Tetralogy of Fallot (TOF) is a complex congenital heart defect and the microRNAs regulation in TOF development is largely unknown. Herein, we explored the role of miRNAs in TOF. Among 75 dysregulated miRNAs identified from human heart tissues, miRNA‐940 was the most down‐regulated one. Interestingly, miRNA‐940 was most highly expressed in normal human right ventricular out‐flow tract comparing to other heart chambers. As TOF is caused by altered proliferation, migration and/or differentiation of the progenitor cells of the secondary heart field, we isolated Sca‐1+ human cardiomyocyte progenitor cells (hCMPC) for miRNA‐940 function analysis. miRNA‐940 reduction significantly promoted hCMPCs proliferation and inhibited hCMPCs migration. We found that JARID2 is an endogenous target regulated by miRNA‐940. Functional analyses showed that JARID2 also affected hCMPCs proliferation and migration. Thus, decreased miRNA‐940 affects the proliferation and migration of the progenitor cells of the secondary heart field by targeting JARID2 and potentially leads to TOF development.
1 November 2021 in International Journal of General Medicine
Objective: To evaluate the powers of European Heart Surgery Risk Assessment System II (EuroSCORE II) and the Society of Thoracic Surgeons (STS) score in predicting in-hospital and medium-term mortality of patients undergoing coronary artery bypass grafting (CABG). Methods: Totally 1628 Chinese patients were included between January 2000 and January 2018. Their perioperative clinical data were collected and the patients were closely followed up. According to the length of follow-up time, the total cohort was divided into 1-year, 2-year, 3-year, 4-year and 5-year groups. The in-hospital and medium-term risk prediction of EuroSCORE II and STS score were comparatively assessed by calibration, discrimination, decision curve analysis (DCA), net reclassification index (NRI), integrated discrimination improvement (IDI) and Bland-Altman analysis. Results: About 36 (2.21%) patients died during hospitalization. Both EuroSCORE II and STS score performed extremely well in predicting in-hospital mortality (area under curve = 0.900 and 0.879, respectively). However, calibration and discrimination analyses showed gradual decrease when these two risk evaluation systems were used to predict mortality during the follow-up period. At the same time, the predictive ability of EuroSCORE II was better than STS score. DCA curves showed that the performances of the two evaluation systems were roughly equal between the threshold probability of 0% to 20%. The percentage of correct reclassification of EuroSCORE II was 21.64% higher than that of STS score in predicting 2-year postoperative mortality. The IDI index showed that the predictive capabilities of these two systems were roughly equivalent. Bland-Altman analysis showed no significant difference between the values of the two systems. Conclusion: EuroSCORE II and STS score have excellent predictive powers in predicting in-hospital mortality of patients undergoing CABG. In particular, EuroSCORE II is superior in calibration and discrimination. The prediction efficiency of the two risk evaluation systems is still acceptable for two-year postoperative mortality, but decreases year by year.
1 July 2020 in Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Background: Acute 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 Methods: The 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.Results: In 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.Conclusion: We 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.
The Effects of Obesity on Mortality Following Coronary Artery Bypass Graft Surgery: A Retrospective Study from a Single Center in China - Article abstract #929912
Objectives: To assess and compare the predictive ability of three risk evaluation systems (SinoSCORE, EuroSCORE II and the STS risk evaluation system) in patients aged ≥70, and who underwent coronary artery bypass grafting (CABG) in East China. Methods: Three risk evaluation systems were applied to 1,946 consecutive patients who underwent isolated CABG from January 2004 to September 2016 in two hospitals. Patients were divided into two subsets according to their age: elderly group (age ≥70) with a younger group (age <70) used for comparison. The outcome of interest in this study was in-hospital mortality. The entire cohort and subsets of patients were analyzed. The calibration and discrimination in total and in subsets were assessed by the Hosmer–Lemeshow and the C statistics respectively. Results: Institutional overall mortality was 2.52%. The expected mortality rates of SinoSCORE, EuroSCORE II and the STS risk evaluation system were 0.78(0.64)%, 1.43(1.14)% and 0.78(0.77)%, respectively. SinoSCORE achieved the best discrimination (the area under the receiver operating characteristic curve (AUC) = 0.829), followed by the STS risk evaluation system (AUC = 0.790) and EuroSCORE II (AUC = 0.769) in the entire cohort. In the elderly group, the observed mortality rate was 4.82% while it was 1.38% in the younger group. SinoSCORE (AUC = .829) also achieved the best discrimination in the elderly group, followed by the STS risk evaluation system (AUC = .730) and EuroSCORE II (AUC = 0.640) while all three risk evaluation systems all had good performances in the younger group. SinoSCORE, EuroSCORE II and the STS risk evaluation system all achieved positive calibrations in the entire cohort and subsets. Conclusion: The performance of the three risk evaluation systems was not ideal in the entire cohort. In the elderly group, SinoSCORE appeared to achieve better predictive efficiency than EuroSCORE II and the STS risk evaluation system.