Polymorphisms but not mutations of the KCNQ1 gene are associated with lone atrial fibrillation in the Chinese Han population.

BACKGROUND: Recent studies suggest that mutation of the slow delayed rectifier potassium channel (IKs) contributes to familial atrial fibrillation (FAF). In the current study, we identified common genetic variants of KCNQ1 and explored the potential association between KCNQ1 polymorphism with lone AF (LAF). METHODS: Clinical data and blood samples were collected from 190 Han Chinese patients with sporadic AF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified six known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 190 LAF patients and 190 healthy controls. RESULTS: One of the SNPs in KCNQ1 was strongly associated with LAF; significant allelic association was detected rs59233444 (P = 0.013, OR = 1.469, 95% confidence interval (CI): 1.083-1.993). A multiple regression analysis indicated that rs59233444 is an independent risk factor for LAF. Twelve new variants were identified in KCNQ1, including one in the 5'-UTR, two in the 3'-UTR, six in introns, two synonymous substitutions, and one missense substitution. Variants c.1009C>T, c.1860C>T, and c.+2285C>T were not present in the 190 controls, and the others were identified in controls at various frequencies. CONCLUSIONS: rs59233444, a common SNP but not mutation in the coding regions of the KCNQ1 gene, is a risk factor for LAF in Chinese Han population.

[KCNQ1 mutation in patients with lone atrial fibrillation].

OBJECTIVE: Recent studies suggest that mutation of the slow delayed rectifier potassium channel [I(Ks)] contributes to familial atrial fibrillation (FAF). In the current study, we explored the potential association between KCNQ1 polymorphism with lone AF (LAF). METHODS: Clinical data and blood samples were collected from 95 Han Chinese patients with LAF and matched healthy controls. Variants of the KCNQ1 gene were identified using single-strand conformational polymorphism (SSCP) analysis. A case-control association study in KCNQ1 identified four known single-nucleotide polymorphisms (SNPs) during SSCP screening of the 95 LAF patients and 190 healthy controls. RESULTS: Three new variations were identified in KCNQ1 from 95 sporadic LAF including 1 in 5'UTR(c.-22T > C), 1 in exon9 synonymous mutation (c.1008C > T) and 1 in intron region (c.1590 + 31A > T). These variations were heterozygous and not presented in 190 healthy controls. Highly significant difference was detected between LAF group and control groups in rs760419 polymorphism. Logistic regression revealed that rs760419 was independent risk factor for LAF(OR = 2.056, P = 0.001). CONCLUSIONS: KCNQ1 mutation is associated with LAF and rs760419 polymorphism is a susceptible marker for LAF.

Progress in the study and treatment of peri-device leak after left atrial appendage closure.

For patients with atrial fibrillation with an increased risk of stroke and contraindications to long-term anticoagulation, percutaneous left atrial appendage closure (LAAC) has become an important alternative to long-term oral anticoagulation. Incomplete closure of the LAAC during the procedure leads to faster blood flow in the interstitial space around the device, resulting in peri-device leak (PDL), which is not uncommon. Studies are still inconclusive in determining the incidence, long-term safety, and management of PDL. Therefore, this article reviewed the progress made in the research and treatment of PDL after LAAC.

[Ion channelopathies and inherited arrhythmia].

Ion channelopathies are the mainly etiopathogenisis of inherited arrhythmia. Those arrhythmia syndromes are commonly caused by ion channel gene mutation, which can be classified as sodium,potassium and calcium ion channel mutation.Changes in the genes encoding for cardiac ion channel subunits produce modification in the function of the channels, and cause the dysfunctions of cardiac electrical activity; and the clinical manifestation is malignant arrhythmia.

Halofuginone protects HUVECs from H2O2-induced injury by modulating VEGF/JNK signaling pathway.

