Heart failure (HF) is a clinical syndrome characterized by myocardial remodeling, pathological fibrosis, and chronic sterile inflammation. Within the pathophysiological network of HF and its complex comorbidities, neutrophil extracellular traps (NETs) have been identified as key pathological mediators driving tissue damage. This review aims to explore the regulatory mechanisms of NETs in the progression of heart failure (HF) and their cross-organ pathological effects, and to summarize the latest research advances in NET-targeted interventions for the treatment of HF. NETs are reticular structures composed of antimicrobial proteins, such as myeloperoxidase (MPO) and histones, attached to a decondensed DNA scaffold. Under pathological conditions, excessive NET release and impaired clearance trigger inflammatory cascades. Aberrant NETs formation significantly promotes cardiac remodeling and pathological fibrosis by mediating immunothrombosis, inducing cardiomyocyte apoptosis, and activating fibroblasts.NETs serve as a critical pathophysiological link connecting HF to systemic comorbidities. Therapeutic strategies targeting NETs primarily include inhibiting PAD4 or associated signaling axes to block NETs formation, utilizing enzymatic reactions to facilitate NETs clearance, uncovering the novel potential of established clinical agents, and employing nanotechnology-based precision delivery systems. These findings offer new avenues for precision immunotherapy in HF and highlight considerable potential for clinical translation.

Background Myocardial ischemia-reperfusion injury (MIRI) constitutes a significant contributor to the increased incidence of post-ischemic heart failure. The primary mechanisms underlying MIRI involve oxidative stress and mitochondrial calcium overload in reperfused cardiomyocytes. Regulating the homeostasis of the mitochondrial-associated endoplasmic reticulum membranes (MAMs) to improve endoplasmic reticulum-mitochondrial communication is expected to treat MIRI, but there are currently no clear targeted drugs. The Shenfuyixin Granules (SFYX) exhibit capabilities in lowering reactive oxygen species levels, curtailing apoptosis, and improving mitochondrial performance in cardiomyocytes. However, its therapeutic role in MIRI remains unclear. Aim of the study This study aims to clarify the effect of SFYX on mitochondrial calcium overload after MIRI and elucidate its potential mechanism of action. Methods The rat MIRI model was established by short-time ligation of the left anterior descending coronary artery and reperfusion, and SXNI (3.275g/kg, 6.55g/kg, 13.1g/kg) was administered for treatment. Network pharmacology combined with molecular docking has revealed the specific molecular mechanism by which SFYX regulates mitochondrial calcium homeostasis in the myocardium. The improvement effect of SFYX on MIRI was evaluated by western blotting (WB), TUNEL staining, immunofluorescence staining, etc. A hypoxia/reoxygenation (H/R) model of myocardial cells was simultaneously established, MIRI was simulated in vitro, and the mechanism was verified using WB, fluorescent probes, mitochondrial function and other related tests. Results Network pharmacological analysis and molecular docking indicated that SFYX might improve MIRI by reducing mitochondrial calcium overload through the cGMP-PKG signaling pathway and calcium signaling pathway, and the key blood-entering components could stably bind to cGMP and PKG. In vivo experiments confirm that SFYX significantly attenuates myocardial injury associated with MIRI and alleviates levels of oxidative stress and apoptosis through the sGC/PKG pathway. In vitro experiments verify that SFYX regulates MAMs via the sGC/PKG signaling pathway, thereby stabilizing mitochondrial function, alleviating calcium overload and oxidative stress, and ultimately combating MIRI. Conclusion This study suggests that SFYX prophylactic administration can alleviate mitochondrial calcium overload by targeting MAMs through the sGC/PKG signaling axis and has a preventive effect on MIRI. These findings indicate that SFYX may become a potential drug for preventing MIRI in the future.

