Background Mitochondrial DNA (mtDNA) leakage after myocardial ischemia/reperfusion (MI/R) injury activates inflammation and pyroptosis. Although toll-like receptor 4 (TLR4) is a known mediator of MI/R injury, its interplay with mtDNA remains unclear. This study investigates the cardioprotective mechanism of allicin, focusing on its disruption of the TLR4-mtDNA axis. Purpose This study aimed to clarify the mechanisms of inflammatory response and pyroptosis in MI/R injury and the therapeutic targets of allicin. Methods The cardioprotective mechanism of allicin was investigated in both in vivo and in vitro MI/R models. In Sprague-Dawley rats, different concentrations of allicin were administered pre-reperfusion. Myocardial injury, cytosolic mtDNA leakage, and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 (NLRP3)-gasdermin D (GSDMD) pathways were assessed. Network pharmacology combined with molecular dynamics simulation identified TLR4 as a candidate signaling pathway for validation. In H9C2 cells subjected to OGD/R, the role of TLR4 in mtDNA-induced inflammatory response and pyroptosis, and the therapeutic mechanism of allicin, were studied using TLR4 agonist RS09 and inhibitor resatorvid. Myocardial injury markers, cytosolic mtDNA leakage, cGAS-STING and NLRP3-GSDMD pathway activity, and TLR4 expression were measured. Results In vivo experiments demonstrated that allicin alleviated MI/R injury, suppressed cytosolic mtDNA leakage, and inhibited the cGAS-STING-mediated inflammatory response and the NLRP3-mediated pyroptosis pathways. Subsequent network pharmacology and molecular dynamics simulation identified TLR4 as a potential mediator of these effects. In vitro studies revealed that TLR4 activation promotes mtDNA-dependent inflammation and pyroptosis, which were effectively suppressed by allicin or TLR4 inhibition. Conclusion TLR4 activation aggravates MI/R injury by promoting mitochondrial damage and cytosolic mtDNA leakage, which activates the pro-inflammatory (cGAS-STING) and pro-pyroptotic (NLRP3-GSDMD) pathways. Allicin protects against MI/R injury by inhibiting TLR4 activation and the subsequent mtDNA-induced pathways, thereby reducing inflammation and pyroptosis.

BACKGROUND:PANoptosis is a newly identified form of programmed cell death characterized by necroptosis, pyroptosis, and apoptosis. However, the mechanism of myocardial PANoptosis in myocardial ischemia-reperfusion (MI/R) remains unclear. Allicin is a promising drug for MI/R treatment, and the targets for myocardial PANoptosis remain to be explored. PURPOSE:This study aims to clarify the mechanism of myocardial PANoptosis during MI/R and therapeutic targets of allicin. METHODS:Sprague-Dawley rats were used to establish MI/R models. Allicin (3.6 mg/kg) was injected via the tail vein 5 min before reperfusion. Myocardial damage (cardiac function, structure, cTnT, CK-MB and apoptosis), PANoptosome components (RIPK1/3, caspase-8, ASC and NLRP3), PANoptosis indicators (MLKL, GSDMD, IL-1β/18 and caspase-3) were assessed to evaluate the cardioprotective effects of allicin. Subsequently, the potential signaling pathway related to PANoptosis and therapeutic targets of allicin were screened through transcriptomic analysis, and TLR4 signaling was selected for verification. Then, H9C2 cells were used to establish an oxygen-glucose deprivation/reperfusion (OGD/R) model. The TLR4 inhibitor TAK-242, agonist RS09, and allicin were used to clarify the pathological role of TLR4 in myocardial PANoptosis and the therapeutic target of allicin by measuring the indicators of myocardial damage, PANoptosis and TLR4 expression. RESULTS:In vivo experiments revealed that allicin alleviated MI/R injury and reduced both myocardial PANoptosome components and PANoptosis. Based on transcriptomic analysis and published studies, the TLR4 signaling pathway was selected to verify the pathological role in PANoptosis and the therapeutic effects of allicin. In vitro experiments demonstrated that TLR4 activation further aggravated OGD/R-induced PANoptosis and increased TLR4 expression. Conversely, both allicin and the TLR4 inhibitor suppressed myocardial PANoptosis and TLR4 expression. CONCLUSION:Allicin can reduce myocardial PANoptosis and ameliorate MI/R injury by inhibiting TLR4 activation. These findings provide a new target and strategy for the treatment of MI/R injury.

