OBJECTIVE:To confirm the efficacy of Yiqi Huoxue formula (, YQHX) on heart failure with reduced ejection fraction (HFrEF), and elucidate its potential effect on calcium homeostasis. METHODS:Cardiac specific calcium/calmodulin-dependent protein kinase II delta C isoform (CaMKⅡδC)-overexpression transgenic mice (C-CaMKⅡδC+/- Tg mice) and calcium/calmodulin-dependent protein kinase II delta B isoform (CaMKⅡδB)-overexpression transgenic mice (C-CaMKⅡδB+/- Tg mice) were established by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 technique, and their genotypes and phenotypes were identified thereafter. C57BL/6 mice and transgenic mice were divided into seven groups in random, each containing eight mice. The groups were Control group, CaMKⅡδB model group, CaMKⅡδB treatment group (B Treated), CaMKⅡδB inhibitor group (B Inhibitor), CaMKⅡδC model group (C Model), CaMKⅡδC treatment group (C Treated), CaMKⅡδC inhibitor group (C Inhibitor). B and C Treated groups were given YQHX once a day for 4 weeks by gavage. The cardiac function and structure were evaluated using echocardiogram. The myocardial cellular status and fibrosis were detected by hematoxylin and eosin staining and Masson staining. Calcium transients and calcium leakage from cardiac ventricular myocytes were detected to reflect calcium homeostasis, and the expressions of CaMKⅡδB, CaMKⅡδC, hypertrophy factors, calcium pathway-related genes, and the level of calcium handling proteins were assessed by western blotting and reverse transcription-quantitative polymerase chain reaction. RESULTS:We found CaMKⅡδB and CaMKⅡδC transgenic mice showed HFrEF phenotype. YQHX improved the systolic function of the CaMKⅡδB transgenic mice, reduced the cross-sectional area of cardiomyocytes, inhibited the overexpression of CaMKⅡδB and hypertrophy-related genes (B-type natriuretic peptide, myocyte enhancer factor 2, and atrial natriuretic factor), and increased calcium handling protein sarcoendoplasmic reticulum Ca2+ adenosine triphosphatase 2a (SERCA2a) and calcium capacity. YQHX improved the cardiac systolic function of CaMKⅡδC transgenic mice, reduced the ventricular diameter and cardiomyocyte cross-sectional area, alleviated myocardial fibrosis, increased SERCA2a expression and calcium capacity, and reduced calcium leakage. CONCLUSION:Our results suggest that YQHX improved HFrEF by inhibiting CaMKIIδB overexpression, which may be related to reduced expression of hypertrophy-related factors, and increased SERCA2a expression to increase calcium reserve. In addition, YQHX improved HFrEF by inhibiting CaMKIIδC overexpression, which may be related to reduce calcium leakage, and increase SERCA2a expression to increase calcium reserve.

BACKGROUND AND OBJECTIVES:The early identification of coronary artery disease (CAD) is a challenging task. Direct diagnosis of CAD often requires invasive procedures and complex and expensive imaging techniques. The carotid artery is superficial. It can be easily examined with non-invasive ultrasound. This makes it a potential "window" for overall arterial health and CAD risk. This study uses bibliometric methods. It reviews and visualizes research on the correlation between the coronary and carotid arteries. The goal is to show the field's development, identify research hotspots, and evaluate the use of carotid assessment in CAD risk prediction. MATERIALS AND METHODS:We retrieved and included 419 studies on the coronary-carotid correlation published between January 1, 2005, and September 26, 2025, from the Web of Science Core Collection (WoSCC). Bibliometric analysis and visualization were performed using CiteSpace, VOSviewer, and the R package. RESULTS:This study analyzed 419 publications from 62 countries, 890 institutions, and 2,885 authors, published across 204 journals. The United States leads research in this domain. The University of Washington in the U.S. and Queen's University in Canada were the most productive institutions. The most prolific author was SABA L from the University of Cagliari, Italy, with 18 published papers and 516 co-citations. Research output in this area continues to grow. Atherosclerosis published the most articles on this topic, with 39 publications. The core keywords in this field are atherosclerosis, intima-media thickness, prediction, coronary artery disease, and associations. The latest hotspots are atherosclerosis risk assessment, the carotid artery as a coronary 'window' and surrogate marker, and "machine learning" and "deep learning" for precision diagnosis and treatment. DISCUSSION:The analysis shows the carotid artery is a useful tool for assessing overall CAD risk. The research focus has clearly changed. It moved from proving anatomical connections to using this knowledge for personal patient predictions. Applying artificial intelligence to the indicator detection of coronary arteries and carotid arteries is expected to enhance the diagnostic level of coronary artery diseases. AI-assisted ultrasound imaging technology may have a profound impact on the diagnosis and treatment of cardiovascular diseases. CONCLUSIONS:Future work should strengthen broader regional cooperation and forward-looking validation, developing towards more precise and automated approaches to ensure measurable patient benefits.

