Congenital heart disease (CHD) is a common birth defect in children, and surgical intervention is the primary treatment. The traditional standard median sternotomy (MS) has drawbacks such as significant trauma and obvious scarring. The right axillary incision (RAI) has gradually become a conventional approach due to its advantages of preserving thoracic cage integrity, small incision size, rapid recovery, and hidden scarring. However, there is currently a lack of relevant guidelines and consensus for its application. This consensus adopts the international Delphi process, systematically searching domestic and foreign literature on CHD from 1982 to 2024. It uses the GRADE system for evidence grading and, through multidisciplinary expert discussions, clarifies the applicable CHD types, surgical techniques, establishment of extracorporeal circulation, organ protection strategies, management of special disease types, and approaches to common complications of RAI. Results show that RAI is strongly recommended for most simple congenital heart diseases (CHDs) (e.g., simple ventricular septal defect, atrial septal defect), weakly recommended for some complex CHDs (e.g., mild tetralogy of Fallot), and not recommended for complex CHDs such as transposition of the great arteries or in children with severe right thoracic deformity. Additionally, it standardizes key operational parameters: weight (5-30 kg as optimal), age (6 months-6 years as preferred), incision location, extracorporeal circulation cannulation, and organ protection measures. This consensus provides an evidence-based basis for standardizing the clinical application of RAI in open-heart surgery for CHD, ensuring surgical safety and efficacy.

The objective of this study was to compare clinical outcomes of total arch replacement (TAR) combined with stented elephant trunk (SET) implantation and hybrid aortic arch repair (HAAR) for type A acute aortic dissection (TA-AAD) in patients older than 60 years.We studied records of patients with TA-AAD older than 60 years in our hospital between January 2016 and December 2018. About 68 patients underwent TAR combined with SET implantation (SET group), and 56 patients underwent HAAR (hybrid group). Outcomes included operative data, postoperative data, and 2 years of follow-up data.Comparing with the SET group, the hybrid group experienced shorter time on surgery duration (p < 0.001), cardiopulmonary bypass (p < 0.001), aortic cross-clamp (p < 0.001), mechanical ventilation (p < 0.001), ICU stay (p < 0.001), and hospital length of stay (p < 0.001). The hybrid group showed a lower rate of pulmonary infection and renal failure (p = 0.023; p = 0.022, respectively). Blood product use was less in the hybrid group (p < 0.001). The hybrid group had a trend toward reducing the 30-day mortality rate, stroke, and transient mental dysfunction. The hybrid group had a trend toward improving the 2-year survival rate and reintervention-free rate, but the results did not reach a significant level.Hybrid procedure could be safely performed in patients older than 60 years with TA-AAD. This procedure may be associated with encouraging surgical results and promising outcomes in the early and mid-term.

The purpose of this study was to compare the impact of modified heart preservation techniques with conventional heart preservation techniques on heart transplant recipients. The goal was to determine if these modified preservation techniques could extend the preservation of the donor heart without increasing the risk of recipient mortality. A retrospective analysis was carried out on 763 cases of orthotopic heart transplantation performed at Wuhan Union Hospital and Nanjing First Hospital, from September 2008 to October 2022. Among these, 656 cases underwent modified heart preservation and were assigned to the study group, while 107 cases underwent conventional heart preservation and were designated as the control group. Detailed information from both groups was collected and compared, including demographic and donor characteristics, survival status, disease type, and recipient/donor characteristics. The study revealed that the modified heart preservation method did not increase the risk of mortality compared to the conventional method. However, it was found that patient factors such as diagnostic classification, recipient age, and donor age significantly influenced mortality risk and were strongly associated with patient survival. The preservation time of the donor heart was significantly longer in the study group compared to the control group, without affecting the survival of the transplant recipients. The findings of our study suggest that modified heart preservation techniques hold promise as a potential method for prolonging heart preservation time. Despite extending the preservation period, these modified techniques did not increase the mortality risk in heart transplant recipients. This could potentially allow for more flexibility in the long-distance transport and preservation of hearts, thereby broadening the scope of viable donors for heart transplantation.

