Background: Cardiomyocyte apoptosis plays a critical role in ventricular remodeling and heart failure following acute myocardial infarction (AMI). The Rho kinase signaling pathway is known to be involved in this pathological process. Butylphthalein, a compound with neuroprotective effects, may exert cardioprotective effects by regulating this pathway. Objective: This study aims to investigate the effects of butylphthalein on hemodynamic parameters and cardiomyocyte apoptosis in a rat model of AMI and to explore whether these effects are mediated through the Rho kinase signaling pathway. Methods: Fifty SD rats were randomly divided into five groups: Sham, AMI model, butylphthalein, fasudil (a Rho kinase inhibitor) and combination therapy. AMI was induced by ligation of the left anterior descending coronary artery. Two weeks post-surgery, hemodynamic parameters—including left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and maximal rate of rise and fall of ventricular pressure (±dp/dtmax)—were measured. Cardiomyocyte apoptosis was assessed using TUNEL staining. The expression levels of Bcl-2, Bax, RhoA, ROCK1 and the p-MYPT1/MYPT1 ratio were detected by Western blot. Results: Rats in the AMI model group exhibited significant hemodynamic impairment and increased cardiomyocyte apoptosis. Compared with the model group, butylphthalein treatment significantly improved LVSP and ±dp/dtmax, reduced LVEDP, decreased the number of TUNEL-positive cells, upregulated Bcl-2 expression, downregulated Bax expression and suppressed the expression of RhoA/ROCK1 and the p-MYPT1/MYPT1 ratio (all P<0.05). The combination of butylphthalein and fasudil resulted in enhanced therapeutic effects, suggesting a synergistic inhibition of Rho kinase activity. Conclusion: Butylphthalein attenuates cardiomyocyte apoptosis and improves cardiac function in rats with AMI, likely through inhibition of the Rho kinase signaling pathway. These findings support its potential as a therapeutic agent for AMI.All experiments were performed on male Sprague-Dawley rats (n=50).
Abstract: Background: Sepsis-induced cardiomyopathy (SICM), a significant cardiovascular complication of sepsis, necessitates prompt and effective management. While timely antimicrobial treatment forms the bedrock of early sepsis management, the relationship between the timing of piperacillin/tazobactam administration and the development of SICM remains incompletely characterized. Objectives: The primary objective of this study was to investigate the association between early piperacillin/tazobactam administration and SICM incidence and short-term outcomes. A secondary objective was to identify factors associated with SICM and to develop an exploratory model for its prediction. Methods: This single-center, retrospective observational study included 149 adults with sepsis admitted between January 2023 and January 2026. Patients were categorized into two groups: Early treatment (≤1 h; n=68) or delayed treatment (>1 h; n=81). SICM was assessed using echocardiographic criteria. Clinical outcomes were compared using univariate and multivariable logistic regression. Internal validation was performed using 1,000 bootstrap resamples. Results: SICM occurred in 15/68 (22.06%) early-treatment patients and 33/81 (40.74%) delayed-treatment patients (P=0.014). Twenty-eight-day mortality was 14.71% versus 29.63% (P=0.029) and ICU and total hospital stays were shorter in the early-treatment group (both P<0.001). Delayed treatment (OR=2.354, 95% CI 1.044–5.310), SOFA ≥8 (OR=2.762, 95% CI 1.215–6.279), NT-proBNP ≥1500 pg/mL (OR=3.019, 95% CI 1.320–6.906) and each 0.1-ng/mL elevation in cTnI (OR=1.208, 95% CI 1.037–1.408) were independently linked to SICM. The model AUC was 0.842 (95% CI 0.776–0.908); Hosmer–Lemeshow P=0.409. Conclusion: Early administration of piperacillin/tazobactam was associated with lower SICM incidence and improved short-term outcomes. However, because this study is retrospective, a causal relationship cannot be definitively established. Furthermore, the exploratory prediction model developed warrants external validation to confirm its generalizability and accuracy.
Abstract: Background: Dual antiplatelet therapy (DAPT) is essential for secondary prevention of coronary artery disease (CAD), but gastrointestinal (GI) intolerance often leads elderly patients to self-reduce the dose or discontinue medication. Objectives: To compare the effects of monthly alternating aspirin and clopidogrel versus continuous DAPT on GI symptoms, medication adherence and 6‑month major adverse cardiovascular events (MACE) in elderly community patients with stable CAD. Methods: This retrospective cohort study included 160 elderly patients with stable CAD, who were non-randomly assigned to alternating DAPT (n=80) or continuous DAPT (n=80) according to their documented antiplatelet regimens in clinical practice. GSRS, MMAS-8 and adverse events were evaluated at baseline and 6 months. Results: At 6 months, the observation group’s GSRS total score remained stable (15.14±4.52 to 15.84±4.89, +0.70, P>0.05), while the control group significantly worsened (15.18±4.48 to 19.59±5.67, +4.41, P<0.05); the between-group difference was significant (P<0.05). The MMAS-8 score was higher in the observation group (7.58±0.76 vs. 6.94±1.15, P<0.001), with higher adherence rates (72.50% vs. 51.25%, P=0.006). Total GI adverse events were lower in the observation group (6.25% vs. 18.75%, P=0.017), but GI bleeding did not differ significantly. MACE occurred in 3 cases (3.75%) in each group (P=1.000); however, statistical power was severely insufficient to infer cardiovascular non‑inferiority. Conclusion: Alternating monthly use of aspirin and clopidogrel during the 6-month observation period of this study did not show a significant increase in the risk of MACE. Under these conditions, this regimen attenuated the progressive worsening of gastrointestinal symptoms in elderly patients (scores remained stable rather than significantly worsening) and significantly improved medication adherence. Within this study's specific population (stable elderly CAD patients) and 6-month observation window, this strategy offers a promising alternative worthy of further investigation. Its long-term benefits and cardiovascular safety require confirmation by prospective large-scale trials.