ETHNOPHARMACOLOGICAL RELEVANCE:Shensong Yangxin (SSYX) capsule, a well-known Chinese patent medicine, is widely applied in the treatment of atrial fibrillation (AF). AIM OF THE STUDY:To determine the efficacy and safety of SSYX as adjunctive therapy on recurrence after ablation in AF patients. MATERIALS AND METHODS:A systematic search was conducted across eight databases to identify randomized controlled trials (RCTs) involving SSYX therapy after first AF ablation until 1st July 2025. The primary outcome was AF recurrence, and safety endpoint was also examined. The quality of evidence was assessed using the GRADE framework. The protocol was prospectively registered on PROSPERO (CRD420251012453). RESULTS:Nine studies comprising 2199 patients were included. Anti-arrhythmic drugs (AADs) plus SSYX reduced early recurrence by 45% (RR 0.55, 95% CI: 0.42 to 0.71, P < 0.001; I2 = 0%) in overall AF populations, and late recurrence by 38% (RR 0.62, 95% CI: 0.47 to 0.81, P < 0.001; I2 = 0%) in persistent AF. Moreover, no statistically significant difference was observed in the incidence of adverse events between SSYX and control groups. A moderate and low level of evidence were identified for late and early recurrence, separately. CONCLUSION:Combination therapy with AAD and SSYX after ablation could safely and effectively reduce early recurrence across AF populations and late recurrence only for persistent AF. This evidence highlights the potential of SSYX as a potential adjuvant treatment option after AF ablation. However, extrapolation to Western populations requires caution.

Chronic myocardial ischemia (CMI) is a key pathological condition in coronary artery disease (CAD), yet small animal models for CMI are limited. This study developed and characterized a CMI mouse model using ApoE-/- mice fed a high-fat diet for 3 months. Cardiac function was assessed through electrocardiography (ECG), myocardial action potential, and perfusion echocardiography. The model group exhibited elevated cholesterol, aortic lipid plaques, and T-wave flattening, correlated with atherosclerosis severity. Impaired myocardial perfusion, reduced ATP content, and accelerated inner cardiomyocyte repolarization were also observed. PET/CT scans revealed filling defects, while myocardial contractile function showed reactive suppression under CMI conditions. This model replicates CMI’s pathological features, providing a valuable tool for studying CAD progression and treatment.