IntroductionHeart failure with preserved ejection fraction (HFpEF) is a highly complex clinical syndrome associated with significant morbidity and mortality. Its underlying mechanisms are poorly understood, treatment options are limited, the disease burden on patients is substantial, and clinical outcomes are poor. Previous clinical studies have preliminarily suggested that Shengxian Yixin Granule (SXYX) is an effective herbal formula for the treatment of HFpEF, but it lacks high-quality clinical evidence. This study therefore plans to conduct a randomized controlled trial (RCT) to evaluate the efficacy and safety of SXYX in treating HFpEF, aiming to provide a new therapeutic strategy for this condition.MethodsThis study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. It will be conducted at four Chinese medicine hospitals in China. A total of 148 eligible patients with HFpEF will be enrolled and randomly assigned in a 1:1 ratio to the SXYX group or the placebo group. The SXYX group will receive Shengxian Yixin Granule, while the placebo group will receive a matching placebo. Both groups will receive standard Western medical therapy as background treatment. The treatment duration for all groups is 24 weeks. The primary outcome is the change in peak VO2 (assessed by cardiopulmonary exercise testing) from baseline to 24 weeks. Secondary outcome measures include the change in peak oxygen uptake from baseline to 12 weeks, NT-proBNP, echocardiographic parameters, NYHA functional class, 6-minute walk test distance (6MWT), Traditional Chinese Medicine (TCM) syndrome scale, major symptoms and signs, EQ-5D score, and coagulation function. These outcomes will be used to evaluate the efficacy of SXYX. Routine blood, urine, and stool tests, liver and kidney function tests, electrocardiograms, and adverse events will be used to assess the safety of SXYX. Wearable monitoring devices will be used for out-of-hospital, dynamic, and multidimensional assessment of patients’ exercise tolerance, including heart rate, blood oxygen saturation, step count, and walking distance.DiscussionThis study will evaluate the efficacy and safety of SXYX in treating HFpEF. The findings will provide a scientific basis for the clinical application of SXYX.Clinical Trial Registrationhttps://itmctr.ccebtcm.org.cn, identifier ITMCTR2026000833.

Hyperlipidemia(HLP) is a significant independent risk factor for the occurrence and development of cardiovascular and cerebrovascular diseases. Currently, the common clinical lipid-lowering agents include statins(inhibiting HMG-CoA reductase), fibrates(activating PPARα), cholesterol absorption inhibitors(blocking NPC1L1), and PCSK9 inhibitors(preventing LDLR degradation). However, clinical concerns remain about the combination use of multiple drugs, hepatorenal toxicity, and poor adherence to long-term application. The sterol regulatory element-binding protein(SREBP) pathway serves as a master regulator of lipid synthesis, concurrently controlling multiple steps in this process. Targeted intervention of the overactivated SREBP pathway has emerged as a novel research direction for regulating lipid metabolism disturbances, though it remains largely in the preclinical stage of drug research and development. TCM demonstrates multi-target and holistic regulatory advantages in regulating the SREBP pathway. Studies reveal that TCM compounds(Zexie Decoction, Xiangsha Liujunzi Decoction, and so on) and active constituents(berberine, curcumin, and so on) can systematically ameliorate lipid metabolic disturbances by inhibiting SREBP-1c/2 activation and the expression of downstream genes such as FAS, ACC, and HMGCR. This review summarized clinical trials and experimental research in recent years on the mechanisms by which TCM prevents and treats HLP by regulating the SREBP pathway, aiming to provide theoretical basis and new insights for the prevention and treatment of HLP as well as further research.

Myocardial ischemia-reperfusion injury (MIRI) is a key factor affecting the prognosis of myocardial infarction patients. Currently, there remains a lack of specific drugs targeting MIRI, and it is unclear whether Piceatannol-3'-O-β-D-glucopyranoside (PG) improves MIRI through metabolic reprogramming. Therefore, this study takes a clinically oriented approach, using multi-omics technologies to investigate how PG regulates metabolic reprogramming to improve MIRI. The study focuses particularly on PG's regulation of lactate and lactylation. Results indicate that PG enhances LVEF and LVFS, reduces cTnI and CK-MB levels, decreases ROS, lactate, and LDH levels, and increases ATP expression, thereby improving cardiac function. Metabolomics results based on clinical serum samples indicate that PG can reduce lactate and pyruvate levels. The results of research conducted on animal subjects suggest that exogenous lactate supplementation has the capacity to attenuate the cardioprotective effects of PG. PG intervention significantly suppressed the expression of PDK4, MCT1, and ACSL4 proteins while enhancing GPX4 protein expression, inhibiting lipid peroxidation, and improving mitochondrial structure and function. However, the overexpression of PDK4 led to a diminution of the PG-mediated enhancement in MIRI. Overexpression of NDUFS1 K170 lactylation similarly impaired the PG-mediated improvement of MIRI. Therefore, we conclude that PG improves MIRI by inhibiting NDUFS1 K170 lactylation through metabolic reprogramming regulation. The present study provides novel targets and therapeutic agents for MIRI intervention, while also offering fresh insights into the pathogenesis of MIRI.

