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Glaucocalyxin D (GLD), an ent-kaurane diterpenoid isolated from Isodon species, exhibits extensive pharmacological potential; however, its mechanism of action against acute myeloid leukemia (AML) remains to be elucidated. The present study employed a combined network pharmacology and experimental approach to elucidate the anti-AML mechanisms of GLD. Potential targets were identified using database mining and a protein-protein interaction network was constructed. The Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses highlighted the JAK-STAT signaling pathway as central to action by GLD. Molecular docking predicted stable binding of GLD to core targets, including STAT3. Experimental validation in HEL and K562 AML cells demonstrated that GLD potently and dose-dependently inhibits cell proliferation, with efficacy similar to the standard chemotherapeutic agent doxorubicin. Mechanistically, GLD suppressed the phosphorylation of JAK2 and STAT3. GLD also induced mitochondrial apoptosis by modulating the Bcl-2/Bax ratio and triggered [G.sub.2]/M phase arrest by downregulating cyclin B1 and CDK1. These findings delineated a coherent mechanism whereby GLD exerts anti-leukemic effects by inhibiting the JAK-STAT pathway, supporting its potential as a novel lead compound for AML therapy in the future. Key words: glaucocalyxin D, acute myeloid leukemia, network pharmacology, molecular docking, JAK-STAT signaling pathway

Background Insulin resistance (IR) has been recognized as a critical factor in the progression of cardiovascular disease (CVD), yet its association with cardiovascular-kidney-metabolic (CKM) syndrome remains incompletely understood. This study aimed to evaluate the impact of IR, as measured by the estimated glucose disposal rate (eGDR), on the risk of future CVD events in individuals with CKM stages 0–3. Methods This study included 325,312 participants from the UK Biobank with CKM stages 0–3. IR was quantified using eGDR, a non-insulin-dependent metric, with lower values indicating greater IR. Participants were stratified into quartiles based on eGDR distribution. The primary outcome was incident CVD, including coronary heart disease, stroke, atrial fibrillation, heart failure, and peripheral artery disease. Results In the CKM 0–3 cohort, eGDR demonstrated the highest predictive value for future CVD events among non-insulin-dependent IR metrics. Incorporating eGDR significantly improved the predictive performance of the PREVENT Cardiovascular Disease Risk Equations (AUC: PREVENT Equations + eGDR 0.743 vs. PREVENT Equations 0.719,  p  < 0.001). Over a median follow-up of 13.57 years, 48,433 incident CVD cases were identified. The adjusted rates of CVD incidence (95% confidence interval [CI]) across eGDR quartiles (Q1–Q4) were 3.84 (3.62–4.07), 3.82 (3.66–3.98), 3.53 (3.41–3.65), and 3.37 (3.25–3.50) per 1000 person-years. RCS analysis revealed a significant nonlinear association between eGDR and CVD incidence ( p for overall < 0.001; p for nonlinear = 0.020), with greater risk reduction at higher eGDR levels. A significant trend toward reduced CVD risk was observed across higher eGDR quartiles, with Q3 and Q4 demonstrating statistically significant reductions relative to Q1 (HR 0.920, 95% CI 0.871–0.971; and 0.883, 95% CI 0.827–0.942, respectively; p for trend < 0.001). Kaplan–Meier analysis further confirmed a graded decrease in CVD risk with increasing eGDR levels (log-rank p  < 0.001). Conclusion This study establishes a strong association between IR severity and long-term CVD risk in individuals with CKM syndrome stages 0–3. The eGDR, a reliable surrogate marker of IR, independently predicts future CVD events and provides incremental predictive value beyond the PREVENT equations. These findings underscore the clinical utility of eGDR for risk stratification in CKM populations. Graphical Abstract

