Background:The presence of a small aortic annulus (SAA) in patients undergoing aortic valve replacement (AVR) remains a clinical challenge in cardiac surgery. Continuous suture technique (CST) has been considered to allow implantation of relatively larger prostheses compared with interrupted pledgeted suture (IPS). This study aimed to compare early clinical outcomes of CST versus IPS in patients with SAA who underwent surgical AVR. Methods:Between 2023 to 2025, 250 patients who received surgical AVR with implanted prostheses size <23 mm at our department were enrolled for retrospective analysis: 99 in the CST group and 151 in the IPS group. Early clinical outcomes were analyzed using propensity score matching, with postoperative peak aortic velocity as the primary endpoint. Results:The CST group exhibited comparable early clinical outcomes to the IPS group, with no postoperative paravalvular leak observed. Shorter surgery time (P=0.03) and cross-clamp time (P=0.045) were shown in the raw CST group; this advantage also reached a significant difference in the isolated AVR subgroup analysis. Our cohort presented that AVR with CST was associated with significantly lower peak aortic velocity compared with IPS in both raw cohort {2.0 [interquartile range (IQR), 1.7-2.2] vs. 2.2 (IQR, 2.0-2.6) m/s; P<0.001} and propensity-matched analyses (P=0.03). Multivariable linear regression also confirmed CST as an independent predictor of reduced postoperative peak aortic velocity (coefficient -0.192; 95% confidence interval, -0.292 to -0.092; P<0.001). Conclusions:The treatment with CST in AVR could be a valid and well-promoted alternative strategy for patients with SAA and showed a trend toward better hemodynamic performance compared to the traditional IPS approach.

Ferroptosis is a recently identified type of regulated necrosis, and glutathione peroxidase 4 (GPX4) has been recognized as a key enzyme that protects against ferroptosis. However, the role of platelet ferroptosis in systemic lupus erythematosus (SLE) has not been explored. This study aimed to investigate the role of GPX4-mediated platelet ferroptosis in SLE. GPX4 protein expression in platelets was detected by Western blot and immunofluorescence analysis. The correlation of platelet GPX4 expression with SLE clinical characteristics was evaluated. The ability of platelet activation and ferroptosis was detected, and the release of oxidized DNA by platelets was tested. In addition, GPX4 inhibitor and activator were used to evaluate the effect of GPX4 on platelet ferroptosis and oxidized DNA release. Finally, MRL/lpr mice were treated with GPX4 activator 1 or vehicle and the severity of lupus disease was assessed. Platelets of SLE patients showed lower expression of GPX4, which was negatively correlated with disease activity and plasma oxidized DNA levels. These platelets were more activated, prone to ferroptosis, and released higher levels of oxidized DNA. In vitro, GPX4 inhibitor induced ferroptosis and oxidized DNA release in healthy control platelets, whereas the GPX4 activator 1 protected SLE platelets. In MRL/lpr mice, treatment with GPX4 activator 1 alleviated lupus severity, reduced platelet ferroptosis, and decreased oxidized DNA release. SLE platelets exhibit low GPX4 expression and are more susceptible to ferroptosis, highlighting the critical role of GPX4 downregulation-mediated platelet ferroptosis in the development of SLE. Therefore, activation of GPX4 may represent a therapeutic strategy for SLE.