ObjectiveObstructive sleep apnea (OSA) is a highly prevalent sleep disorder strongly linked to obesity and substantially increases the risk of cardiovascular and metabolic diseases. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and aerobic exercise have shown potential in improving OSA through distinct metabolic and physiological mechanisms. However, direct comparative evidence of their efficacy remains limited. This network meta-analysis aimed to compare the effects of SGLT2 inhibitors, GLP-1 receptor agonists, and aerobic exercise on OSA severity in overweight or obese patients.MethodsWe searched four electronic databases, PubMed, EMBASE, the Cochrane Library, and Web of Science, for articles published before October 31, 2025, without language restrictions. The analysis primarily included randomized controlled trials (RCTs); a limited number of case–control studies were also incorporated due to the scarcity of direct comparative evidence. Primary efficacy outcomes were mean changes in the apnea–hypopnea index (AHI), body mass index (BMI), mean peripheral oxygen saturation (SpO2), and Epworth Sleepiness Scale (ESS) score. The certainty (confidence) of the evidence for every network estimate was appraised with the Confidence in Network Meta-Analysis (CINeMA) framework, which operationalizes the GRADE approach for network meta-analysis.ResultsA total of 15 studies (13 RCTs and 2 case–control studies) involving 1,877 participants were included in the analysis. GLP-1 receptor agonists demonstrated the greatest reduction in AHI compared with placebo (mean difference [MD] = −15.28 events/h; 95% CI, −22.22 to −8.35). They also showed significant benefit versus placebo in lowering BMI (MD = −1.78 kg/m2; 95% CI, −2.15 to −1.41) and improving mean SpO2 (MD = 0.40%; 95% CI, 0.25 to 0.55). Although GLP-1 receptor agonists yielded a statistically significant improvement in ESS score versus placebo (MD = −0.20; 95% CI, −0.26 to −0.14), this effect was an order of magnitude below the 2-point minimal clinically important difference (MCID) for the ESS and is therefore not clinically meaningful. Aerobic exercise ranked highest in surface under the cumulative ranking curve (SUCRA) analysis for this outcome. No network estimate was rated as high certainty. Confidence was moderate for the effect of GLP-1 receptor agonists on BMI, low for their effects on AHI, mean SpO2, and ESS score versus placebo, and very low for all remaining comparisons, mainly because of within-study bias, imprecision, and suspected reporting bias.ConclusionCompared with placebo, GLP-1 receptor agonists reduced AHI and BMI and improved mean SpO2, and ranked highest for these outcomes in the SUCRA analysis. Comparisons between the active interventions, however, were largely non-significant and rested on indirect evidence, and the certainty of the evidence was moderate at best, being low or very low for most comparisons. This treatment hierarchy should therefore be regarded as hypothesis-generating rather than as a basis for firm clinical recommendations. Within these limits, these findings suggest that GLP-1 receptor agonists may offer a promising therapeutic approach for managing OSA in overweight or obese patients with metabolic comorbidities, though this remains to be confirmed in larger, high-quality, head-to-head trials.