Background Insulin resistance and muscle loss are interrelated processes linked to cardiovascular disease (CVD), but they are rarely assessed together. We investigated the association between a novel integrated biomarker—triglyceride–glucose muscle-loss index (TyG–MLI)—and incident CVD in a large prospective cohort. Methods A total of 277,418 UK Biobank participants free of CVD at baseline were included. TyG–MLI was calculated as ln[(triglycerides × fasting glucose)/2] × (cystatin C/creatinine). Incident CVD was identified through hospital admissions and death registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Over a median follow-up of 15.1 years, 40,398 participants developed CVD. Crude CVD incidence increased steadily across TyG–MLI quartiles, and the cumulative incidence curves demonstrated clear separation on Kaplan–Meier analysis (log-rank p  < 0.001). Higher TyG–MLI was independently associated with greater CVD risk when modeled either continuously (per 1-SD: HR 1.17; 95% CI 1.16–1.18) or categorically (Q4 vs. Q1: HR 1.48; 95% CI 1.44–1.53). Restricted cubic spline analyses demonstrated a non-linear association across the TyG–MLI distribution. Sensitivity analyses yielded consistent results. In body mass index-stratified analyses, TyG–MLI showed stronger associations with CVD than TyG index, particularly among normal-weight and underweight individuals. Conclusions TyG–MLI, a composite marker reflecting insulin resistance and muscle loss, was independently associated with incident CVD in this large population-based cohort. These findings suggest that TyG–MLI captures cardiometabolic risk beyond traditional measures and may be particularly informative in individuals without obesity. Graphical abstract

Background: Globally, acute myocardial infarction (AMI) is among the primary causes of mortality. The ideal approach for blood pressure (BP) management for patients experiencing ST-segment elevation myocardial infarction (STEMI) who receive percutaneous coronary intervention (PCI) remains a topic of ongoing debate. Current guidelines on BP management lack specific recommendations for STEMI patients undergoing PCI, resulting in substantial individual variability and uncertainties in clinical treatment strategies. This research seeks to determine the ideal BP levels linked to the lowest risk of in-hospital mortality and long-term adverse endpoints in STEMI patients receiving PCI. Methods: This retrospective study analyzed data from the China Acute Myocardial Infarction (CAMI) Registry, enrolling 10,482 STEMI patients undergoing PCI at 108 Chinese hospitals from January 2013 to September 2014. The primary outcome was in-hospital mortality. Secondary outcomes included 2-year all-cause mortality, severe bleeding, and major adverse cardiac and cerebrovascular events (MACCEs), defined as a combination of all-cause mortality, myocardial infarction (MI), or stroke. The analysis of the relationship between admission systolic blood pressure (SBP)/diastolic blood pressure (DBP) and the primary and secondary outcomes as continuous and categorical variables was conducted using restricted cubic spline (RCS) analysis and Cox regression models. Results: RCS analysis revealed that a J-shaped association existed between admission SBP/DBP and the risk of the primary outcome, with significant nonlinearity (both p < 0.001). Both lower and higher SBP/DBP levels were linked to an elevated risk of in-hospital mortality. The ideal SBP/DBP levels to minimize the in-hospital mortality risk were 157/94 mmHg. Compared to the reference SBP/DBP group (120–129/70–79 mmHg), lower admission SBP (<109 mmHg) or DBP (60–69 mmHg) significantly elevated the risk of the primary outcome. The adjusted hazard ratio (HR) for SBP levels of 100–109 mmHg and <100 mmHg was 1.08 (95% confidence interval (CI): 1.00–1.17; p = 0.0395 and p = 0.043, respectively), and for DBP of 60–69 mmHg, the adjusted HR was 1.07 (95% CI: 1.01–1.14, p = 0.0305). Similarly, the J-shaped curve was also noted between SBP/DBP and secondary outcomes, such as all-cause mortality, severe bleeding and MACCEs. However, no significant non–linear relationship was observed between SBP/DBP and recurrent MI at 2-year follow-up. Conclusions: Among STEMI patients undergoing PCI, a J-curve relationship in in-hospital mortality was observed with a nadir at 157/94 mmHg. Similar J-shaped trends were also observed for secondary outcomes including all-cause mortality, severe bleeding and MACCEs. However, no significant nonlinear correlation was found between admission BP and recurrent MI within 2 years. Clinical Trial Registration: NCT01874691, https://www.clinicaltrials.gov/study/NCT01874691?term=NCT01874691&rank=1.

