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Abstract We built up a risk stratification model to divide acute type A aortic dissection (aTAAD) patients into low- and high-risk groups, further, to evaluate the risk factors for postoperative mortality. A total of 1364 patients from 2010 to 2020 in our center were retrospectively analyzed. More than twenty clinical variables were related with postoperative mortality. The postoperative mortality of the high-risk patients was doubled than the low-risk ones (21.8% vs 10.1%). The increased operation time, combined coronary artery bypass graft, cerebral complications, re-intubation, continuous renal replacement therapy and surgical infection were risk factors of postoperative mortality in low-risk patients. In addition, postoperative lower limbs or visceral malperfusion were risk factors, axillary artery cannulation and moderate hypothermia were protective factors in high-risk patients. A scoring system for quick decision-making is needed to select appropriate surgical strategy in aTAAD patients. For low-risk patients, different surgical treatments can be performed with similar clinical prognosis. Limited arch treatment and appropriate cannulation approach are crucial in high-risk aTAAD patients.

Abstract Objective Repair or replacement remains debatable in rheumatic heart disease. To regain optimal mean transvalvular pressure gradients and end-diastolic peak flow velocity, the modified release technique combined peeling in the anterior leaflet and separated the shortened chordal. In the end, the short and mid-term outcomes of the modified release technique were evaluated. Methods We retrospectively analyzed a series of 128 patients with rheumatic mitral stenosis, from January 2018 to July 2021 in our center. All patients undergoing mitral valve repair were using the modified release technique. The effect of mitral valve repair was evaluated by intraoperative transesophageal echocardiography and postoperative transthoracic echocardiography. Results All the 128 patients successfully repaired the mitral valve. The intraoperative transesophageal echocardiography showed trivial or mild regurgitation. The aortic valve was repaired without obvious regurgitation in 12 cases, 5 cases received an aortic valve replacement, 89 cases underwent tricuspid annuloplasty. There were no blood transfusions in most patients, no deaths nor complications during peri-operation, also, no deaths and adverse events were observed during the follow-up period from 3 to 42 months. During the follow-up, 122 cases had no mitral valve regurgitation and 2 cases of moderate regurgitation, 4 cases of mild to moderate regurgitation. The mean peak flow velocity was 1.2 ± 0.3 m / s, no new-onset stenosis occurred. Conclusion Modified release technique is safe and feasible. Its durability is acceptable in the short and mid-term, with no new-onset stenosis during the follow-up.

BackgroundInsulin resistance (IR) is a significant risk factor for cardiometabolic diseases and a defining feature of type 2 diabetes mellitus (T2DM). This study aimed to examine the potential value of triglyceride-glucose (TyG) index as a predictor of prognosis in coronary heart disease (CHD) patients with T2DM after coronary artery bypass grafting (CABG) surgery and to facilitate the identification of those at high risk of major adverse cardiovascular events (MACEs) for closer monitoring or possible early intervention.MethodsThis study enrolled 386 T2DM patients who underwent CABG surgery at Nanjing Drum Tower Hospital. Patients were separated into two groups according to the median preoperative TyG Index. The Kaplan-Meier plot was used to compare the rate of MACEs-free survival in T2DM patients after CABG. The independent risk factors for the occurrence of MACEs were investigated using multivariate analysis. Nomogram was used to depict the predictive model.ResultsSignificantly more MACEs occurred in individuals with higher medians of the TyG index (65 (33.7%) vs. 39 (20.2%), p=0.003). TyG index [hazard ratio (HR) 12.926], LVEF [hazard ratio (HR) 0.916], and NYHA functional class III/IV [hazard ratio (HR) 4.331] were identified as independent predictors of MACEs incidence in post-CABG T2DM patients by multivariate analysis. The area under the curve (AUC) for predicting MACEs using the TyG index was 0.89 at five years. Combining the TyG index, LVEF, and NYHA functional class III/IV to build a novel risk assessment model for postoperative MACEs, the AUC climbed to 0.93 at five years. With AUCs, the nomogram comprised of the TyG index, LVEF, and NYHA functional class III/IV demonstrated strong specificity in the training and test sets.ConclusionsThe incidence of MACEs is high among post-CABG T2DM patients with a high TyG index. TyG index improves the diagnostic accuracy of MACEs, especially at long-term follow-up. A high TyG index may serve as an early warning signal for individuals to undertake lifestyle adjustments that can reduce the progression or incidence of MACEs.

Introduction Heart failure (HF) is a growing global public health burden. However, due to the very limited regenerative capacity of mature cardiomyocytes in the adult mammalian heart, conventional treatments can only improve the symptoms of HF but fail to restore cardiac function. Heart transplantation is limited by a severe shortage of donors. Cell-based transplantation for the treatment of HF has become a promising strategy. Human-induced-pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been tested in animal models to assess safety and efficacy. This study aims at evaluating the safety and efficacy of epicardial injection of hiPSC-CMs in patients with advanced HF during coronary artery bypass grafting (CABG) surgery.Methods This study is a dose-escalation, placebo-controlled, single-centre phase I/IIa clinical trial. Dose escalation will be guided by a modified 3+3 design for three doses (1×108, 2×108 and 4×108 cells, sequentially). Patients with advanced heart failure will be enrolled and randomly allocated to receive epicardial injection of hiPSC-CMs during CABG surgery or CABG surgery alone, followed by a 12-month follow-up investigation. The primary endpoint is to assess the safety of hiPSC-CMs transplantation, including haemodynamic compromised sustained ventricular arrhythmias and newly formed tumours during 6 months postoperatively. The secondary endpoint is to evaluate the efficacy of epicardial injection of hiPSC-CMs and CABG surgery combination by comparison with CABG surgery alone.Ethics and dissemination The study protocol has been approved by the Institutional Ethical Committee of Nanjing Drum Tower Hospital (No. SC202000102) and approved by National Health Commission of the PRC (MR-32-21-014649). Findings will be disseminated to the academic community through peer-reviewed publications and presentation at national and international meetings.Trial registration number NCT03763136.