Abstract: Background: Head and neck squamous cell carcinoma (HNSCC) exhibits pronounced molecular heterogeneity and limited durable response to immune checkpoint blockade (ICB). Cellular senescence is an emerging modulator of the tumor microenvironment, yet a validated senescence-based prognostic system for HNSCC remains lacking. Objectives: To develop and validate a senescence-based scoring system (SceScore) for predicting prognosis, characterizing immune microenvironment features and guiding therapeutic decision-making in HNSCC. Methods: Seven senescence- and metabolism-related gene sets were evaluated across 30 TCGA pan-cancer cohorts. Differentially expressed senescence genes in HNSCC were integrated using 101 machine learning algorithm combinations under a leave-one-out cross-validation (LOOCV) framework to construct SceScore. Prognostic performance was validated in three independent GEO cohorts (GSE42743, GSE65858, GSE41613). Associations with immune infiltration, drug sensitivity and tumor mutational burden (TMB) were systematically assessed. Single-cell and spatial transcriptomic datasets were analyzed to validate cellular origins and the spatial distribution of SceScore. Results: Senescence features showed the strongest pan-cancer association with survival and immune phenotypes. An eight-gene SceScore independently predicted overall survival across all HNSCC cohorts. High SceScore correlated with advanced stage, elevated TMB and an immunosuppressive microenvironment enriched for M0 macrophages and regulatory T cells, with upregulated PD-1/PD-L1, CTLA-4 and IDO1 expression. High-SceScore tumors exhibited reduced sensitivity to platinum-based chemotherapy but greater sensitivity to EGFR inhibitors. Single-cell analysis identified SPP1+ tumor-associated macrophages as the primary drivers of high SceScore and spatial transcriptomics confirmed their preferential enrichment at the tumor–stroma invasive front. Conclusion: SceScore is a robust, independently validated prognostic tool that captures senescence-driven immunosuppression in HNSCC, offering a clinically actionable framework for risk stratification and therapeutic decision-making, including guidance for ICB and targeted therapy selection.
Abstract: Background: Ulcerative colitis is chronic inflammatory bowel disease defined by aberrant immune response and recurrent intestinal mucosal inflammation. Anti-inflammatory and antioxidant sesquiterpene alpha-cubebene is thought to ameliorate UC pathogenesis via down-regulation of ICAM1 expression, inhibition of NFκB and MAPK-mediated inflammatory pathways. Objectives: To investigate ICAM1 as a biomarker and therapeutic target for cell adhesion and leukocyte migration, and to explore alpha-cubebene as a potential ICAM1 inhibitor for the first time. Methods: ICAM1 structure was retrieved from RCSB PDB database and docked by CB-dock2. ADMET and drud likeness analysis of alpha-cubebene were evaluated by SwissADME, pkCSM and Deep-PK softwares. Stereochemistry of ICAM1 was assessed through Ramachandran plot and hydrophobicity analysis. Protein-protein interaction was established by STRING analysis and Gene Ontology (GO) followed by MD simulation. For in-vivo validation, Ulcerative colitis was induced in 30 male Albino Wistar rats using 2% DSS administered orally for four weeks, randomized into six groups (n = 5/group) and then treated with different concentrations of α-cubebene and Mesalamine for one month. Therapeutic efficacy was evaluated by assessing disease activity and experimental parameters and histopathological analysis. Results: Molecular docking and MD simulation of ICAM1 and alpha-cubebene revealed Vina score of -6.1kcal/mol showing it a stable protein. Network pharmacology, protein-protein interactions, STRING and GO enrichment analysis revealed therapeutic targeting of ICAM1 interactions can be a potential therapeutic approach for alleviating UC. In in-vivo studies, DSS administration significantly increased the disease activity score compared with normal control (P = 0.001), while α-cubebene treatment markedly and dose-dependently attenuated disease severity. The highest α-cubebene dose (100 µL, 10 mg/kg/day) restored the disease activity score of ICAM1 towards normal and demonstrated greater therapeutic efficacy than Mesalamine. Histopathological results further confirmed it. Conclusion: Alpha-cubebene could serve as an effective candidate for phytotherapy of UC via specifically affecting inflammatory response mediated by ICAM1.
