefit over CABG in sub-group 2.There was no significant difference in the risk of all-cause death between PCI and CABG in subgroup 1 and subgroup 3 in both the training data and testing data.Among the total study population,the multivariable analysis revealed significant dif-ferences in the risk of all-cause death among patients in three subgroups.CONCLUSIONS The combination of age and LVEDD identified by machine learning can contribute to decision-making and risk assessment of death in patients with severe TVD.The present results suggest that PCI is a better choice for young patients with severe TVD characterized by left ventricular dilation.展开更多
1 Introduction In China's Mainland,hospitalization expenses for patients with cardiovascular and cerebrovascular diseases have rapidly increased since 2004 and currently exceed the growth rate of the national gros...1 Introduction In China's Mainland,hospitalization expenses for patients with cardiovascular and cerebrovascular diseases have rapidly increased since 2004 and currently exceed the growth rate of the national gross domestic product.[1]One reason for these high expenses is that the traditional"one-size-for-all"medical model results in low treatment efficacy.Precision and individualized medical models may help reduce the medical burden and provide a sustainable medical model.展开更多
Stroke is a major cause of adult death and disability worldwide.Epidemiological and animal studies have provided strong evidence that the pathogenesis of stroke is multi-factorial and induced by a combination of envir...Stroke is a major cause of adult death and disability worldwide.Epidemiological and animal studies have provided strong evidence that the pathogenesis of stroke is multi-factorial and induced by a combination of environmental and genetic risk factors,but the identifica-tion of individual causative variants remains little known.Genetic influences are likely to be polygenic with small effect sizes,and stroke itself consists of a number of different subtypes which may each have different genetic profiles.In addition,various ethnic populations may have different stroke risk,such as Asian race.The reasons for high risk of stroke among the Chinese,especially hemorrhagic stroke,remain unknown.Most human studies have taken a candidate gene approach using case-control methodology.To be reliably detected,small relative risks require large sample sizes,probably 1000 patients or more.Genome-wide association(GWA)study is an unbiased and comprehensive approach to identify common risk alleles for complex diseases.Recently,a multistage GWA study has identified three loci on chromosomes 2q,8q and 9p to be associated with intracranial aneurysm in European and Japanese populations.Another GWAfinding is the identification of risk variants for cardioembolic stroke on chromosome 4q25 in European populations.In this review,we mainly focus on the results from case-control association studies on genetic factors that play a role in the risk of ischemic and hemorrhagic stroke in Chinese population.The combined effects of multiple susceptibility genes for stroke risk are also summarized.展开更多
基金This work was supported by the grants from National Natural Science Foundation of China （project 81170286 to FAN XH, project 81300184 to WANG XJ）. We thank the patients for their participations in our study.
文摘Background Biomarker-assisted diagnosis of acute aortic dissection （AAD） is important for diagnosis and treatment. However, identification of biomarkers for AAD in blood is a challenging task. The aim of this study is to search for new potentially microRNA （miRNAs） biomarkers in AAD. Methods The miRNAs expression profiles in ascending aortic tissue and plasma were examined by microarray analysis in two sets or groups. The tissue group was composed of four patients with AAD and four controls of healthy male organ donors. The plasma group included 20 patients with AAD and 20 controls without cardiovascular disease. Bioinformatics was used to analyze the poten- tial targets of the differentially expressed miRNAs. Results Our study revealed that in AAD patients, the aortic tissue had 30 differentially expressed miRNAs with 13 up-regulated and 17 down-regulated, and plasma had 93 differentially expressed miRNAs, of which 33 were up-regulated and 60 were down-regulated. Four miRNAs were found to be up-regulated in both aortic tissue and plasma in AAD patients. The predicted miRNA targets indicated the four dysregulated miRNAs mainly targeted genes that were associated with cell-cell adhesion, extracellular matrix metabolism, cytoskeleton organization, inflammation, and multiple signaling pathways related to cellular cycles. Con- clusions Four miRNAs, which are up-regulated both in aortic tissue and in plasma in AAD patients, have been identified in this study. These miRNAs might be potential diagnostic biomarkers for AAD. Larger sample investigations are needed for further verification.