This study investigates the role of DNA methyltransferase 1 (DNMT1) in T cell senescence and heart transplant rejection using mouse models and clinical data. In the mouse heart transplantation model, DNMT1 was found to be highly expressed in graft-infiltrating T cells. Using Dnmt1flox/floxCd4cre/+ mice, researchers demonstrated that T cell-specific knockout of DNMT1 led to long-term graft survival by impairing effector differentiation and promoting senescence in CD4+ T cells rather than in CD8+ T cells. Whole-genome methylation sequencing and RNA sequencing revealed that DNMT1 knockout decreased methylation of the cyclin-dependent kinase inhibitor 1A (CDKN1A) promoter, upregulating CDKN1A expression. Depletion of CDKN1Ahigh cells reversed DNMT1-inhibitor-induced T cell senescence. Clinically, increased T cell senescence was observed in post-transplant patients and is known to increase with age. Additionally, data from the UNOS database showed lower rejection rates in older recipients (age >65). These findings suggest that DNMT1 ablation accelerates CD4+ T cell senescence by altering CDKN1A methylation, thereby reducing T cell function and mitigating rejection. DNMT1 may thus serve as a potential therapeutic target for heart transplant rejection.

Accurate quantification of aortic valve calcification (AVC) on contrast-enhanced computed tomography angiography (CTA) is pivotal for planning surgical and transcatheter aortic valve replacement. The optimal Hounsfield unit (HU) threshold for calcification detection on contrast-enhanced images remains unresolved, and every prior validation study has relied on non-contrast Agatston scoring—itself an imaging estimate—as the reference standard. This study validated two widely used fixed HU thresholds (450 HU and 850 HU) and a self-configuring nnU-Net deep learning model against ex vivo gravimetric calcium weight as an absolute physical ground truth. Four hundred patients were included in a retrospective cohort study with a pre-specified temporal validation split: 300 with CT-confirmed AVC and 100 with normal aortic valves. Fifty chronologically later AVC patients who underwent elective open surgical aortic valve replacement (SAVR) within seven days of clinically indicated pre-operative contrast-enhanced CTA formed the locked surgical validation cohort; their excised native leaflets underwent standardised high-temperature ashing (550 °C, 12 h) and analytical weighing (precision 0.1 mg) to obtain gravimetric calcium mass. The remaining 350 cases served exclusively for nnU-Net development (280 training / 70 internal validation). CT-derived calcium mass-equivalent estimates were quantified on the validation cohort and compared with gravimetric weight using Pearson and Spearman correlation and Bland-Altman analysis. The nnU-Net achieved the strongest observed correlation with gravimetric weight (Pearson r = 0.967; bias + 6.2 mg; RMSE 13.7 mg), significantly outperforming the 450 HU threshold for correlation (r = 0.864; bias + 36.2 mg; RMSE 42.1 mg; Steiger p < 0.001) and showing a non-significant trend toward stronger correlation than 850 HU (r = 0.929; bias + 17.5 mg; RMSE 23.9 mg; Steiger p = 0.085). Compared with 850 HU, nnU-Net provided lower bias and RMSE, although the difference in Pearson r did not reach statistical significance. The 450 HU method exhibited significant proportional bias (p = 0.024), whereas neither 850 HU nor nnU-Net did. The nnU-Net achieved a mean Dice coefficient of 0.873 and intersection-over-union of 0.812. Against physically weighed calcium, nnU-Net deep learning segmentation provided the most favourable overall performance profile on contrast-enhanced CTA, with the lowest bias and RMSE and the strongest observed correlation. The improvement in Pearson correlation over 850 HU represented a non-significant trend, whereas the error and agreement metrics favoured nnU-Net. Among fixed thresholds, 850 HU substantially outperformed 450 HU, offering direct physical-rather than surrogate imaging-evidence to support 850 HU as the preferred fixed threshold in standard contrast-enhanced protocols.

