Background Pediatric LMNA-related dilated cardiomyopathy (DCM) carries extreme risks of malignant arrhythmias and sudden cardiac death. While cardiac resynchronization therapy with defibrillator (CRT-D) is life-saving, small body size and coronary anatomy make lead stability technically challenging. Case Summary An 11-year-old boy with LMNA-related DCM (c.1622G>A, p.R541H) experienced ventricular fibrillation arrest requiring extracorporeal membrane oxygenation support. A CRT-D was implanted using an active-fixation quadripolar left ventricular (LV) lead in the coronary vein. Subsequent refractory ventricular tachycardia was managed with epicardial radiofrequency ablation. Postoperatively, LV ejection fraction improved from 16% to 35.9%, and QRS duration narrowed from 150 to 120 ms. No arrhythmia recurrence was observed at the 3-month follow-up. Discussion Adapting adult active-fixation technology for the pediatric anatomy ensures lead stability. An integrated “dual-track” strategy—combining resynchronization with epicardial ablation—effectively manages the malignant electromechanical phenotype in high-risk LMNA carriers. Take-Home Message Active-fixation LV leads, integrated with epicardial ablation, provide a stable and effective “dual-track” strategy for managing malignant arrhythmias in pediatric LMNA-mutation carriers.

Fusion protein AML1-ETO and chemokine receptor CXCR4 are crucial therapeutic targets for AML, the former plays a key role in differentiation blockade and leukemogenesis, and the latter is closely associated with drug resistance and relapse. This work developed a unified platform (referred as to E5-LNP@siAE) to integrate AML1-ETO-targeted RNA interference (RNAi) and CXCR4 antagonism by employing lipid nanoparticle (LNP) technology and antagonistic peptide E5 modification. The E5-LNP@siNC was slightly negative charged with 121.8 nm in diameter, showing homogenous spherical morphology and stability in PBS and 10

AIMS:Ultra-small Pt NPs on Au nanorods (Au@Pt NRs) is a typical bimetallic nanomaterial. Due to their superior optical and catalytic ability, they are widely investigated in biomedical fields. However, the toxicity has not been fully studied. METHODS:Based on previous intravenous injection studies, this work evaluated the tissue distribution, histopathological characteristics, hematology, and serum biochemical indicators of Au@Pt NRs in C57BL/6 mice through intraperitoneal injection. RESULTS:Within 16 days, it mainly accumulated in the liver and spleen, exhibiting time-dependent redistribution. On Day 1, catalase (CAT) activity and superoxide dismutase (SOD) expression in liver and kidney slightly decreased, then returned to normal. Blood cell counts changed more significantly after intraperitoneal injection, but within normal range. H&E staining revealed inflammatory cell infiltration and changes in liver lobule structure. Levels of liver and kidney function indicators, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and uric acid (UA), decreased within 16 days. Liver injury marker cytokeratin18 (CK18) and kidney injury marker alpha-smooth muscle actin (α-SMA) showed no significant changes. CONCLUSION:In summary, Au@Pt NRs administered via different routes show slightly different distributions and histological changes, and their safety was acceptable, confirming their potential for biomedical applications via the intraperitoneal route.

BACKGROUND AND AIMS:Lipid abnormalities-particularly low-density lipoprotein cholesterol (LDL-c) and lipoprotein(a) [Lp(a)]-have been implicated in aortic stenosis (AS), yet translation into clinically actionable risk assessment remains underdeveloped, especially regarding sex-specific evaluation. This study aims to quantify sex-specific associations between a comprehensive lipid profile and the risks of AS and aortic regurgitation (AR), and to identify the most informative markers and marker combinations for improved risk assessment. METHODS:In 365,771 UK Biobank participants (mean age 56.1±8.07 years; 55.74% female) free of baseline cardiovascular disease. Routine lipid traits underwent hierarchical clustering and were related to incident AS and AR using sex-stratified Cox models. Discordance analyses and time-dependent concordance index were employed to compare risk assessment performance of different markers. RESULTS:Hierarchical clustering revealed three clusters in both sexes-an apolipoprotein B (apoB)-containing cluster and an apolipoprotein A containing cluster-while Lp(a) occupied an independent branch. During a median follow-up of 13.8 years, there were 3118 incident AS and 1239 AR cases. Total cholesterol, apoB, LDL-c, non-high-density lipoprotein cholesterol in apoB-containing cluster and Lp(a) were each independently associated with higher AS risk in both sexes (all P < 0.01), with Lp(a) conferred additional sex-specific effect (P for interaction = 0.004). Discordance analyses showed that apoB outperformed LDL-c in association with AS. Addition of Lp(a) to ApoB or LDL-c improved AS risk prediction over either marker alone-especially in men. No lipid trait was associated with AR. CONCLUSION:ApoB may substitute for LDL-c as the primary particle-burden marker, whereas Lp(a) should be incorporated as an independent sex-specific risk enhancer in AS risk assessment. These results support sex-specific, multi-biomarker assessment to optimize AS risk stratification and future preventive strategies.