ETHNOPHARMACOLOGICAL RELEVANCE:The Qiliqiangxin (QLQX) capsule is a prominent traditional Chinese medicine formulation developed based on the collateral disease theory, specifically for the treatment of heart failure (HF). Its composition includes 11 medicinal botanicals, such as Huang Qi, Ren Shen, and Dan Shen, and is designed to tonify qi, activate blood circulation, and promote diuresis. Supported by over 20 years of extensive clinical application, modern pharmacological research, and stringent quality control, QLQX has been incorporated into the national heart failure guidelines in China. AIM OF THE STUDY:This study evaluates the efficacy and safety of QLQX as adjunctive therapy for heart failure with reduced ejection fraction (HFrEF). METHODS:We systematically searched seven databases until February 24, 2025, for randomized controlled trials (RCTs) evaluating QLQX in patients with HFrEF. Two independent researchers screened trials, extracted data, and assessed the risk of bias using the Cochrane RoB 2.0 tool. Meta-analyses were conducted for efficacy and safety outcomes, with evidence quality evaluated through the GRADE framework. RESULTS:Twenty-four RCTs (n = 5580) were included. Compared with conventional treatments (CTs) alone, QLQX adjunctive therapy significantly reduced the risk of cardiovascular death (RR = 0.82, 95 %CI [0.69, 0.96], P = 0.02), hospitalization for HF (RR = 0.78, 95 %CI [0.67, 0.91], P = 0.001), and composite cardiovascular events by 18 % (RR = 0.82, 95 %CI [0.73, 0.92], P = 0.0005), with evidence quality rated as moderate. QLQX significantly improved cardiac function parameters compared to controls: increased left ventricular ejection fraction (MD = 7.14, 95 % CI [6.75, 7.54], P < 0.05), reduced left ventricular end-diastolic diameter (MD = -5.25, 95 % CI [-5.75, -4.75], P < 0.05), improved NYHA class (RR = 1.19, 95 %CI [1.14, 1.25]), decreased NT-proBNP (SMD = -2.01, 95 %CI [-2.26, -1.95], P < 0.05), and increased 6-min walking distance (MD = 44.80, 95 %CI [42.37, 47.22], P < 0.05). CONCLUSION:QLQX adjunct therapy effectively reduces cardiovascular death and HF hospitalization while improving cardiac function in HFrEF, with favorable safety. Large-scale multicenter RCTs with extended follow-up are required to confirm long-term benefits and address existing study limitations.

Abdominal aortic calcification (AAC) is a well-established predictor of cardiovascular morbidity and mortality. Although insulin resistance (IR) is implicated in vascular calcification, evidence on the association between IR surrogates and severe AAC remains limited. A cross-sectional analysis of 1230 participants was conducted using data from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES). Multiple regression and generalized additive models (GAM) were employed to evaluate the associations between IR surrogates (TyG index, homeostasis model assessment of insulin resistance (HOMA-IR), and METS-IR) and severe AAC. The predictive performance of the triglyceride glucose (TyG) index and its derived indicators in predicting severe AAC was assessed using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Multiple regression analysis revealed a positive association between TyG index (calculated from fasting triglyceride and glucose levels) and severe AAC risk (OR = 1.642, 95% CI: 1.050, 2.570, P = .030) after adjusting for confounders. This association persisted even after adjusting for metabolic syndrome and log (HOMA-IR). Trend tests and GAM confirmed a linear dose-response relationship between the TyG index and severe AAC. Subgroup analysis revealed that this relationship was stronger in women. ROC and AUC analyses demonstrated that the TyG index could reliably predict severe AAC (AUC = 0.858). No significant association was found between HOMA-IR, METS-IR, and severe AAC. An elevated TyG index was associated with an increased risk of severe AAC, independent of metabolic syndrome. These findings underscore the critical importance of managing the TyG index to reduce the risk of severe AAC and have important implications for clinical practice and epidemiological studies.

Heart failure is often described as a condition of "energy depletion." However, in heart failure with preserved ejection fraction (HFpEF), particularly when associated with metabolic conditions such as obesity and diabetes, the heart may face a state of fuel overload. This fuel overload disrupts mitochondrial function, leading to the heart's inability to effectively adjust substrate utilization in response to variations in nutritional status, energy substrate availability, and hemodynamic load, resulting in loss of metabolic flexibility and subsequent adverse effects on cardiac function and structure. Thus, an in-depth analysis of the role of metabolic flexibility in the pathophysiology of HFpEF could pave the way to addressing this clinical challenge. This review addresses: (1) the alterations in metabolic flexibility observed in cardiometabolic disease and HFpEF; (2) the implications of metabolic flexibility in the staging, classification, diagnosis, and prognosis of HFpEF; and (3) current HFpEF therapeutic strategies that improve myocardial metabolic flexibility.

