Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

Objective To explore the clinical characteristics and short-term prognosis of postoperative acute myocardial infarction (PAMI) after cardiac surgery. Methods A retrospective study was conducted on 45 PAMI patients who underwent coronary angiography after cardiac surgery at Zhongshan Hospital, Fudan University, from February 2015 to February 2025. General information, type of surgery, onset time and causes of PAMI, and in-hospital recovery condition were collected. Univariate logistic regression was used to analyze factors related to in-hospital survival. Results The patients’ age was (62.40±11.72) years, 31 cases (68.89%) were male, 21 cases (46.67%) had hypertension. Twenty-six patients (57.78%) underwent cardiac valve surgery, and 16 patients (35.56%) received coronary artery bypass grafting. The onset time of PAMI was 24 (0, 48) hours, with 38 cases (84.44%) developing within 48 hours after surgery. Twenty-eight patients (62.22%) presented with new lesions in coronary arteries/bypass grafts, and 20 patients (44.44%) were considered to have thrombus-induced PAMI. Nine patients died in hospital, 13 patients failed to recover and were discharged automatically, and 23 patients were discharged after recovery. Univariate logistic regression analysis showed that new lesion in coronary arteries/bypass grafts was risk factor for in-hospital survival (OR=0.235, P=0.036). Conclusions PAMI frequently occurs within 48 hours post-cardiac surgery, and thrombosis is the most common cause of PAMI. New lesions in coronary arteries/bypass grafts are closely correlated with poor short-term prognosis.

Objective To investigate the predictive value of D-dimer for in-hospital mortality and heart failure with reduced ejection fraction (HFrEF) in patients with acute myocardial infarction (AMI). Methods A total of 688 patients with AMI who were hospitalized at Zhongshan Hospital, Fudan University, from January 2020 to December 2023 were retrospectively enrolled. Demographic and clinical characteristics, laboratory findings, echocardiographic parameters, and in-hospital outcomes were collected. Patients were divided into four groups according to D-dimer quartiles, and trend tests were used to compare changes in each indicator with increasing D-dimer levels. The primary endpoints were in-hospital mortality and HFrEF. Multivariable logistic regression analysis was performed to assess the independent associations of D-dimer with in-hospital mortality and HFrEF. Receiver operating characteristic (ROC) curve analysis was used to evaluate its predictive performance. Results Differences and trend tests among four groups for age, creatinine, peak cardiac troponin T, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction, HFrEF incidence, and in-hospital mortality were statistically significant (P＜0.05). Multivariable logistic regression analysis showed that elevated D-dimer was associated with an increased risk of in-hospital mortality in patients with AMI (OR＝1.251, 95%CI 1.093–1.432, P＝0.001), and HFrEF (OR＝1.075, 95%CI 1.028–1.124, P＝0.002). ROC curve analysis showed that the area under the curve (AUC) of D-dimer for predicting in-hospital mortality and HFrEF were 0.871 and 0.716, respectively. At a cutoff value of 0.47 mg/L, the sensitivity and specificity of D-dimer in predicting HFrEF were 81.9% and 52.1%, respectively; at a cutoff value of 2.18 mg/L, the sensitivity and specificity of D-dimer in predicting in-hospital mortality were 63.6% and 93.8%, respectively. Restricted cubic spline analysis demonstrated significant non-linear associations between D-dimer and the risks of in-hospital mortality and HFrEF (P＜0.001). Conclusions Elevated D-dimer level is significantly associated with increased risks of in-hospital mortality and HFrEF in patients with AMI and shows acceptable predictive performance. As a simple and readily available laboratory biomarker, D-dimer may provide useful information for early risk stratification and clinical management in patients with AMI.

Objective To investigate the diagnositic performance of cardiac myosin-binding protein C (cMyBP-C) in cardiovascular immune-related adverse events (CV-irAE), and to evaluate its potential as a novel biomarker of myocardial injury. Methods Cancer patients receiving immune checkpoint inhibitors (ICI) therapy at Zhongshan Hospital, Fudan University, from January 2025 to September 2025 were enrolled. Patients were divided into the positive group (high-sensitivity cardiac troponin T [hs-cTnT]≥99th percentile [14 pg/mL], n＝78) and the negative group (hs-cTnT＜99th percentile, n＝56). A control group (n＝231) consisted of cancer patients without prior anti-tumor therapy and healthy individuals. Levels of cMyBP-C, hs-cTnT, creatine kinase isoenzyme-MB (CK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. The screening reference value of cMyBP-C was established using the 99th percentile method. Diagnositic performance was evaluated by receiver operating characteristic (ROC) curves and area under the curve (AUC). The association between cMyBP-C level and myocardial edema assessed by cardiac magnetic resonance (CMR) was analyzed using Spearman correlation. Results The difference in cMyBP-C levels among the three groups was statistically significant (P＜0.001). Based on the 99th percentile of the control group, the screening reference value of cMyBP-C was determined to be 5.86 pg/mL. ROC curves showed that cMyBP-C achieved an AUC of 0.919 (95%CI 0.898–0.939) for detecting the risk of CV-irAE, comparable to CK-MB (AUC＝0.917, 95%CI 0.896–0.939, P＝0.682) and superior to NT-proBNP (AUC＝0.876, 95%CI 0.850–0.902, P＜0.001). After excluding non-cardiovascular adverse events, the AUC of cMyBP-C increased to 0.934, CK-MB was 0.893, and NT-proBNP was 0.877. Spearman correlation analysis revealed that among patients with ICI-associated myocarditis (n＝21), cMyBP-C level was positively correlated with the extent of myocardial edema assessed by CMR ( ρ＝0.64, P＝0.002). Conclusions cMyBP-C is significantly elevated in patients with CV-irAEs, demonstrating diagnositic performance comparable to or better than conventional biomarkers, and reflecting the burden of myocardial inflammation. These findings suggest that cMyBP-C may serve as a valuable complementary diagnositic biomarker for CV-irAEs.