Background The difference between estimated glomerular filtration rate (eGFRdiff), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation and the CKD-EPI creatinine equation, has significant clinical implications. Objective This study aimed to investigate the association between eGFRdiff and in-hospital mortality in acute coronary syndrome (ACS) patients and assess whether eGFRdiff improves the predictive performance of the Global Registry of Acute Coronary Events (GRACE) score. Methods We retrospectively analyzed data from 3731 ACS patients hospitalized at the China-Japan Friendship Hospital. eGFRdiff was defined as CKD-EPI creatinine-cystatin C eGFR minus CKD-EPI creatinine eGFR. Patients were categorized into negative (eGFRdiff < -10 mL/min/1.73m²), midrange (-10 to 10 mL/min/1.73m²), and positive (>10 mL/min/1.73m²) groups. The primary outcome was in-hospital death. Results During hospitalization, 146 (3.91%) patients died. Multivariable logistic regression analysis demonstrated that lower eGFRdiff was independently associated with higher in-hospital mortality (negative vs. midrange group: odds ratio [OR] 1.84, 95% confidence interval [CI] 1.14-2.98; per 10 mL/min/1.73m² increment: OR 0.71, 95% CI 0.58-0.87). Restricted cubic splines analysis revealed a nonlinear relationship between eGFRdiff and in-hospital mortality in the overall cohort and chronic kidney disease (CKD) subgroup, but a linear association in non-CKD patients. Incorporating eGFRdiff into the GRACE score improved its predictive accuracy for in-hospital mortality, particularly in non-CKD patients. Conclusion eGFRdiff is inversely associated with in-hospital mortality risk in ACS patients. The integration of eGFRdiff into the GRACE score enhances risk stratification, suggesting that monitoring eGFRdiff may aid in clinical decision-making for ACS management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among patients with cardiovascular disease but remains underrecognized in routine cardiology practice. To address the limited prospective evidence on its progression and clinical impact, we established the CHAIN cohort, a prospective multicenter study enrolling approximately 15 000 adults undergoing coronary evaluation across 40 tertiary hospitals in China. Baseline assessment includes comprehensive cardiometabolic profiling and vibration-controlled transient elastography for evaluation of liver fibrosis and steatosis. Participants will undergo long-term follow-up with repeated liver assessments every 6-12 months. Primary outcomes include liver-related events and major adverse cardiovascular events, while secondary outcomes include longitudinal changes in liver fibrosis and steatosis and their associations with cardiometabolic risk factors and clinical outcomes. This cohort will provide longitudinal evidence to support risk stratification and integrated heart-liver management in cardiovascular care.

This manuscript describes the successful use of a dual-balloon overlapping post-dilation technique to achieve optimal stent expansion and apposition in a markedly dilated right coronary artery (RCA) where conventional high-pressure post-dilation with a single, maximum-sized non-compliant balloon failed.

