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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.
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Anciano , Humanos , Masculino , Antihipertensivos/uso terapéutico , Presión Sanguínea , China , Medicamentos Genéricos/uso terapéutico , Estudios ProspectivosRESUMEN
Genetic as well as genomic study has advanced the development of precision medicine. We are marching on the road for right patients who are receiving more and more right treatment at right time. In hypertension field, precision medicine is available, actionable and affordable. First and the most practical advancement is monogenic hypertension, the disease-genes have been found for at least 17 types of monogenic hypertension. These patients can be precisely treated according to their carried gene mutation. Secondly, pharmacogenetic and pharmacogenomic guided anti-hypertensive drug selection, very promising but lack of clinic outcome data to support widely clinical application. Majority of hypertension are due to multiple genetic and environmental factors. GWAS fund some genetic variants related to primary hypertension, but these variants can only be responsible for 1-10% of blood pressure variation. We have a long way to go in exploring the real cause of primary hypertension.
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OBJECTIVE@#Identification of new risk factors is needed to improve prediction of adverse outcomes in patients with three-vessel disease (TVD). The present study aimed to evaluate the prognostic values of serum chloride and sodium levels in patients with TVD.@*METHODS@#We used data from a prospective cohort of consecutive patients with angiographically confirmed TVD. The primary endpoint was all-cause death. Cox proportional hazard regression was used to analyze the relationship of serum chloride and sodium levels with long-term outcomes of TVD patients.@*RESULTS@#A total of 8,318 participants with available serum chloride and sodium data were included in this analysis. At baseline, patients in the low tertiles group of serum chloride level (⪕ 102.0 mmol/L) or serum sodium level (⪕ 139.0 mmol/L) had more severe disease conditions. During a median follow-up of 7.5-year, both low serum chloride level and low serum sodium level were found to be associated with an increased risk for mortality in univariate analysis. However, when both parameters were incorporated into a multivariate model, only low serum sodium level remained to be an independent predictor of all-cause death (hazard ratio: 1.16, 95% confidence interval: 1.01-1.34, P = 0.041). Modest but significant improvement of discrimination was observed after incorporating serum sodium level into the Synergy between percutaneous coronary intervention (PCI) with Taxus and Cardiac Surgery score.@*CONCLUSION@#Serum sodium level is more strongly associated with long-term outcomes of TVD patients compared with serum chloride level. Low serum sodium level is an independent risk factor for mortality, but only provides modest prognostic information beyond an established risk model.
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , China , Epidemiología , Cloruros , Sangre , Enfermedad de la Arteria Coronaria , Sangre , Diagnóstico , Mortalidad , Pronóstico , Estudios Prospectivos , Sodio , SangreRESUMEN
<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>Four single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA 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.</p><p><b>RESULTS</b>Among the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 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 rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] ×109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] ×109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed.</p><p><b>CONCLUSIONS</b>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.</p>
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Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Receptores de IgG , Genética , Arteritis de Takayasu , GenéticaRESUMEN
