The rising prevalence of metabolic syndrome in Chinese adults ≥ 45 years reflects rapid socioeconomic and lifestyle changes. C-reactive protein (CRP) and triglyceride-glucose (TyG) index, biomarkers of chronic inflammation and insulin resistance, jointly drive metabolic dysregulation. However, their combined index (CTI/CRP-TyG Index) remains understudied in mortality prediction. This prospective cohort included 9,055 participants from China Health and Retirement Longitudinal Study (CHARLS) database. CTI was categorized into quartiles (Q1-Q4). Kaplan-Meier curves and Cox regression (adjusting for sociodemographics, lifestyle, and clinical factors) were used in survival analysis. Restricted cubic splines (RCS), subgroup analysis and ROC/NRI/IDI evaluated CTI-mortality associations and predictive model performance. During follow-up, 221 deaths occurred, showing declining survival rates with higher CTI quartiles (98.50%→95.63%, p < 0.001). The highest CTI quartile had 3.48-fold mortality risk (HR = 3.48, 95%CI:2.25–5.40, p < 0.001). Subgroup analysis revealed stronger CTI-mortality associations in participants aged ≥ 55, primary education, or cardiovascular history, with overall HR = 2.76 (95%CI:2.20–3.47, p < 0.001). RCS and ROC analysis demonstrated that CTI quartiles linearly correlated with mortality (p < 0.001), and improved the efficiency of predictive models (AUC:0.849 vs 0.829, p = 0.008; NRI = 0.425, IDI = 0.029, p < 0.05). CTI quartiles increase elevated mortality of Chinese adults over 45, driven by CRP/triglyceride/glucose synergy. Targeting these biomarkers may lower mortality of metabolic-aging populations.

The C-reactive protein/triglyceride-glucose index (CTI) integrates inflammatory and insulin-resistance-related metabolic information, but the dose–response shape and robustness of its association with mortality remain uncertain. We analysed 11,221 adults aged ≥ 45 years from the China Health and Retirement Longitudinal Study, with mortality follow-up through 2020. Because proportional-hazards diagnostics indicated time dependence, the Cox estimate represented an average hazard ratio over follow-up. During a median follow-up of 8.4 years, 1,133 deaths occurred. Each empirical interquartile-range increase in CTI was associated with a higher average hazard of all-cause mortality after adjustment (hazard ratio 1.48, 95% confidence interval 1.37–1.60); the highest versus lowest quartile hazard ratio was 2.05 (1.72–2.45; P for trend < 0.001). The approximately linear association remained positive after excluding participants with C-reactive protein > 10 mg/L or deaths within two years and among complete cases. The association appeared stronger during the first five years, although the CTI-by-time interaction was not statistically significant. In exploratory internal analyses, adding CTI modestly increased apparent discrimination (C-index, 0.785 to 0.793; 5-year area under the curve, 0.795 to 0.803). CTI summarizes inflammatory and metabolic information associated with mortality, although its modest apparent incremental prognostic contribution requires external validation.

BackgroundThe early and accurate diagnosis of acute myocardial infarction (AMI) remains a critical challenge in clinical practice. While inflammation is a cornerstone of AMI pathogenesis, translating specific inflammatory pathways into clinically actionable tools requires an integrative analytical approach. The discovery of reliable molecular biomarkers reflecting these pathways is crucial for advancing diagnostic precision. This study aims to bridge this gap by employing a multiomics and machine learning strategy to identify and validate a robust diagnostic signature derived from lipopolysaccharide (LPS)-related immune responses.MethodsWe performed an integrated transcriptomic analysis using five Gene Expression Omnibus (GEO) datasets. Differential expression, functional enrichment, and weighted gene coexpression network analysis (WGCNA) were conducted to pinpoint AMI-associated modules. A core diagnostic gene panel was refined through a consensus machine learning-driven feature selection pipeline incorporating LASSO, support vector machine-recursive feature elimination (SVM-RFE), and random forest algorithms. The immune microenvironment was profiled using CIBERSORT, and patient stratification was achieved via consensus clustering. The clinical utility of the final signature was evaluated by constructing and validating a machine learning-based diagnostic model and a corresponding nomogram.ResultsOur multiomics workflow identified an eight-gene LPS-related signature (S100A9, SERPINA1, S100A12, MCEMP1, MAFB, C5AR1, RNASE2, and VSIG4) with high diagnostic accuracy across independent cohorts. A machine learning-optimized neural network model (NNET) and LASSO regression both achieved an area under the curve (AUC) of 0.859. Immune deconvolution revealed significant shifts in neutrophil and macrophage subsets, correlating strongly with signature genes. Unsupervised learning delineated two distinct AMI subtypes, with Cluster A exhibiting a hyperinflammatory phenotype characterized by the upregulation of this signature.ConclusionThis study establishes a novel, machine learning-curated multiomics signature that captures TLR4 axis-related innate immune activation in AMI. The derived diagnostic model and nomogram offer a direct path for clinical translation, potentially aiding in rapid patient stratification. Furthermore, the identification of immune-endotypic subtypes paves the way for biomarker-guided personalized therapeutic strategies, moving beyond a one-size-fits-all approach to AMI management. Prospective validation in real-world clinical settings is warranted.