BACKGROUND: Halofuginone, which is the main active ingredient of Dichroa fabrifuga, was used to inhibit the synthesis of type I collagen and played increasingly important roles in tumor therapy. This study aims to investigate the protective effects of halofuginone on human umbilical vein endothelial cells (HUVECs) from H2O2-induced apoptosis and oxidative stress. METHODS: Propidium iodide and Annexin-V double staining assay was used to measure the apoptosis. Cell viability assay, the measurements of reactive oxygen species (ROS) parameters malondialdehyde and superoxide dismutase, western-blot assays, and quantitative PCR were used to elucidate the effects and mechanisms of halofuginone in protecting H2O2-induced injury. RESULTS: The results showed that halofuginone counteracted H2O2-induced cell viability decline and PCNA downregulation. Furthermore, halofuginone decreased ROS levels and protected HUVECs from H2O2-induced apoptosis. In detail, it showed that H2O2 induced a transient activation of Mitogen-activated protein kinases members ERK1/2 and p38, whereas induced a sustained activation of c-Jun N-terminal kinase (JNK), which play dominant roles in triggering apoptosis. Inhibition of JNK activation also inhibited H2O2-mediated apoptosis. Finally, it was shown that halofuginone upregulated VEGF expressions, which functioned by inhibiting sustained JNK activation, thus protecting HUVECs. CONCLUSION: Halofuginone has powerful effects in protecting HUVECs from H2O2-induced apoptosis, via upregulating VEGF and inhibiting overactivated JNK phosphorylation. Halofuginone might be a promising preventive drug for cardiovascular diseases.

Comparison of dabigatran and warfarin used in patients with non-valvular atrial fibrillation: Meta-analysis of random control trial.

BACKGROUND: Dabigatran is a kind of oral anticoagulant and there was little review only about dabigatran and warfarin used in patients with atrial fibrillation. This meta-analysis only assesses the dabigatran and warfarin used in patients with atrial fibrillation. DESIGN: Cochrane Library, PubMed, Clinical Trials.gov, CNKI, and WanFang databases were searched. The primary endpoint was the incidence of stroke and the second endpoints were the incidence of bleeding and embolic events. RESULTS: Six RCTs and 20086 patients were included in our meta-analysis. No significant difference was obtained between 110 mg dabigatran and warfarin on the endpoint of stroke (risk ratio (RR), 0.90; 95% confidence interval [CI], 0.71-1.12; P = .34; I = 0%) and embolic events p (RR, 0.89; 95% CI, 0.71-1.12; P = .32; I = 0%). However, the 110 mg dabigatran associated lower incidence of bleeding (RR, 0.81; 95% CI, 0.69-0.95; P = .01; I = 0%) compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower rate of stroke (RR, 0.96; 95% CI, 0.83-1.12; P = .62; I = 0%) and embolic events (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%) but similar in the incidence of bleeding (RR, 0.67; 95% CI, 0.53-0.86; P = .001; I = 0%). CONCLUSION: No significant difference was obtained between 110 mg dabigatran and warfarin in the incidence of stroke and embolic events. However, the 110 mg dabigatran associated lower incidence of bleeding compare with warfarin. When compared with 150 mg dabigatran, warfarin associated with lower incidence of stroke and embolic events but similar in the incidence of bleeding.

Diffusion-weighted magnetic resonance imaging of the liver in hepatitis B patients with Child-Pugh a cirrhosis.

The purpose of this study was to test the hypothesis that cirrhotic change of liver in hepatitis B patients observed in Child-Pugh classification based on clinical assessment would be reflected in the apparent diffusion coefficient (ADC) values calculated from diffusion-weighted magnetic resonance (MR) imaging. Twenty-seven patients with hepatitis B Child-Pugh class A cirrhosis and 10 control subjects were referred for measurement values of the liver on a 3.0-T MR unit. The results revealed that ADCs were significantly lower in hepatitis B patients with Child-Pugh class A compared with control subjects (p < 0.01). In conclusion, our preliminary study showed that hepatitis B patients with Child-Pugh class A had reduced ADC values in liver vis-a-vis normal subjects.

A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co­expression analysis.

The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co­expression analysis. The microarray dataset associated with HCM (E­GEOD­36961) was obtained from the European Molecular Biology Laboratory­European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co­expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co­expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T­complex protein 1 (CCT)/T­complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co­expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM.

Attractors of hypertrophic cardiomyopathy using maximal cliques and attract methods.