This multicenter observational analysis, based on prospectively collected data from a 1-year disease-management cohort, assessed secondary prevention status at enrollment and 1-year unplanned readmission among 2,896 patients with cardiovascular and cerebrovascular diseases in China. Patients included 1,061 with stable angina (CAD), 427 with myocardial infarction (MI), 1,141 with cerebral infarction (CI), and 267 with intracerebral hemorrhage (ICH), recruited from three regions between August 2020 and March 2021. Data on demographics, Traditional Chinese Medicine (TCM) syndromes, and medications were analyzed. Logistic regression was used to examine factors associated with blood pressure, lipid, and glucose target achievement, as well as 1-year readmission. Among 2,698 patients with available target-control data, the blood pressure target-achievement rate was 45.4

The association between immunocyte phenotypes and dilated cardiomyopathy (DCM) has been explored, however the exact pathogenesis of the relationship between immune cells and DCM is unclear. This bidirectional two-sample Mendelian randomization (MR) research aims to further validate the causal link between 731 immunocyte phenotypes and DCM. Summary statistics from a genome-wide association study data of individuals with European ancestry were utilized, including 1444 DCM cases and 353,937 controls, as well as 3757 European adults for the 731 immunocyte phenotypes. Causal effects were estimated using inverse variance weighted, MR-Egger regression, weight median estimator, weighted mode, and simple mode. Sensitivity analysis was conducted to confirm data robustness and feasibility. Based on the inverse variance weighted findings, 14 immunocyte phenotypes were risk factors for DCM ( P < .05, odds ratio [OR] > 1), while 15 immunocyte phenotypes exhibited a protective effect on DCM ( P < .05, OR < 1). The results of reverse MR analysis suggested evidence that DCM occurrence might elevate the levels of 17 immunocyte phenotypes ( P < .05, OR > 1) and decrease the levels of 9 immunocyte phenotypes ( P < .05, OR < 1). Our research indicated that CD28 on secreting regulatory T cell could mitigate the occurrence of DCM, and reciprocally, the progression of DCM could reduce the level of CD28 on secreting regulatory T cell. This study confirmed the bidirectional genetic predictive relationship between immunocyte phenotypes and DCM, underscoring the complex interplay between DCM and the immune system.

Heart failure (HF) is a terminal cardiovascular syndrome related to systemic hypoxia. Hypoxia is considered a fundamental pathophysiological process, and the resulting tissue response depends on the severity and duration of exposure. Hypoxia-inducible factors (HIFs) promote adaptation to hypoxic conditions by regulating the expression of multiple hypoxia-responsive genes. Its short-term activation during acute hypoxia exerts cardioprotective effects, whereas chronic activation induces pathological hypertrophy, depending on the disease context. Therefore, HIF-mediated hypoxic responses in HF may involve hierarchical adaptations to hypoxia. This review discusses the role of HIFs in the physiology and pathology of HF, focusing on metabolic remodeling, angiogenesis, cardiac inflammation, and circadian influences, as well as their potential effects on myocardial performance. Furthermore, the therapeutic potential of HIF-targeting compounds in HF treatment will be reviewed. Overall, whether targeting HIF-induced changes in HF is an effective strategy remains to be established; thus, research in this field is urgently needed.

Introduction: In recent years, ShenSong YangXin capsule (SSYX) has gained widespread application in China as an adjunctive therapy for patients with chronic heart failure combined with atrial fibrillation (CHF-AF). However, its efficacy and safety profile remain subject to debate, and there is a notable lack of relevant systematic reviews and meta-analyses on this topic.Methods: A comprehensive search was conducted across seven databases up to August 25, 2025, identifying eligible randomized controlled trials (RCTs). Meta-analysis, subgroup analysis, and sensitivity analysis were performed using RevMan 5.4 and Stata 15.1. The Risk of Bias 2.0 tool was used to evaluate study quality, and publication bias was assessed with Egger’s test in Stata. Trial sequential analysis and the GRADE framework were utilized to assess the cumulative evidence and certainty of outcomes. The study protocol was prospectively registered with PROSPERO (CRD42023482018).Results: The meta-analysis included 17 RCTs comprising a total of 1756 patients from China. Results indicated that SSYX combined with conventional medication significantly improved clinical efficacy in patients with CHF-AF [RR 1.18 (95% CI 1.11, 1.25), p < 0.00001] and reduced the incidence of major adverse cardiovascular events (MACE) [RR 0.31 (95% CI 0.23, 0.41), p < 0.00001]. Statistically significant improvements were also observed in the following outcomes: B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, QT dispersion (QTd), ventricular rate, and AF duration. Adverse reactions were reported in 11 trials. According to the GRADE framework, one outcome (MACE) was supported by moderate-certainty evidence, three outcomes (clinical efficacy, QTd, and ventricular rate) were graded as low-certainty, and the remaining six outcomes were assessed as having very low-certainty evidence.Conclusion: The combination therapy incorporating SSYX showed potential benefits compared to conventional treatment alone in patients with CHF-AF. However, the overall certainty of evidence is limited. Therefore, these findings require careful interpretation and further large-scale, rigorously designed RCTs are warranted to provide more robust evidence regarding the efficacy and safety of SSYX.