基金China National Center for Biotechnology Development fund(Nos.2018YFC1312400,2018YFC1312405)National Science and Technology Pillar Program during the Twelfth Five-year Plan Period(No.2011BAI11B04)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(No.2016-I2M-1-006)。
文摘Background:Generic drugs are bioequivalent to their brand-name counterparts;however,concerns still exist regarding the effectiveness and safety of generic drugs because of small sample sizes and short follow-up time in most studies.The purpose of this study was to evaluate the long-term antihypertensive efficacy,cost-effectiveness and cardiovascular outcomes of generic drugs compared with brand-name drugs.Methods:In a multicenter,community-based study including 7955 hypertensive patients who were prospectively followed up for an average of 2.5 years,we used the propensity-score-matching method to match the patients using brand-name drugs to those using generic drugs in a ratio of 1:2,2176 patients using brand-name drugs and 4352 patients using generic drugs.Results:There were no significant differences between generic drugs and brand-name drugs in blood pressure(BP)-lowering efficacy,BP control rate,and cardiovascular outcomes including coronary heart disease and stroke.The adjusted mean(95%confidence interval[CI])of systolic BP(SBP)-lowering was-7.9 mmHg(95%CI,-9.9 to-5.9)in the brand-name drug group and-7.1 mmHg(95%CI,-9.1 to-5.1)in the generic drug group after adjusting for age,sex,body mass index,number of antihypertensive drugs and traditionally cardiovascular risk factors.Among patients aged<60 years,brand-name drugs had a higher BP control rate(47%vs.41%;P=0.02)and a greater effect in lowering SBP compared with generic drugs,with the between-group difference of 1.5 mmHg(95%CI,0.2-2.8;P=0.03).BP control rate was higher in male patients using brand-name drugs compared with those using generic drugs(46%vs.40%;P=0.01).Generic drugs treatment yielded an average annual incremental cost-effectiveness ratio of$315.4 per patient per mmHg decrease in SBP compared with brand-name drugs treatment.Conclusions:Our data suggested that generic drugs are suitable and cost-effective in improving hypertension management and facilitating public health benefits,especially in low-and middle-income areas.
基金We are very grateful to the patients and doctors who participated in the study and for the help and co-operation of the clinic staff. This work was supported by a grant from the National Natural Science Foundation of China to Dr. FAN XH （No. 81570430）.
文摘Objectives Inflammation has been shown to be related with acute aortic dissection （AAD）. The present study aimed to evaluate the association of white blood cell counts （WI3Cc） on admission with both in-hospital and long-term all-cause mortality in patients with uncom- plicated Stanford type B AAD. Methods From 2008 to 2010, a total of 377 consecutive patients with uncomplicated type B AAD were enrolled and then followed up. Clinical data and WBCc on admission were collected. The primary end points were in-hospital death and long-term all-cause death. Results The in-hospital death rate was 4.2%, and the long-term all-cause mortality rate was 6.9% during a median follow-up of 18.9 months. WBCc on admission was identified as a risk factor for in-hospital death by univariate Cox regression analysis as both a continuous variable and a categorical variable using a cut off of 11.0 × 109 cell/L （all P 〈 0.05）. After adjusting for age, sex and other risk factors, elevated admission WBCc was still a significant predictor for in-hospital death as both a continuous variable [hazard ratio （HR）： 1.052, 95% CI： 1.024-1.336, P = 0.002] and a categorical variable using a cut off of 11.0 × 109 cell/L （HR： 2.056, 95% CI： 1.673-5.253, P = 0.034）. No relationship was observed between WBCc on admission and long-term all-cause death. Conclusions Our results indicate that elevated WBCc upon admission might be used as a predictor for increased risk of in-hospital death in uncomplicated type B AAD. There might be no predictive value of WBCc for the long-term survival of type B AAD.
基金This study wass supported by grants from the National Natural Science Foundation of China （No. 81470503 and No. 81470380）, and grant from the Ministry of Science and Technology of China （No. 2015AA020407）.
文摘Background： Takayasu arteritis （TA） is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. Methods： Four single nucleotide polymorphisms （SNPs） those locate in the IL12B region （rs56167332）, the MLX region （rs665268）, the FCGR2A/FCGR3A locus （rsi0919543）, and the HLA-B/M1CA locus （rs12524487）, associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. Results： Among the four SNPs, rs 10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs 10919543 at the FCGR2A/FCGR3A locus is a high risk factor （odds ratio [OR] = 6.532, 95% confidence interval [C1] = 2.402 - 17.763, P 〈 0.001 ） for TA. Among TA patients, the level of eosinophil granulocytes （Eos） in the peripheral blood was observed to be higher in the GG group of rs 10919543 （n = 23, Eos = 0. I 1 [0.08, 0.17] x 109/L） than the GA ＋ AA group （n = 100, Eos = 0.08 [0.05, 0.13] 10/L, P = 0.028）. No correlation between the genotypes of the other three SNPs and TA patients was observed. Conclusions： Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.
基金This work was supported by a grant from Chinese Academy of Medical Sciences Initiative for Innovative Medicine(CAMS-I2M),No.2016-I2M-3-006.