<p><b>BACKGROUND</b>Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiac disease predominantly caused by mutations in desmosomal protein genes. Previous genetic analyses of the Chinese ARVC population are limited to small size and restriction to a single gene. This study was aimed to investigate the genotype in a large series of Chinese patients with ARVC through comprehensively screening nine ARVC-causing genes.</p><p><b>METHODS</b>A total of 100 unrelated ARVC patients and 300 age, gender and ethnicity matched healthy controls were genetically tested with multiplexing targeted resequencing for nine previously reported ARVC-causing genes, including plakophilin-2, desmoplakin, desmoglein-2, desmocollin-2, plakoglobin, transforming growth factor beta-3, transmembrane protein 43, desmin and Lamin A/C.</p><p><b>RESULTS</b>Fifty-nine mutations were identified in 64% of the patients, among which, 93% were located in desmosomal protein genes. Plakophilin-2 mutations accounted for 54% of the total and 58% of the desmosomal mutations, with a truncating mutation type making up about 2/3 of the plakophilin-2 mutations. Only four mutations were found in non-desmosomal genes; two in transmembrane protein 43 and two in transforming growth factor beta-3. Two of them (one of each gene) appeared as single missense mutations. No mutation was identified in desmin or Lamin A/C. Multiple mutations were found in 23% of the patients, with plakophilin-2 being found in 57% of the multi-mutation carriers.</p><p><b>CONCLUSIONS</b>Plakophilin-2 was the most common gene mutation that was identified in Chinese ARVC patients. Non-desmosomal genes should be added to desmosomal protein genes when performing molecular genetic screening in patients with suspected ARVC.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Displasia Ventricular Derecha Arritmogénica , Genética , Metabolismo , Pueblo Asiatico , Desmina , Genética , Desmogleína 2 , Genética , Mutación , Placofilinas , Genética , gamma Catenina , GenéticaRESUMEN
<p><b>BACKGROUND</b>The association between fish consumption and heart failure (HF) incidence is inconsistent.</p><p><b>METHODS</b>We performed a systematic search of Pubmed and Embase (from 1953 to June 2012) using key words related to fish and HF. Studies with at least three categories of fish consumption reporting both relative risk (RR) and corresponding 95% confidence interval (CI) for HF incidence were included. The pooled RR and 95%CI were calculated using a fixed or random-effects model. The generalized least squares regression model was used to quantify the dose-response relationship between fish consumption and HF incidence.</p><p><b>RESULTS</b>Five prospective cohort studies including 4750 HF events of 170 231 participants with an average of 9.7-year follow-up were selected and identified. Compared with those who never ate fish, individuals with higher fish consumption had a lower HF incidence. The pooled RRs for HF incidence was 0.99 (95%CI, 0.91 to 1.08) for fish consumption 1 to 3 times per month, 0.91 (95%CI, 0.84 to 0.99) for once a week, 0.87 (95%CI, 0.81 to 0.95) for 2 to 4 times per week, and 0.86 (95%CI, 0.84 to 0.99) for 5 or more times per week. An increment of 20 g of daily fish intake was related to a 6% lower risk of HF (RR: 0.94, 95%CI, 0.90 to 0.97; P for trend = 0.001).</p><p><b>CONCLUSIONS</b>This meta-analysis suggests that there is a dose-dependent inverse relationship between fish consumption and HF incidence. Fish intake once or more times a week could reduce HF incidence.</p>
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Animales , Femenino , Humanos , Masculino , Peces , Insuficiencia Cardíaca , Epidemiología , Incidencia , Estudios Prospectivos , Alimentos MarinosRESUMEN
<p><b>BACKGROUND</b>Left ventricular hypertrophy (LVH) and geometric abnormality are associated with morbidity and mortality of cardiovascular disease and stroke. Hypertension is the major cause of LVH. Yet the prevalence and other risk factors of LVH and geometric abnormality in Chinese hypertensive population are unknown. The objective of this study was to investigate the prevalence and risk factors of LVH and geometric abnormality in community-based Chinese hypertensive population.</p><p><b>METHODS</b>The study was a community-based cross-sectional study, and comprised 4270 hypertension patients with integrated clinical and echocardiographic data. Left ventricular mass was measured by transthoracic echocardiography. LVH was diagnosed by using the criteria of over 49.2 g/m(2.7) for men and 46.7 g/m(2.7) for women. LV geometric patterns (normal, concentric remodeling, concentric or eccentric hypertrophy) were calculated according to LVH and relative wall thickness. Logistic regression model was used to determine the odds ratio (OR) and 95% confidence intervals (CI) of the risk factors of LVH.