Objective:Ischemic heart failure (IHF) is a multifaceted syndrome associated with significant mortality and high hospitalization rates globally. Yiqi Huoxue prescription (YQHX) has been incorporated into clinical practice, showing significant therapeutic efficacy. However, to date, the pharmacological mechanisms remain vague. We combined multi-omics, machine learning, and molecular docking strategies to elucidate the mechanisms by which YQHX protects against IHF. Methods:Clinically, the efficacy and safety of YQHX in improving cardiac function in IHF patients were observed. Transcriptomic, proteomic, and targeted metabolomic analyses were performed on serum samples from IHF patients and healthy individuals before and after YQHX intervention. Multi-omics association analysis integrating machine learning identified the potential mechanisms underlying YQHX's effects. Key ingredient-targets interactions were validated in vitro experiments. Results:After 12 weeks of treatment, YQHX significantly decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD, -1180.28; 95% CI: -2107.23 to -253.32), enhanced left ventricular ejection fraction (LVEF) (MD, 4.78; 95% CI: 2.23 to 7.32), and improved 6-minute walk distance (6MWD). No serious adverse events were observed during the study. Multi-omics integration analysis revealed that platelet activation NET formation, HIF-1 signaling pathway, TCA cycle, and glycolysis are indispensable pathways for the treatment of IHF. Machine learning has identified H3-3A, HMGB1, SOD2, ACTG1, PGAM1, FGA, LDHA, FN1, VWF, and ACO2 as critical molecular targets of YQHX treatment. Clinical research further demonstrated that YQHX treatment beneficially modulates energy metabolism, improves coagulation system functions, and ameliorates inflammatory responses in IHF. Molecular docking revealed that astragaloside I/III/IV, isoastragaloside I/II, paeoniflorin, and hydroxysafflor yellow A are likely active compounds contributing to YQHX's therapeutic effects, and these findings were further validated through in vitro experiments. Conclusion:YQHX combats IHF via multi-target and multi-pathway mechanisms, including energy metabolism reprogramming, coagulation system enhancement, and immune-inflammatory response modulation, positioning it as a potential therapeutic strategy for IHF.

Background:Heart failure (HF) secondary to acute myocardial infarction (AMI) remains a public health concern. Peripheral blood mononuclear cells (PBMCs) are the essential initiators of heart failure after myocardial infarction (HFpAMI). We aimed to identify PBMCs-related critical genes as diagnostic biomarkers for HFpAMI and analyze the immune infiltration patterns. Methods:Differential expression genes (DEGs) from PBMCs microarray data of AMI with or without HF were identified. Functional enrichment analysis was used to explore the biological roles of DEGs. Subsequently, candidate biomarkers were identified using machine learning and the MCODE plugin, with ROC used to describe the accuracy. CIBERSORT was utilized to investigate immune infiltration. Multi-level validation of our findings was conducted, including RNA-seq profiling of the external cohort, RT-qPCR, and flow cytometry analyses on PBMCs samples. Results:In the comparison between 30 HFpAMI and 34 non-HF samples, 27 DEGs were identified. Functional enrichment analysis suggested that DEGs may be involved in the pathological process of HFpAMI by participating in immune-inflammatory response. Employing machine learning and MCODE assessment, we identified three robust potential biomarkers (CLU, FOS, and CXCL8). Immunological analysis revealed a marked increase in neutrophils and decrease in CD4T cells. In the external validation cohort, RNA-seq analysis demonstrated consistent upregulation of CLU, FOS, and CXCL8 in HFpAMI compared to non-HF controls. RT-qPCR and flow cytometry further corroborated these expression trends and their correlations with neutrophil infiltration, CD4T cells and M2 macrophage concentration reductio, aligning with bioinformatics predictions. ROC analysis validated the diagnostic efficacy of these biomarkers, with CLU exhibiting the highest AUC (0.833, 95% CI: 0.679-0.988), followed by FOS (0.809, 95% CI: 0.64-0.977) and CXCL8 (0.802, 95% CI: 0.635-0.970). Conclusions:Significantly upregulated DEGs, including CLU, FOS, and CXCL8, might be served as novel diagnostic biomarkers for HFpAMI, and dysregulated immune infiltration hinted possible the immune system intervention point in the setting of HFpAMI.

