Atrial fibrillation (AF) is one of the most prevalent heart rhythm disorder. The causes of AF include age, male sex, diabetes, hypertension, valve disease, and systolic/diastolic dysfunction. But on molecular level, its mechanisms are largely unknown. In this study, we collected 10 patients with persistent atrial fibrillation, 10 patients with paroxymal atrial fibrillation and 10 healthy individuals and did Methylation EPICBead Chip and RNA sequencing. By analyzing the methylation and gene expression data using machine learning based feature selection method Boruta, we identified the key genes that were strongly associated with AF and found their interconnections. The results suggested that the methylation of KIF15 may regulate the expression of PSMC3, TINAG, and NUDT6. The identified AF associated methylation-expression regulations may help understand the molecular mechanisms of AF from a multi-omics perspective.
BackgroundAcute myocardial infarction (AMI) has high morbidity and mortality worldwide. However, the pathogenesis of AMI is still unclear, and the impact of circular RNAs (circRNAs) on AMI has rarely been recognized and needs to be explored.Materials and MethodsThe circRNA array was applied to investigate the expression level of circRNAs in the blood samples of coronary arteries of three AMI patients and three normal persons. Principal component analysis (PCA) and unsupervised clustering analysis were performed to reveal the distinguished expression patterns of circRNAs. The miRNA expression profiles of AMI patients were identified from a public dataset from the Gene Expression Omnibus (GEO) database (GSE31568). The miRNA binding sites on the circRNAs were predicted by miRanda. The miRNA enrichment analysis and annotation tool were used to explore the pathways that the dysregulated circRNAs may participate in.ResultsIn total, 142 differentially expressed circRNAs, including 89 upregulated and 53 downregulated in AMI samples, were identified by the differential expression analysis. AMI patients had quite different circRNA expression profiles to those of normal controls. Functional characterization revealed that circRNAs that had the potential to regulate miRNAs were mainly involved in seven pathways, such as the Runt-related transcription factor-1 (RUNX1) expression and activity-related pathway. Specifically, hsa_circRNA_001654, hsa_circRNA_091761, hsa_circRNA_405624, and hsa_circRNA_406698 were predicted to sponge four miRNAs including hsa-miR-491-3p, hsa-miR-646, hsa-miR-603, and hsa-miR-922, thereby regulating RUNX1 expression or activity.ConclusionWe identified dysregulated blood circRNAs in the coronary arteries of AMI patients and predicted that four upregulated circRNAs were involved in the regulation of RUNX1 expression or activity through sponging four miRNAs.
Atrial fibrillation (AF), known as the most common arrhythmia in the developed world, affects 1.5-2.0% of the population. Numerous basic studies have been carried out to identify the roles of electric and structural remodeling in the pathophysiological changes of AF, but more explorations are required to further understand the mechanisms of AF development. Proteomics enables researchers to identify protein alterations responsible for the pathological developing progresses of diseases. Compared to the genome, the proteome is closely related to the disease phenotype and can better manifest the progression of diseases. In this study, AF patients proteomically analyzed to identify possible mechanisms. Totally 20 patients undergoing cardiac surgery (10 with paroxysmal AF and 10 with persistent AF) and 10 healthy subjects were recruited. The differentially expressed proteins identified here included AKR1A1,
Background Preoperative risk evaluation systems are significant and important to the allocation of medical resources and the communication between doctors and patients. The European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) is widely used in clinical practice. Cardiac troponin T (cTnT) can specifically and accurately reflect myocardial injury. Whether EuroSCORE II can improve the predictive power after integrating with cTnT is still unclear. This study was a retrospective single center study designed to assess the predictive ability of EuroSCORE II integrated with cTnT for patients undergoing isolated off-pump coronary artery bypass grafting (OPCABG). Methods This retrospective and observational cohort study included 1887 patients who underwent first isolated OPCABG. cTnT was detected within 48 h before operation in each patient. According to myocardial injury, patients were divided by cTnT into 4 stages. A new risk evaluation system was created through logistic regression with EuroSCORE II and myocardial injury classification as covariates. Then the two risk evaluation systems were comparatively assessed by regression analysis, receiver operator characteristic curves, net reclassification index, Bland–Altman plots and decision curve analysis. Results There were 43 in-hospital deaths, with a mortality of 2.30% (43/1887). The logistic regression analysis showed that preoperative myocardial injury classification was a significant risk factor for in-hospital mortality in both total cohort (OR 1.491, 95%CI 1.049–2.119) and subsets (OR 1.761, 95%CI 1.102–2.814). The new risk evaluation system has higher calibration and discrimination power than EuroSCORE II, both for overall cohort and subsets. Especially, the new system has obvious advantages in discrimination power in the subset of acute myocardial infarction (AUC 0.813 vs. 0.772, 0.906 vs. 0.841, and 0.715 vs. 0.646, respectively). Conclusions Both myocardial injury classification and EuroSCORE II are independent risk factors of in-hospital mortality in OPCABG patients. The new risk evaluation system has higher predictive ability than EuroSCORE II, especially in patients with a recent history of AMI.