Patients with diabetes constitute a substantial proportion of those with acute myocardial infarction (AMI) and exhibit distinct pathophysiological characteristics. However, existing guideline-recommended traditional and generic risk prediction models show limited performance in this specific population. Based on the China Acute Myocardial Infarction (CAMI) registry, 6,091 diabetic patients with AMI were enrolled and randomly divided into training and test sets (8:2). A comprehensive set of 62 multidimensional candidate features was extracted, and three feature selection strategies were applied to develop 12 machine learning models across six algorithm categories. All models underwent hyperparameter tuning via five-fold cross-validation in the training set, with the optimal combination selected according to the area under the receiver operating characteristic curve (AUROC). Two post-hoc ensemble strategies-stacking and probability averaging-were then employed to explore various combinations of top-performing models from different algorithm categories. Across six algorithm categories, the predictive models developed using 11 features selected by Elastic Net had the optimal performance. After evaluating various fusion strategies, the ensembled GLM + TabNet model was ultimately selected as the CAMI-DM model 2.0, achieving an AUROC of 0.875 in the test set. To balance the predictive performance and model simplicity, the CAMI-DM model 1.0 adopted a linear framework and was developed using five features from consensus feature selection Strategy, with an AUROC of 0.821 in the test set. Comparative analyses revealed that the CAMI-DM 2.0 outperformed CAMI-DM 1.0 in terms of discrimination, accuracy, calibration, and clinical net benefit. Furthermore, CAMI-DM 1.0, with its simplified structure, still outperformed the GRACE score in the overall predictive performance and generalizability. This study focused on the specific population of AMI patients with diabetes, and for the first time developed two dedicated models to predict in-hospital mortality risk.

Abstract Gemcitabine (GEM) is a first-line therapeutic option for pancreatic cancer; however, it has low efficacy due to rapidly developed drug resistance and severe dose-limiting myelosuppression. To enhance its therapeutic effect, this study developed a novel peptide−drug conjugate using a CXCR4 antagonistic peptide as the targeting head and gemcitabine as the drug payload, based on the characteristics of pancreatic tumor cells highly expressing CXCR4 that mediates immunosuppression and tumor progression through interaction with its specific ligand CXCL12. The therapeutic effect of the conjugate (P12-GEM) was investigated using pancreatic ductal adenocarcinoma cell lines and an orthotopic pancreatic cancer mouse model. Its myelosuppressive effect was assessed from the perspective of hematological toxicity profiles. The results showed that P12-GEM maintained a cell-killing capability comparable to that of GEM while effectively inhibiting the phosphorylation of Erk and P38, thereby reducing CXCL12-mediated tumor cell migration and adhesion to stromal cells. In a tumor-bearing mouse model, P12-GEM demonstrated superior antitumor efficacy compared to GEM and significantly extended animal survival. Moreover, P12-GEM reduced the proportion of tumor-associated macrophages and increased the infiltration of CD8+ T cells in the tumor microenvironment without reducing platelet and white blood cell counts in the peripheral blood. In summary, P12-GEM possesses dual functions of CXCR4 antagonism and tumor cell killing, contributing to reversal of the immunosuppressive microenvironment and alleviation of myelotoxicity.

Chronic mitral regurgitation (MR) is associated with adverse clinical outcomes, and the role of renin-angiotensin system inhibitors (RASI) in patients with MR remains uncertain. This study evaluated the association between RASI use patterns and 2-year all-cause mortality and disease progression in patients with primary MR (PMR) and secondary MR (SMR). This registry-based study included 3,297 patients with moderate-to-severe chronic MR from the China Valvular Heart Disease registry, including 955 with PMR and 2,342 with SMR. RASI use was assessed at baseline and during follow-up, and patients were categorized as always users, never users, or inconsistent users. The primary endpoint was 2-year all-cause mortality. The secondary endpoint was change in MR severity. Associations between RASI use and outcomes were assessed using multivariable Cox regression, propensity-score matching, and time-varying Cox analyses. Consistent RASI use was associated with lower 2-year all-cause mortality in both PMR and SMR. In multivariable Cox regression, never users had higher mortality risk than always users in both cohorts (PMR: HR 5.40, 95