ObjectiveTo investigate the differences in two-dimensional speckle tracking echocardiography (2D-STE) parameters among patients with different types of acute decompensated heart failure (ADHF) and their correlation with left ventricular ejection fraction (LVEF).MethodsNinety-eight patients hospitalized due to ADHF were included in this study. Patients were divided into two subgroups based on their LVEF using a cutoff of ≤49%: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). All patients underwent transthoracic echocardiography and 2D-STE.ResultsCompared to the HFrEF group,the HFpEF group showed significantly higher absolute values of GLSA4C, GLSA2C, GLSA3C, and LV-GLS values (P < 0.05), as well as higher absolute values of LASR-ED, LASRD-ED, LASRT-ED, RVFWSL, and RV4CSL values (P < 0.05). The HFrEF subgroup had higher LAFI and LASI values compared to the HFpEF group (P < 0.05). In the HFrEF subgroup, LVEF was negatively correlated with GLSA4C, GLSA2C, GLSA3C, LV-GLS, RVFWSL, RV4CSL, LASr-ED, LASrct-ED, as well as LAFI and LASI (P < 0.05). However, LVEF was positively correlated with LASrcd-ED (P < 0.05). In the HFpEF subgroup, LVEF was negatively correlated only with GLSA4C, GLSA2C, GLSA3C and LV-GLS (P < 0.05). After controlling for related variables (LVEF), the correlations between LV-GLS and LASr-ED, LASrcd-ED, and LASrct-ED remained significant in both groups of heart failure patients (P < 0.05). In HFrEF patients, the correlations between RVFWSL and LASr-ED, LASrcd-ED, and LASrct-ED disappeared (P > 0.05). In HFpEF patients, RVFWSL was negatively correlated with LASr-ED (P < 0.05), positively correlated with LASrct-ED (P < 0.05), but its correlation with LASrcd-ED disappeared (P > 0.05).ConclusionSignificant differences exist in 2D-STE parameters between the HFrEF and HFpEF groups, and LVEF correlates with these parameters. After adjusting for LVEF, LV-GLS remains correlated with various parameters in different heart failure groups. Our findings suggest a stronger interdependence between right ventricular and left atrial mechanics in HFpEF patients compared to HFrEF patients, evidenced by the persistence of correlations between RV free wall strain and LA reservoir/pump strain after adjusting for LVEF.

BackgroundCoronary microvascular disease (CMVD) is a major cause of angina in patients with ischemia and nonobstructive coronary arteries (INOCA) syndrome. It is characterized by an imbalance between myocardial oxygen supply and demand, leading to reduced exercise tolerance and impaired quality of life. Because of heterogeneous diagnostic approaches and the lack of disease-modifying therapies, CMVD remains underdiagnosed and undertreated. Shexiang Tongxin Dropping Pill (STDP), a traditional Chinese medicine formulation, has shown protective effects on the coronary microvasculature in preclinical and preliminary clinical studies. However, high-quality randomized evidence and objective functional validation are still lacking. This study therefore aims to evaluate the efficacy and safety of STDP in patients with CMVD using cardiopulmonary exercise testing (CPET) as the primary functional outcome and to develop an artificial intelligence (AI)-assisted myocardial contrast echocardiography (MCE) tool to improve CMVD detection and subgroup classification.DesignThis is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial with a nested diagnostic design. CMVD will be diagnosed by stress MCE, and eligibility will require evidence of reduced myocardial perfusion or perfusion defects. Eligible patients with CMVD will be randomized at a 1:1 ratio to receive STDP or a matched placebo for 12 weeks. The primary endpoint is the change in peak oxygen uptake (peak VO₂) measured by cardiopulmonary exercise testing (CPET). The secondary outcomes include other CPET indices, angina severity, quality of life, and circulating biomarkers. The nested diagnostic study uses retrospectively and prospectively collected MCE datasets to develop AI-based models for automated myocardial segmentation, perfusion curve analysis, and CMVD classification, with performance assessed against established reference standards.DiscussionBy combining quantitative microvascular imaging, functional exercise assessment, and AI-assisted diagnostics in a single protocol, this study proposes a therapeutic-diagnostic framework for CMVD. This study is expected to provide high-quality randomized evidence for the use of STDP in CMVD and to offer a scalable and objective approach to improve diagnosis, risk stratification, and individualized management in patients with functional coronary ischemia.Clinical Trial registrationhttp://itmctr.ccebtcm.org.cn/, International Traditional Medicine Clinical Trial Registry (ITMCTR), TMCTR2025000414.