</p><p><b>RESULTS</b>The prevalence of LVH was 42.7% in 4270 hypertensive patients, with 37.4% in males and 45.4% in females, respectively. The prevalence of concentric remodeling, concentric or eccentric hypertrophy was 24.7%, 20.2%, and 22.6%, respectively. In Logistic regression model, female (OR 1.3, 95%CI 1.1 - 1.5, P < 0.01), age (OR 1.02, 95%CI 1.01 - 1.03, P < 0.01), body mass index (OR 1.2, 95%CI 1.15 - 1.20, P < 0.01), systolic blood pressure (OR 1.02, 95%CI 1.01 - 1.03, P < 0.01), and serum triglyceride (OR 1.10, 95% CI 1.00 - 1.20, P < 0.01) were risk factors of LVH. Female, age, body mass index, systolic blood pressure and serum triglyceride were also risk factors of left ventricular geometric abnormality.</p><p><b>CONCLUSIONS</b>The echocardiographic LVH is the major complication of patients with hypertension in rural area of China, especially for women. To effectively treat hypertension, weight loss and control of serum triglyceride may help to prevent LVH in hypertensive population.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Transversales , Ecocardiografía , Ventrículos Cardíacos , Patología , Hipertensión , Epidemiología , Hipertrofia Ventricular Izquierda , Epidemiología , Prevalencia , Factores de RiesgoRESUMEN
<p><b>BACKGROUND</b>Liddle's syndrome is a rare autosomal-dominant monogenic form of salt-sensitive hypertension. This study aimed to screen the gene mutation in β and γ subunits of the epithelial sodium channel (ENaC) of a Chinese family with Liddle's syndrome, an autosomal dominant form of hypertension.</p><p><b>METHODS</b>DNA samples from the proband with early-onset, treatment-resistant hypertension and suppressed plasma renin activity were initially screened for mutations in the C-terminal exons of the ENaC β or γ subunit genes, using amplification by polymerase chain reaction and direct DNA sequencing. We also screened the C-terminus of SCNN1B and SCNN1G in family members, and screened for the mutation in 150 controls.</p><p><b>RESULTS</b>Genetic analysis of the β ENaC gene revealed a missense mutation of CCC to TCC at codon 616 in the proband, her mother and her grandmother. One hundred and fifty randomly selected controls had not the mutation, indicating that this is not a common genetic polymorphism. There was no mutation of the γ ENaC gene in any of the individuals examined.</p><p><b>CONCLUSIONS</b>Through direct DNA sequencing analysis, we established the diagnosis of Liddle's syndrome for the proband and her families, and provided tailored therapies to this abnormality. These results provide further evidence that Pro616Ser is a critical amino acid that has a key role in the inhibition of sodium channel activity.</p>
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Adolescente , Femenino , Humanos , Masculino , Análisis Mutacional de ADN , Canales Epiteliales de Sodio , Genética , Síndrome de Liddle , Genética , Mutación Missense , LinajeRESUMEN
<p><b>BACKGROUND</b>Severe bilateral carotid stenosis caused by atherosclerosis has not been unusual in the elderly. Such patients have high stroke risk. Many studies show that carotid artery stenting (CAS) is an alternative to treat unilateral carotid stenosis. However, the optimal procedural strategy of bilateral carotid stenosis remains unclear. The purpose of our study was to evaluate the safety of simultaneous bilateral carotid artery stenting (SBCAS) compared with unilateral carotid artery stenting (UCAS).</p><p><b>METHODS</b>In this single-center retrospective study, we analyzed 234 consecutive patients who underwent carotid stenting from January 2005 to December 2009. Thirty-nine patients (16.7%) of them underwent SBCAS, and the others (n = 195) underwent UCAS. Indication for CAS was defined as carotid artery diameter reduction > 60% (symptomatic) or > 80% (asymptomatic). Six-month and 30-day hemodynamic depression (HD), hyperperfusion syndrome (HPS), stroke, death and myocardial infarction (MI) after carotid stenting were assessed.</p><p><b>RESULTS</b>SBCAS group had no more HD and HPS compared with UCAS group at 30 days (HD: 28.2% vs. 20.0%, P = 0.396; HPS: 2.6% vs. 2.1%, P = 0.262). Moreover, there was no statistically significant difference between SBCAS group and UCAS group in major stroke, death, MI and their combinations within 30 days (major stroke: 0 vs. 3.6%, P = 0.604; death: 2.6% vs. 1.5%, P = 0.520; MI: 2.6% vs. 0.5%, P = 0.306; and their combinations: 5.1% vs. 4.6%, P = 1.000) and 6 months (major stroke: 0 vs. 3.6%, P = 0.604; death: 5.1% vs. 2.1%, P = 0.262; MI: 5.1% vs.1.0%, P = 0.130 and their combinations: 7.7% vs. 5.1%, P = 0.459).</p><p><b>CONCLUSIONS</b>The patients undergoing SBCAS had no more events than those undergoing UCAS in 30-day and 6-month follow-up. Our finding suggests that SBCAS appears to be as safe as UCAS.</p>