ObjectiveFunctional complete revascularisation (FCR) has been proven to be associated with superior prognosis following percutaneous coronary intervention. Whether guideline-directed medical therapy (GDMT) still impacts clinical outcomes in patients who have achieved FCR requires further evaluation.MethodsThe study population was drawn from patients who achieved FCR in the FAVOR III China trial, defined as a quantitative flow ratio (QFR)-based residual functional Synergy between percutaneous coronary intervention with taxus and cardiac Surgery score of 0, measured only in vessels with QFR≤0.80. GDMT was defined as the combination of single or dual antiplatelet therapy, a beta-blocker and a statin, with or without an ACE inhibitor or angiotensin receptor blocker, according to contemporary guideline recommendations. Patients were categorised into the GDMT group (compliance with all 4 agents) or non-GDMT group (compliance with 0–3 agents). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) at 3 years, a composite of death, myocardial infarction, stroke and ischaemia-driven revascularisation.ResultsAmong 3221 (85.2%) patients who achieved FCR, a total of 1964 (61.2%), 1919 (59.9%), 1545 (48.4%), 1483 (46.6%) and 1084 (35.3%) patients adhered to GDMT at 1 month, 6 months, 1 year, 2 years and 3 years, respectively. The MACCE occurred in 313 (10.2%) patients through 3 years. The rate of MACCE was similar between GDMT and non-GDMT groups within the first year, but significantly lower in the GDMT group from the second year (adjusted HR: 0.66, 95% CI: 0.51 to 0.85; p<0.01) and sustained until the third year (adjusted HR: 0.65, 95% CI: 0.50 to 0.85; p<0.01), compared with the non-GDMT group.ConclusionsIn patients who achieved FCR, the benefit of good adherence to GDMT remained significant, starting from the second year and continuing up to 3 years.Trial registration number NCT03656848.

Introduction: This study was performed to develop a multiplex fluorescent PCR method for the concurrent detection of six fastidious bacteria associated with respiratory tract infections. These bacteria include Streptococcus pneumoniae（SPN）, Bordetella pertussis (BP), Neisseria meningitidis (NM), Legionella pneumophila (LP), Moraxella catarrhalis (MC), and Haemophilus influenzae (HI). Methodology: A multiplex fluorescent PCR test using SYBR Green as a DNA dye was developed and optimised. Clinical samples from 296 children with respiratory tract infections were then tested using the proposed method to assess its applicability for detecting the six pathogens. Results: The SYBR Green-based multiplex fluorescent PCR method was successfully employed for the simultaneous identification of five pathogens through the analysis of melting curves and determination of the melting temperatures (Tm) values. However, the method exhibited limitations in distinguishing HI, necessitating separate detection using singleplex fluorescent PCR for this pathogen. In the methodological evaluation involving 296 clinical specimens, the multiplex fluorescent PCR successfully detected SPN, MC, NM, BP, and LP with sensitivities of 97.3%, 96.3%, 85.7%, 95.7%, and 80%, and areas under the ROC curve (AUC) of 0.977, 0.978, 0.927, 0.976 and 0.900, respectively. Conclusions: Compared to conventional bacterial culture methods, the multiplex fluorescent PCR method with SYBR Green as the DNA dye is a sensitive and cost-effective approach for the simultaneous and rapid identification of five fastidious bacteria, making it a valuable alternative for clinical diagnostic laboratories.

IntroductionPatients with acute myocardial infarction (AMI) and multivessel disease are at elevated risk of recurrent events. Radial wall strain (RWS), a novel indicator derived from angiography, has emerged as a potentially useful adjunct to optical coherence tomography (OCT) for assessing plaque vulnerability. The NASCENT trial is a prospective, multicentre cohort study designed to assess the natural history of coronary plaque in this high-risk AMI population and investigate the predictive value of angiography-based RWS for lesion progression, compared with OCT-assessed vulnerable plaque.Methods and analysisFollowing successful culprit lesion revascularisation for AMI patients with multivessel disease, we assessed eligible non-culprit lesions (30%–80% diameter stenosis) in non-flow-limiting, non-infarct-related arteries (Murray law-based quantitative flow ratio >0.80) using OCT and offline RWS analysis. The primary endpoint is lesion progression at 1 year, defined as a ≥20% increase in diameter stenosis percentage measured by quantitative coronary angiography. Between April 2024 and April 2025, 131 patients were enrolled. The 1-year angiographic and OCT follow-ups will be completed by May 2026. Clinical follow-ups are planned at 1 month, 6 months, 1 year and annually up to 3 years. As the first prospective trial comparing angiography-based RWS with OCT for predicting lesion progression in the AMI population, this study may provide crucial evidence for RWS as a valuable tool for risk stratification and clinical decision-making.Ethics and disseminationThe protocol has been approved by the Institutional Review Board and Ethics Committee (Fuwai Hospital Approval No. 2023-2039) and will be conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all participants. The study results will undergo peer-reviewed publication.Trial registration numberNCT06040073.