Background:Hydroxysafflor yellow A (HSYA) possesses a variety of pharmacological activities which has been demonstrated to be effective against ischemic heart disease (IHD). This study aimed to comprehensively examine the efficacy and summarize the potential mechanisms of HSYA against IHD in animal models. Methods:We conducted electronic searches for preclinical studies on PubMed, Embase, Web of Science, Cochrane Library, CNKI, SinoMed, Wanfang, and Chinese VIP databases from inception to 31 January 2024. The CAMARADES checklist was chosen to assess the quality of evidence. STATA 14.0 software was utilized to analyze the data. The underlying mechanisms were categorized and summarized. Results:Twenty-eight studies involving 686 rodents were included and the mean score of methodology quality was 5.04 (range from 4 to 7). Meta-analysis observed that HSYA could decrease myocardial infarction size (SMD: -2.82, 95%CI: -3.56 to -2.08, p < 0.001) and reduce the levels of biomarkers of myocardial injury including cTnI (SMD: -3.82, 95%CI: -5.20 to -2.44, p < 0.001) and CK-MB (SMD: -2.74, 95%CI: -3.58 to -1.91, p < 0.001). HSYA displayed an improvement in cardiac function indicators including LVEF, LVSP, +dp/dt max and -dp/dt max. Furthermore, HSYA was able to reduce the levels of MDA, TNF-α and IL-6, while increasing SOD and NO levels. Mechanistically, the protective effect of HSYA in alleviating myocardial injury after ischemia may be associated with NLRP3 inflammasome, Bcl-2, Bax, caspase-3, eNOS proteins, and TLR/NF-κB, Nrf2/HO-1, JAK/STAT, PI3K/Akt, AMPK/mTOR, VEGFA pathways. Conclusion:This study demonstrates that HSYA exerts cardioprotective effects in decreasing infarct size, reducing myocardial enzymes and improving cardiac function, which may be mediated by anti-inflammatory, antioxidant, anti-apoptotic, regulation of autophagy, improvement of microcirculation and promotion of angiogenesis. However, the absence of safety assessment, lack of animal models of co-morbidities, and inconsistency between timing of administration and clinical practice are limitations of preclinical studies. Systematic Review Registration:clinicaltrials.gov, Identifier, CRD42023460790.

ETHNOPHARMACOLOGICAL RELEVANCE:Heart failure (HF) remains a critical challenge in cardiovascular therapeutics. Qishentaohong granules (QSTH), formulated under the traditional Chinese medicine Qi-Blood theory, have demonstrated clinical efficacy in HF management through randomized controlled trials. However, their precise mechanisms of action remain unclear. OBJECTIVE:To investigate the mechanistic role of QSTH in regulating mitochondrial homeostasis for HF amelioration. METHODS:HF murine models and cardiomyocyte hypertrophy models were developed for QSTH intervention. Cardiac function and structural integrity were assessed via echocardiography and histopathological staining. Mitochondrial fission (FIS1, MFF) and mitophagy markers (p62, LC3B, PARKIN) were quantified by Western blot in vivo and in vitro. Mitochondrial ultrastructure was analyzed using transmission electron microscopy (TEM) and two-photon excitation polarized fluorescence (TEPF) microscopy. In vitro mechanistic studies employed pathway inhibitors and Pink1 siRNA to validate regulatory pathways. Molecular alterations were evaluated through Western blot, qRT-PCR, and immunofluorescence. RESULTS:QSTH ameliorated myocardial pathology and cardiac function in HF mice through suppression of mitochondrial fission proteins (FIS1, MFF) and activation of mitophagy, indicated by elevated LC3B and PARKIN expression coupled with reduced p62 levels. TEPF microscopy revealed enhanced mitochondrial network integrity in QSTH-treated cardiomyocytes. In vitro, QSTH attenuated hypertrophy by modulating reactive oxygen species (ROS), mitochondrial membrane potential, and apoptosis. Mechanistically, QSTH activated PINK1 expression/phosphorylation, inhibited CaMKIIδ T287 phosphorylation, and regulated DRP1 S616 phosphorylation, thereby balancing mitochondrial fission-mitophagy dynamics via the CaMKIIδ-DRP1-PINK1 pathway. CONCLUSION:QSTH restores cardiomyocyte mitochondrial homeostasis through modulation of the CaMKIIδ-DRP1-PINK1 pathway, effectively attenuating hypertrophy, improving cardiac function, and reducing fibrosis in HF models.