To investigate the prevalence, distribution and ablation of non-pulmonary vein (PV) triggers in older patients with paroxysmal atrial fibrillation (AF). A total of 694 patients aged 65–80 receiving index ablation for paroxysmal AF were included. These patients were divided as follows: patients without low-voltage areas (LVA) (n = 437), LVA patients with modification (n = 175), and LVA patients without modification (n = 82). Following propensity score matching (PSM) analysis, two sets of matched groups emerged: LVA patients without modification (Group A, n = 77) and patients without LVA (Group B, n = 77), and patients without LVA (Group C, n = 168) and LVA patients with modification (Group D, n = 168). The clinical endpoint was defined as the detection of ATA lasting longer than 30 s through ECG documentation or Holter recordings following the index ablation. Fifty-seven (8.2

OBJECTIVE:To investigate the efficacy and potential mechanisms of MGFKP on rabbit atherosclerotic models. METHODS:The left carotid balloon injury surgery were used to establish the rabbit atherosclerotic model, followed by the administration of MGFKP from the second postoperative for 6 weeks. Left carotid ultrasound and histological analysis were determined to evaluate the anti-atherosclerotic efficacy of MGFKP. Additionally, LC-MS and network pharmacology were conducted to identify the active ingredients of MGFKP and their targets, respectively. Lastly, core targets were selected to validate using immunohistochemical staining, western blot or ELISA. RESULTS:The results revealed that the vascular diameters difference, plaque area, plaque thickness, and ratio of vessel lumen to vessel cross-section radius were significantly improved following treatment with MGFKP (P<0.05). 539 ingredients of MGFKP were identified by LC-MS, and 23 ingredients were screened using SwissADME for network pharmacology. After combining the results of PPI and KEGG analyses with published literature, TLR4, NF-κB, IL-1β, and TNF-α were selected for the ensuing analyses. Molecular docking of most compounds showed satisfactory docking energy between TLR4, NF-κB, IL-1β, and TNF-α with their matched compounds. Finally, immunohistochemical analysis of TLR4 and western blot results of NF-κB, TNF-α, and IL-1β demonstrated that these proteins levels were obviously increased in the model group and significantly decreased in MGFKP group (P<0.05). The levels of TNF-α, IL-6, IL-1β were also significantly reduced following MGFKP treatment. CONCLUSIONS:MGFKP is a potential drug for the treatment of atherosclerosis, and might suppress the TLR4/NF-κB inflammatory pathway to alleviate atherosclerotic plaque progression.

Background: Significant differences often exist between estimated glomerular filtration rates (eGFR) calculated using various biomarkers. However, the relationship between these eGFR methods and atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) remains unclear. Methods: Thus, this study employed a retrospective analysis of 523 patients with AF who underwent an initial RFCA between July 2019 and October 2022. The eGFR was calculated using three methods based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula: serum creatinine (eGFRcr), serum cystatin C (eGFRcys), and a combination of both (eGFRcrcys). Cox regression models were used to explore the relationship between eGFR and AF recurrence. Results: Over a 1-year follow-up period, 174 (33.3%) patients experienced AF recurrence after RFCA. Multivariable Cox regression analysis indicated that only eGFRcys showed a consistent, significant inverse association with AF recurrence (hazard ratio (HR) = 0.990, 95% confidence interval (CI): 0.982–0.998, p = 0.019). In contrast, eGFRcrcys showed borderline significance after full adjustment (p = 0.067). Meanwhile, stratifying by optimal cutoff values identified an association for eGFRcys ≤64.280 mL/min/1.73 m2, and eGFRcrcys ≤76.093 mL/min/1.73 m2 with significantly higher recurrence risks after full adjustment (p = 0.008 and p = 0.036, respectively). Additionally, incorporating eGFRcys or eGFRcrcys into the baseline risk model led to a greater improvement in predictive accuracy than adding eGFRcr. Conclusions: The association between eGFR and AF recurrence after ablation appears to vary depending on the measurement methods; eGFRcys seems to provide the most reliable information. Incorporating eGFRcys into the pre-ablation risk stratification may enhance patient management and improve outcomes for patients undergoing AF ablation.