Climate change has amplified the variability and intensity of cold weather, contributing to a growing health burden. Cold exposure serves as a significant, yet preventable, environmental trigger for acute chest pain–related life-threatening cardiovascular diseases (CVDs), such as acute coronary syndrome, acute aortic dissection, and pulmonary embolism. This scientific statement synthesizes multidisciplinary evidence from meteorology, environmental epidemiology, basic science, and clinical research to offer an updated evaluation of the impact of cold exposure on these acute chest pain-related life-threatening CVDs. The evidence consistently demonstrates that cold weather significantly increases the incidence of such events, often with delayed effects lasting several days to weeks. Vulnerable groups, including the elderly, individuals with chronic conditions, and those of lower socioeconomic status, are particularly at risk. Data also suggest that interventions, including central heating, integrated health warning systems, and appropriate personal protective measures, can effectively mitigate the associated risks. Based on this evidence, the statement provides expert consensus recommendations across clinical, policy, and behavioral domains. Strengthening prevention and response to cold-related cardiovascular risks is essential for building climate-resilient health systems and mitigating the health impacts of climate change.

Adult murine cardiomyocytes serve as a pivotal model for cardiovascular research. High-quality isolation is essential for studying disease mechanisms and drug screening. Current methods, however, are limited by reliance on specialized equipment and inconsistent efficiency, necessitating a more convenient and reliable protocol. We developed an optimized, Langendorff-free method for isolating cardiomyocytes and cardiac fibroblasts from adult mice. Following anesthesia, an enzymatic digestion solution was infused directly via the aortic root, utilizing the coronary circulation to achieve efficient tissue dissociation. This approach yielded adult mouse cardiomyocytes with high viability, intact morphology, and suitability for long-term culture, comparable to the standard Langendorff technique. Functionally, the isolated cardiomyocytes retained robust responsiveness to pathological stimuli, including hypoxia and adrenergic agonists (isoprenaline, norepinephrine, phenylephrine), demonstrated by characteristic alterations in contractile function, relaxation kinetics, and calcium handling. Furthermore, cardiac fibroblasts co-isolated using this protocol could be successfully activated by TGF-β, showing significant upregulation of myofibroblast markers (e.g., α-smooth muscle actin) and pro-fibrotic signaling pathways. This study establishes a novel, efficient, and accessible method for the simultaneous isolation of functional cardiomyocytes and cardiac fibroblasts from adult mice. The protocol overcomes key limitations of existing techniques and provides a reliable platform for in vitro mechanistic studies and drug discovery in cardiovascular disease.

ABSTRACT Pheochromocytoma typically presents with sustained or paroxysmal hypertension, but initial manifestation as acute non‐ST‐segment elevation myocardial infarction (NSTEMI) is rare. Peri‐procedural hemodynamic fluctuations are often dramatic, making diagnosis and management challenging. We report a 51‐year‐old male admitted with chest tightness for 17 days. Elevated troponin and coronary angiography showing multivessel disease with total occlusion of the mid‐left anterior descending artery (LAD) led to a preliminary diagnosis of NSTEMI. During percutaneous coronary intervention, blood pressure surged to 240/130 mmHg; intravenous nitroprusside caused an instantaneous drop to 95/55 mmHg, with rapid rebound to >200 mmHg upon withdrawal, showing no clear temporal relationship with drug administration. Postoperatively, large rapid blood pressure oscillations persisted, associated with postural changes but without patient discomfort. Workup revealed markedly elevated plasma catecholamines: dopamine 77.58 pg/mL (normal 0–20), normetanephrine 1881.63 pg/mL (0–145), and norepinephrine 5,724.04 pg/mL (217–1,109). CT and PET‐CT identified a left retroperitoneal mass (59×34×44 mm, SUVmax 14.6), suggestive of pheochromocytoma. Surgical resection was performed, and histopathology with immunohistochemistry confirmed the diagnosis. Postoperatively, the patient required no antihypertensive medications and blood pressure remained stable. This case illustrates a rare pheochromocytoma presentation as secondary hypertension manifesting as acute myocardial infarction, characterized by extreme peri‐procedural hemodynamic instability during PCI and an “all‐or‐none” response to conventional antihypertensive therapy, ultimately cured by surgical resection.