Acute myocardial infarction (AMI) remains a major cause of cardiovascular mortality worldwide. The inflammatory immune response after AMI plays a dual role: it facilitates the clearance of necrotic tissue but can also exacerbate injury, significantly affecting patient outcomes. Conventional anti-inflammatory therapies are often limited by systemic toxicity and insufficient targeting, highlighting the need for more refined approaches. This review systematically examines the interplay between AMI's key inflammatory immune mechanisms—including neutrophil N1/N2 phenotypic switching, macrophage M1/M2 polarization, and Treg/Th17 lymphocyte balance—and advancements in nanoparticle-based drug delivery systems (NP-NDDSs) designed to target these mechanisms. NP-NDDSs utilize properties such as size-dependent accumulation, surface functionalization, and stimuli-responsive release (e.g., to pH, ROS, or enzymes) to improve spatiotemporal control over drug delivery. Various nanocarriers, including organic (e.g., liposomes, polymers), inorganic (e.g., gold, silica), and biomimetic (e.g., cell membrane- or exosome-based) systems, have shown potential in influencing neutrophil extracellular trap formation, macrophage phenotype, and lymphocyte activity. These developments suggest that NP-NDDSs could help control excessive inflammation, support tissue repair, and limit adverse remodeling. Nevertheless, challenges in targeting precision, manufacturing scalability, and long-term biosafety remain to be addressed. By summarizing current advances and identifying future needs, this review aims to provide a basis for developing targeted therapies against immune-mediated injury in AMI.

Background:Immunotherapy has redefined the treatment era for metastatic non-small cell lung cancer (NSCLC); therefore, this study aimed to explore trends in survival and cardiovascular disease (CVD) mortality risk before and after the widespread adoption of immunotherapy. Methods:This research utilized information from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute and the Wide-Ranging Online Data for Epidemiologic Research (CDC-WONDER) database from the Centers for Disease Control and Prevention. The study population comprised patients with metastatic NSCLC from the pre- (2011-2014) and post-immunotherapy (2016-2019) periods. Survival determinants and CVD mortality trends were analyzed using propensity score matching, Kaplan-Meier survival analyses, competing risk models, and accelerated failure time (AFT) models. Results:A total of 78,028 metastatic NSCLC patients were enrolled in the study, with significant improvements noted in overall survival (OS) and cancer-specific survival (CSS) in the later stages of immunotherapy. The AFT model analysis identified treatment modality, pathological subtype, metastatic site, and some non-medical factors as survival determinants. The interaction analyses revealed that the survival differences among certain subgroups intensified in the post-immunotherapy period. Despite the lack of significant differences in CVD mortality and subgroup composition between the two periods, CVD mortality risk remained high compared with the general U.S. population. Conclusion:Survival of patients with metastatic NSCLC has improved significantly since the introduction of immunotherapy. However, survival differences between some subpopulations continue to intensify, while CVD mortality risk also remains a key concern.

ETHNOPHARMACOLOGICAL RELEVANCE:Shenlian-Fumai Formula (SLFM) is a traditional Chinese medicine (TCM) prescription that originates from the classical formulas Gui Pi Tang and Huanglian Wendan Tang. It has been further developed within the TCM Qi-Blood theory for the management of palpitations and related cardiac symptoms. Clinical trials have evaluated SLFM in patients with ventricular arrhythmias (VAs) associated with heart failure (HF). AIM OF THE STUDY:To evaluate the cardioprotective and antiarrhythmic effects of SLFM in a mouse model of HF with VAs and to explore its underlying mechanisms with a focus on sodium channel regulation. MATERIALS AND METHODS:HF was induced in male C57BL/6 J mice by transverse aortic constriction (TAC). Mice were randomly divided into six groups: Control, HF model (Model), SLFM low-dose (SLFM-L, 4.66 g/kg/d), SLFM medium-dose (SLFM-M, 9.31 g/kg/d), SLFM high-dose (SLFM-H, 18.62 g/kg/d), and Mexiletine (0.32 g/kg/d) groups. Cardiac function was evaluated by echocardiography, serum BNP, heart and lung weight indices, and myocardial histology were also assessed. Electrocardiographic (ECG) parameters and VA occurrence were recorded at baseline and after isoproterenol injection. Patch-clamp was used to assess action potentials (APs) and sodium currents (INa) in isolated cardiomyocytes. The role of CaMKII was examined using KN93. qPCR detected expression levels of CaMKII and SCN5A. RESULTS:SLFM dose-dependently improved cardiac function, reduced BNP, alleviated myocardial fibrosis, and lowered VA incidence. It also restored action-potential duration (APD), increased INa density, and normalized channel kinetics. These effects were partially associated with modulation of CaMKII and SCN5A mRNA expression. CONCLUSION:SLFM exhibits antiarrhythmic and cardioprotective effects in HF by regulating sodium channel function and CaMKII signaling, highlighting its potential as a therapeutic option for HF-related VAs. However, all data were obtained from a single batch of SLFM, limiting generalizability and requiring validation with additional batches and harvest years.