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angioplastia de Balón , Estenosis Carotídea , Terapéutica , Hemodinámica , Complicaciones Posoperatorias , Estudios Retrospectivos , Stents , Factores de TiempoRESUMEN
<p><b>OBJECTIVE</b>To evaluate the clinical features in Chinese patients with apical hypertrophic cardiomyopathy (AHCM) and typical hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>This retrospective analysis included 160 patients hospitalized in Fuwai hospital. Patients were divided into three groups: apical hypertrophic cardiomyopathy (AHCM, n = 41) group, non-obstructive typical hypertrophic cardiomyopathy group [NOHCM, LVOT < 30 mm Hg (1 mm Hg = 0.133 kPa) at rest, n = 52] and obstructive typical hypertrophic cardiomyopathy (OHCM, LVOT ≥ 30 mm Hg at rest, n = 67). Clinical features, diagnosis, therapy, and plasma levels of biomarkers of these three groups were analyzed.</p><p><b>RESULTS</b>(1) The age at disease onset was older in AHCM group than in OHCM group [(49.9 ± 13.6) years vs. (41.4 ± 14.6) years, P < 0.01]. Exertional dyspnea appeared more often in HCM patients than in AHCM patients, NT-proBNP level was significantly lower in AHCM patients than in OHCM patients (P = 0.001). Plasma CK-MB, LDH, TnI and MYO levels were similar among the three groups. (2) Thirty-three AHCM patients were first hospitalized for suspected coronary heart disease (CHD) and CHD was excluded in 18 cases (43.9%). (3) The frequency of giant negative T waves (depth ≥ 10 mm) on ECG was 43.9%, 13.5% and 4.4% (P < 0.01) in AHCM, NOHCM and OHCM respectively. Half of AHCM patients showed left ventricular high voltage on ECG. (4) Cardiac magnetic resonance imaging is superior to echocardiography on correctly diagnosing AHCM.</p><p><b>CONCLUSION</b>AHCM patients differ from typical OHCM patients in clinical characteristics. There were significant differences on echocardiography and electrocardiography features among three groups. Cardiac magnetic resonance imaging and giant negative T waves on ECG are helpful for the diagnosis of AHCM.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pueblo Asiatico , Cardiomiopatía Hipertrófica , Clasificación , Diagnóstico , Ecocardiografía , Electrocardiografía , Imagen por Resonancia Magnética , Estudios RetrospectivosRESUMEN
<p><b>BACKGROUND</b>Tumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy (LVH) in hypertensive patients.</p><p><b>METHODS</b>Four representatives of all the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations (n = 2120 and n = 324).</p><p><b>RESULTS</b>We found that only the tag SNP (rs5029939) was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH (odds ratio (OR) (95% confidence interval (CI)) 0.58 (0.358 - 0.863), P = 0.035; OR (95%CI) = 0.477 (0.225 - 0.815), P < 0.05, respectively). Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations (all P < 0.01).</p><p><b>CONCLUSION</b>These findings indicate that the SNP (rs5029939) in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Transversales , Proteínas de Unión al ADN , Ecocardiografía , Predisposición Genética a la Enfermedad , Genotipo , Hipertensión , Genética , Hipertrofia Ventricular Izquierda , Genética , Péptidos y Proteínas de Señalización Intracelular , Genética , Proteínas Nucleares , Genética , Fenotipo , Polimorfismo de Nucleótido Simple , Genética , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfaRESUMEN
<p><b>OBJECTIVE</b>In this study we investigated the functional restoration of nonsense mutations in the SCN5A gene.</p><p><b>METHODS</b>The readthrough-enhancing reagents were introduced to HEK293 cells to suppress one nonsense mutation W822X in the SCN5A gene. Patch-clamp was used to record the whole-cell current and dynamics. Western blot and immunofluorescence staining were used to certify the expression and the location of the sodium channel.</p><p><b>RESULTS</b>In transfected HEK293 cells, the nonsense mutation in SCN5A inhibited the expression level of full-length protein, and the sodium currents from the mutant channels were less than 3% of the wild-type level. Readthrough enhancement by decreasing translation termination efficiency with a siRNA targeting eukaryotic release factor eRF3a (a GTPase that binds eRF1), the sodium current from the mutant cDNAs was restored to as much as 30% of the wild-type. After the treatment by the readthrough-enhancing reagents, the channels from cDNA carrying W822X remained the features of wild-type phenotype, and Western blot and immunochemical staining also showed the expression of full-length channel proteins.</p><p><b>CONCLUSION</b>Readthrough-enhancing reagents could effectively suppress nonsense mutations in SCN5A and partially restore the function of sodium channel and the expression of full-length channels.</p>
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Humanos , Codón sin Sentido , Células HEK293 , Técnicas de Placa-Clamp , Plásmidos , ARN Interferente Pequeño , Canales de Sodio , Genética , Metabolismo , TransfecciónRESUMEN
<p><b>BACKGROUND</b>A few recent studies have reported that inflammation is associated with the prognosis of acute aortic dissection (AD). There is, however, no systemic investigation regarding the role of plasma C-reactive protein (CRP) and white blood cell (WBC) levels in predicting in-hospital clinical events of acute type A AD.</p><p><b>METHODS</b>The levels of high-sensitivity CRP and WBC counts were systemically determined after admission in 36 patients with acute type A AD. The variations of plasma CRP and WBC levels in different time windows (admission, 1, 2, 3, 4, 6, 8 days) in patients with acute type A AD were analyzed between patients with events and without events.</p><p><b>RESULTS</b>During hospitalization, five patients died, and increased levels of CRP and WBC were found in patients died with acute type A AD compared with patients survived (P < 0.01, respectively). Medical treatment may significantly decrease inflammatory response in survived patients with acute type A AD. Additionally, patients with complication of pleural effusion showed higher CRP and WBC levels (P = 0.046, P = 0.018, respectively). Lower WBC levels were found in survived patients treated medically (P = 0.001). Moreover, mean CRP and WBC levels had positive correlations with aortic diameter (r = 0.364, P = 0.000; r = 0.333, P = 0.000, respectively) and age (r = 0.270, P = 0.000, respectively), while negative correlations with the time from onset of symptoms to hospital admission (r = -0.229, P = 0.000, r = -0.200, P = 0.002, respectively). Univariate analysis showed that age ≥ 65 years, CRP ≥ 12.05 mg/L, WBC ≥ 12.16 × 10(9)/L, aortic diameter ≥ 48 mm, pleural effusion and diastolic blood pressure ≥ 105 mmHg were associated with hospital mortality. While CRP ≥ 12.05 mg/L, WBC ≥ 12.16 × 10(9)/L, aortic diameter ≥ 48 mm were strongly associated with hospital mortality in multiple Logistic regression analysis.</p><p><b>CONCLUSIONS</b>The results suggested that CRP and WBC were preferred markers for predicting the clinical events in patients with acute type A AD, especially death during hospitalization. Therefore, further study enrolling larger cohort, prospective study would be warranted.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Disección Aórtica , Sangre , Diagnóstico , Aneurisma de la Aorta Torácica , Sangre , Diagnóstico , Proteína C-Reactiva , Metabolismo , Recuento de Leucocitos , Métodos , Modelos LogísticosRESUMEN
Marfan syndrome is a systemic disorder of connective tissue, caused by mutations in the FBN1, TGFBR1 or TGFBR2 genes. This syndrome is characterized by involvement of three major systems, skeletal, ocular, and cardiovascular. The continuing improvements in molecular biology and increasing availability of molecular diagnosis in clinical practice allow recognition of Marfan syndrome in patients with incomplete phenotypes. Additionally, molecular analyses could also be used for preimplantation genetic diagnosis. The identification of a mutation allows for early diagnosis, prognosis, genetic counseling, preventive management of carriers and reassurance for unaffected relatives. The importance of knowing in advance the location of the putative family mutation is highlighted by its straightforward application to prenatal and postnatal screening.