Background: Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital heart defect that might lead to myocardial ischemia and sudden cardiac death (SCD). Despite that AATS guidelines recommended indefinite daily aspirin medication after surgery for AAOCA, efficacy of antiplatelet therapy (APT) remains unclear. The purpose of this study is to evaluate and compare the clinical results of different antiplatelet strategies after unroofing procedure for AAOCA. Methods: A total of 86 patients who underwent surgical unroofing of AAOCA at Guangdong Provincial People's Hospital between Jun 2013 and Sept 2025 were enrolled in this retrospective study. All patients accepted routine electrocardiogram (ECG), transthoracic echocardiogram (TTE), and computed tomography angiography (CTA) before operation, as well as repeated TTE at discharge and latest follow-up. The cohort was divided into three subgroups according to the APT after surgery: the control (no antiplatelet therapy) group, the single antiplatelet therapy (SAPT) group and the dual antiplatelet therapy (DAPT) group. Results: The cohort comprised 61 males and 25 females, with a mean age of 162.4 (118.4, 306.3) months at surgery and a median follow-up of 13.1 (8.8, 23.7) months. There were 10 patients in the control group, 47 in the SAPT group, and 29 in the DAPT group. Baseline characteristics were comparable among three groups ( P ＞0.05). There was no significance regarding echocardiographic and ECG results at discharge and follow-up ( P ＞0.05), except for latest left ventricular ejection fraction (LVEF) between the control and SAPT group ( P =0.038). Mid-term follow-up revealed no significant difference in terms of cardiac function and recurrence of symptoms ( P ＞0.05), but a higher incidence of bleeding in both APT groups than in the control group [ P = 0.034, adjusted odds ratio (OR) = 7.39 and 11.31, adjusted 95% confidence interval (CI) = 0.40-135.40 and 0.60-212.70 for SAPT and DAPT, respectively]. Conclusions: APT doesn't contribute to better prognosis for AAOCA patients undergoing surgical unroofing, but is associated with higher risk of hemorrhage. A larger and multi-center cohort is required to assess risk factors that might demand individualized APT.

Background:A bicuspid aortic valve (BAV) is a common congenital heart disease. The primary treatment for this condition involves the surgical replacement of both the aortic valve and the ascending aorta, typically through the Bentall procedure. Traditionally, the timing of surgery in patients with BAV and aortic dilation is based on the maximum ascending aortic diameter. However, numerous patients who experienced adverse outcomes did not fulfil the established surgical criteria, highlighting the necessity for new predictive factors to guide surgical decisions more effectively. Thus, this study aimed to identify alternative parameters in patients with BAV that could serve as early indicators of surgical intervention and to establish clear threshold values. Methods:A retrospective analysis was conducted among 101 patients diagnosed with BAV at our institution between January 2004 and December 2023 who underwent follow-up computed tomography angiography. Demographic and clinical data were collected, focusing on the influence of ascending aortic volume on adverse outcomes, measured from the aortic annulus to the origin of the brachiocephalic artery. Results:The average ascending aortic volume, length, and diameter were 99,496.51 mm3, 90.94 mm, and 38.79 mm, respectively. Logistic regression analysis identified that only ascending aortic volume (p = 0.0338) and volume-to-height ratio (p = 0.0331) were significantly associated with adverse outcomes. In a multiple logistic regression model, the volume-height index (VHI) was independently associated with adverse outcomes (odds ratio (OR) 1.0008, 95% confidence interval (CI) 1.00023-1.00182; p = 0.048). Receiver operating characteristic (ROC) analysis determined the optimal cutoff value for the VHI as 66,340.5 mm3/m (area under the curve (AUC) = 0.797, 95% CI 0.676-0.896). The Kaplan-Meier curve showed that the event-free survival rate of patients with a VHI >66,340.5 mm3/m was consistently lower than that of the low VHI group; The difference between the two groups was statistically significant (log rank p < 0.0001). Conclusion:The VHI is a strong predictor of adverse outcomes in patients with a BAV and can guide surgical intervention decisions.

Abnormal cardiac valve development may lead to functional impairment in adulthood. BMPR2, a highly conserved receptor of the BMP family, exists in two subtypes (bmpr2a and bmpr2b) in zebrafish. However, the roles of bmpr2a and bmpr2b in valve development remain unclear. In this study, we generated three bmpr2a/b mutant zebrafish strains, namely, bmpr2a- and bmpr2b-knockout zebrafish (bmpr2a -/- and bmpr2b -/- , respectively) using CRISPR/Cas9 and bmpr2a and bmpr2b double-knockout zebrafish (bmpr2a -/- ;bmpr2b -/- ) according to bmpr2a -/- and bmpr2b -/- hybridization. Using cardiac function assessment (M-mode), we characterized the cardiac developmental phenotypes of the three zebrafish mutant strains. Transcriptomic profiling (RNA-seq) was combined with whole-mount in situ hybridization (WISH) and qRT-PCR to validate gene-expression changes. The results indicated that bmpr2a -/- , bmpr2b -/- , and bmpr2a -/- ;bmpr2b -/- mutant zebrafish strains exhibited valve developmental defects at 52 hours post-fertilization (hpf), followed by cardiac contractile dysfunction. RNA-seq revealed upregulation of cardiac markers (myl9a, myl9b, tnnc1a, cmlc1, myl7, and nppa) and valve-related genes (fn1b, has2, and nfatc1), along with the downregulation of klf2a, as validated by WISH and qRT-PCR. Pathway analysis identified the ECM-receptor interaction as a key regulatory axis of bmpr2a/b-mediated valve development. In this study, we demonstrate that bmpr2a and bmpr2b cooperatively regulate cardiac contractile function and valve development in zebrafish, providing insights into BMPR2-mediated cardiovascular morphogenesis in humans.