OBJECTIVE:To evaluate the effect of Yiqi Liangxue Shengji prescription (, YQLXSJ) on cardiac function and outcomes in acute myocardial infarction (AMI) patients with myocardial ischemia-reperfusion injury (MIRI) and to determine its clinical efficacy. METHODS:This prospective, randomized, double-blind, placebo-controlled trial enrolled hospitalized patients with AMI who underwent percutaneous coronary intervention and experienced MIRI either intraoperatively or postoperatively. Participants were randomly allocated to the treatment group, which received YQLXSJ, or the control group, which received a placebo, concurrent with standard Western Medicine therapy. The intervention period lasted 8 weeks. The primary outcome measure was left ventricular ejection fraction (LVEF), determined by echocardiography. Secondary outcomes included N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) levels, left ventricular internal diameter, major adverse cardiovascular events (MACE), angina pectoris scores, and Chinese medicine evidence scores. RESULTS:Following 8 weeks of intervention, the treatment group demonstrated a significant increase in LVEF and a marked reduction in NT-proBNP when compared to the control group. There was also a significant decrease in peak cTnI levels, Chinese medicine evidence scores, and angina pectoris scores. The control group's left ventricular end-systolic diameter (LVESD) significantly increased compared to baseline after 8 weeks (P < 0.05), whereas the treatment group's LVESD showed no significant change from baseline (P > 0.05). Although the treatment group showed a downward trend in MACE incidence compared to the control group, this difference was not statistically significant (P > 0.05). CONCLUSIONS:This study demonstrated that the addition of YQLXSJ to standard therapy can improve cardiac function and alleviate clinical symptoms in AMI patients with MIRI, and also showed a potential to mitigate the incidence of MACE. Furthermore, YQLXSJ displayed a favorable safety profile in clinical application.

BACKGROUND:Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is a highly prevalent and deadly condition. Histone 3 trimethylation at lysine 36 (H3k36me3)-a chromatin signature induced by the histone methyltransferase SETD2 (SET domain containing 2)-correlates with changes in gene expression in human failing hearts; however, its role remains poorly understood. This study investigates the role of SETD2 in cHFpEF. METHODS:Chromatin immunoprecipitation sequencing and RNA sequencing were used to investigate H3k36me3-related transcriptional regulation. Mice with cardiomyocyte-specific deletion of SETD2 (c-SETD2-/-) were generated and subjected to high-fat diet feeding and L-NAME treatment for 15 weeks to induce cHFpEF. Cardiac function and exercise tolerance were assessed by echocardiography and treadmill exhaustion test. A selective pharmacological inhibitor of SETD2, EZM0414, was also tested in cHFpEF mice. Mechanistic experiments were performed in cultured cardiomyocytes exposed to palmitic acid. SETD2 signaling and the effects of EZM0414 were also investigated in cardiomyocytes from patients with cHFpEF and control donors. RESULTS:SETD2 was upregulated in cHFpEF mouse hearts, and its chromatin mark H3k36me3 was involved in lipid metabolism and highly enriched on the promoter of the Srebf1 gene, encoding for SREBP1 (sterol regulatory binding protein 1). SETD2 activation in cHFpEF led to SREBP1 upregulation, triglyceride accumulation, and lipotoxic damage. Of note, cardiomyocyte-specific deletion of SETD2 in mice prevented heart failure with preserved ejection fraction-related hypertrophy, diastolic dysfunction, and lung congestion while improving exercise tolerance. SETD2 deletion blunted H3K36me3 enrichment on Srebf1 promoter, thus leading to a marked rewiring of the cardiac lipidome and restoration of autophagic flux. In vivo treatment with the SETD2 inhibitor EZM0414 recapitulated the effects of SETD2 deletion. Silencing of SETD2 in palmitic acid-treated cardiomyocytes prevented SREBP1 upregulation, whereas SETD2 overexpression mirrored lipotoxic damage. Finally, SETD2 was upregulated in left ventricle specimens from patients with cHFpEF while EZM0414 attenuated cardiomyocyte stiffness. CONCLUSIONS:Targeting SETD2 might prevent lipotoxic injury in cHFpEF.