Valvular heart disease (VHD) affects over 209 million people worldwide, with calcific aortic valve disease (CAVD) playing an increasingly dominant role. However, no effective pharmacotherapies are currently available. Existing animal or cellular models are limited by insufficient physiological relevance or lack of scalability. Here, we report for the first time engineered valvular tissues (EVTs) constructed from human induced pluripotent stem cell (hiPSC)-derived valvular interstitial cells (VICs). This model was fabricated using a three-dimension (3D) hydrogel system (fibrinogen/Matrigel/collagen I), enabling anisotropic alignment of VICs with high tissue integrity that closely mimics native valve architecture and supports tissue-level biomechanical testing.Uniquely, we engineered hiPSC-derived cardiomyocytes into myocardial tissues and assembled them with EVTs to create a biomechanically active composite tissue. This design cleverly leverages the spontaneous contraction of cardiomyocytes to provide cyclic mechanical stimulation to the engineered valve, thereby validating that mechanical stress significantly exacerbates calcification. Under calcification-inducing conditions, EVTs robustly mimic key features of CAVD, including matrix remodeling, fibrosis, RUNX2 upregulation, and hydroxyapatite deposition. Biomechanical testing confirmed increased stiffness and reduced extensibility in calcified tissues, consistent with clinical observations.Furthermore, we performed time-series transcriptomic analysis throughout the in vitro culture and calcification induction process. This analysis not only confirmed a high degree of similarity between EVTs and native valves (R > 0.8) but also revealed that EVT calcification follows an osteogenic differentiation trajectory comparable to native valve calcification. Weighted gene co-expression network analysis (WGCNA) identified six potential central regulators of calcification; through subsequent small-molecule inhibition and pharmacological intervention, we definitively validated SAMHD1 as the core regulator through inflammatory signal pathway. Recombinant SAMHD1 protein significantly reduced calcification, improved tissue elasticity, and attenuated dysfunction in both static and mechanically loaded models.Our work establishes an innovative EVTs model with quantifiable tissue mechanical properties; pioneers the integration of myocardium-valve engineered tissues to construct a self-driven, cyclically stressed myocardium-valve composite model; and identifies SAMHD1 as a highly promising therapeutic target for CAVD.

Transcatheter aortic valve replacement (TAVR), also known as transcatheter aortic valve implantation (TAVI), is an interventional technology in which an artificial aortic valve is compressed and assembled outside the body, then delivered through a catheter and implanted at the site of the diseased aortic valve, thereby functionally replacing the native valve. Two versions of the Chinese expert consensus on TAVR were issued in China in 2015 and 2020, respectively. To promptly update the field's understanding of TAVR and to promote its broader, more standardized, and higher-quality application in China, an expert panel has developed this new version of the consensus. This consensus includes substantial updates compared with the previous version, covering topics such as the epidemiology of aortic valve disease, recent advances in TAVR research, indications, procedural standards, post-procedural antithrombotic therapy, prevention and management of complications, management of special cases, and future development trends. This consensus integrates international research evidence and references international guidelines to ensure rigor and evidence-based recommendations, while also incorporating domestic research findings and clinical practice in China, thereby enhancing both its forward-looking perspective and practical applicability.

BackgroundAtherosclerosis (AS) is a chronic inflammatory vascular disease characterized by immune dysregulation, metabolic disturbance, and progressive vascular remodeling. Although anoikis resistance has been extensively investigated in cancer biology, its involvement in immune-cell persistence and plaque progression in AS remains poorly understood.MethodsWe integrated two publicly available bulk transcriptomic datasets (GSE100927 and GSE28829) to identify differentially expressed genes (DEGs) and performed weighted gene co-expression network analysis (WGCNA) to determine disease-associated gene modules. Anoikis-related candidate genes were obtained by intersecting DEGs, WGCNA-derived module genes, and a curated anoikis-related gene set, and were further prioritized using least absolute shrinkage and selection operator (LASSO) regression and random forest algorithms. Immune infiltration and cell type–specific expression patterns were evaluated using CIBERSORT and single-cell RNA sequencing (scRNA-seq) analyses. The expression of the leading candidate was validated using both in vitro and in vivo experiments.ResultsWe identified eight core anoikis-related hub genes—HAVCR2, CD36, PLAU, TNF, PYCARD, SERPINA1, BLNK, and CHI3L1—that were closely associated with AS. These genes were enriched in inflammatory and metabolic pathways and showed strong diagnostic performance across validation analyses, with AUC values greater than 0.83. Immune deconvolution and single-cell transcriptomic analyses revealed that the anoikis-related signature was predominantly localized to macrophage and T-cell compartments within atherosclerotic lesions. Among the identified candidates, HAVCR2 showed the most consistent disease-associated pattern. HAVCR2 expression was markedly increased in oxLDL-stimulated THP-1-derived macrophages and was enriched in macrophage-rich atherosclerotic lesions in high-fat diet–fed ApoE−/− mice, supporting its association with lipid-induced macrophage activation and vascular inflammation.ConclusionThis study defines a macrophage-centered anoikis-related immune signature in atherosclerosis and identifies HAVCR2, together with CD36, PLAU, TNF, PYCARD, SERPINA1, BLNK, and CHI3L1, as potential biomarkers and candidate targets for future diagnostic and therapeutic investigation.