Myocardial fibrosis, driven by fibroblast activation following myocardial infarction (MI), represents a significant pathological process contributing to heart failure progression. Interleukin-11 (IL-11) is recognized as a key mediator in fibrotic pathologies across multiple organs, including the heart. This study demonstrates consistent and specific upregulation of IL-11 expression in a mouse MI model. A single intrapericardial injection of the IL-11-blocking antibody hIL-11 MAB resulted in a modest attenuation of post-MI fibrosis. Subsequently, encapsulation of hIL-11 MAB within reactive oxygen species (ROS)-sensitive hydrogels significantly prolonged drug retention at the injury site, leading to markedly improved therapeutic efficacy. Hydrogel-delivered hIL-11 MAB effectively preserved cardiac structure and function by reducing scar fibrosis, specifically decreasing scar thickness and marginal zone area. IL-11 blockade mediated reduced collagen deposition and enhanced left ventricular contractility, concomitant with a decrease in fibrotic tissue stiffness. These findings provide compelling evidence supporting IL-11 as a therapeutic target for myocardial fibrosis and highlight a novel delivery strategy for developing improved anti-fibrotic interventions.

Importance Maternal adult congenital heart disease (ACHD) has been associated with increased offspring congenital heart disease (CHD), but evidence from resource-limited regions remains scarce. The association between maternal acquired heart disease (AHD) and offspring CHD is unknown. Objective To quantify the overall and subtype-specific CHD risk in offspring associated with maternal ACHD and AHD, examine the association of maternal ACHD and AHD with outcomes in offspring with CHD, and identify maternal factors that may modify the associations between maternal cardiac diseases and offspring CHD risk. Design, Setting, and Participants This prospective birth cohort study enrolled pregnant women receiving prenatal care between August 1, 2011, and December 31, 2021, at a major cardiac referral center in China. Participants included pregnant women with ACHD, with AHD, or without cardiac disease and were followed up through delivery; their offspring were followed up until 1 year of age. All follow-ups were completed by December 15, 2023. Data were analyzed from April 1, 2024, through April 31, 2025. Exposures Maternal ACHD and AHD, confirmed via the center's electronic medical records. Main Outcomes and Measures The main outcome was offspring CHD, which was diagnosed using echocardiography. Log-binomial regression was used to estimate relative risks (risk ratios [RRs]) and 95% CIs. Adverse outcomes were compared using pairwise tests. Stratification analyses identified potential effect modifiers. Results A total of 14 336 pregnant women with 15 677 offspring (8480 males [54.1%]) were included. The mean (SD) maternal age and gestational age at enrollment were 31.4 (4.5) years and 16.4 (6.4) weeks, respectively. Both maternal ACHD and AHD were associated with higher CHD risk in offspring (RR, 1.71 [95% CI, 1.26-2.31] and 1.38 [95% CI, 1.02-1.87], respectively). Minor CHDs, particularly septal defects, were the subtypes with the greatest magnitude of associations with maternal ACHD (RR, 2.95; 95% CI, 1.97-4.43) and AHD (RR, 2.28; 95% CI, 1.50-3.45). Right ventricular outflow tract obstruction (RR, 6.17; 95% CI, 3.59-10.60) and valvular heart disease (RR, 1.65; 95% CI, 1.11-2.45) were the key contributors to offspring CHD risk. Preterm birth had higher rates among offspring with CHD and mothers with ACHD as well as offspring with CHD and mothers without ACHD compared with offspring without CHD and mothers without cardiac disease (12 of 39 [30.8%] and 121 of 780 [15.5%] vs 1287 of 14 088 [9.1%]; all P < .001). Higher rates of chromosomal (5 of 39 [12.8%] and 38 of 780 [4.9%] vs 75 of 14 088 [0.5%]; all P < .001) and genetic aberrations (3 of 39 [7.7%] and 16 of 780 [2.1%] vs 57/14 088 [0.4%]; all P < .001) were found among offspring with CHD and mothers with AHD as well as offspring with CHD and mothers without AHCD compared with offspring without CHD and mothers without cardiac disease. Associations between maternal cardiac disease and offspring CHD were robust in primiparous women (ACHD: RR, 2.15 [95% CI, 1.48-3.11], P for interaction < .001; AHD: RR, 1.73 [95% CI, 1.17-2.56], P for interaction = .02) and those with periconceptional exposure to hazardous substances (ACHD: RR, 2.22 [95% CI, 1.56-3.16], P for interaction < .001; AHD: RR, 1.57 [95% CI, 1.05-2.36], P for interaction = .02). Conclusions and Relevance In this cohort study, maternal ACHD and AHD were associated with increased risks and adverse outcomes of offspring CHD. Targeted modification of identified maternal factors could help mitigate offspring CHD risk in this high-risk population.