BackgroundPatients with heart failure (HF) have a poor prognosis and continue to pose a global threat to human health. Consequently, it is crucial to employ bioinformatic approaches to analyze functional alterations within the transcriptome. This analysis should be conducted in conjunction with transcriptome sequencing data from a large sample of clinical myocardial tissue, in order to identify the core pathogenic mechanisms in heart failure myocardial tissue.MethodTranscriptome data from HF patient myocardial biopsies underwent Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs). These DEGs were intersected with key genes identified via Weighted Gene Co-expression Network Analysis (WGCNA) in HF. Functional enrichment analysis was performed on the DEGs. Selected key genes were experimentally validated using RT-qPCR in hypertrophic cardiomyocyte models. Single-cell data dimensionality reduction, clustering, and visualization were achieved using Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP). Cell types were annotated with SingleR and CellMarker, and single-cell functional enrichment was performed using the “irGSEA” R package.ResultsRRA of transcriptome data from five studies identified 102 DEGs. Functional enrichment analyses (GO, KEGG, GSEA) revealed associated functional alterations. WGCNA highlighted a key module enriched for energy metabolism-related genes, with the mitochondrial matrix and inner membrane identified as their primary subcellular locations. Integrating RRA-derived DEGs with WGCNA key module genes yielded 14 crucial genes, validated experimentally in a hypertrophic cardiomyocyte model. Analysis of single-cell RNA-seq data identified cold shock domain containing C2 (CSDC2) and Single-pass membrane and coiled-coil domain-containing protein 4 (SMCO4) as cardiomyocyte-specific genes within this set. Subpopulations of cardiomyocytes with high or low expression of SMCO4 and CSDC2 showed strong associations with alterations in fatty acid metabolism, adipogenesis, and oxidative phosphorylation pathways.ConclusionIntegrated transcriptomic analysis identified 12 key genes linked to HF, which were validated in a hypertrophy model. Single-cell data showed SMCO4 and CSDC2 are specifically expressed in cardiomyocytes and regulate fatty acid metabolism. This suggests SMCO4 and CSDC2 contribute to HF by altering fatty acid metabolism in heart cells, revealing new disease mechanisms.

OBJECTIVE:To determine the efficacy and safety of adjunct Shuxuening Injection (SXN) on conventional therapy in patients with unstable angina (UA) which provides a complementary choice and its evidence for clinical medication for treating UA. METHODS:In this multicenter, randomized, double-blind, placebo-controlled trial, 469 patients with UA from 25 hospitals in China who had an episode of angina within 48 hours were randomly assigned 3:1 to SXN and placebo group for 10 days in addition to conventional treatment. The primary outcome is the frequency of angina pectoris attacks after 10 days of intervention. The secondary outcomes are the frequency of angina pectoris attacks on day 30, the duration of angina pectoris symptoms, the visual analogue scale (VAS) score, total score of angina pectoris symptoms, the Global Registry of Acute Coronary Events (GRACE) score, total ischemia burden (TIB), and the level of high-sensitivity C-reactive protein (hs-CRP). RESULTS:A total of 469 participants from 25 hospitals in China were enrolled in this trial. After 10 days of treatment, the frequency and duration of angina pectoris attacks, VAS score, and total score of angina pectoris symptoms exhibited a significant improvement in the SXN group compared to the placebo group both on days 10 and 30 (all p < 0.05). The GRACE risk score classification, TIB, and hs-CRP levels in the SXN group showed no statistically significant decrease compared to the control group on day 10 (all p > 0.05). The medication compliance, concomitant medication, and rates of adverse events were similar between the two groups (p > 0.05). CONCLUSION:In patients with UA, SXN added on conventional treatment reduced the frequency and duration of angina pectoris attacks, even after discontinuation of the intervention for 20 days.