Objective To explore the effects of Ginkgo biloba extract (GBE) on cardiac microvascular endothelial cells (CMECs) under oxygen and glucose deprivation/reperfusion (OGD/R) condition and its molecular mechanisms. Methods An OGD/R-induced injury model was established in CMECs. According to different intervention, CMECs were divided into four groups: normoxia blank control group (WT group), WT + GBE group, OGD/R group, and OGD/R + GBE group. Cell apoptosis was detected by flow cytometry technology in each group. The oxidative stress was examined by MitoSox staining. The migration abilities were measured by scratch assay. The expressions of PERK/eIF2α/CHOP, nuclear factor kappa B (NF-κB), and endothelial cell function markers were detected by Western blotting. Results Compared with the WT group, the endothelial cell apoptosis level in the OGD/R group significantly increased, with markedly aggravated cellular dysfunction. The expressions of p-NF-κB, vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (ICAM-1) were significantly upregulated (P＜0.05), and the activation of the CHOP signaling pathway was notably enhanced (P＜0.05). After intervention with GBE, endothelial cell apoptosis caused by OGD/R injury was significantly reduced, oxidative stress and inflammation levels were markedly downregulated, and the expression of p-NF-κB was considerably decreased (P＜0.05), while the CHOP signaling pathway was notably inhibited (P＜0.05). Furthermore, it was found that GBE could promote expression of SIRT6 to regulate the above molecules, thereby alleviating cardiac microvascular endothelial cell injury under OGD/R condition. On the contrary, when SIRT6 was knocked down, the protective effects were significantly reduced. Conclusions GBE improves endothelial cell dysfunction, endoplasmic reticulum stress, and endothelial cell apoptosis caused by OGD/R injury by promoting the expression of SIRT6 protein, thus regulating the NF-κB inflammatory pathway and CHOP signaling pathway.

One of its primary surgical treatments of tricuspid regurgitation is tricuspid valve biological valve replacement. Catheter tricuspid valve-in-valve implantation is a novel interventional alternative for biological valve failure. The non-invasive lung fluid measuring device remote dielectric sensing (ReDSTM) has been increasingly incorporated into clinical practice as a means of monitoring chronic heart failure in recent years. This report describes the process and outcomes of the first instance of perioperative lung fluid volume evaluation following transcatheter tricuspid valve implantation utilizing ReDSTM technology. The patient has a short-term, substantial increase in postoperative lung fluid volume as compared to baseline.

Objective To explore the role and related mechanism of neutrophil membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Neu-NP) in cardiac repair after acute myocardial ischemia-reperfusion (MI/R) injury in mice. Methods The male C57 mouse model of acute MI/R injury was established and randomly divided into three groups: PBS control group (injection of 200 μL PBS), NP treatment group (injection of 0.5 mg/mL NP 200 μL), and Neu-NP treatment group (injection of 0.5 mg/mL Neu-NP 200 μL). Neutrophil membranes were extracted and fused with PLGA nanoparticles to construct biomimetic Neu-NP. The in vivo homing ability of Neu-NP was assessed using ex vivo imaging technology in the MI/R injury model, and the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the myocardium were measured using enzyme linked immunosorbent assay one day and three days after administration. Echocardiography was used to determine cardiac function indicators of MI/R injured mice 28 days post-administration. Immunofluorescence staining was used to observe angiogenesis repair and inflammatory cell infiltration in mouse heart tissue. Results Neu-NP, engineered by integrating neutrophil membranes with nanoparticles, inherited surface receptors (TNF-αR and IL-6R) and functioned as decoys for inflammatory targeting. Compared with the PBS control group and NP treatment group, the secretion levels of TNF-α and IL-6 in the damaged myocardium of the Neu-NP treatment group were significantly decreased one and three days after administration (P＜0.05); 28 days after administration, the cardiac ejection fraction in the Neu-NP treatment group was significantly higher than that in the other two groups (P＜0.05). Immunofluorescence staining indicated a significant increase in the proportion of angiogenesis in the myocardial infarction area and a significant reduction in inflammation cell infiltration (P＜0.05). Conclusions Neu-NP plays an important role in cardiac tissue repair after MI/R injury by alleviating inflammatory factors in the damaged area and promoting angiogenesis.

Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

BACKGROUND: Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear. METHODS: The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated. RESULTS: Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1  directly. CONCLUSION This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Autophagy/drug effects* ; Myocytes, Cardiac/metabolism* ; Cardiomyopathies/metabolism* ; Beclin-1/genetics* ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Doxorubicin