Although the fibrosis-4 index (FIB‐4) was initially established as a liver fibrosis marker, recent studies have demonstrated its significant association with elevated risk of coronary artery disease(CHD). This study was conducted using data from five National Health and Nutrition Examination Surveys (NHANES) cycles between 2009 and 2018. Multivariable logistic regression analysis revealed a significant, positive relationship between FIB-4 and CHD.In sensitivity analyses, the highest FIB-4 quartile (Q4) showed a 4.22-fold increased CHD risk versus Q1 (OR = 4.22, 95

Introduction:Inflammatory bowel disease (IBD) includes Crohn's disease (CD) and ulcerative colitis (UC). Epidemiological studies have found that patients with IBD are more likely to suffer from cardiovascular diseases (CVDs) than the general population. However, so far, no exact causal association has been demonstrated between IBD and CVDs, and more research is needed to clarify this relationship. Material and methods:The two-sample Mendelian randomization (MR) method was used to explore the causal effect of IBD on CVDs. The exposure factor was IBD, including CD and UC. The outcome was CVDs, including chronic heart failure, atrial fibrillation, coronary heart disease, myocardial infarction and hypertension. The single nucleotide polymorphisms (SNPs) are all from the FinnGen genome-wide association study sample database. The CD samples included 210,300 controls and 807 cases, and the UC samples included 215,806 controls and 2701 cases. The samples included are all European samples. SNPs associated with Crohn's disease and ulcerative colitis were extracted from the IEUGWAS database and quality control and screening were carried out. Inverse variance weighted (IVW), MR-Egger, weighted median and other methods were used to study the causal relationship between them and CVDs. Finally, Cochrane's Q test, MR-Egger and the leave-one method were used for sensitivity analysis. Results:In this study, 4 SNPs strongly associated with Crohn's disease and 12 SNPs strongly associated with ulcerative colitis were screened. The IVW method of genetic prediction revealed a positive correlation between Crohn's disease and the risk of chronic heart failure (OR =1.02; 95% CI: 1.00-1.04), and there was a positive correlation between ulcerative colitis and the risk of chronic heart failure (OR = 1.03; 95% CI: 1.00-1.06). IVW, MR-Egger and weighted median showed that Crohn's disease and ulcerative colitis were not associated with the risk of atrial fibrillation, coronary heart disease, myocardial infarction or hypertension. Sensitivity analysis showed that the results are robust. Conclusions:Crohn's disease and ulcerative colitis are associated with an increased risk of chronic heart failure, but they are not associated with the risk of other CVDs.

BACKGROUND:Lingguizhugan decoction (LGZG), a typical Chinese herbal formula, has remarkable clinical effects for treating pulmonary hypertension (PH) with unclear ingredients and mechanisms. This study aimed to evaluate the efficacy of LGZG and the mechanism of its active ingredients in treating PH. METHODS:The PH patient phenotype was characterized by transcriptomic assay of peripheral blood mononuclear cells (PBMCs) and multiplex cytokine profiling of serum. The active ingredients of LGZG were identified by UPLC-Q-TOF-MS. The monocrotaline (MCT)-induced PH model was performed to evaluate the effects of LGZG and its active ingredients in vivo. The interleukin-33 (IL-33)-induced RAW264.7 cells and the mouse pulmonary artery smooth muscle cells (mPASMCs) were applied to explored phenotype and mechanism of the active ingredients of LGZG by immunofluorescence, western blotting and RT-qPCR in vitro. RESULTS:Inflammatory receptor activity in PBMCs and serum interleukin-6 (IL-6) levels were elevated in PH patients. Porinic acid B, cinnamic acid, atractylenolide I and glycyrrhizin (PCAG) were characterized and combined to treat the PH, And the IL-33/Growth stimulation expressed gene 2 (ST2) pathway may be the potential mechanism by transcriptomic analysis of lung tissues. Both in vivo and in vitro experiments confirmed that PCAG inhibited the IL-33/ST2 pathway, reduced macrophage polarization, and suppressed IL-6 secretion. Moreover, ST2 overexpression in macrophages attenuated the inhibitory effect of PCAG. Using a co-culture system of macrophages and mPASMCs, we demonstrated that PCAG reduced mPASMCs phenotypic switching by suppressing macrophage-derived IL-6 secretion. CONCLUSION:The active ingredient of LGZG, PCAG, inhibits the progression of PH by preventing macrophage polarization and IL-6 secretion through the IL-33/ST2 pathway.