Abstract Laparoscopic renal denervation (RDN) represents a specialized approach for hypertension, particularly when conventional methods face limitations. While catheter-based RDN has demonstrated significant efficacy in recent large-scale clinical trials and has been integrated into international guidelines, its effectiveness can be constrained by complex renal anatomy or incomplete ablation. We developed a novel laparoscopic RDN system, comprising an integrated radiofrequency (RF) clamp, RF generator, and cooling pump, to achieve more controlled adventitial ablation. This study aims to evaluate the safety, feasibility, and optimal parameters of this new system in a preclinical swine model. Sixteen pigs were divided into an immediate group (n = 10) for power optimization and a 28-day follow-up group (n = 6). An optimal setting of 10 W for 10 s was identified, balancing effective nerve injury with minimal vascular damage. In the 28-day follow-up group, this setting was associated with a significant reduction in systolic blood pressure (median 125.5 to 109.0 mmHg, p = 0.010) and serum norepinephrine (217.56 to 170.47 ng/L, p = 0.017). Our novel laparoscopic RDN system demonstrates feasibility and safety, providing a potential rescue strategy or supplementary therapy for specific patient populations, such as non-responders to endovascular treatment or those with complex vascular anatomy.

Cardiac fibrosis is a major driver of heart failure and a key therapeutic target. Here, we demonstrated the role of atonal homologue 8 (ATOH8) in the modulation of cardiac fibrosis in heart failure. The expression of ATOH8 was significantly reduced in patients with heart failure and in the left ventricular tissues of model mice. ATOH8 silencing resulted in the worsening of fibrosis, and adenovirus- induced overexpression of ATOH8 attenuated the progression of cardiac fibrosis under in vitro conditions. RNA sequencing analysis demonstrated that ATOH8 potentially influences cardiac fibrosis by modulating the TGF-/Smad signaling pathway. This was verified through ATOH8 silencing experiments, which showed a marked reduction in the expression of Smad7-a known inhibitor of fibrosis. Further investigation into the molecular mechanisms via immunoprecipitation mass spectrometry indicated that ATOH8 can directly bind to the transcription factor RUNX2, which was found to directly interact with the promoter region of Smad7 to suppress its expression. Accordingly, ATOH8 silencing was found to enhance RUNX2-mediated transcriptional repression of Smad7. The findings collectively imply that ATOH8 attenuates cardiac fibrosis through the RUNX2/Smad7 axis, although interactions with other fibrotic proteins need to be explored further. Through in vivo experiments in model mice of heart failure, we were able to demonstrate that the targeted overexpression of ATOH8 in fibroblasts via adeno-associated virus-9 carrying periostin significantly alleviated cardiac fibrosis and dysfunction induced by transverse aortic constriction surgery. Thus, the findings presented here indicate that ATOH8 potentially represents a novel biomarker and therapeutic target for the attenuation of cardiac fibrosis.