Background:Acute myocardial infarction (AMI) is a significant contributor to global morbidity and mortality. Allicin exhibits promising therapeutic potential in AMI as a primary bioactive component derived from garlic; however, its underlying mechanisms remain incompletely elucidated. Methods:Our study induced AMI in mice by ligating the left coronary artery, and administered allicin orally for 28 days. The cardioprotective effects of allicin treatment were comprehensively assessed using echocardiography, histopathological examinations, intestinal barrier function, and serum inflammatory factors. The potential mechanisms of allicin were elucidated through analysis of metagenomics and serum metabolomics. Network pharmacology (NP) was used to further investigate and validate the possible molecular mechanisms of allicin. Results:Our findings revealed allicin's capacity to ameliorate cardiac impairments, improve intestinal barrier integrity, and reduce serum IL-18 and IL-1β levels after AMI. Further analysis demonstrated that the administration of allicin has the potential to ameliorate intestinal flora disorder following AMI by modulating the abundance of beneficial bacteria, such as g_Lactobacillus, g_Prevotella, g_Alistipes, and g_Limosilactobacillus, while reducing the abundance of harmful bacteria g_Parasutterella. Additionally, it exhibits the ability to enhance myocardial energy metabolism flexibility through modulating metabolites and key enzymes associated with the fatty acid metabolic pathway. Mechanistically, NP and in vivo experiments indicated that allicin might suppress pyroptosis and reduce inflammatory response via blocked activation of the NF-κB-mediated NLRP3/Caspase-1/GSDMD pathway. Moreover, Spearman correlation analysis suggested a significant association between the allicin-induced alterations in microbiota and metabolites with cardiac function and inflammatory cytokines. Conclusion:Our study demonstrated that allicin alleviated myocardial injury and reduced inflammatory response by inhibiting the NF-κB-mediated NLRP3/Caspase-1/GSDMD pathway while remodeling microbiota disturbance, improving serum metabolic disorder, and enhancing the intestinal barrier. These research findings offer a novel perspective on the potential therapeutic value of allicin as an adjunctive dietary supplement to conventional treatments for AMI.

Background: Anemia and iron deficiency (ID) are common in patients with acute myocardial infarction (AMI), especially those in intensive care units (ICU). This study investigated the impact of hemoglobin (Hb) and ID on the short-term mortality of critically ill patients with AMI. Methods: Overall 992 AMI patients with their first ICU admission were included in this analysis. ID was defined as serum ferritin <100 ng/mL or transferrin saturation (TSAT) <20%. Patients were categorized into four groups according to their Hb concentrations and the presence of ID. Kaplan-Meier survival analysis was used to assess differences in all-cause mortality between the different groups, and Cox regression models to identify risk factors for all-cause mortality. Results: Anemia was present in 89.5% of patients, while 65.9% suffered from ID. Patients in the group with Hb <9 g/dL and without ID were the youngest, yet they exhibited the highest severity scores. The Kaplan–Meier analysis showed that this group had a higher rate of all-cause mortality compared to the other three groups (Log-rank test p = 0.005). Moreover, multivariate Cox regression analysis revealed that Hb <9 g/dL and no ID was associated with a higher risk of all-cause mortality at 120 days (hazard ratio 1.512, 95% confidence interval 1.031–2.217, p = 0.034) when compared to the reference group (Hb ≥9 g/dL and no ID). Additionally, multivariate Cox regression analysis showed that lower Hb was linked to increased rates of all-cause mortality at 30, 60, 90, and 120 days. Elevated levels of ferritin and TSAT were also associated with increased all-cause mortality at 60, 90, and 120 days. Compared to patients without ID, those with ID had a decreased risk of all-cause mortality at 60, 90, and 120 days. Conclusions: Anemia and ID were prevalent in ICU patients with AMI. Patients with Hb <9 g/dL and without ID showed higher 120-day all-cause mortality. Additionally, lower Hb, elevated ferritin, and increased TSAT levels were identified as significant risk factors for short-term all-cause mortality in these patients.