Background The heterogeneous etiology and limited therapeutic options of pediatric restrictive cardiomyopathy (RCM)underscore the urgent need to elucidate its molecular mechanisms and identify potential treatment targets. Methods We performed integrated transcriptomic and proteomic analyses on myocardial tissues from 7 pediatric RCM patients and 3 control donors. Differentially expressed genes (DEG) were detected, with log(2) transformed fold change (log2FC)>1 or log2FC < -1 as well as P < 0.05 after the correction of false discovery rates (FDR) as the threshold. Then, the same proteins as DEGs were identified from the proteomic profiling for the further analysis. The t-test was adopted and the differentially expressed proteins (DEPs) with P < 0.05 after FDR correction and an FC > 1.5 or <0.67 were labeled as significant dysregulation. Furthermore, pathway enrichment was further conducted based on DEGs and DEPs, respectively. RNA and protein validation studies (including real-time polymerase chain reaction and western blot) were conducted to confirm key molecular alterations. Finally, bioinformatic approaches were employed to predict potential therapeutic candidates targeting the identified pathways. Results Multi-omics integration revealed 23 consistently dysregulated genes/proteins central to RCM pathogenesis (FDR adjusted P < 0.05). RNA validation confirmed significant expression changes in most hub genes, while protein-level assays demonstrated marked downregulation of CKB, PGAM2, and TPM2 in RCM myocardium (P < 0.05). Functional enrichment analysis highlighted the involvement of these molecules in critical pathways, including muscle contraction, sarcomere organization, and extracellular matrix remodeling. Drug prediction analysis identified several repurposed candidates, including phenytoin, diazepam, and paricalcitol, which may target these aberrant pathways. Conclusions This study elucidates the fundamental molecular mechanisms underlying muscle contraction and energy metabolism in RCM, while simultaneously translating these insights into clinically actionable strategies. Specifically, it identifies the downregulation of key proteins as potential biomarkers and proposes drug repurposing strategies informed by pathway analysis. These findings offer a novel perspective on the pathophysiology of RCM and establish an evidence-based foundation for the development of targeted diagnostic and therapeutic tools.

Background and Aims Calcific aortic valve disease lacks effective pharmacotherapy and is tightly linked to ageing. Since nicotinamide adenine dinucleotide (NAD(+)) steadily declines with age, this study investigated whether cell-type-specific disruption of NAD(+ )salvage metabolism drives valvular inflammation and calcification. Methods This study combined integrated human aortic-valve bulk RNA-seq with single-cell transcriptomics to map NAD+ pathways. Effects of nicotinamide phosphoribosyltransferase (NAMPT) loss or gain were tested in heterozygous, endothelial-specific, and myeloid-specific Nampt-knockout mice and in cultured valvular endothelial cells and macrophages. Therapeutic potential was evaluated with early vs late nicotinamide mononucleotide supplementation. UK Biobank proteomics and Mendelian randomization examined associations between circulating NAMPT and aortic stenosis. Results In aged human valves, NAMPT-mediated salvage exhibited the steepest suppression within valvular endothelial cells, triggering NAD(+) depletion, SIRT1 inactivation, and hyper-acetylated nuclear factor kappa-B, thereby resulting in an ICAM-1-rich inflammaging profile. Recruited macrophages displayed paradoxical NAMPT up-regulation and secreted extracellular NAMPT that signalled through TLR4 on endothelial cells, amplifying valvular inflammation. Genomic analyses revealed that elevated plasma NAMPT conferred a higher risk of aortic stenosis. On the other side, myeloid Nampt deletion generated a senescent phenotype marked by FOXA2 acetylation and MMP13-driven collagen disruption, accelerating leaflet calcification. Early nicotinamide mononucleotide therapy restored valvular NAD(+,) dampened endothelial inflammation, limited macrophage infiltration, and attenuated calcification, while delayed treatment was less effective. Conclusions Calcific aortic valve disease is initiated by endothelial NAD(+) insufficiency and magnified by metabolically diverse macrophages. This compartmentalized NAD+ circuit couples inflammaging to matrix catastrophe. Early NAD(+) repletion via nicotinamide mononucleotide and interventions targeting NAMPT warrant clinical evaluation as potential therapies for calcific aortic valve disease.