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Humanos , Fibrilina-1 , Fibrilinas , Síndrome de Marfan , Diagnóstico , Genética , Patología , Proteínas de Microfilamentos , Genética , Mutación , Diagnóstico Prenatal , Ética , Métodos , Proteínas Serina-Treonina Quinasas , Genética , Receptores de Factores de Crecimiento Transformadores beta , GenéticaRESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of Qihong capsule (QH) on HeLa cells infected by coxsackievirus B3 (CVB3) in vitro and its potential antiviral mechanism.</p><p><b>METHODS</b>HeLa cells were infected by CVB3 in vitro. XTT assay and plaque inhibition assay were performed to determine the 50 % effective dose, (ED50), 50 % inhibitory concentration (IC50), and 50% cytotoxicity concentration (CC50) of QH and the control drug, ribavirin. The total therapeutic index (TI) was calculated. Anti-viral time-course experiments were performed to compare the anti-viral effects at different time points. The inhibitory effects of QH on the attachment and penetration of CVB3 were also observed.</p><p><b>RESULTS</b>XTT assay and plaque inhibition assay showed that the ED50 and IC50 were (7.16+/-0.80) mg/L and (2.63+/-0.50) mg/L in QH group and (4.35+/-0.40) mg/L and (1.92+/-0.30) mg/L in ribavirin group, respectively. CC50 was 16-fold higher in QH group than in ribavirin group QH: (1 648+/-219) mg/L vs. Ribavirin: (103+/-14) mg/L. Time-course studies demonstrated that antiviral effect of QH was mainly found 0-4 hours after infection. QH effectively blocked the attachment and penetration of CVB3 into cells.</p><p><b>CONCLUSION</b>By inhibiting the attachment and penetration of CVB3, QH can effectively inhibit the invasion of virus in vitro with low toxicity.</p>
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Humanos , Antivirales , Farmacología , Cápsulas , Medicamentos Herbarios Chinos , Farmacología , Enterovirus Humano B , Células HeLa , Concentración 50 InhibidoraRESUMEN
<p><b>BACKGROUND</b>Hypertrophic cardiomyopathy (HCM) is a primary autosomal dominant inheritant myocardial disease with heterogeneity in clinical manifestations, natural history and prognosis. Even carrying an identical gene mutation among family members, a variety of clinical phenotypes have been found in patients with HCM. Modifier genes may contribute to the diversity. The plasma levels of atrial natriuretic peptides (ANP) were found previously to be elevated in HCM. Our studies suggested that ANP gene promoter polymorphism is associated with left ventricular hypertrophy in hypertension. The present study aimed to determine whether the two SNPs in the ANP gene are associated with HCM.</p><p><b>METHODS</b>We determined the relationships between the ANP gene polymorphism and HCM in 262 HCM patients and 614 age- and sex-matched healthy individuals. All of the subjects were genotyped for -A2843G and A188G polymorphisms.</p><p><b>RESULTS</b>The genotype frequency in the -A2843G and A188G polymorphisms of the ANP gene was not significantly different between the HCM patients and controls. The -A2843G and A188G polymorphisms were also not associated with clinical phenotype in cardiomyopathy patients.</p><p><b>CONCLUSIONS</b>The polymorphisms of the ANP gene are not associated with increasing risk of HCM or clinical phenotypes. The variations of the ANP gene may not serve as a genetic modifier for the development of HCM.</p>
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Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Factor Natriurético Atrial , Genética , Cardiomiopatía Hipertrófica , Genética , Estudios de Casos y Controles , Ecocardiografía , Genotipo , Desequilibrio de Ligamiento , Fenotipo , Polimorfismo Genético , GenéticaRESUMEN
<p><b>BACKGROUND</b>Mutations in the fibrillin-1 gene have been identified in patients with Marfan syndrome (MFS). This study aimed to identify the molecular defects in the fibrillin-1 gene in a Chinese family with Marfan syndrome, accompanied by aortic aneurysms/dissection.</p><p><b>METHODS</b>Two patients and one non-carrier in the family underwent complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of these individuals in the family as well as 50 healthy normal controls. Polymerase chain reaction amplification and direct sequencing of all 65 coding exons of fibrillin-1 gene were analyzed.</p><p><b>RESULTS</b>We found a novel mutation (c.8547T > G, p.Tyr2849X) in exon 65 of fibrillin-1 gene in a Chinese proband with Marfan syndrome, accompanied by aortic aneurysms/dissection. Sudden death at a young age of affected members was seen due to aortic aneurysms/dissection. By evaluating genotype-phenotype correlations of patients with mutations in the 3' end of fibrillin-1 gene (exons 64 and 65), we also found that the presence of nonsense mutations occurring in exons 64 and 65 appeared to be an indicator of early-onset aortic risk and sudden death.</p><p><b>CONCLUSIONS</b>These results expand the mutation spectrum of fibrillin-1 gene and help in the study of the molecular pathogenesis of Marfan syndrome, indicating that mutations occurring in the 3' end of fibrillin-1 gene may play an independent functional role in the pathogenesis of Marfan syndrome.</p>