Objective: The study attempted to explore how allicin reduces oxidative stress levels by promoting SHP2 expression to inhibit p-PERK in I/R mice. Methods: The GEO database and RNA sequencing were used to predict downstream gene. TTC staining was used to visualize the myocardial infarction area. Masson staining was used to assess the level of fibrosis. IF was used to examine the expression of SHP2, CTGF, ROS. RT-PCR analysis was used to quantify the expression of SHP2 mRNA. Western blot was used to detect the protein expression levels of SHP2, p-PERK, MFN1, NLRP3, NOX2, and NOX3. Results: GEO and transcriptomic data revealed low expression of SHP2 in the heart tissues I/R mice. In the I/R mouse model, TTC staining result showed that allicin can reduce the area of myocardial infarction; Masson staining results indicated that allicin can reduce fibrosis; Macrophage transcriptome sequencing found SHP2 is a target gene of allicin; Immunofluorescence showed allicin can increase SHP2; qPCR results showed allicin can raise SHP2 mRNA level; Immunofluorescence indicated that allicin can inhibit ROS in myocardial infarction tissue, but the specific SHP2-KD eliminates changes in ROS. Western blot analysis demonstrated allicin can increase SHP2 protein and reduce the expression of p-PERK, MFN1, NLRP3, NOX2, and NOX3; SHP2-KD eliminates the expression differences in p-PERK, MFN1, NLRP3, NOX2, and NOX3. Conclusions: Allicin can modulate p-PERK activation by enhancing the expression of SHP2, thereby inhibiting myocardial ischemia-reperfusion-induced oxidative stress in mice.

Cardiovascular disease (CVD) remains the predominant cause of mortality and disability worldwide. Against this backdrop, finding effective drugs for the pharmacological treatment of CVD has become one of the most urgent and challenging issues in medical research. Garlic (Allium sativum L.) is one of the oldest plants and is world-renowned for its dietary and medicinal values. Allicin (diallyl thiosulfinate) is one of the primary natural active ingredients in garlic, which has been proven to have powerful cardioprotective effects and mediate various pathological processes related to CVD, such as inflammatory factor secretion, myocardial cell apoptosis, oxidative stress, and more. Therefore, allicin holds a promising application prospect in the treatment of CVD. This review summarized the biological functions of allicin and its potential mechanisms in CVD, including antioxidation, anti-inflammation, and anti-apoptosis effects. Reckoning with these, we delved into recent studies on allicin's cardioprotective effects concerning various CVDs, such as atherosclerosis, hypertension, myocardial infarction, arrhythmia, cardiac hypertrophy, heart failure, and cardiotoxicity. Further, considering the tremendous advancement in nanomedicine, nanotechnology-based drug delivery systems show promise in addressing limitations of allicin's clinical applications, including improving its solubility, stability, and bioavailability. Through this review, we hope to provide a reference for further research on allicin in cardioprotection and drug development.