The global rise in obesity has become a public health crisis. During the onset of obesity, disrupted catecholamine signals have been described to contribute to excess fat accumulation, however, the molecular and metabolic change of subcutaneous adipose tissue (SAT) upon chronic high-fat feeding has rarely been investigated. Here, we show that chronic high-fat feeding caused a significant decrease in the expression of thermogenic genes and acquisition of partial deleterious features of visceral fat in SAT. Upregulated miR-149-3p was involved in this obesity-induced “visceralization” of SAT via inhibiting PRDM16, a master regulator that promoted SAT thermogenesis. Reduction of miR-149-3p significantly increased PRDM16 expression in SAT, with improved whole-body insulin sensitivity, decreased SAT inflammation, and liver steatosis in high-fat fed mice. These findings provided direct evidence of the anti-obese and anti-diabetic effect of PRDM16 in the obese background for the first time and identified that miR-149-3p could serve as a therapeutic target to protect against diet-induced obesity and metabolic dysfunctions. Keywords: diet-induced obesity, miR-149-3p, Prdm16, subcutaneous adipose tissue, thermogenesis

The induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from a male child with Danon disease. Next-generation sequencing (NGS) revealed a stop gained mutation c.467 T > G in LAMP2 gene. PBMCs were reprogrammed by using non-integrating Sendai reprogramming kits. It is a possible cell model to screen alternative medicine treatment of the Danon disease.

Circular RNAs (circRNA) are involved in a variety of human heart diseases, however, circRNA expression profiles and circRNA-miRNA-mRNA regulatory network in human atrial fibrillation (AF) especially with valvular heart diseases (VHD) remain poorly understood. A high-throughput RNA sequencing was used to investigate the differentially expressed circRNAs in left atrial appendage from VHD patients with or without persistent AF. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the potential functions of the host genes of differentially expressed circRNA and their downstream targets. CircRNA–miRNA-mRNA regulatory network was constructed to identify mechanisms underlying circRNAs. qRT-PCR and sanger sequencing were further performed to validate the results. Compared with sinus rhythm (SR) patients, there were 3094 upregulated and 4472 downregulated circRNAs in AF patients respectively. The expression of 10 most differentially expressed circRNAs (circ 255-ITGA7, circ 418-KCNN2, circ 13913-MIB1, circ 44670-BARD1, circ 44782-LAMA2, circ 81906-RYR2, circ 35880-ANO5, circ 22249-TNNI3K, circ 3136-TNNI3K, circ 56186-TNNI3K) between SR and persistent AF patients were verified by qRT-PCR. In addition, specific back-splicing sites of these circRNAs was confirmed by sanger sequencing. GO and KEGG pathway analysis indicated that cAMP signal pathway and Wnt signal pathway might play important role in the development of AF in VHD patients, which might be affected by circRNAs. This study provided a preliminary landscape of circRNAs expression profiles which are involved in persistent AF due to VHD, and established the possibility for future related researches in this field.

Background: Insulin resistance (IR) is a significant risk factor for cardiometabolic diseases and a defining feature of type 2 diabetes mellitus (T2DM). This study aimed to examine the potential value of triglyceride-glucose (TyG) index as a predictor of prognosis in coronary heart disease (CHD) patients with T2DM after coronary artery bypass grafting (CABG) surgery and to facilitate the identification of those at high risk of major adverse cardiovascular events (MACEs) for closer monitoring or possible early intervention. Methods: This study enrolled 386 T2DM patients who underwent CABG surgery at Nanjing Drum Tower Hospital. Patients were separated into two groups according to the median preoperative TyG Index. The Kaplan-Meier plot was used to compare the rate of MACEs-free survival in T2DM patients after CABG. The independent risk factors for the occurrence of MACEs were investigated using multivariate analysis. Nomogram was used to depict the predictive model. Results: Significantly more MACEs occurred in individuals with higher medians of the TyG index (65 (33.7%) vs. 39 (20.2%), p=0.003). TyG index [hazard ratio (HR) 12.926], LVEF [hazard ratio (HR) 0.916], and NYHA functional class III/IV [hazard ratio (HR) 4.331] were identified as independent predictors of MACEs incidence in post-CABG T2DM patients by multivariate analysis. The area under the curve (AUC) for predicting MACEs using the TyG index was 0.89 at five years. Combining the TyG index, LVEF, and NYHA functional class III/IV to build a novel risk assessment model for postoperative MACEs, the AUC climbed to 0.93 at five years. With AUCs, the nomogram comprised of the TyG index, LVEF, and NYHA functional class III/IV demonstrated strong specificity in the training and test sets. Conclusions: The incidence of MACEs is high among post-CABG T2DM patients with a high TyG index. TyG index improves the diagnostic accuracy of MACEs, especially at long-term follow-up. A high TyG index may serve as an early warning signal for individuals to undertake lifestyle adjustments that can reduce the progression or incidence of MACEs. [ABSTRACT FROM AUTHOR]