This study aimed to develop and validate a machine learning (ML)-based model for predicting 6-month all-cause mortality in patients diagnosed with infective endocarditis (IE), using retrospective data from a single tertiary care center. Additionally, key prognostic features were identified through model interpretability analysis. A cohort of 444 patients with IE was retrospectively assessed and randomly divided into a training set (n = 310) and a test set (n = 134). Following feature selection, a Cox proportional hazards model and four ML-based survival models: Random Survival Forest, Extremely Randomized Survival Trees (EST), eXtreme Gradient Boosting, and Support Vector Machine were established. Model performance was assessed using the concordance index (C-index), time-dependent area under the curve (AUC), and Kaplan–Meier survival analysis. The model demonstrating optimal performance underwent interpretability analysis using Shapley additive explanations and an exploratory online tool was developed to demonstrate its functionality. Nine predictors were selected for model construction: hemoglobin concentration, presence of severe valvular regurgitation, occurrence of septic shock, New York Heart Association (NYHA) classification, serum albumin level, intracerebral hemorrhage, neutrophil percentage, history of coronary heart disease, and receipt of surgical intervention. The EST model demonstrated the highest predictive performance in the test set (C-index: 0.852), with the smallest discrepancy in performance between the training and test datasets, indicating favorable generalizability. Time-dependent AUCs at 30, 90, and 180 days were 0.957, 0.925, and 0.855, respectively. Surgical intervention was modeled as a protective factor, associated with lower mortality risk, while intracerebral hemorrhage, higher NYHA class, severe valvular regurgitation, and septic shock were associated with increased risk. The EST model demonstrated a high predictive accuracy for 6-month mortality in patients with IE, outperforming both conventional and other ML models. Its robust performance and interpretability suggest that, following rigorous external and multicenter validation, it may serve as a hypothesis-generating tool for risk stratification. It is not yet validated for direct clinical application and should currently be considered exploratory.

Background:Transcatheter edge-to-edge repair (TEER) has become an effective alternative for treating degenerative mitral regurgitation (DMR) in patients at high surgical risk. The SQ-Kyrin-M TEER system (SQ-Kyrin-M system) is a novel TEER device developed in China. This study aimed to evaluate the feasibility, safety, and 12-month clinical efficacy of the SQ-Kyrin-M system in patients with high-risk degenerative mitral regurgitation. Methods:In this prospective, multicenter, single-arm study (ClinicalTrials.gov: NCT06467110), 120 patients with symptomatic DMR (grade ≥3+) had the device implanted. The primary endpoint was the clinical success rate at 12 months. Secondary endpoints included technical, device, and procedural success rate; New York Heart Association (NYHA) class improvement; Kansas City Cardiomyopathy Questionnaire (KCCQ) score change; and mitral regurgitation (MR) reduction. Safety endpoints encompassed all-cause mortality, cardiovascular mortality, and major adverse event rate. Results:A total of 120 patients received the TEER procedure across 25 participating sites in China; the mean age was 71.9 years, and the mean Society of Thoracic Surgeons (STS) risk score was 9.3. At 12 months, the Kaplan-Meier estimates were 82.5% for clinical success, 7.6% for all-cause mortality, and 10.8% for major adverse events; MR ≤2+ and MR ≤1+ were achieved in 91.7 and 70.4% of the patients, respectively; 88.9% of patients were in NYHA class I or II; and KCCQ score had improved by 18.9 points. Favorable left ventricular remodeling was observed with sustained reductions in left ventricular end-diastolic and end-systolic volumes. Conclusions:This study demonstrates that the SQ-Kyrin-M system is a safe and effective therapeutic option for DMR patients.

There is a strong correlation between delayed diagnosis and high mortality rate in pulmonary arterial hypertension (PAH). Recent research indicates that circular RNAs (circRNAs) may serve as potential diagnostic biomarkers for PAH. This study aimed to identify important circRNAs associated with PAH to support early diagnosis and explore possible key disease mechanisms. GSE171827 and GSE113439 were obtained from the Gene Expression Omnibus (GEO) database to evaluate differentially expressed circular RNAs (DECs) and genes (DEGs). MicroRNAs (miRNAs) related to PAH were obtained from the Human microRNA Disease Database (HMDD). We validated changes in DEC expression levels using RT-qPCR in hypoxia- and normoxic-induced human pulmonary artery endothelial cells. Then, the potential relationship between DEC expression levels and mean pulmonary artery pressure (mPAP) in PAH patients was investigated. Finally, bioinformatics analyses were performed to construct a competing endogenous RNA (ceRNA) network and excavate the potential functions of DECs. Only hsa_circ_0005623 expression was significantly downregulated in PAH. Low hsa_circ_0005623 expression levels in the plasma of PAH patients were significantly associated with mPAP (p < 0.001). A ceRNA network comprising 1 circRNA (hsa_circ_0005623), 4 miRNAs (has-miR-424-5p, has-miR-503-5p, has-miR-331-3p, and has-miR-17-3p), and 10 mRNAs (CDH5, ANGPT2, DLL4, CLDN5, ANGPTL4, EDN1, HEY1, GATA2, CLEC14A, and ADM) was identified. Functional enrichment analysis of these 10 hub genes showed enrichment in endothelium development and blood vessel endothelial cell migration. These results suggest that hsa_circ_005623 in plasma is a potential biomarker for early PAH and may play an important role in the development of PAH.