BACKGROUND AND AIMS:Iron deficiency is a major public health concern. We aimed to assess the predictive capability of 4 iron metabolism biomarkers for all-cause and cardiovascular disease-specific mortality in U.S. patients with congestive heart failure (CHF). METHODS AND RESULTS:1904 CHF patients aged ≥20 years were enrolled from NHANES, 1999-2000 to 2017-2018. All analyses were weighted to provide nationally representative estimates. Among 1905 CHF patients, mean age was 71 years, and 1024 (53.8%), 459 (24.1%), 206 (10.8%), and 216 (11.3%) were Non-Hispanic Black, Non-Hispanic White, Hispanic-Mexican American, and Hispanic-Other Hispanic, respectively. During follow-ups, 1080 deaths occurred. Median follow-up time was 5.08 years. Per-unit increase in natural-logarithmic-transformed iron and transferrin saturation decreased all-cause mortality risk separately by 33.0% (adjusted hazard ratio: 0.670, 95% confidence interval: 0.563 to 0.797, P < 0.001) and 32.6% (0.674, 0.495 to 0.917, 0.013), and per-unit increase in transferrin receptor increased mortality risk by 33.7% (1.337, 1.104 to 1.618, 0.004). Two derivates from 3 significant iron biomarkers were generated - transferrin receptor to natural-logarithmic-transformed iron ratio (TRI) and transferrin receptor to natural-logarithmic-transformed transferrin saturation ratio (TRTS), which were significantly associated with all-cause mortality, with per-unit increase corresponding to 2.692- and 1.655-fold increased all-cause mortality risk (P: 0.003 and 0.023). Only iron and TRTS were associated with the significant risk of cardiovascular disease-specific mortality (P: 0.004 and 0.017). CONCLUSIONS:Our findings identified 3 iron metabolism biomarkers that were individually, significantly, and independently associated with all-cause mortality in patients with CHF, and importantly 2 derivates generated exhibited stronger predictive capability.

This study aims to explore the specific mechanism by which miR-155 regulates SHP2 expression in mouse ischemia-reperfusion (I/R) induced necroptosis. Various methods including cardiac ultrasound, TTC staining, Masson staining, TUNEL staining, and Western blotting were used to examine changes in the morphology and function of the rat left ventricle, myocardial fibrosis, as well as the expression of proteins related to tissue and cardiomyocyte necroptosis pathways. In vivo results showed that knockdown (KD) of miR-155 significantly improved cardiac ultrasound parameters (EF, FS, LVAW;d, and LVAW;s), reduced the myocardial infarction area, myocardial fibrosis, and cell apoptosis in I/R mice, upregulated cardiac SHP2 protein expression, and other proteins including p-ERK1/2, NLRP3, GSDMD, caspase-3, caspase-4, and caspase-11 were also significantly decreased. In vitro experiments showed that compared with the SHP2 WT miR-155 KD group, SHP2 protein expression was significantly increased in the SHP2 WT miR-155 KD group, while the expression of other proteins was significantly reduced, consistent with in vivo results. MiR-155 can regulate ERK1/2 and NLRP3 through SHP2. After adding the ERK1/2 inhibitor U0126 to cardiomyocytes from SHP2 KO mice, it was found that the expression of proteins other than SHP2 significantly decreased compared to SHP2 KO cells without the inhibitor. In summary, low expression of miR-155 promoted the expression of SHP2 and improved mouse I/R-induced necroptosis by inhibiting the activation of the ERK1/2 pathway.