Background:This study aimed to evaluate the efficacy of a novel virtual myectomy procedure in guiding thoracoscopic trans-mitral myectomy. Methods and Results:Clinical data from 37 patients who underwent thoracoscopic trans-mitral septal myectomy guided by virtual myectomy between April 2019 and October 2021 were retrospectively analyzed. Enhanced cardiac CT images were imported into Mimics software to perform virtual myectomy. The short-axis two-chamber plane, perpendicular to the interventricular septum (IVS), was marked for each segment from the basal septum to the apex. IVS thickness was continuously measured at each marked segment, and a figurative digital model determined the resection extent. The cohort consisted of 22 women (59.46 %) with a mean age of 53.14 ± 13.62 years. No deaths or permanent pacemaker implantations occurred. Septal thickness decreased significantly from 20.49 ± 3.85 to 11.28 ± 2.53 mm (P < 0.001), resulting in a marked reduction in obstruction (90.84 ± 28.78 to 11.59 ± 11.06 mmHg, P < 0.001). Twelve patients (32.43 %) underwent mitral valve replacement. The virtual resection's length, width, thickness, and volume showed strong positive correlations with the actual resection (R = 0.76-0.89). The virtual model's septal thickness was moderately correlated with the actual resection volume (R = 0.51, P < 0.01). Conclusions:Virtual myectomy effectively guided septal myectomy, with favorable outcomes in selected patients. This approach, combined with preoperative 3D simulation and printing, enables precise planning for complex cases.

Recent advancements in fully convolutional networks (FCNs) have significantly improved medical image segmentation. Ensemble methods are often used to further enhance performance, with diversity among learners being a critical factor. However, many current approaches focus on diversifying training samples or predictions while overlooking the diversity of internal multi-scale features. This oversight can lead to high correlations among features across different learners, limiting overall effectiveness. Additionally, traditional quantization methods aim to minimize accuracy loss by maintaining a rigid quantization process. This rigidity can eliminate the randomness introduced by quantization, further reducing ensemble diversity and effectiveness. In this paper, we propose a novel approach called Quantization-based Deep Diversified Ensemble (QDD-Ens) for medical image segmentation. Our method enhances the diversity of internal features among ensemble learners through two mechanisms: deep diversified loss, which focuses on feature diversity rather than segmentation accuracy, and deep diversified quantization, which preserves beneficial randomness in quantization process. Furthermore, QDD-Ens facilitates a deeper form of ensemble learning by employing a meta-learner to integrate diversified features at multiple resolution levels from various base learners, which are diversified by two above diversify enhancement mechanisms. Extensive experiments on five public medical image segmentation datasets show that our method significantly improves segmentation accuracy and outperforms existing ensemble techniques. The source code is publicly available to support future research. (https://github.com/JerRuy/QDD-Ens)