OBJECTIVES:We evaluated the safety and efficacy of transcatheter aortic valve replacement (TAVR) up to 1-year follow-up for patients with severe pure aortic valve regurgitation (AR) or mixed severe aortic valve regurgitation and aortic valve stenosis (AR+AS) using a novel self-expandable bioprosthesis. METHODS:From 2021 to 2022, transapical TAVR using Ken-Valve (Jenscare Biotechnology Ltd, Ningbo, China) was performed in 142 symptomatic patients (mean age 70.3 ± 5.5 years) with pure AR (n = 109) or AR+AS (n = 33) across 15 hospitals in China. All patients were considered high-risk or inoperable after heart team evaluation, with a mean Society of Thoracic Surgeons score of 5.9 ± 3.0%, and 99.3% in NYHA class III/IV. Procedural characteristics, echocardiography data, and clinical outcomes up to 1-year were analysed. RESULTS:Technical success was achieved in 97.2% of cases. Two (1.4%) patients were converted to open surgery due to unsuitable anatomy or valve migration during the procedure. New permanent pacemakers were implanted in 20 (14.1%) patients. Three (2.1%) patients had stroke, and 3 (2.1%) patients had major bleeding. Thirty-day mortality was 2.1%, and all-cause mortality at 1-year was 5.6% (8/142). Mean aortic valve gradient and effective orifice area (EOA) at 1-year postoperatively were 9.4 ± 5.4 mmHg and 1.9 ± 0.6 cm2, respectively. Significant improvement in clinical symptoms, positive left ventricular remodelling, and quality of life were observed up to 1-year. There was no significant difference in mortality, complications, and haemodynamic performance between patients with pure AR and AR+AS at 1-year. CONCLUSIONS:TAVR using the Ken-Valve was safe and effective in patients with pure AR or mixed AR+AS in mid-term. CLINICAL REGISTRATION NUMBER:NCT03788590.

BACKGROUND:Early graft failure within 90 postoperative days is the leading cause of mortality after heart transplantation. Existing risk scores, based on linear regression, often struggle to capture the complex, multifactorial biological interactions necessary for personalised donor-recipient matching. This study utilised explainable machine learning (ML) to identify robust predictors of 90-day graft failure and developed a clinically interpretable, ML-informed nomogram designed specifically for cross-population generalisability. METHODS:Using the UNOS registry (2008-2020; n=25 200), XGBoost/Random Forest models identified 90-day graft failure predictors from 32 donor-recipient variables. Explainable AI (SHapley Additive exPlanations) analysis revealed key predictors and their non-linear interactions, which were translated into a clinically applicable nomogram. External validation was performed on a large, single-centre Chinese cohort (Wuhan Union Hospital ; 2018-2023; n=563), assessing performance via area under the curve (AUC), calibration and decision curve analysis (DCA). FINDINGS:The final model incorporated eight predictors: recipient factors (prior cardiac surgery, age, bilirubin, body mass index (BMI)), donor factors (age, gender, BMI) and cold ischaemia time. The XGBoost-derived nomogram demonstrated consistent discrimination (AUC 0.67, 95% CI 0.64 to 0.70) and calibration. Patients stratified into the high-risk group (top quantile by nomogram score) had a 2.4-fold increased hazard of graft failure (HR 2.42, 95% CI 2.11 to 2.78). DCA confirmed the model's clinical utility across a wide range of risk thresholds (0.0-0.4). External validation in the Chinese cohort affirmed its generalisability (AUC 0.67). CONCLUSION:This study introduces an ML-informed nomogram for 90-day graft failure, validated across USA and Chinese populations. By translating ML insights into a clinically interpretable tool using routinely available pretransplant variables, it bridges a key translational gap in transplant risk prediction. This tool can aid in optimising donor-recipient matching and personalising post-transplant management, with the potential to help address geographic disparities in heart transplant outcomes.