More frequent and more intense heat waves and greater drought stress will occur in the future climate environment. Short-term extreme heat and drought stress often occur simultaneously after winter wheat anthesis, which has become the major constraint threatening future wheat yield. In this study, short-term heat, drought and their combination stress were applied to wheat plants after anthesis, and all wheat plants were restored to the outdoor normal temperature and full watering after stress treatment. The aim of the current study was to evaluate the role of nitrogen (N) in modulating the effects of post-anthesis short-term heat, drought and their combination stress on photosynthesis, N metabolism-related enzymes, the accumulation of N and protein and growth, as well as on the yield and water (WUE) and N use efficiency (NUE) of wheat after stress treatment. The results showed that compared with low N application (N1), medium application (N2) enhanced the activities of nitrate reductase (NR) and glutamine synthase (GS) in grains under post-anthesis heat and drought stress alone, which provided a basis for the accumulation of N and protein in grains at the later stage of growth. Under post-anthesis individual stresses, N2 or high application (N3) increased the leaf photosynthetic rate (An), PSII photochemical efficiency and instantaneous WUE compared with N1, whereas these parameters were usually significantly improved by N1 application under post-anthesis combined stress. The positive effect of increased An by N application on growth was well represented in a higher green leaf area, aboveground dry mass and plant height, and the variation in An can be explained more accurately by the N content per unit leaf area. Short-term heat, drought and combined stress after anthesis resulted in a pronounced decrease in yield by reducing grain number per spike and thousand kernel weight. The reduction in NUE under combined stress was higher than that under individual heat and drought stress. Compared with N1, N2 or N3 application significantly prevented the decrease in yield and NUE caused by post-anthesis heat and drought stress alone. However, N1 application was conducive to improving the productivity, WUE and NUE of wheat when exposed to post-anthesis combined stress. The current data indicated that under short-term individual heat and drought stress after anthesis, appropriately increasing N application effectively improved the growth and physiological activity of wheat compared with N1, alleviating the reduction in yield, WUE and NUE. However, under combined stress conditions, reducing N application (N1) may be a suitable strategy to compensate for the decrease in yield, WUE and NUE.
Background Coronary artery bypass graft (CABG) surgery has become a routine surgical procedure for patients with occlusive coronary artery atherosclerosis. Worldwide, increasing levels of obesity are associated with ischemic heart disease and systemic comorbidities. This retrospective study from a single center in China aimed to investigate the effects of obesity on patient mortality following CABG surgery. Material/Methods Patients undergoing CABG (N=1471) were grouped according to body mass index (BMI) as normal weight (N=596), overweight (N=684), or obese (N=191). Baseline clinical characteristics and outcomes were recorded. Logistic regression analysis was performed for 30-day postoperative mortality. Kaplan-Meier survival curves were plotted, and Cox regression analysis investigated risk and protective factors for long-term mortality, with subgroup analysis for differences between on-pump and off-pump CABG groups. Results The 30-day postoperative mortality was 5.0% in the normal-weight group, 1.3% in the overweight group, and 0% in the obese group. BMI was an independent protective factor for 30-day postoperative mortality (odds ratio=0.748; 95% confidence interval, 0.640–0.874; P <0.001). The 10-year mortality for the groups was 13.2% (normal), 7.8% (overweight), and 12.7% (obese). The >20-year mortality rates for the groups were 33.0% (normal), 41.5% (overweight), and 12.7% (obese). There was no significant correlation between BMI and long-term mortality. Being overweight had a protective effect against long-term mortality in the off-pump CABG subgroup. Conclusions An “obesity paradox” was identified in postoperative outcomes in patients following CABG surgery, with an increased BMI associated with reduced 30-day postoperative mortality. This association was more significant in the off-pump CABG group.
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