Liming Lei

Systemic inflammation and depressive symptoms are both associated with adverse cardiovascular prognosis, but their combined prognostic value after percutaneous coronary intervention (PCI) remains uncertain. This study examined the individual and joint associations of inflammatory score (IS) and clinically relevant depressive symptoms with traditional major adverse cardiovascular events (MACE). A total of 487 patients with angiographically confirmed coronary artery disease were included. Depressive symptoms were assessed using the 9-item Patient Health Questionnaire (PHQ-9), with PHQ-9 ≥ 10 used as the primary definition of clinically relevant depressive symptoms. IS was calculated from z-scores of C-reactive protein and white blood cell count and dichotomized using the original cohort-specific median cutoff (-0.78). The primary outcome was traditional MACE. Cox regression, restricted cubic spline, additive interaction, and exploratory discrimination analyses were performed. During follow-up, 134 patients (27.5%) experienced MACE. After extensive cardiovascular adjustment, PHQ-9 ≥ 10 remained independently associated with MACE (HR 1.91, 95% CI 1.08-3.39, P = 0.027), whereas high IS alone was not significant (HR 1.34, 95% CI 0.89-2.00, P = 0.159). Patients with both high IS and PHQ-9 ≥ 10 had the highest MACE risk compared with those with low IS and PHQ-9 < 10 (HR 3.50, 95% CI 1.58-7.76, P = 0.002). hs-CRP threshold analyses were less consistent, and additive interaction estimates were imprecise. PHQ-9 ≥ 10 was independently associated with traditional MACE. Coexistence of high IS and PHQ-9 ≥ 10 identified a high-risk subgroup, although IS and additive interaction findings require cautious interpretation.

This study explored the incidence and risk factors of acute kidney injury (AKI) in patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing

The connection between low-density lipoprotein cholesterol (LDL-C) levels and postoperative outcomes following cardiac valve surgery (CVS) remains controve

Marfan syndrome (MFS) is an inherited autosomal dominant disorder that affects connective tissue with an incidence of about 1 in 5,000 to 10,000 people. 90% of MFS is caused by mutations in the fibrillin-1 (FBN1) gene. We recruited a family with MFS phenotype in South China and identified a novel variant. This study investigated whether this genetic variant is pathogenic and the potential pathway related to lipid metabolism in MFS. A three-generation consanguineous family was recruited for this study. Whole exome sequencing (WES) was utilized on family members. The 3D structure of the protein was predicted using AlphaFold. CRISPR/Cas9 was applied to generate a similar fbn1 nonsense mutation (fbn1+/−) in zebrafish. RNA-seq analysis on zebrafish was performed to identify potential pathways related to MFS pathogenesis. Our study identified a novel variant [NM_000138.5; c.7764 C > G: p.(Y2588*)] in FBN1 gene from the family and identified the same site mutation among the proband along with her son and daughter. Structural modeling showed the p.Y2588* mutation resulted from a truncated protein. Compared to wild-type zebrafish, the F2 generation fbn1+/− zebrafish exhibited MFS phenotype. RNA-seq analysis indicated that many genes related to leptin are up-regulating, which could affect bone development and adipose homeostasis. A novel variant was identified in FBN1 gene. In a zebrafish model, we found functional evidence supporting the pathogenicity of the detected nonsense mutation. Our research proposes a possible mechanism underlying the relationship between lipid metabolism and MFS. These findings can help improve the clinical diagnosis and treatment of MFS.

Cardiomyopathy is a group of disease characterized by structural and functional damage to the myocardium. The etiologies of cardiomyopathies are diverse, spanning from genetic mutations impacting fundamental myocardial functions to systemic disorders that result in widespread cardiac damage. Many specific gene mutations cause primary cardiomyopathy. Environmental factors and metabolic disorders may also lead to the occurrence of cardiomyopathy. This review provides an in‐depth analysis of the current understanding of the pathogenesis of various cardiomyopathies, highlighting the molecular and cellular mechanisms that contribute to their development and progression. The current therapeutic interventions for cardiomyopathies range from pharmacological interventions to mechanical support and heart transplantation. Gene therapy and cell therapy, propelled by ongoing advancements in overarching strategies and methodologies, has also emerged as a pivotal clinical intervention for a variety of diseases. The increasing number of causal gene of cardiomyopathies have been identified in recent studies. Therefore, gene therapy targeting causal genes holds promise in offering therapeutic advantages to individuals diagnosed with cardiomyopathies. Acting as a more precise approach to gene therapy, they are gradually emerging as a substitute for traditional gene therapy. This article reviews pathogenesis and therapeutic interventions for different cardiomyopathies.

Background: Gastrointestinal bleeding (GIB) is a notable complication in patients diagnosed with aortic dissection (AD). We evaluated the outcomes and identified the risk factors associated with GIB in patients with AD. Methods: A retrospective case-control study was conducted on patients diagnosed with type A aortic dissection (TAAD) who underwent total aortic arch replacement (TAAR) at our institution from July 2021 to July 2023. Comprehensive clinical data, laboratory findings, and imaging results were meticulously gathered and analyzed to identify potential risk factors linked to GIB in this patient cohort. Results: Of the 198 AD patients who underwent TAAR, 38 (19.2%) developed postoperative GIB (GIB group), with a median interval of 7 days between surgery and bleeding onset. The GIB group exhibited significantly higher mortality (26.3% vs. 3.1%, Pvs. 7 (IQR, 5–12) days, Pvs. 71 (IQR, 34–148) hours, P54 years [odds ratio (OR): 3.529], intraoperative red blood cell (RBC) transfusion >600 mL (OR: 3.865), and concomitant celiac trunk and superior mesenteric artery (SMA) hypoperfusion (OR: 15.974) as independent risk factors for GIB in AD patients. Conclusions: GIB subsequent to TAAR in AD patients is linked to adverse prognosis. Factors such as advanced age, extensive intraoperative transfusion, and gastrointestinal (GI) perfusion abnormalities may heighten the risk of GIB in this patient population.