文摘Gene diagnosis refers to the use of genetic testing in the diagnosis of inheritable conditions,which has gradually been applied in clinical practice with the completion of the gene sequencing efforts of the Human Genome Project and the advancement of gene detection technology.In the specialty field of cardiology,monogenic cardiovascular diseases are defined as monogenic inherited diseases with cardiovascular damage as the only phenotype,or accompanied by cardiovascular damage.Although the incidence of such diseases is relatively low,in the country of China with its vast population of 1.33 billion,the sheer volume of patients with monogenic cardiovascular diseases is alarming.With early onset,severe symptoms,and poor prognosis,delays in diagnosis and treatment of monogenic cardiovascular diseases often have serious consequences.Gene testing is perfectly suited for early diagnosis of monogenic cardiovascular diseases,especially for“pre-symptomatic”diagnosis.In this article,we generally review the characteristics of common monogenic cardiovascular diseases,summarize the progress of the standardized application of gene testing technology in clinical practice,describe the applicable population and condition of genetic testing for different monogenic cardiovascular diseases,analyze the practicality of genetic diagnosis of these inheritable conditions,and provide guidance on identifying suitable candidates for gene diagnosis.In conclusion,gene diagnosis provides new insights into the way physicians diagnose diseases,and is well-positioned to guide clinical decision making and treatment,especially in cardiology.
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(grant number 2016-I2M-1-002)the Beijing Municipal Natural Science Foundation(grant number 7181008)Capital’s Funds for Health Improvement and Research(grant number 2018-2-4033).
文摘BACKGROUND Three-vessel disease(TVD)with a SYNergy between PCI with TAXus and cardiac surgery(SYNTAX)score of≥23 is one of the most severe types of coronary artery disease.We aimed to take advantage of machine learning to help in de-cision-making and prognostic evaluation in such patients.METHODS We analyzed 3786 patients who had TVD with a SYNTAX score of≥23,had no history of previous revascularization,and underwent either coronary artery bypass grafting(CABG)or percutaneous coronary intervention(PCI)after enrollment.The patients were randomly assigned to a training group and testing group.The C4.5 decision tree algorithm was applied in the training group,and all-cause death after a median follow-up of 6.6 years was regarded as the class label.RESULTS The decision tree algorithm selected age and left ventricular end-diastolic diameter(LVEDD)as splitting features and divided the patients into three subgroups:subgroup 1(age of≤67 years and LVEDD of≤53 mm),subgroup 2(age of≤67 years and LVEDD of>53 mm),and subgroup 3(age of>67 years).PCI conferred a patient survival benefit over CABG in sub-group 2.There was no significant difference in the risk of all-cause death between PCI and CABG in subgroup 1 and subgroup 3 in both the training data and testing data.Among the total study population,the multivariable analysis revealed significant dif-ferences in the risk of all-cause death among patients in three subgroups.CONCLUSIONS The combination of age and LVEDD identified by machine learning can contribute to decision-making and risk assessment of death in patients with severe TVD.The present results suggest that PCI is a better choice for young patients with severe TVD characterized by left ventricular dilation.
基金supported by the National Natural Science Foundation of China(No.81870286)the CAMS Innovation Fund for Medical Sciences(CAMS-I2M,2016-I2M-1-002)。
文摘1 Introduction In China's Mainland,hospitalization expenses for patients with cardiovascular and cerebrovascular diseases have rapidly increased since 2004 and currently exceed the growth rate of the national gross domestic product.[1]One reason for these high expenses is that the traditional"one-size-for-all"medical model results in low treatment efficacy.Precision and individualized medical models may help reduce the medical burden and provide a sustainable medical model.
基金supported by the Ministry of Science and Technology of China(Nos.2006CB503805,2009DFB30050,and G200056901).
文摘Stroke is a major cause of adult death and disability worldwide.Epidemiological and animal studies have provided strong evidence that the pathogenesis of stroke is multi-factorial and induced by a combination of environmental and genetic risk factors,but the identifica-tion of individual causative variants remains little known.Genetic influences are likely to be polygenic with small effect sizes,and stroke itself consists of a number of different subtypes which may each have different genetic profiles.In addition,various ethnic populations may have different stroke risk,such as Asian race.The reasons for high risk of stroke among the Chinese,especially hemorrhagic stroke,remain unknown.Most human studies have taken a candidate gene approach using case-control methodology.To be reliably detected,small relative risks require large sample sizes,probably 1000 patients or more.Genome-wide association(GWA)study is an unbiased and comprehensive approach to identify common risk alleles for complex diseases.Recently,a multistage GWA study has identified three loci on chromosomes 2q,8q and 9p to be associated with intracranial aneurysm in European and Japanese populations.Another GWAfinding is the identification of risk variants for cardioembolic stroke on chromosome 4q25 in European populations.In this review,we mainly focus on the results from case-control association studies on genetic factors that play a role in the risk of ischemic and hemorrhagic stroke in Chinese population.The combined effects of multiple susceptibility genes for stroke risk are also summarized.