Objective: The impact of underweight or low-BMI donors on heart transplantation (HTx) outcomes remains poorly understood. This study aims to investigate the effect of underweight donors on post-transplant outcomes. Methods: We retrospectively analyzed 574 patients divided into 2 groups based on donor BMI: underweight donors (BMI < 20 kg/m2, n = 101, 17.6%) and normal-weight donors (BMI 20-25 kg/m2, n = 473, 82.4%). Baseline variables and postoperative outcomes were compared using the Student's t-test for continuous variables and the chi-squared test for categorical variables. Propensity score matching (PSM) was performed to balance baseline differences and control for confounders. Survival analysis was performed using the Kaplan-Meier method. Results: The matched cohort included 71 patients per group, with balanced baseline characteristics. Compared to the normal-weight group, recipients of underweight donors had significantly higher rates of respiratory complications (64.8% vs. 47.9%, p = 0.042), neurological complications (15.9% vs. 4.2%, p = 0.021), renal complications (17.4% vs. 5.6%, p = 0.029), and longer postoperative hospital stay (37.2 vs. 28.4 days, p < 0.001). No significant difference was observed in hospital mortality (2.8 vs. 4.2%, p = 0.649). The overall follow-up time was 72.2 ± 1.9 months (range 68.5 to 75.8). The 1-, 3-, and 5-year survival rates for the underweight and normal-weight donor BMI groups were 83.1% vs. 85.9% (p = 0.624), 75.6% vs. 80.2% (p = 0.527), and 72.0% vs. 77.3% (p = 0.468), respectively. Conclusions: Patients receiving hearts from underweight donors demonstrate comparable long-term survival to those from normal-weight donors but have a higher risk of postoperative complications. These findings suggest that underweight donors could be cautiously utilized to expand the donor pool, offering lifesaving opportunities to recipients who might otherwise experience adverse outcomes due to donor scarcity, albeit with an increased risk of postoperative complications.

OBJECTIVES:Left Ventricular Assist Devices have become an important therapy for advanced heart failure. We present 2-year results of the prospective, multicentre clinical trial in China, showing long-term efficacy and safety of a novel miniaturized magnetically levitated, continuous-flow left ventricular assist system. METHODS:Patients were adults with a left ventricular ejection fraction <30% and a cardiac index < 2.0 L/min/m2 without inotropic, or dependence on continuous intravenous inotropes. Clinical data, including survival status, laboratory parameters, adverse events, and functional status, were collected at baseline and at 3, 6, 12, and 24 months and analysed. The primary end-point was the composite of survival at 2 years (on device support, transplant, or recovery), free of disabling stroke or device replacement. RESULTS:A total of 50 patients were enrolled in 12 centres between January 2022 and July 2022. At the 2-year follow-up, 39 patients (78%) remained on device support, 3 patients (6%) received heart transplants, and 1 patient (2%) had the device explanted due to cardiac recovery. The 2-year event-free survival was 86% (95% Confidence Interval [CI]: 73.3% - 94.2%). Major adverse events included right heart failure (n = 2, 4%), stroke (n = 3, 6%), driveline infection (n = 6, 12%), and gastrointestinal bleeding (n = 2, 4%). No haemolysis or device malfunction occurred. CONCLUSIONS:This study demonstrates promising long-term effectiveness and safety of the Corheart 6 left ventricular assist system for circulatory support in patients with advanced heart failure.ClinicalTrials.gov: NCT05353816.

Calcific aortic valve disease (CAVD) is a serious heart valve condition with increasing global prevalence. Currently, transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) represents the only available treatment strategy, as no pharmaceutical therapies for CAVD are approved. The aim of this study was to identify compounds capable of inhibiting osteogenic differentiation of human aortic valve interstitial cells (hVICs), a process critically implicated in CAVD pathogenesis, and to elucidate the underlying molecular mechanism. From an in-house library of 88 compounds screened via dot-blotting, we identified chipericumin D, a natural compound extracted from Hypericum monogynum L., as a candidate exhibiting potent inhibitory activity against hVIC osteogenic differentiation. Network pharmacology analysis, molecular docking, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), and surface plasmon resonance (SPR) collectively demonstrated direct binding of chipericumin D to the epidermal growth factor receptor (EGFR). Furthermore, chipericumin D suppressed activation of the EGFR/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in hVICs cultured under osteogenic medium (OM) conditions. These findings indicate that chipericumin D is a promising therapeutic candidate for CAVD, and provide preliminary evidence that EGFR constitutes a novel molecular target for CAVD intervention.