Vincristine (VCR) is a first-line chemotherapeutic agent for pediatric T-cell acute lymphoblastic leukemia (T-ALL), while its clinical efficacy is limited by dose-dependent peripheral neurotoxicity. As T cells in normal physiological environments experience various mechanical forces and VCR targets a mechanosensitive cellular microtubule, in this study, we developed a magnetically actuated mechanical stimulation (MAMS) strategy utilizing superparamagnetic Fe3O4 nanoparticles (IONPs) and an external static magnetic field (MF), which combined with VCR to significantly enhance the chemosensitivity of T-ALL cells. It was demonstrated that the IONPs primarily bound to the membrane of Jurkat cells and formed ordered assembly structures under MF, which disrupted cellular homeostasis by activating the calcium-NFAT-FasL signaling pathway, hyperpolarizing mitochondria, reprogramming metabolism, and disrupting cytoskeletal assembly. In conclusion, the MAMS strategy sensitized Jurkat cells to VCR by multilevel interference with the homeostasis of cells, providing a promising approach for developing more effective and less cytotoxic T-ALL treatment regimens.

Introduction: Acute Myeloid Leukemia (AML) is characterized by the clonal expansion of undifferentiated myeloid precursors and is associated with notably higher incidence and mortality rates in the elderly population. While the BCL-2 inhibitor Venetoclax has transformed the therapeutic landscape for patients with AML who were ineligible for intensive therapy, primary and acquired resistance remained major obstacles to durable responses. Methods: In this study, an ultra-small Prussian Blue nanozyme (USPBNP)-based "maturation-priming" strategy was investigated to enhance Venetoclax sensitivity. USPBNPs were synthesized and characterized for physicochemical properties and enzyme-mimetic activities. Their differentiation-inducing effects were evaluated in Venetoclax-sensitive MOLM-13 cells, acquired-resistant RMOLM-13 cells, primary-resistant OCI-AML3 cells, murine C1498 AML cells, an AML1-ETO/KITD816V murine transplant model, and primary human AML bone marrow mononuclear cells. Cellular maturation was assessed by morphological analysis and flowcytometric detection of lineage-associated markers. Venetoclax sensitization was evaluated by apoptosis assays, mitochondrial membrane potential analysis, and detection of apoptosis-related proteins. Results: In vitro, USPBNPs effectively reshaped the leukemic phenotype, driving differentiation in MOLM-13, RMOLM-13, and OCI-AML3 AML cells, evidenced by the reduced nucleo-cytoplasmic ratio as well as up-regulated CD11b, CD14, CD235a and CD41a. The "maturation-priming" effects were also confirmed through cross-species models in C1498 murine AML cells and a refractory AML1-ETO/KITD816V murine transplant mice model in vivo and in human clinical specimen. This phenotypic maturation lowered the apoptotic threshold of Venetoclax, resulting in mitochondrial membrane potential collapse, Caspase-3 activation, and the down-regulation of the resistance-associated protein MCL-1. Conclusion: These findings supported USPBNPs as a maturation-priming approach in AML models with distinct genetic backgrounds and Venetoclax resistance patterns. The combination of USPBNPs and Venetoclax coupled differentiation induction with apoptosis and might provide a potential strategy for improving Venetoclax responsiveness in AML.

Acute myeloid leukemia (AML) is characterized by differentiation arrest and apoptosis resistance, frequently with mitochondrial dysfunction and aberrant heat shock protein 60 (HSP60) overexpression as key drivers of malignant progression. Platinum-based nanozymes exhibit multi-enzymatic activity but lack organelle specificity, limiting their therapy efficacy. Based on that there are abundant HSP60 in mitochondrial, we constructed a peptide-conjugated nanozyme PtNPs-P17 by conjugation platinum nanoparticle (PtNPs) and HSP60-targeting peptide P17. It was shown that PtNPs-P17 retained intrinsic oxidase (OXD), peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT)-like activities while acquiring the targeting ability. In the myeloperoxidase (MPO)-positive AML cell line MOLM-13, PtNPs-P17 specifically localized to mitochondria in cells, significantly increasing the production of reactive oxygen species (ROS), oxygen and especially singlet oxygen due to its multi-enzymatic redox regulatory function, which disrupted mitochondrial membrane potential and triggered mitophagy evidenced by the elevated LC3BII/actin ratio and LC3B-mitochondria co-localization. Moreover, PtNPs-P17 induced dual inhibition of mitochondrial respiration and glycolysis, leading to total NAD levels reduced. These metabolic perturbations together resulted in the differentiation of the AML cells, with up-regulated levels of CD235a, CD11b, and CD41a, and enhanced apoptosis. In a refractory AML mouse model, PtNPs-P17 significantly down-regulated the HSP60 expression while reduced spleen GFP+ leukemia cells, suggesting significantly enhanced anti-leukemia effects compared to PtNPs. In conclusion, it was demonstrated that PtNPs-P17 targeted mitochondrial HSP60 to induce mitophagy by orchestrating multi-enzymatic redox regulation and mitochondrial reprogramming, thereby overcoming AML differentiation block and apoptosis resistance. This study provides a novel AML therapy option via precise mitochondrial targeting and metabolic intervention, highlighting the translational potential of HSP60-targeted multi-enzyme nanozymes.