Background: Ductus arteriosus (DA) close depends on the mature development and extracellular matrix (ECM) accumulation of vascular smooth muscle cells (VSMCs). This study aims to explore the function and interaction of transforming growth factor β (TGF-β) and Notch signaling pathway on VSMCs. Methods: An in vitro experiment was conducted on mouse VSMCs and supplementations of TGF-β, Notch signaling pathway ligand (Jagged-1), and inhibitor SAHM1. Transfections were constructed on VSMCs with two siRNAs of Smad4 and overexpressed Smad4 plasmid. ELISA measured the reactive oxygen species (ROS) level. Cell apoptosis was evaluated by TdT-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry. Immunofluorescence (IF) analysis was used to detect the expression and localization of Smad4. The expression levels of ECM-related proteins and Smads were measured by western blotting and real-time quantitative PCR (RT-qPCR) analyses. Results: The higher concentration of TGF-β1 induced cell apoptosis (p < 0.001), increased ROS level (p < 0.001), and promoted ECM accumulation by regulating nuclear Smad4. Silencing Smad4 significantly impeded ECM accumulation induced by TGF-β1. The Notch pathway ligand Jagged-1 promoted ECM formation and activated Smad2–4 proteins, while Notch pathway inhibitor SAHM1 had the opposite effect. Further results confirmed that the Notch pathway induced Smad4 transcription (p < 0.001), thereby enhancing the function of the TGF-β1/Smads pathway. Moreover, Smad4 overexpression was found to induce ECM accumulation. Conclusions: Our present study explored the interaction of the Notch and TGF-β signaling pathways on ECM accumulation of VSMCs. The Notch pathway induced the transcription of Smad4, leading to enhanced ECM accumulation in VSMCs. This effect is achieved through co-regulation with TGF-β1.

Background: Previous models for predicting delirium after cardiac surgery remained inadequate. This study aimed to develop and validate a machine learning-based prediction model for postoperative delirium (POD) in cardiac valve surgery patients. Methods: The electronic medical information of the cardiac surgical intensive care unit (CSICU) was extracted from a tertiary and major referral hospital in southern China over 1 year, from June 2019 to June 2020. A total of 507 patients admitted to the CSICU after cardiac valve surgery were included in this study. Seven classical machine learning algorithms (Random Forest Classifier, Logistic Regression, Support Vector Machine Classifier, K-nearest Neighbors Classifier, Gaussian Naive Bayes, Gradient Boosting Decision Tree, and Perceptron.) were used to develop delirium prediction models under full (q = 31) and selected (q = 19) feature sets, respectively. Result: The Random Forest classifier performs exceptionally well in both feature datasets, with an Area Under the Curve (AUC) of 0.92 for the full feature dataset and an AUC of 0.86 for the selected feature dataset. Additionally, it achieves a relatively lower Expected Calibration Error (ECE) and the highest Average Precision (AP), with an AP of 0.80 for the full feature dataset and an AP of 0.73 for the selected feature dataset. To further evaluate the best-performing Random Forest classifier, SHAP (Shapley Additive Explanations) was used, and the importance matrix plot, scatter plots, and summary plots were generated. Conclusions: We established machine learning-based prediction models to predict POD in patients undergoing cardiac valve surgery. The random forest model has the best predictive performance in prediction and can help improve the prognosis of patients with POD.

Objective: The present study aimed to prospectively evaluate the role of metagenomic next-generation sequencing (mNGS) in the etiological diagnosis of patients with perioperative infective endocarditis (IE).Methods: From May 1st, 2019 to December 31st, 2020, a total of 99 patients with IE were enrolled in the present study according to the modified Duke criteria, etiological, and pathological results. 11 non-IE patients undergoing heart valve surgery in the same period were selected as the control group. A blood culture test was performed immediately after admission, and the valves harvested operatively were examined by blood culture and mNGS.Results: In the IE group, there were 29 cases (29.3%) with positive blood culture, 16 cases (16.2%) with positive valve culture, and 85 cases (85.9%) with positive valve mNGS. Compared to culture-based detection, mNGS achieved better performance with a sensitivity, specificity, area under the curve (AUC) of 0.859, 0.727, and 0.793, respectively. The combined approach using culture and mNGS further improved the diagnostic accuracy (sensitivity 89.9%, specificity 72.7%, AUC 0.813). Preoperative white blood cell (P = 0.029) and neutrophils (P = 0.046) were identified as independent factors affecting the detection rate of mNGS. In the mNGS-positive group, 95 strains of pathogens were found and 10 cases were identified with mixed infection. There were 72 gram-positive bacteria and 14 gram-negative bacteria. mNGS positive group displayed higher species richness than mNGS negative group with enrichment of Streptococcus sanguis, Streptococcus buccalis, and Streptococcus griseus. Proteobacteria and Actinomycetes were enriched in mNGS negative group. Notably, six patients showed disconcordant results between culture and mNGS. Rothia aeria was identified in the blood culture, valve culture, and valve mNGS in one patient. Bartonella Quintana and Coxiella burnetii, which were fastidious intracellular bacteria, were found in two blood and valve culture-negative cases.Conclusions: mNGS outperformed the conventional culture method and displayed high accuracy in detecting pathogens in IE patients. This study provided support for the use of mNGS in the etiological diagnosis of IE.