Qing Zhou

Insulin resistance (IR) is a key driver of cardiovascular disease (CVD), the leading cause of global mortality. This study evaluated the prognostic value of two surrogate IR indices—the McAuley index and the Metabolic Score for Insulin Resistance (METS‐IR)—for predicting all‐cause and CVD mortality. Data from 22,308 NHANES participants with established CVD (1999–2018) was analyzed. Outcomes were all‐cause and CVD mortality. Cox proportional hazards models and restricted cubic splines assessed associations, while machine learning methods (random forest, XGBoost, CoxBoost, DeepHit) evaluated predictive performance. Model interpretability was assessed using SHapley Additive exPlanations (SHAP). Over a median 9.2‐year follow‐up, 3484 deaths occurred, including 1093 from CVD. A higher McAuley Index was inversely associated with risk, with each 1‐unit increase predicting a 9.2% reduction in all‐cause and 11.3% reduction in CVD mortality. Higher METS‐IR values were associated with increased mortality. Restricted cubic spline analysis confirmed significant U‐shaped relationships. Across nine models, the Cox model demonstrated the best performance (C‐index: 0.87 for all‐cause and 0.85 for CVD mortality), with time‐dependent AUCs consistently above 0.8. SHAP analysis highlighted the McAuley Index and METS‐IR as leading predictors. The McAuley Index and METS‐IR are robust, independent predictors of all‐cause and CVD mortality. Their integration with interpretable machine learning enhances risk stratification, underscoring the role of metabolic dysfunction and central adiposity in long‐term outcomes. These indices may help identify high‐risk patients who could benefit from targeted interventions.

Aims: Methyltransferase like 3 (METTL3) plays a crucial role in cardiovascular diseases, but its involvement in atrial fibrillation (AF) remains unclear. The study aims to explore the relationship between METTL3 and AF in atrial myocytes. Methods and results: The protein level of METTL3 was evaluated in left atrial appendages (LAAs) from patients with persistent AF and in experimental AF models. cAMP-responsive element modulator (CREM) transgenic mice and CaCl2-acetylcholine (ACh)-injected mice were used as AF mice models. Methyltransferase like 3 was globally and atrial conditionally deleted in vivo to assess its role in AF. Confocal fluorescence microscopy was employed to examine calcium handling in atrial myocytes. Methylated RNA immunoprecipitation sequencing was performed to identify the downstream target genes of METTL3. Methyltransferase like 3 protein and RNA N6-methyladenosine (m6A) modification levels were significantly reduced in the LAAs of patients with AF and experimental AF models. Genetic inhibition of METTL3 promoted the development of AF in CREM transgenic mice and CaCl2-ACh-injected mice. Knockdown of METTL3 in atrial myocytes resulted in enhanced calcium handling. Reduced METTL3 levels increased SR Ca2+-ATPase Type 2a activity by up-regulating protocadherin gamma subfamily A, 10. Decreased METTL3 protein in atrial myocytes was attributed to down-regulation of cAMP-responsive element-binding protein 1/ubiquitin-specific peptidase 9 X-linked axis. Conclusion: Our study established the pathophysiological role of METTL3 involved in the development of AF and provided a potential mechanism-based target for its treatment.

EuroSCORE II is one of the most widely utilized cardiovascular surgery risk scoring systems. Recently, a new online score calculator, namely the German Registry of Acute Aortic Dissection Type A (GERAADA), was launched to predict 30-day surgical mortality for acute type A aortic dissection (ATAAD) patients. The aim of this study is to evaluate the predictive performance of these two scores. We calculated the two scores for 1346 ATAAD patients from January 2012 to December 2021. The overall performance was evaluated using Brier scores and Hosmer-Lemeshow statistics. Receiver Operating Characteristic (ROC) curves were employed to assess diagnostic ability, and the standardized mortality ratio (SMR) was utilized to evaluate calibration. The GERAADA score and EuroSCORE II predicted 30-day mortality rates of 14.7% and 3.1%, respectively, while the observed rate was 12.5%. The predictive ability of EuroSCORE II (AUC 0.708, 95% CI: 0.664–0.792) was superior to that of the GERAADA score (0.648, 95% CI: 0.605–0.692). The GERAADA score had higher sensitivity but lower specificity than EuroSCORE II. And the GERAADA score may overestimate mortality (0.76, 95% CI: 0.65–0.89), while EuroSCORE II may underestimate the mortality rate (3.17, 95% CI: 2.92–3.44). The EuroSCORE II was superior in predicting surgical mortality among ATAAD patients. But the observed 30-day mortality rate certified a good calibration for the GERAADA score.

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.