OBJECTIVE:To compare the distribution, aetiology, treatment patterns and 2-year outcomes of moderate to severe valvular heart disease (VHD) between men and women in China. DESIGN:Nationwide, prospective, multicentre cohort study. SETTING:46 tertiary hospitals across China, representing a mix of primary and secondary care settings. PARTICIPANTS:A total of 13 917 adult patients with moderate-to-severe VHD were enrolled between April and June 2018. Of these, 6296 (45.24%) were women. Inclusion criteria included moderate or severe native valve disease, infective endocarditis or prior valve intervention. INTERVENTIONS:Patients received either conservative therapy or valve interventions, including surgical repair/replacement or transcatheter procedures. Intervention decisions were based on clinical assessment. MAIN OUTCOME MEASURES:2-year all-cause mortality, cardiovascular mortality, heart failure hospitalisation and major adverse cardiovascular events. Multivariable Cox and logistic regression analyses were conducted to identify outcome predictors. RESULTS:The overall intervention rate was 31.72%, with no gender difference (men: 31.26% vs women: 32.27%). Among the 5427 patients with severe symptomatic VHD, 49.11% received interventional therapy. The sex-specific pattern was particularly significant in severe symptomatic multiple valvular heart disease, where women had a higher propensity for intervention (p<0.001, OR: 1.19-1.66). In severe symptomatic aortic regurgitation patients, women were less likely to receive valve replacement (p=0.03, OR: 0.39-0.95).The 2-year survival rate was 90.85% with no gender difference (men: 90.41% vs women: 91.38%, p=0.086). Valve intervention improved survival to 97.0%, with no gender disparity (men: 96.92% vs women: 97.01%, p=0.87). Multivariate Cox regression confirmed no significant gender effect (p>0.05). CONCLUSIONS:Significant gender differences exist in VHD aetiology and subtypes in China. Women had more rheumatic VHD, while men had more degenerative and functional VHD. Intervention improved survival, with no gender disparity. Age and VHD subtype influenced intervention rates and prognosis, supporting individualised, sex- and age-stratified management strategies. TRIAL REGISTRATION NUMBER:NCT03484806.

Hematological malignancies are characterized by pronounced metastatic potential associated with the chemokine receptor 4/stromal cell-derived factor-1α (CXCR4/CXCL12) signaling axis, high relapse rates, and a profoundly immunosuppressive tumor microenvironment, all of which severely limit the long-term efficacy of existing therapeutic strategies. Herein, we developed a CXCR4-targeted lipid nanozyme platform (Pt-LNP@E5), in which platinum nanozyme catalytic units and E5 peptide were hierarchically integrated to synergistically achieve metastasis blockade and immune microenvironment remodeling. E5 peptide-mediated CXCR4-specific recognition enabled precise tumor cell accumulation of Pt-LNP@E5 and effectively antagonized CXCR4/CXCL12-driven metastatic signaling, thereby markedly suppressing tumor cell migration and dissemination. Meanwhile, the lipid nanocarrier significantly increased the systemic circulation half-life of the platinum nanozyme and maintained catalytic activity. Within the tumor cell microenvironment, the catalytic system selectively generated reactive oxygen species, which not only induced efficient tumor cell killing but also promoted the transition of the immune microenvironment from an immunosuppressive to an activated state, thereby enhancing antitumor immune responses. These synergistic therapeutic effects were validated in two hematological malignancy models, demonstrating significant tumor growth inhibition, metastasis blockade, and immune microenvironment remodeling. In summary, Pt-LNP@E5 represents a promising strategy for the development of novel platinum-based nanomedicines with broad therapeutic potential.