IntroductionMany causes lead to sympathetic-vagus imbalance, which promotes the development of hypertension and accelerates the process of target organ damage. Many studies have shown that exercise training and heart rate variability (HRV) biofeedback can improve diseases caused by autonomic nerve dysfunction, such as hypertension. Based on these theories and the Yin-Yang balance theory of traditional Chinese medicine and Cannon’s homeostasis theory, we have developed an assessment system of autonomic nerve regulation system and a harmony instrument. In this study, we aimed to find a new way to control blood pressure of hypertensive patients via cardiopulmonary resonance indices-based respiratory feedback training.Methods and analysisThis is a prospective, randomised, parallel-controlled clinical trial, which aims to evaluate the effectiveness and safety of biofeedback therapy and exercise rehabilitation combined intervention in hypertension management. 176 healthy individuals will be recruited to get their autonomic nerve function parameters as normal control, while 352 hypertensive patients will be enrolled and randomly divided into a conventional treatment group and an experiment group in a ratio of 1:1. All patients will continue to receive standard hypertension blood pressure treatment, except that patients in the experiment group will have to complete additional daily respiratory training for 6 months. The primary outcome is the difference of clinical systolic blood pressure (SBP) between the two groups after 6 months of intervention. The secondary outcomes include the changes in the mean SBP and diastolic blood pressure (DBP) by 24-hour blood pressure monitoring, home SBP, clinical and home DBP, clinical and home heart rate, the standard-reaching rate of clinic and home SBP and the incidence of composite endpoint events at 6 months.Ethics and disseminationThis study has been approved by the clinical research ethics committee of China-Japan Friendship Hospital (No. 2018-132 K98-2), the results of this study will be disseminated via peer-reviewed publications or conference presentations.Trial registration numberChinese Clinical Trial Registry, ChiCTR1800019457, registered on 12 August 2018.

In order to explore the computerized tomography (CT) based on three-dimensional reconstruction of coronary artery model, the functional evaluation was made after percutaneous coronary intervention (PCI). In this study, 90 patients with coronary heart disease who received elective PCI were selected. The blood flow reserve fraction (FFR) and SYNTAX score were calculated by three-dimensional reconstruction of CT images, followed up for 2–4 years. According to the SYNTAX score, 0–22 points were defined as the low group (28 cases), 23–32 points as the medium group (33 cases), and 33 points as the high group (29 cases). In this paper, the accuracy, sensitivity, and specificity of CT images of three-dimensional reconstructed coronary artery model are 91%, 73%, and 62%, respectively. The follow-up results showed that the incidence of major adverse cerebrovascular events in the high group was significantly higher than that in the low group and the middle group, and the difference was statistically significant ( P < 0.05). Pearson correlation analysis showed that SYNTAX score was related to serum total cholesterol ( r  = 0.234, P = 0.003), triglyceride ( r  = 0.237, P = 0.014), low-density lipoprotein cholesterol ( r  = 0.285, P = 0.004), and ApoB/ApoA1 ( R  = 0.004). In this study, FFR is calculated by CT images based on three-dimensional reconstruction of coronary artery model, which can provide support for the diagnosis and treatment of coronary heart disease. SYNTAX score can be used as a risk predictor for PCI patients with coronary heart disease.

This study aims to investigate the regulatory effect of Xuesaitong (XST) and miR-3158-3p on angiogenesis. All mice were randomly assigned into Sham group, Model group, XST group, XST + miR-3158-3P-overexpression (miRNA-OE) group. XST was found to increase the left ventricular anterior wall thickness at end diastole and end systole (LVAWd and LVAWs), left ventricular internal dimension at end diastole and end systole (LVIDd and LVIDs), fractional shortening (FS), and ejection fraction (EF) and decrease the proportion of fibrotic areas in mice. In contrast to those in Sham group, the protein expressions of Nur77, p-PI3K, HIF-1α, VEGFs, COX-2 in the heart tissues of mice in Model group were elevated and further increased after XST treatment in comparison with those in Model group. Nur77-/- mice were utilized. It was found that XST enhanced cell viability through a methyl thiazolyl tetrazolium assay and facilitated angiogenesis in each group, as assessed by a catheter formation assay. Specifically, XST was shown to promote the formation of blood vessels. Moreover, the protein expression levels of Associated proteins in the heart tissues of Nur77-/- mice were dramatically reduced in mice in Model and XST group compared with those in WT mice. Additionally, the above-mentioned protein expressions in the heart tissues of Nur77-/- mice did not change significantly in mice in Model + miRNA-OE + XST group compared with those in WT mice, suggesting that miR-3158-3p can specifically inhibit the expression of Nur77. In conclusion, XST inhibits miR-3158-3p targeting Nur77 to facilitate myocardial angiogenesis in mice with myocardial infarction.