PURPOSE:This study aimed to investigate whether exposure to them increases the risk of hypertension (HTN) and evaluated the mediating role of sex hormones and the modifying effect of lifestyle. METHODS:This study recruited 560 pairs of HTN cases and matched controls. After applying inclusion and exclusion criteria, 444 pairs were included. Plasma pyrethroid and serum sex hormone levels were measured. Cox regression models were used to assess the association between pyrethroid exposure and HTN risk. Quantile G-computation (QGC), Bayesian Kernel Machine Regression (BKMR),and adaptive elastic-net to (AENET) were employed to evaluate the effects of pyrethroid mixture exposure on HTN. Mediation analyses were performed to examine the role of sex hormones, and interaction analyses were conducted to assess the modifying effect of lifestyle. RESULTS:In model 3, six pyrethroids were positively associated with HTN in males and females (hazard ratio (HR): 1.216-1.930), and pyrethroid mixture exposure was positively associated with HTN in males(HR: 1.513, 95% confidence interval (CI): 1.299-1.762), with fenvalerate identified as the primary contributor. Meanwhile, the increased HTN risk associated with pyrethroid exposure was exacerbated by lower socioeconomic status, current or former smoking, current or former drinking, and a BMI ≥ 24 kg/m2. Progesterone exhibited a partial mediating effect on the association between pyrethroid exposure and HTN in males and females, with a mediation proportion of 2.9%-27.6% (P < 0.05). CONCLUSION:Pyrethroid exposure was associated with an increased risk of HTN. This association was influenced by specific lifestyle and partially mediated by progesterone.

Although adrenal vein sampling (AVS) is the standard method for subtype diagnosis in patients with primary aldosteronism (PA), the methods used to sample the adrenal vein are not standardized. The aim of this study was to establish the optimal method for sampling the adrenal vein based on the pathological findings after surgery for PA. We enrolled 168 consecutive patients who were diagnosed to have PA and underwent AVS at our institution between 2019 and 2023. The impact of sampling by gentle negative pressure (GNP) on the accuracy of diagnosis of the PA subtype was compared with that of sampling by gravity, whereby blood flows out naturally. AVS was performed successfully on both sides in 139 patients using the two sampling methods. Subtype diagnosis using the two sampling methods was concordant in 128 (92.1%) of the 139 patients and discordant in 11 (7.9%). Among the 11 patients with a discordant subtype diagnosis, unilateral adrenalectomy was performed in three with the right unilateral subtype by gravity and the bilateral subtype by GNP, one with the bilateral subtype by gravity and the right unilateral subtype by GNP, and one with the left unilateral subtype by gravity and the bilateral subtype by GNP. The pathological findings after surgery showed that the false-negative rate was 20% (1/5) with data obtained by the gravity method and 80% (4/5) with data obtained by the GNP method. Bilateral AVS took significantly longer when sampling was performed by the gravity method than when it was performed by GNP (p < 0.01). The gravity method may be preferable to GNP for AVS in patients with PA.

Ferroptosis represents a significant target for mitigating myocardial ischemia-reperfusion (I/R) injury. Existing literature indicates that estrogen (17β-estradiol, E2) can alleviate such injuries through various pathways. However, the specific mechanisms by which E2 may confer protection against myocardial I/R injury through the inhibition of ferroptosis remain to be fully elucidated. This study employed a mouse model of left anterior descending coronary artery ligation to investigate the protective effects of E2 on myocardial I/R injury, with a particular focus on its inhibitory effects on ferroptosis and PHLDA3 in both hypoxia-reoxygenation (H/R) and I/R models. A bioinformatics analysis was conducted to evaluate the impact of estrogen receptor GPER knockout on PHLDA3 expression and ferroptosis. Loss-of-function approaches were employed to elucidate the role of PHLDA3 in ferroptosis during myocardial I/R injury. Our findings demonstrate that E2 can ameliorate myocardial I/R injury, primarily by inhibiting ferroptosis. Notably, PHLDA3 expression levels were significantly elevated during ischemia-reperfusion events; however, E2 was observed to suppress this expression. Bioinformatics analysis indicated that PHLDA3 levels increased following GPER knockdown, and the inhibitory effect of E2 on PHLDA3 expression could be partially reversed by GPER inhibitors (G15) in animal models. Furthermore, the suppression of PHLDA3 reduced ferroptosis and mitigated the severity of myocardial I/R injury. Utilizing mass spectrometry and co-immunoprecipitation methodologies, we have elucidated a potential mechanism in which PHLDA3 directly binds to and interacts with proteins involved in the process of ferroptosis. Our findings demonstrate that E2 effectively suppresses ferroptosis and mitigates myocardial I/R injury by downregulating PHLDA3 expression through the activation of the GPER receptor.