Objective: This study utilized network meta-analysis (NMA) to compare the efficacy of five commonly used traditional Chinese medicine monomers in reducing intimal hyperproliferation in arterial balloon injury models. Methods: Relevant literature up to January 2024 was systematically retrieved from seven major databases. The intima-to-media (I/M) ratio was chosen as the primary outcome measure. The risk of bias in animal studies was assessed using the SYstematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Statistical analysis was conducted using Stata 17 software. Results: A total of 43 studies were included in this meta-analysis. NMA results showed that in the rat model, compared to the control group, GS (SMD: 0.99, 95%CI: 1.25 to -0.73), ASIV (SMD: 1.16, 95%CI: 1.65 to -0.67), TMP (SMD: 0.68, 95%CI: 1.31 to -0.05), and TPNS (SMD: 1.36, 95%CI: 1.91 to -0.80) exhibited inhibitory effects on postoperative intimal hyperproliferation, reducing the I/M ratio. In the rabbit model, compared to the control group, TPNS (SMD: 1.23, 95%CI: 1.97 to -0.49) inhibited postoperative intimal hyperproliferation and reduced the I/M ratio. Superiority ranking analysis suggested that total Panax notoginseng saponin (TPNS) might be the most effective traditional Chinese medicine monomer in reducing intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio. Conclusion: NMA indicates that traditional Chinese medicine monomers can effectively reduce postoperative intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio, with TPNS showing optimal efficacy. However, the research on TIIA is insufficient, and the limited sample size may affect the robustness of the results. Furthermore, the majority of research on traditional Chinese medicine monomers is currently limited to the experimental stage, lacking further clinical validation. Conducting standardized animal experiments and reporting their findings can enhance the quality of evidence from animal studies, laying the foundation for future clinical trials.

Panax quinquefolius saponins (PQS) and Panax notoginseng saponins (PNS) are key bioactive compounds in Panax quinquefolius L. and Panax notoginseng, commonly used in the treatment of clinical ischemic heart disease. However, their potential in mitigating myocardial ischemia-reperfusion injury remains uncertain. This study aims to evaluate the protective effects of combined PQS and PNS administration in myocardial hypoxia/reoxygenation (H/R) injury and explore the underlying mechanisms. To investigate the involvement of HIF-1α/BNIP3 mitophagy pathway in the myocardial protection conferred by PNS and PQS, we employed small interfering BNIP3 (siBNIP3) to silence key proteins of the pathway. H9C2 cells were categorized into four groups: control, H/R, H/R + PQS + PNS, and H/R + PQS + PNS+siBNIP3. Cell viability was assessed by Cell Counting Kit-8, apoptosis rates determined via flow cytometry, mitochondrial membrane potential assessed with the JC-1 fluorescent probes, intracellular reactive oxygen species detected with 2′,7′-dichlorodihydrofluorescein diacetate, mitochondrial superoxide production quantified with MitoSOX Red, and autophagic flux monitored with mRFP-GFP-LC3 adenoviral vectors. Autophagosomes and their ultrastructure were visualized through transmission electron microscopy. Moreover, mRNA and protein levels were analyzed via real-time PCR and Western blotting. PQS + PNS administration significantly increased cell viability, reduced apoptosis, lowered reactive oxygen species levels and mitochondrial superoxide production, mitigated mitochondrial dysfunction, and induced autophagic flux. Notably, siBNIP3 intervention did not counteract the cardioprotective effect of PQS + PNS. The PQS + PNS group showed downregulated mRNA expression of HIF-1α and BNIP3, along with reduced HIF-1α protein expression compared to the H/R group. PQS + PNS protects against myocardial H/R injury, potentially by downregulating mitophagy through the HIF-1α/BNIP3 pathway.