BACKGROUND:Heart failure (HF) represents the terminal stage of various cardiovascular diseases, with current treatment options remaining limited. Shenfuyixin Granules (SFYX) have been integrated into clinical practice, demonstrating significant therapeutic efficacy. However, the underlying mechanisms of action are still not fully understood. PURPOSE:This study aims to investigate whether SFYX promotes mitochondrial autophagy and enhances cardiac function in HF following myocardial infarction via the SIRT3/FOXO1 signaling axis. METHODS:The rat model of HF was established by ligation of the left anterior descending artery, while in vitro experiments were conducted using H9C2 cells. The blood-entry components of SFYX were identified using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Network analysis, integrating proteomics and transcriptomics, was conducted to determine the active components of SFYX and elucidate the key regulatory mechanisms involved in its treatment of HF. After a 4-week intervention with SFYX, cardiac function was assessed via echocardiography. Myocardial infarct size was measured using triphenyl tetrazolium chloride (TTC) staining, while H&E and Masson staining were employed to evaluate myocardial tissue fibrosis and hypertrophy. Mitochondrial function was assessed using transmission electron microscopy and JC-1 dye. Cell apoptosis was detected via TUNEL assay. Additionally, molecular docking was performed to assess the binding affinity between key components of SFYX and autophagy-related proteins. Mechanistically, the expression levels of SIRT3, FOXO1, P62, and BNIP3 were determined using quantitative PCR and Western blotting. RESULTS:UPLC-MS/MS analysis revealed 21 blood-entry components in SFYX. Integrated analyses of network pharmacology, proteomics, and transcriptomics indicated that SFYX may ameliorate HF by stimulating mitochondrial autophagy through activation of the SIRT3/FOXO1 pathway. Compared with the model group, SFYX significantly attenuated myocardial hypertrophy, apoptosis, and fibrosis while enhancing autophagy, which may be partially attributed to the recovery of mitochondrial function. We propose that SFYX enhances mitochondrial function by reducing membrane potential and reactive oxygen species (ROS) production. Further results demonstrated that SFYX treatment upregulated SIRT3 and FOXO1 levels while inhibiting FOXO1 acetylation. Furthermore, the levels of mitophagy-associated proteins (ATG5, ATG7, BNIP3, and LC3B-II), which are downstream mediators of FOXO1, were enhanced by SFYX. Activation of SIRT3 or overexpression of FOXO1 enhanced the cardioprotective efficacy of SFYX, whereas inhibition of SIRT3 or silencing of FOXO1 partially reversed SFYX-induced favorable activities. Molecular docking analysis revealed that Glyceryl linolenate, a blood-entry component of SFYX, exhibited a strong binding affinity for SIRT3. CONCLUSION:This study demonstrates that SFYX exerts cardioprotective effects against HF through the deacetylation-regulated activation of SIRT3/FOXO1 signaling-mediated mitophagy and apoptosis. These findings indicate that SFYX represents a promising therapeutic candidate for the treatment of HF.