BACKGROUND: Our study was designed to identify the differential attractor modules related with hypertrophic cardiomyopathy (HCM) by integrating clustering-based on maximal cliques algorithm and Attract method. METHODS: We firstly recruited the HCM-related microarray data from ArrayExpress database. Next, protein-protein interaction (PPI) networks of normal and HCM were constructed and re-weighted using spearman correlation coefficient (SCC). Then, maximal cliques were found from the PPI networks through the clustering-based on maximal cliques approach. Afterwards, highly overlapped cliques were eliminated or merged according to the interconnectivity, and then modules were obtained. Subsequently, we used Attract method to identify differential attractor modules, following by the pathway enrichment analyses for genes in differential attractor modules. RESULTS: After removing the cliques with nodes less than or equal to 4, 926 and 1118 maximal cliques in normal and HCM PPI networks were obtained for module analysis. Then, we obtained 32 and 55 modules from the PPI networks of normal and HCM, respectively. By comparing with normal condition, there were 5 module pairs with the same or similar gene composition. Significantly, based on attract method, we found that these 5 modules were differential attractors. Pathway enrichment analyses indicated that proteasome, ribosome and oxidative phosphorylation were the significant pathways. CONCLUSIONS: Proteasome, ribosome and oxidative phosphorylation might play pathophysiological roles in HCM.

Ablation of idiopathic ventricular arrhythmia using zero-fluoroscopy approach with equivalent efficacy and less fatigue: A multicenter comparative study.

The efficacy of a completely zero-fluoroscopy (ZF) approach for the catheter ablation of idiopathic ventricular arrhythmias (VAs) and whether it has advantages over the conventional fluoroscopy (F) approach are still unknown. The aim of this study was to compare the safety and efficacy of a completely ZF approach with those of the conventional F approach in the ablation of idiopathic VAs.We conducted a prospective study involving 7 centers in China. Consecutive patients (n = 489, mean age 45.3 ±â€Š15.3 years, 44.8% male) with idiopathic VAs were recruited. Eligible participants were assigned to either a ZF (n = 163) or F (n = 326) approach at a ratio of 1:2. The completely ZF approach was successful in 163 (100%) patients for electrophysiological study, and in 151 patients (94.4%) for arrhythmia ablation with 9 cases having to switch to the F approach due to the need for coronary angiography. There was no significant difference between the ZF approach and F approach in procedural success rate (84.1% vs 85.4%, respectively), arrhythmia recurrence (1.9% vs 2.2%), or severe complications (0.6% vs 0.9%). The medical staffs using the ZF approach did not wear heavy protective apparels, thus experienced significantly less fatigue compared with those using the F approach (2.1 ±â€Š0.7 vs 3.9 ±â€Š1.6, P < 0.05).The completely ZF approach is as safe and efficient as the conventional F approach for the electrophysiological study and the ablation of idiopathic VAs. The medical staffs using ZF approach felt less fatigue and received less exposure to radiation.

[Magnetic Response of Dust-loaded Leaves in Parks of Shanghai to Atmospheric Heavy Metal Pollution].

To reveal the magnetic response to the atmospheric heavy metal pollution in leaves along urban parks, Camphor leaf samples, widely distributed at urban parks, were collected along the year leading wind direction of Shanghai, by setting two vertical and horizontal sections, using rock magnetic properties and heavy metal contents analysis. The results showed that the magnetic minerals of samples were predominated by ferromagnetic minerals, and both the concentration and grain size of magnetite particles gradually decreased with the winter monsoon direction from the main industrial district. A rigorous cleaning of leaves using ultrasonic agitator washer could remove about 63%-90% of low-field susceptibility values of the leaves, and this strongly indicated that the intensity of magnetic signal was mainly controlled by the PMs accumulated on the leaves surfaces. Moreover, there was a significant linear relationship between heavy metals contents (Fe, Mn, Zn, Cu, Cr, V and Pb) and magnetic parameters (0.442 ≤ R ≤ 0.799, P < 0.05), which suggested that magnetic parameters of urban park leaves could be used as a proxy for atmospheric heavy metal pollution. The results of multivariate statistical analysis showed that the content of magnetic minerals and heavy metal indust-loaded tree leaves was affected by associated pollution of industry and traffic.