Background and aims: In Chinese patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), it is essential to evaluate the net clinical benefit (NCB) of fondaparinux compared to low molecular weight heparin (LMWH) in NSTE-ACS patients with varying bleeding and ischemic risks. Methods: This multicenter, prospective, open-label, real-world study enrolled 8066 adult patients undergoing non-emergency percutaneous coronary intervention (PCI) at 88 hospitals from July 2019 to July 2021. Patients received fondaparinux (2.5 mg/d) or LMWH (1 mg/kg, twice/day) were followed up within 6 months. The GRACE and CRUSADE scores were used to stratify the included patients. The primary outcome was the incidence of NCB event (all-cause death, reinfarction, nonfatal stroke, or BARC≥ type 2 bleeding) at 30 days. Results: A total of 5430 patients received fondaparinux and 2636 received LMWH. The NCB outcome occurred in 136 patients (2.5%) receiving fondaparinux and in 110 patients (4.2%) receiving LMWH [HR=0.594 (95% CI: 0.462, 0.764), p<0.001]. The 30-day incidence of BARC≥2 bleeding was significantly lower in the fondaparinux group compared with the LMWH group [68 (1.3%) vs. 66 (2.5%), HR=0.498 (95% CI: 0.355, 0.699), p<0.001].Among patients with lower risk, defined by GRACE score≤140 and CRUSADE scores≤40, fondaparinux significantly reduced the incidence of MACE and BARC ≥ 2 bleeding. Fondaparinux decreased the risk of BARC≥2 bleeding across different risk groups, with absolute risk reductions (ARD) of -0.9% for CRUSADE score≤40, -3.0% for CRUSADE score>40, -1.2% for GRACE score≤140, and -1.7% for GRACE score>140, indicating a more pronounced protective effect in individuals at high bleeding risk. Conclusions: In Chinese patients with NSTE-ACS, fondaparinux effectively diminished the incidence of the NCB event of 30 days compared with LMWH. Additionally, fondaparinux exhibited superior safety than LMWH in patients with high bleeding risk, consistently outperformed LMWH in terms of efficacy and safety in the low-risk group as well. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial CTR1900025366 ### Funding Statement This article did not receive any funding support and was conducted as a spontaneous research by the researchers. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The present study has been approved by the Ethics Committee of Chinese PLA General Hospital (Approval Number: S201915001), and all patients signed informed consent forms prior to enrollment. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available from the corresponding author

The existing risk sores for ST-elevation myocardial infarction (STEMI) patients cannot balance timeliness, feasibility, and accuracy. This study aimed to develop and validate a two-stage scoring system capable of dynamic evaluation for 30-day mortality among STEMI patients. We recruited 3939 patients and randomly assigned (7:3) to derivation (N = 2757) and internal validation (N = 1182) datasets, an independent cohort of 1315 STEMI patients was used for external validation. The two-stage scoring system was developed based on factors associated with 30-day mortality identified by multivariate analysis and their availability in course of management. The first medical contact (FMC) stage risk score comprised six predictors (age, gender, systolic blood pressure, heart rate, Killip class, and anterior myocardial infarction), the in-hospital risk score included serum creatinine and left ventricular ejection fraction on this basis. The area under the curve (AUC) were 0.816, 0.854, 0.843, and 0.876 in derivation and internal validation for FMC and in-hospital stage risk score with satisfactory calibration ability. FMC stage risk score displayed equivalent predictive ability with TIMI risk score and GRACE score, in-hospital stage risk score obtained promotion in AUC, integrated discrimination improvement, and net reclassification improvement (all P < 0.001) compared with the classic risk scores. The reproducibility and effectiveness of the risk scores were statistically confirmed in the external validation cohort. The two-stage scoring system had good ability for predicting 30-day mortality and useful to dynamically identify high-risk STEMI patients. Trial registration: [NCT02641262] [29 December 2015].