An ultra-sensitive fluorescent biosensor based on CDs-Eu@ZIF-8 Modified Fe3O4@AuNPs Magnetic Nanoparticles was constructed for sensitive detection of DENV-2 Nucleocapsid Protein 1 (NS1). Briefly, we doped Eu3+ into carbon dots using a new synthesis method, preparing Eu3+-doped carbon dots with novel excitation and emission wavelengths (CDs-Eu). Compared with CDs, CDs-Eu exhibits superior fluorescence properties. The fluorescence material was encapsulated in zeolitic imidazolate frameworks (ZIF-8) to form stable and signal amplification nanoparticles CDs-Eu@ZIF-8. To achieve highly sensitive detection of NS1, we fabricated multilayered fluorescent nanocomposites of Fe3O4@AuNPs-DNA3-CDs-Eu@ZIF-8. Additionally, Ab1 was immobilized on protein A/G magnetic beads (A/G MB) for target capture, and the other antibody (Ab2) was conjugated to the DNA1/DNA2 duplex to form target detection probes. In the presence of NS1 protein, the Ab1 immobilized on A/G MB and Ab2 composite (Ab2-DNA1/DNA2) simultaneously recognized the target NS1, and after magnetic separation, EXO III was introduced to hydrolyze the DNA1 strands, resulting in the release of the DNA2 strands. The liberated DNA2 strands hybridize with the complementary DNA3 strands immobilized on Fe₃O₄@AuNPs-DNA3-CDs-Eu@ZIF-8 nanoparticles, forming DNA2/DNA3 duplexes. This hybridization triggers the dissociation of the CDs-Eu@ZIF-8 nanocomposites from the nanoparticle surface. Furthermore, EXO III degrades the DNA3 strands in the duplex, leading to the release of DNA2, which acts as a catalytic DNA walker to initiate cyclic hybridization and degradation events, thereby amplifying the fluorescence signal. The platform demonstrates high sensitivity and a broad dynamic range for NS1 detection, achieving a linear response from 0.02 ng/mL to 10³ ng/mL with a detection limit of 18.2 pg/mL.

Colorectal cancer (CRC) is a serious threat to human health with the third morbidity and the second cancer-related mortality worldwide. It is urgent to explore more effective strategy for CRC because of the acquired treatment resistance from the non-surgical conventional therapies, including radiation, chemotherapy, targeted therapy and immunotherapy. Ferroptosis is a novel form of programmed cell death characterized by iron-dependent lipid peroxidation species (ROS) accumulation and has been identified as a promising target for cancer treatment, especially for those with treatment resistance. In this review, we mainly summarize the recent studies on the influence and regulation of ferroptosis by which (including gut microbiota) modulating the metabolism of iron, amino acid and lipid. Thus this analysis may provide potential targets for inducing CRC ferroptosis and shed lights on the future application of ferroptosis in CRC.

This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone Ⅱ_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.

Background: Coronary heart disease (CHD) is the most common cardiovascular disease facing human beings. Cardiac remodelling is an important pathological factor for the progression of heart failure (HF) after CHD. At present, Chinese medicine is widely used in the treatment of HF, but there are still some drugs lack of evidencebased and mechanism evidence. Multi-omics techniques can deep explore candidate pathogenic factors and construct gene regulatory networks.This trial is intended to evaluate the effect on Huoxin pill (HXP) in the treatment of HF after programmable communication interface (PCI). Meantime, multi-omics analysis technique will be used to target the fundamental pathological links of cardiac remodelling, so as to study the mechanism of HXP in the treatment of HF after PCI. Methods: This study is a randomized, double-blind, placebo-controlled trial. Sixty patients with HF undergoing PCI are recruited from the First Affiliated Hospital of Henan University of CM. All selected patients will be randomly attributed to receive conventional treatment + HXP or placebo. The packaging, dosage and smell of placebo and heart activating pill were identical. The primary outcome is NYHA cardiac function grade, while the secondary outcomes included Lee's HF score, exercise tolerance test, and quality of life evaluation. Additional indicators include cardiac ultrasound, electrocardiogram, 24-h dynamic electrocardiogram, myocardial injury indicators, and energy metabolism indicators. Discussion: This study may provide a new treatment option for patients with HF after PCI and provide evidence for the treatment of CHD and HF with HXP. Trial registration: 2023-10-08 registered in China Clinical Trial Registry, registration number ChiCTR2300076402.