OBJECTIVE:We investigated the association between the serum creatinine (SCr) level at admission to an intensive care unit (ICU) for cardiac arrest (CA) and subsequent acute kidney injury (AKI). METHODS:Data were from a previous study that was conducted at a single secondary care institute. Patients were included if they received successful cardiopulmonary resuscitation (CPR) after in-hospital CA (IHCA) or out-of-hospital CA (OHCA) and were admitted to an ICU. Patients were excluded if their SCr level at admission was missing or if they were younger than 18 years old. A total of 435 patients were screened for eligibility. 61 patients were excluded and the records of 374 patients who met the inclusion and exclusion criteria were examined. RESULTS:Two multivariate models that adjusted for confounding factors showed that the SCr level at admission was independently associated with AKI in patients who received successful CPR. Receiver operating characteristic (ROC) analysis showed that an increased SCr level at admission was associated with subsequent AKI (area under the curve [AUC]: 0.823, 95% CI: 0.781, 0.865), and that the optimal SCr cutoff level was 1.15 mg/dL. CONCLUSION:An increased SCr level at ICU admission for CA was independently associated with subsequent AKI without sex-related discrepancies, and the optimal cutoff level was 1.15 mg/dL.

Background: Totally thoracoscopic surgery (TTS) and right lateral thoracotomy (RLT) are both extensively utilized in the surgical repair for atrial septal defect (ASD). However, RLT is generally considered in low-weight pediatric patients as a result of restricted surgical exposure. This study aims to introduce an RLT approach for ASD repair in adults and compare its clinical outcomes with TTS. Methods: We conducted a retrospective analysis of the clinical data of 23 adult patients who underwent ASD repair at Guangdong Provincial People's Hospital between June and October 2024. Patients were divided into two groups based on the surgical approach they adopted: group totally thoracoscopic surgery (TTS, n = 12) and group right lateral thoracotomy (RLT, n = 11). All individuals finished a follow-up three months after surgery. Operative parameters, postoperative courses, echocardiographic measurements and laboratory investigations were compared between the two groups. Results: The total surgical duration was significantly longer in group RLT compared with group TTS [(234.00 +/- 47.93) min vs. (175.17 +/- 52.36) min, p = 0.011]. Group RLT exhibited a significantly higher respiratory index (RI) at <6 h postoperatively (1.00 +/- 0.58 vs. 0.30 +/- 0.37, p = 0.01) and significantly lower levels of soluble suppression of tumorigenicity 2 (sST2) [(136.61 +/- 43.12) ng/mL vs. (199.08 +/- 33.56) ng/mL, p = 0.037] and cardiac troponin (cTnT) [(277.04 +/- 89.85) pg/mL vs. (343.30 +/- 482.40) pg/mL, p = 0.047] at 12-24 h postoperatively. Echocardiographic measurements showed no significant differences between two groups, except for a more pronounced reduction in left atrial (LA) size at discharge in group TTS [(5.00 +/- 3.64) mm vs. (0.09 +/- 4.44) mm, p = 0.008]. Conversely, group RLT demonstrated a less significant decrease in glutamyl transpeptidase (GGT) [(1.00 +/- 6.00) U/L vs. (5.25 +/- 3.86) U/L, p = 0.026] but a more significant decrease in blood urea nitrogen (BUN) [(1.81 +/- 1.10) mg/dL vs. (0.81 +/- 1.07) mg/dL, p = 0.038]. Conclusions: RLT for ASD repair in adults demonstrated comparable clinical outcomes to TTS in terms of postoperative recovery and cardiac function and also produced fewer scars than TTS. Our study proved the feasibility, safety and cosmetic effects of uniport RLT for ASD repair in adults when compared with TTS.

Aim Tetralogy of Fallot (TOF) is the most common cyanotic heart disease. This study aimed to demonstrate the effects of preoperative oxygen saturation on the early prognosis of TOF and identify risk factors associated with early complications. Method A cohort of 1,138 patients who were diagnosed and underwent one-stage surgical repair in this hospital were retrospectively included in this study. The cohort was divided into three groups according to preoperative oxygen saturation: group 1 (<= 75%, n=275), group 2 (75%-85%, n=339), and group 3 (>= 85, n=524). Results There were 16 early deaths (16 of 1,138) and no late deaths in this study. The total mortality rate was 1.41%, which was not significantly different among the three groups. Major adverse events (MAE)- including death, extracorporeal membrane oxygenation assistance, delayed sternal closure, and re- operation during hospitalisation-were reported in 11.81% of patients in group 1, 7.93% in group 2, and 5.61% in group 3 (p=0.008). Multivariable risk analysis showed that atrial septal defect fenestration (p=0.002), aortic cross-clamp time (p=0.027), and McGoon ratio (p=0.046) were associated with MAE. By propensity score matching, the lower McGoon ratio was significantly related to MAE. Conclusions The surgical outcomes were acceptable, with low mortality and MAE rates. The McGoon ratio, not oxygen saturation, presented as a determining factor of MAE.