Retained intravascular or intracardiac foreign bodies are rare but well-recognized in the surgical literature. However, delayed septic pulmonary embolism resulting from a retained transcardiac foreign body has not been previously reported. This case report describes a 57-year-old woman who presented with fever and cough for one month and worsening dyspnea over three days. Two years prior, she had been struck by a metallic object from a lawnmower but did not seek medical attention. Chest radiography demonstrated a linear metallic foreign body in the right lower lung field. Transthoracic echocardiography showed a rod-shaped structure confined to the right atrium, with vegetations surrounding the foreign body and extending into the right ventricle. CT angiography was subsequently performed, which identified a metallic foreign body traversing the diaphragm from the liver into the right heart, as well as emboli in the distal branches of the right pulmonary artery. Surgical exploration via median sternotomy confirmed a metallic rod measuring 10 cm in length and 0.5 cm in diameter penetrating the liver, diaphragm, and right atrium. The rod was successfully removed together with the pulmonary emboli. Pathological analysis demonstrated Aspergillus infection. The patient was discharged in stable condition and completed postoperative oral voriconazole therapy. Although penetrating cardiac foreign bodies may initially be nonfatal, the present case illustrates their potential for late-onset fungal colonization and embolic complications, highlighting the importance of timely surgical removal and vigilant follow-up.

The in vivo performance of tissue-engineered heart valves remains constrained by a persistent early failure triad at the blood-material interface, namely thrombosis, unresolved inflammation, and slow endothelialization. Here, a bioinstructive multilayer valve scaffold is engineered to address these interfacial barriers through spatially integrated structural and biological functions. The scaffold comprises a digitally programmable 3D-printed framework, a silk fibroin wrapping layer, and a hydrogel biointerface incorporating Arg-Gly-Asp/GelMA adhesive cues together with H2S-releasing microgels. This layered design endows the construct with valve-relevant tensile properties while simultaneously programming the immune-endothelial microenvironment. The hydrogel biointerface promotes endothelial migration, proliferation, and angiogenic activity, whereas sustained H2S delivery biases macrophages toward a pro-resolving M2-like phenotype and suppresses inflammatory activation. Transcriptomic analysis further reveals coordinated upregulation of endothelial programs related to endothelial repair, migration, and proliferation, accompanied by attenuation of stress- and inflammation-associated responses. In vivo, the scaffold mitigates thromboinflammatory reactions, shows preliminary anti-calcification performance, and supports endothelialization under blood-contacting conditions. Together, this work establishes a layered bioactive engineering approach that converts a passive 3D-printed structural scaffold into a regenerative, hemocompatible, and immunoregulatory biofunctional valve scaffold. This strategy offers a promising design principle for the further development of regenerative valve scaffolds.

Calcification remains a critical barrier to the long-term durability of glutaraldehyde-fixed decellularized bioprosthetic heart valves, despite their favorable biocompatibility and reduced thrombogenicity. Here, we identify polyaspartic acid (PASP) as a potent inhibitor of valve calcification. PASP modulates key pathological pathways by suppressing osteogenic differentiation (e.g., BMP2 and RUNX2), enhancing anti-calcification regulators (e.g., OPN and MGP), and reducing apoptosis in vitro. In addition, its calcium-chelating capability effectively inhibits dystrophic mineral deposition within the extracellular matrix in vivo. To achieve sustained and localized delivery of PASP, we developed a robust hydrogel coating on the valve surface via a surface-catalyzed free-radical polymerization reaction combined with UV-mediated secondary photocrosslinking. This functional coating enables stable encapsulation and controlled release of PASP while preserving mechanical integrity and long-term structural stability, thereby providing durable anti-calcification performance. Collectively, our findings establish a bioinspired and clinically relevant strategy for preserving the structural and functional integrity of bioprosthetic heart valves and provide a generalizable platform for the design of anti-calcification biomaterials for cardiovascular implants.