BACKGROUND:Valvular heart disease (VHD) is a major cause of cardiovascular morbidity and mortality worldwide. The impact of environmental stress on the prognosis of patients with VHD is unknown. This study aims to explore the impact of ambient air pollution exposure on the clinical outcomes of patients with VHD. METHODS:Data were derived from the China-VHD registry, a national multicentre prospective cohort study. Monthly ambient particulate matter with a diameter <2.5 μm (PM2.5) exposure was derived from the ChinaHighAirPollutants (CHAP) dataset at 1×1 km resolution. Using residential address, clinical data from patients diagnosed with VHD between April and June 2018 were linked to ambient PM2.5 exposure concentrations. Patients were followed up until they lost or experienced the primary outcome (defined as all-cause mortality or heart failure hospitalisation) for 2 years. Time-varying Cox proportional hazards regression models were applied to evaluate the association between monthly ambient PM2.5 exposure and outcomes. RESULTS:A total of 12 258 VHD patients were included. Mean age at enrolment was 61.2±13.7 years, and 54.7% were male. Mean baseline ambient PM2.5 exposure was 43.50±12.25 µg/m3. After 2 years of follow-up, 1577 patients (12.9%) experienced the primary outcome. The estimated HR for all-cause mortality or heart failure hospitalisation was 1.24 (95% CI 1.07 to 1.43) for individuals in the highest tertile of monthly ambient PM2.5 exposure compared with those in the lowest tertile. Each IQR (21.80 µg/m³) increase in monthly ambient PM2.5 exposure was associated with a 1.11-fold higher risk of the primary outcome (95% CI 1.04 to 1.18). This association was consistent across subgroups. CONCLUSIONS:Exposure to air pollution was associated with adverse outcomes in patients with VHD. These findings highlight the potential role of a key environmental factor in the progression and prognosis of VHD. TRIAL REGISTRATION NUMBER:NCT03484806.

Acute myeloid leukemia (AML) is characterized by uncontrolled malignant clonal proliferation of leukemic cells resulting from the blockade of myeloid hematopoietic stem/progenitor cell differentiation. The disease-causing fusion protein AML1-ETO (also known as RUNX1-ETO or RUNX1-RUNX1T1) and the chemokine (C-X-C motif) receptor 4 (CXCR4) have been recognized as crucial effectors. Strategies targeting each individual factor have been applied to develop new therapeutic approaches; however, clinical demands remain unmet, and much is still unknown about the crosstalk between the two factors. In this study, we utilized a lipid nanoparticle platform to carry AML1-ETO siRNA and the CXCR4 antagonistic peptide E5 (E5-LNP@siAE) to simultaneously deplete the fusion protein and inhibit CXCR4 activation, aiming to elucidate the crosstalk between the two factors and to develop a novel dual-functional therapeutic approach based on lipid nanoparticles. The resulting nanoparticles were investigated in a refractory AML mouse model (AML1-ETO & C-KITD816V) with a high level of CXCR4 and in the t(8;21)-positive AML cell line Kasumi-1. It was shown that E5-LNP@siAE effectively achieved RNAi of AML1-ETO and antagonism of CXCR4, thereby synergistically inducing effective multi-lineage differentiation, leading to significantly enhanced differentiation-post apoptotic responses of AML cells to homoharringtonine and remarkably prolonged survival in refractory AML mice.

Malignant peripheral nerve sheath tumors (MPNSTs) are fatal and highly aggressive soft tissue tumors that are associated with patients with neurofibromatosis type 1 (NF1). Traditional treatment methods have limited effects, so new treatment strategies need to be developed. Lithium carbonate (Li2CO3) is a type of psychotropic drug and has also been proven to play an important role in tumor treatment. Its nanoscale structure could achieve better therapeutic effects and reduce toxicity. In this study, we utilized MPNST cells (S462) derived from pediatric patients to develop polymeric nanomicelles loaded with Li2CO3 and determined their effects on the proliferation and apoptosis of MPNST cells and the related signaling mechanisms. The results indicated that LM significantly enhanced cellular uptake when exposed to the same concentration of extracellular Li2CO3. Free Li2CO3 inhibited cell proliferation in a concentration-dependent manner. Using a lower concentration could achieve the same or even stronger antitumor effect. The free drug and LM significantly increased the proportion of cells in the G1 and G2/M phases and inhibited the proportion of cells in the S phase (DNA synthesis phase). The effect of LM on the cell cycle was more significant compared with the free drug group. LM also significantly induced apoptosis in MPNST cells. The mechanism study revealed that LM increased the intracellular reactive oxygen species level and thereby inhibited the phosphorylation of ERK. After treatment with the antioxidant NAC, the expression of p-ERK increased, indicating that LM enhanced antitumor activity against MPNST cells by regulating the ROS-ERK signaling pathway. Our results suggested that encapsulating Li2CO3 in nanocarriers might reduce the required dosage and minimize adverse effects, which would provide a promising strategy for optimizing lithium-based therapies in MPNSTs.