Background This study aimed to evaluate the impact of the direct total cavopulmonary connection (dTCPC) procedure on the gut microbiome and metabolome. It also sought to elucidate the features of the gut microbiota community and metabolic profiles in Fontan circulation. Methods We randomly recruited 45 participants above 14 years old undergoing Fontan procedure by typical extracardiac conduit (TCPC group, n = 15), direct total cavopulmonary connection (dTCPC group, n = 16) procedure and healthy control (control group, n = 14) in our institution between May 2023 and October 2023. 16S rRNA amplicon sequencing and untargeted metabolites measurement were performed on their fecal sample. Results The four alpha diversity indexes showed no statistical significance between the dTCPC and TCPC groups (p > 0.05). Orthogonal partial least squares discriminant analysis (OPLS-DA) followed by permutation testing indicated an overfitting effect in the model between the dTCPC and TCPC groups. We observed significant differences in the Chao1 index (p = 0.0236), the ACE index (p = 0.0236), and the unweighted beta diversity (p = 0.0099) between the Fontan group and healthy control group. Strains of Fusobacterium were significantly overrepresented in the Fontan group [with linear discriminant analysis (LDA) scores exceeding (log10) >3]. Functional enrichment analysis revealed a significant overrepresentation of several metabolic pathways. These pathways predominantly included those related to amino acid metabolism, such as histidine metabolism, glycine, serine, and threonine metabolism, and cysteine and methionine metabolism. Additionally, the biosynthesis of unsaturated fatty acids was also notably enriched. Conclusion The dTCPC procedure demonstrated similar gut microbiota composition and metabolic profiles to the traditional ECC procedure in Fontan patients. Notably, the increased abundance of Fusobacterium, reduced microbial biodiversity, and altered metabolic profiles of amino acids and unsaturated fatty acids in the alimentary canal may serve as distinctive characteristics of patients who have undergone Fontan circulation. These findings provide valuable insights into the long-term physiological consequences of Fontan procedure and may inform future clinical management strategies.

Electronic cigarettes (ECs) differ from traditional tobacco smoke but may contribute to cardiopulmonary remodeling. Pulmonary hypertension (PH), characterized by pulmonary artery and right ventricle remodeling, poses a significant risk of mortality in infants, children, and adolescents. However, the impact of maternal EC exposure on PH development in offspring remains unclear. To address this, we established a PH rat model with maternal EC exposure. Maternal EC exposure was initiated on gestation day 12 via electronic nicotine delivery systems. Offspring were administered monocrotaline (MCT) at 6 weeks of age (6-wo) to induce PH. Mechanistic experiments were conducted at 10-week-old (10-wo). Protein expression of NADPH oxidases, DNA methyltransferases, and autophagy-related markers was analyzed by Western blot. Morphological changes and the severity of PH were evaluated via hematoxylin and eosin (HE) staining and echocardiography, respectively. Furthermore, the involvement of the oxidative stress/DNA methylation/autophagy axis in response to maternal EC exposure was confirmed through a combination of ELISA, Western blot, HE staining, and echocardiography. Additionally, ATG5 mRNA expression was measured by qRT-PCR. Compared with control conditions, maternal EC exposure significantly worsened MCT-induced PH in male offspring. This was associated with increased oxidative stress, DNA hypomethylation, and anomalous autophagy in the offspring. In vivo treatment with chloroquine inhibited autophagy and ameliorated PH development in offspring exposed to maternal EC. Furthermore, N-acetylcysteine (NAC), an antioxidant, attenuated maternal EC exposure-induced oxidative stress, DNA hypomethylation, and excessive autophagy, thereby improving PH. DNA hypermethylation also reversed PH development, accompanied by reduced oxidative stress and suppressed autophagy. ATG5, a key regulator of autophagy, was identified as a potential therapeutic target, as its repression mitigated PH in maternal EC-exposed offspring. Maternal EC exposure induces oxidative stress and DNA hypomethylation in offspring, leading to anomalous autophagy and exacerbation of PH development. Targeting ATG5-mediated autophagy may represent a novel therapeutic approach for improving PH outcomes in offspring exposed to maternal EC. Pregnant rats were exposed to either EC vapor or standard air from gestation day 12 until 2 days before delivery, with all offspring undergoing PH induction at 6-wo. Offspring exposed to maternal EC presented increased oxidative stress, which in turn affected DNA methylation patterns. The decreased DNA methylation in male offspring led to the activation of autophagy, exacerbating the development of PH. Treatment with ATG5 siRNA inhibited autophagy and alleviated heightened PH in male offspring with maternal EC exposure.

