Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels mediate pacemaker currents in the atrium. The microRNA (miR) families miR-1 and miR-133 regulate the expression of multiple genes involved in myocardial function, including HCN channels. It was hypothesized that age-dependent changes in HCN2, HCN4, miR-1 and miR-133 expression may contribute to age-associated atrial fibrillation, and therefore the correlation between expression levels, among adult (≤65 years) and aged patients (≥65 years), and sinus rhythm was determined. Right atrial appendage samples were collected from 60 patients undergoing coronary artery bypass grafting. Reverse transcription-quantitative polymerase chain reaction (PCR) and western blot analyses were performed in order to determine target RNA and protein expression levels. Compared with aged patients with sinus rhythm, aged patients with atrial fibrillation exhibited significantly higher HCN2 and HCN4 channel mRNA and protein expression levels (P<0.05), but significantly lower expression levels of miR-1 and miR-133 (P<0.05). In addition, aged patients with sinus rhythm exhibited significantly higher expression levels of HCN2 and HCN4 channel mRNA and protein (P<0.05), but significantly lower expression levels of miR-1 and -133 (P<0.05), compared with those of adult patients with sinus rhythm. Expression levels of HCN2 and HCN4 increased with age, and a greater increase was identified in patients with age-associated atrial fibrillation compared with that in those with aged sinus rhythm. These electrophysiological changes may contribute to the induction of ectopic premature beats that trigger atrial fibrillation.
RESCUE BT Trial Investigators E ndovascular treatment has been shown to significantly increase the reperfusion rate and improve the functional outcomes of patients with acute ischemic stroke due to large vessel occlusion. [1][2][3][4] However, endovascular thrombectomy has historically failed to yield successful reperfusion in approximately 30% of patients. 5 Unsuccessful reperfusion likely arises in part from mechanical thrombectomy devices causing traumatic damage to the vascular endothelium with subendothelial matrix exposure, leading to platelet activation, adhesion, and aggregation and potentially resulting in reocclusion and thromboembolic complications. 6,7 Tirofiban, a highly selective nonpeptide platelet glycoprotein IIb/IIIa inhibitor with a relatively short half-life that can reversibly prevent platelet aggregation, has been proven to reduce the risk of thrombotic complications during percutaneous coronary intervention. [8][9][10] Given the benefit of treatment of acute coronary syndromes, a growing number of studies have evaluated tirofiban as an adjunctive treatment in patients with large vessel occlusion ischemic stroke IMPORTANCE Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.OBJECTIVE To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.DESIGN, SETTING, AND PARTICIPANTS This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well.
Objective: To investigate the diagnostic efficiency of truncal-type occlusion and branching-site occlusion in determining the etiology of intracranial large artery occlusion related acute ischemic stroke (AIS). Methods: Patients with intracranial large artery occlusion related AIS who received stent retriever (SR) thrombectomy from November 2014 to June 2019 were included in the study. All patients underwent angiography before SR thrombectomy, which was used to evaluate the occlusion type. Differences in the distribution of occlusion types in intracranial atherosclerosis (ICAS) and embolism were assessed, and the diagnostic indicators, including the area under the ROC curve (AUC), sensitivity, and specificity were calculated. Results: Of the 115 AIS patients with intracranial large artery occlusion, 42 were classified as having ICAS, and 73 having an embolism. In the ICAS group, branching-site occlusion was responsible for 3 (7%) cases and truncal-type occlusion for 39 (93%) cases, while in the embolism group, branching-site occlusion was responsible for 66 (90%) cases and truncal-type occlusion for 7 (10%) cases; the difference was statistically significant (all P < 0.01). The AUC for ICAS predicted by truncal-type occlusion was 0.916, with a sensitivity of 92.86%, and specificity of 90.41%. Conclusion: Truncal-type occlusion showed a high predictability of ICAS. Determine the etiology of intracranial large artery occlusion related AIS before SR thrombectomy may be most helpful in setting up optimal endovascular treatment strategies.
BackgroundDilated cardiomyopathy (DCM) is characterized by left ventricular enlargement, systolic dysfunction, and heart failure. Both genetic and non-genetic factors have been linked to DCM pathogenesis. Familial DCM (FDCM) accounts for 20%–50% of all DCM cases, highlighting the importance of genetics in pathogenesis. Indeed, more than 40 DCM-associated genes have been identified, including the gene encoding cardiac troponin T type-2 (TNNT2). We examined polymorphisms of the TNNT2 gene in idiopathic DCM (IDCM) patients of Kazak and Han ethnicity compared with healthy Kazak and Han controls.Material/MethodsPeripheral blood samples were collected from 180 patients with IDCM (90 Kazak and 90 Han), and 180 healthy controls (90 Kazak and 90 Han). PCR was used to amplify 15 exons and nearby introns of the TNNT2 gene. The amplified products were sequenced and compared to the standard sequence in PubMed by BLAST and CHROMAS software, to identify mutation sites.ResultsResults from Kazak and Han IDCM patients were complied for Hardy-Weinberg equilibrium analysis. There was a significant difference in the genotype distribution (χ2=6.67, P=0.015) and allele frequency (χ2=5.71, P=0.017) between Kazaks with IDCM and Kazak controls of SNP rs3729547. There was also a difference in the genotype distribution (χ2=6.62, P=0.036) and allele frequency (χ2=4.91, P=0.018) between Han with IDCM and Han controls. The TNNT2 gene polymorphism loci rs3729547 may be associated with the IDCM onset in Kazak and Han patients (OR=2.5, 95% CI: 1.233~5.068).ConclusionsThe TNNT2 polymorphisms might play an important role in susceptibility to DCM in Xinjiang Kazak and Han patients.
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