While Western studies often show an inverse association between occupational status and cardiovascular mortality, its impact on acute myocardial infarction (AMI) characteristics and prognosis in Eastern middle-income countries remains unclear. Using data from the multi-center prospective China Acute Myocardial Infarction (CAMI) registry from January 2013 to January 2016, 11,318 admission AMI patients aged 18–60 years were stratified by occupation: white-collar (22.1

Background:The benefit of statin pretreatment before primary percutaneous coronary intervention (PCI) on myocardial reperfusion and prognosis in ST-segment elevation myocardial infarction (STEMI) remains unclear. In this study, we evaluated whether atorvastatin pretreatment could improve ST-segment resolution (STR) and long-term clinical outcomes in this setting. Methods:From the China Acute Myocardial Infarction Registry, we conducted propensity score matching to compare STR and 2-year major adverse cardiovascular events (MACE, all-cause death, reinfarction, and stroke) in 2426 STEMI patients undergoing primary PCI (1213 patients per group). Results:Within the pretreatment group, 75, 726, 60, and 691 patients received 20 mg, 40 mg, 60 mg or 80 mg atorvastatin respectively. In the matched cohort of 2426 patients with available STR data (1213 pretreated), STR < 50 % occurred in 258 (21 %) patients in the control group versus 159 (13 %) in the pretreatment group (adjusted hazard ratio [HR]: 0.53; 95 % CI: 0.41-0.70). Multivariable analysis showed that atorvastatin pretreatment was significantly associated with lower 2-year MACE rates (6.9 % vs 8.7 %; adjusted HR: 0.68; 95 % CI: 0.48-0.97), which were consistent across multiple subgroups. Conclusion:A single dose of atorvastatin pretreatment before primary PCI significantly improves myocardial reperfusion parameters and may be associated with long-term clinical benefits, supporting further validation in randomized trials.

Background:Early revascularization enables ST-elevation myocardial infarction (STEMI) patients with cardiogenic shock (CS) to initiate oral beta-blockers once hemodynamic stability is achieved, but the impact of such initiation on prognosis remains unknown. We aimed to describe the clinical use of oral beta-blockers and assess its impact on long-term outcomes in STEMI patients with CS in a real-world setting. Materials and methods:The China Acute Myocardial Infarction registry (CAMI) is a prospective observational study that enrolls patients with acute myocardial infarction from three-level hospitals across 31 administrative regions in mainland China. Among 19,112 STEMI patients in the CAMI registry, a total of 744 STEMI patients who presented with CS at admission were analyzed. Multivariate regression models were used to evaluate the impact of in-hospital oral beta-blockers on 2-year outcomes. Inverse probability treatment weighting (IPTW) score was further used to address biases between the groups with and without oral beta-blockers. The primary endpoint was all-cause death. Results:42.7% (n = 318) of the patients initiated in-hospital oral beta-blockers; these patients were in better states and more likely to receive primary percutaneous coronary intervention and secondary prevention at discharge. The crude 2-year all-cause mortality was 41.7%, with a lower rate in patients who received oral beta-blockers (24.2% vs. 54.8%, P < 0.001). However, after multivariate adjustment, patients who received oral beta-blockers showed a non-significant increase in 2-year mortality compared with non-users (HR = 1.29, 95% CI: 0.95-1.75, P = 0.099), and this increase became statistically significant in the subgroup of county-level hospitals (HR = 1.79, 95% CI: 1.03-3.09, P = 0.038, P-interaction = 0.010). Furthermore, after balancing the baseline covariates using IPTW and further adjusting for discharge medications, initiation of oral beta-blockers during hospitalization increased the risk of 2-year all-cause mortality (HR = 1.59, 95% CI: 1.18-2.13, P = 0.002). Conclusion:No benefit of in-hospital oral beta-blockers initiation on long-term all-cause mortality was found in Chinese STEMI patients with CS, and a trend toward increased mortality existed, especially in small-scale hospitals with insufficient experience in CS treatment.