Hypertrophic cardiomyopathy (HCM) is a genetic heart disorder that can lead to sudden cardiac death. Current treatment strategies, such as implantable cardioverter-defibrillators, exhibit limitations in impeding disease progression. Despite the identification of several pathogenic genes, the complex mechanisms underlying HCM remain unclear. This study aims to identify novel pathogenic genes and critical biomarkers for HCM using network-based bioinformatics analysis, with the potential to discover therapeutic targets for pharmaceutical interventions. Gene expression data from 119 HCM patients and 55 healthy donors were analyzed using differential gene expression (DEG) analysis, followed by gene ontology (GO), KEGG and Reactome pathway enrichment studies. A protein-protein interaction (PPI) network was constructed to identify hub genes and their interactions, with a focus on potential drug targets. We identified a key gene module, with TNNT1 emerging as a critical hub gene. TNNT1 was found to significantly influence cardiac development and contribute to HCM pathogenesis. Our findings suggest that TNNT1's role in regulating cardiac contractility could provide a foundation for developing new therapeutic agents targeting this pathway. This study provides novel insights into the molecular mechanisms of HCM and identifies TNNT1 as a potential biomarker for early screening and a promising target for pharmaceutical therapies. The identification of TNNT1 offers opportunities for personalized medicine approaches, which could facilitate the development of drugs aimed at modulating its expression and mitigating disease progression in HCM patients.

Background Non-compaction cardiomyopathy (NCM) is a rare inherited cardiac disorder associated with adverse cardiovascular outcomes, including heart failure, arrhythmias and sudden cardiac death. Currently, the clinical manifestations of NCM lack comprehensive characterisation across different age groups in large-scale studies. This investigation aims to systematically analyse the clinical characteristics of patients with NCM across various age demographics.Methods A retrospective analysis was conducted on 415 patients with NCM treated at the Guangdong Institute of Cardiovascular Disease from January 2013 to January 2023. We comprehensively collected and analysed clinical data, including presenting symptoms, arrhythmia patterns, echocardiographic parameters and cardiac magnetic resonance imaging findings.Results The study cohort (n=415) was stratified into three age groups: infants (0–1 year, n=169), children/adolescents (1–18 years, n=149) and adults (>18 years, n=97). Heart failure was the predominant clinical manifestation across the entire cohort, affecting 112 patients (27%). Notably, heart failure was most prevalent in adult patients (54.6%, n=53), while cardiac murmur was the primary presenting symptom in both infant and child/adolescent groups (19.5%, n=33 and 17.4%, n=26, respectively). Across all age groups, patients with NCM with concurrent mitral regurgitation (MR) demonstrated significantly reduced left ventricular ejection fraction and fractional shortening compared with those without valvular disease (p<0.05). Additionally, left ventricular end-systolic diameter (LVESD) and end-diastolic diameter (LVEDD) were significantly increased in patients with MR (p<0.05). A significant correlation was observed between both LVESD and LVEDD measurements and MR area in patients with NCM (p<0.05).Conclusion Patients with NCM with concomitant MR consistently exhibited left ventricular dilatation and systolic dysfunction across all age groups. Significant age-related variations were observed in clinical presentations, arrhythmia patterns and the prevalence of congenital and valvular heart disease. Understanding these age-specific clinical characteristics is crucial for accurate diagnosis, optimal therapeutic management and future research directions in NCM.