Corrigendum: The neutrophil elastase inhibitor, Sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass

Background: The sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery.Methods: Firstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1^st, 2020 to October 26^th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc.Results: In propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P<0.01), bilateral pulmonary infiltrates (P<0.01), oxygen index (P<0.01), interleukin-6(P=0.02), procalcitonin(P<0.01) and C-reactive protein(P<0.01).Conclusion: Administration of sivelestat might improve postoperative outcomes in patients with ALI after emergent cardiovascular surgery. Our results show that sivelestat may be considered to protect pulmonary function against inflammatory injury by CPB.Registration: http://www.chictr.org.cn/showproj.aspx?proj=166643, identifier ChiCTR2200059102.

Nano/micro fibers have evoked much attention of scientists and have been researched as cutting edge and hotspot in the area of fiber science in recent years due to the rapid development of various advanced manufacturing technologies, and the appearance of fascinating and special functions and properties, such as the enhanced mechanical strength, high surface area to volume ratio and special functionalities shown in the surface, triggered by the nano or micro-scale dimensions. In addition, these outstanding and special characteristics of the nano/micro fibers impart fiber-based materials with wide applications, such as environmental engineering, electronic and biomedical fields. This review mainly focuses on the recent development in the various nano/micro fibers fabrication strategies and corresponding applications in the biomedical fields, including tissue engineering scaffolds, drug delivery, wound healing, and biosensors. Moreover, the challenges for the fabrications and applications and future perspectives are presented.

Background: Several genomic loci of type 2 diabetes (T2D) nominated in genome‐wide association studies (GWAS) have been suggested to regulate metabolism in muscle. However, a large portion of the genetic risk and the underlying regulation remain unexplained. The present study aimed to localize the potentially functional regions or genes at juxtaposed with another zinc finger protein 1 (JAZF1) locus and interpret their possible biological mechanisms in the muscle of T2D.Methods: Seven GWAS datasets including 21,897 T2D patients and 32,710 healthy controls of 772 SNPs within JAZF1 locus were meta‐analysed using unconditional logistic regression. The Sherlock and GTEx protal online algorithms were implemented to show the significant colocalizations. Multiple omics data were integrated to predict the potential biological functions of JAZF1‐AS1 in muscle. The cis regulation of JAZF1‐AS1 was analysed using in vitro cloning in Human skeletal muscle cells (HSkMC).Results: With a cross‐population meta‐analysis of seven GWAS, we identified a linkage disequilibrium (LD) block within intron 1 of JAZF1 that was significantly associated with T2D (false discovery rate < 0.05). The colocalization analysis showed a significant association between genetically determined expression of JAZF1 in skeletal muscle and T2D with a strong probability of colocalization (PP4 = 75.09%). This region also encodes the upstream regulatory region of the antisense non‐coding RNA JAZF1‐AS1. Expression‐quantitative trait loci analysis detected a regulatory SNP within this LD block, rs864745, which is associated with the expression of JAZF1‐AS1 and JAZF1. With in vitro cloning, we further reported the role of JAZF1‐AS1 in cis‐regulating JAZF1 by directly forming RNA double strands. Downregulation of JAZF1, caused by JAZF1‐AS1 depletion, inhibited the glucose uptake and lipid oxidation in skeletal muscle.Conclusions: The present study proposes a strategy for identifying a novel T2D gene at the reported locus and generating a model in which polymorphisms at JAZF1 influence T2D risk through antisense‐mediated gene regulation.

Background: Atrial fibrillation (AF) recurrence after ablation will increase mortality and morbidity during follow up. We attempted to evaluate the relationship between circular RNAs (circRNA) and AF recurrence to establish a predictive model for early intervention. Methods: Patients who received surgical ablation retrospectively were analyzed. The expression of circRNAs were detected in the left atrial appendage. The independent risk factors of late recurrence were analyzed by multivariate analysis. The predictive model was visualized by Nomogram and tested by receiver operating characteristic curve and calibration plot. Kaplan-Meier plot was used to compare the rate of freedom from AF recurrence after surgery. The relationships between circRNAs and clinical characteristics were detected by Spearman’s correlation analysis. Results: A total of 136 patients were enrolled from September 2018 to June 2019, 55 patients experienced late recurrence during one-year follow up. Increased age, longer AF duration and increased circ 81906-RYR2, circ 44782-LAMA2, circ 418-KCNN2 and circ 35880-ANO5 were detected in recurrent patients. Multivariate analysis revealed that increased age (odds ratio (OR)=1.072, P = 0.006), longer AF duration (OR=1.007, P = 0.036) and increased circ 81906-RYR2 (OR=2.210, P < 0.001) were independent risk factors for late recurrence. Area under the curve was 0.77, and the cut-off value was 70 points of the predictive model. Kaplan-Meier plots showed that patients over 70 points tended to experience AF recurrence. Conclusion: Circ 81906-RYR2 could be a new predictor of late recurrence after surgical ablation. A predictive model consists of age, atrial fibrillation duration, and circ 81906-RYR2 was alternative for early intervention of AF recurrence.