Obstructive sleep apnea (OSA) is much common and associated with worse clinical outcomes in patients with hypertrophic cardiomyopathy (HCM), however, the diagnosis of OSA in HCM is still insufficient. We aim to investigate the clinical predictors of OSA in a large series of patients with HCM. A total of 589 patients with HCM who underwent sleep evaluations were retrospectively enrolled. Data from clinical characteristics and polysomnography studies were recorded. OSA was present in 346 patients (58.7%). Patients who had OSA were older, more likely to be male and had more clinical comorbidities such as hypertension, atrial fibrillation and cardiac remodeling. Multivariate logistic analyses showed that male, age, body mass index, hypertension and left ventricular outflow tract obstruction were significant factors associated with OSA. The area under the ROC curve (AUC) was 0.78 (95% CI 0.74–0.82; P < 0.001). These factors were also able to identify moderate to severe OSA with an AUC of 0.77 (95% CI 0.73–0.81; P < 0.001). These findings suggest that identifying HCM patients with high risk for OSA is feasible using characteristics from clinical practices and clinicians should have no hesitate to conduct sleep test in these patients.

Objective: We aimed to conduct a meta-analysis of treatments for large vessel coronary artery disease between drug-coated balloons and drug-eluting stents. Method: We searched databases including PubMed, Web of Science, Cochrane, CNKI, and Wanfang, and selected randomized controlled trials (RCTs) or cohort studies which compared drug-coated balloons (DCBs) with drug-eluting stents (DESs). The reference vessel diameter (RVD) should be greater than 2.75 mm. The results of 12 studies with a total of 2634 patients were included in this meta-analysis. Results: The results showed that the DCB group was not inferior to the DES group in terms of the incidence of target lesion revascularization (TLR). (RR = 1.25, 95% CI: [0.84, 1.85], p = 0.27, I2 = 0%), and the incidence of bleeding events in the DCB group was lower than that in the DES group (RR = 0.30, 95% CI: [0.15, 0.59], p = 0.0004). The results also showed that the post-intervention minimal lumen diameter (MLD) in the DCB group was smaller than that in the DES group. (RR = −0.37, 95% CI: [−0.59, −0.16], p = 0.0007), but the follow-up MLD in the DCB group was not less than that in the DES group (RR = −0.03, 95% CI: [−0.14,−0.08], p = 0.61). Additionally the DCB group had less late lumen loss (LLL) compared with the DES group. (RR = −0.31, 95% CI: [−0.60, −0.02], p < 0.0001). Conclusion: This meta-analysis confirms that in the early and late stages after percutaneous coronary intervention (PCI), DCB is not inferior in efficacy and safety to DES for de novo large coronary lesions with RVD > 2.75 mm.

Background Identifying venous thromboembolism (VTE) is challenging for patients with cardiovascular diseases due to similar clinical presentation. Most hospital-acquired VTE events are preventable, whereas the implementation of VTE prophylaxis in clinical practice is far from sufficient. There is a lack of hospital-acquired VTE prediction models tailored specifically designed for patients with cardiovascular diseases. We aimed to develop a nomogram predicting hospital-acquired VTE specifically for patients with cardiovascular diseases. Material and methods Consecutive patients with cardiovascular diseases admitted to internal medicine of Fuwai hospital between September 2020 and August 2021 were included. Univariable and multivariable logistic regression were applied to identify risk factors of hospital-acquired VTE. A nomogram was constructed according to multivariable logistic regression, and internally validated by bootstrapping. Results A total of 27,235 patients were included. During a median hospitalization of four days, 154 (0.57%) patients developed hospital-acquired VTE. Multivariable logistic regression identified that female sex, age, infection, pulmonary hypertension, obstructive sleep apnea, acute coronary syndrome, cardiomyopathy, heart failure, immobility, central venous catheter, intra-aortic balloon pump and anticoagulation were independently associated with hospital-acquired VTE. The nomogram was constructed with high accuracy in both the training set and validation (concordance index 0.865 in the training set, and 0.864 in validation), which was further confirmed in calibration. Compared to Padua model, the Fuwai model demonstrated significantly better discrimination ability (area under curve 0.865 vs. 0.786, net reclassification index 0.052, 95% confidence interval 0.012–0.091, P  = 0.009; integrated discrimination index 0.020, 95% confidence interval 0.001–0.039, P  = 0.051). Conclusion The incidence of hospital-acquired VTE in patients with cardiovascular diseases is relatively low. The nomogram exhibits high accuracy in predicting hospital-acquired VTE in patients with cardiovascular diseases.