Aims Despite advancements in primary percutaneous coronary intervention (PCI), cardiac dysfunction remains a challenge in patients with ST-segment elevation myocardial infarction (STEMI). Although thymosin beta 4 has shown cardioprotective effects in preclinical MI models, its impact on chronic cardiac functional recovery post ischemia/reperfusion (I/R), especially in STEMI, warrants further investigation. This study aims to explore the therapeutic potential of recombinant human thymosin beta 4 (rhTB4) in both murine models subjected to I/R and in subjects with STEMI post-PCI.Methods and results In C57BL/6J mice, 7-day rhTB4 treatment prevented cardiac dysfunction and fibrosis 28 days post-I/R surgery and significantly reduced plasma NT-proBNP levels at both 1 day and 28 days post-I/R. Similarly, in a permanent ligation model, rhTB4 improved cardiac function and reduced infarct size at 8 weeks post-MI. RNA-seq analysis of I/R heart tissues revealed that rhTB4 modulated the ErbB signaling pathway. In vitro hypoxia/reoxygenation (H/R) models (HL-1, neonatal mouse cardiomyocytes, H9C2) demonstrated that rhTB4 activated the ErbB2/Raf1 signaling pathway, attenuated cardiomyocyte apoptosis and suppressed pro-apoptotic protein Bad expression. The cardioprotective effects of rhTB4 on cardiac function and adverse cardiac remodeling in I/R mice were abolished by ErbB2 inhibition. In a randomized, placebo-controlled, double-blind trial involving 96 STEMI patients, the infarcted areas were significantly reduced in the rhTB4 group, which received the first dose of rhTB4 within 8 h after PCI (n = 43), as compared to the placebo group at the 90-day follow-up. However, the overall differences in infarcted areas were not significantly between the rhTB4 group and the placebo group (n = 96).Conclusion These findings underscore the crucial role of rhTB4 in mitigating cardiac dysfunction in an ErbB2-dependent manner. The clinical relevance of rhTB4 is demonstrated through a randomized controlled trial, emphasizing its translational potential. Further rigorous randomized studies are needed to assess the significance of early rhTB4 use post-myocardial infarction reperfusion.

This review explores the ionic and cellular mechanisms that underlie antiarrhythmic drug therapy, focusing on how modulation of ionic currents influences cardiac action potentials and refractory periods. Reentrant arrhythmias, the most common type of tachyarrhythmias, are managed by strategies that prolong the effective refractory period. The review also discusses the proarrhythmic risks associated with use-dependence and reverse use-dependence of ion channel blockers. Special attention is given to J-wave syndromes, where Ito blockade plays a pivotal role in preventing phase 2 reentry and polymorphic ventricular tachycardia. Mechanistic understanding is essential for enhancing drug safety and therapeutic efficacy in clinical practice.

Background:Fulminant myocarditis (FM) is a severe, rapidly progressing disease with high mortality, and early identification of high-risk patients is crucial for improving outcomes. This study aims to identify factors associated with early mortality in FM and develop a risk prediction model for the early identification of high-risk patients. Methods:A retrospective analysis was conducted using clinical data from 119 patients with FM who were hospitalized at Central China Fuwai Hospital between 2018 and 2023. The patients were divided into a training set (n=83) and a validation set (n=36). Predictive factors were identified through univariate analysis and least absolute shrinkage and selection operator (LASSO) Cox regression, followed by multivariate Cox regression. A nomogram was constructed, and its accuracy was validated using bootstrap and calibration curves. The discriminative ability and clinical utility of the model were assessed using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). Results:Multivariate analysis identified respiratory symptoms, cardiopulmonary resuscitation (CPR), serum creatinine, direct bilirubin, thyroid-stimulating hormone (TSH), lactate, and left ventricular ejection fraction (LVEF) as independent predictors of early mortality. The area under the curve (AUC) for the training set was 0.907 and 0.880 on days 14 and 28, respectively, while the validation set achieved AUCs of 0.853 and 0.942 for the same time points. The overall concordance index (C-index) was 0.889 for the training set and 0.809 for the validation set. Kaplan-Meier analysis demonstrated lower mortality rates in the low-risk group. DCA demonstrated that the model provides a clinical net benefit across a range of probability thresholds, indicating its potential value in clinical decision-making. Conclusions:A predictive model has been developed and validated to identify patients who are at high-risk with FM, based on seven key predictive factors.