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Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fibrilina-1 , Fibrilinas , Genotipo , Síndrome de Marfan , Genética , Proteínas de Microfilamentos , Genética , Mutación , FenotipoRESUMEN
<p><b>OBJECTIVE</b>To identify the disease-causing gene mutations and to reveal the relationship between the genotype and the phenotype in Chinese patients with hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>One hundred unrelated patients with HCM and 120 controls were enrolled in this study. The full encoding exons and flanking sequences of the cardiac myosin binding protein C gene (MYBPC3) were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>A novel missense mutation c.706T > C was identified in exon 6 of MYBPC3 gene in three HCM patients, which resulted a Serine (S) to Glycine (G) exchange at amino acid residue 236 (S236G). The clinical phenotypes of the three patients were different (2 obstructive HCM, 1 non-obstructive HCM). The 120 controls were normal in the genetic test.</p><p><b>CONCLUSIONS</b>The novel S236G mutation in MYBPC3 gene was a hot-spot mutation in Chinese patients with HCM.</p>
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Pueblo Asiatico , Genética , Cardiomiopatía Hipertrófica , Genética , Proteínas Portadoras , Genética , Estudios de Casos y Controles , ADN , Genoma Humano , Mutación , FenotipoRESUMEN
<p><b>BACKGROUND</b>The use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. Reactive oxygen species (ROSs) play an important role in the pathological process of DOX-induced cardiotoxicity. The aim of this study was to evaluate the protective effect of chrysoeriol, a flavone compound, against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism.</p><p><b>METHODS</b>We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, Hoechst33258 staining and measurement of lactate dehydrogenase (LDH) release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells. To find out the mechanism of this protective effect, we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Furthermore, we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTT assay.</p><p><b>RESULTS</b>The results of MTT assay, Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death. Chrysoeriol at a dose of 20 microg/ml notably reduced intracellular ROS, decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels. Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX.</p><p><b>CONCLUSION</b>Chrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.</p>
Asunto(s)
Animales , Humanos , Ratas , Antibióticos Antineoplásicos , Farmacología , Línea Celular , Supervivencia Celular , Doxorrubicina , Farmacología , Flavonas , Flavonoides , Química , Farmacología , Glutatión Peroxidasa , Metabolismo , Células HeLa , Corazón , L-Lactato Deshidrogenasa , Metabolismo , Estructura Molecular , Miocitos Cardíacos , Especies Reactivas de Oxígeno , Metabolismo , Superóxido Dismutasa , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To evaluate the safety and efficacy of carotid artery stenting before open heart surgery.</p><p><b>METHODS</b>Patients with heart disease and severe carotid artery stenosis received carotid stenting before open heart surgery were included in this prospective cohort study. The incidence of stroke, myocardial infarction and death from carotid stenting to 30 days after cardiac surgery was assessed.</p><p><b>RESULTS</b>A total of 42 patients were enrolled. The carotid stenting procedural success rate was 100%. Distal embolic protection devices were used in 97.6% patients (41/42). Thirty-six (85.7%) patients received bypass surgery, 5 patients received bypass and valve replacement surgery (11.9%) and 1 patient received valve replacement surgery (2.4%) post carotid stenting. The incidence of stroke, myocardial infarction and death from carotid stenting to 30 days after cardiac surgery was 2.4% (1/42), 0% and 0% respectively.</p><p><b>CONCLUSIONS</b>Our data from this small cohort study showed that carotid artery stenting before open heart surgery was safe and effective for patients with heart disease and severe carotid artery stenosis.</p>