Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of nigral dopaminergic neurons and abnormal α-synuclein (α-syn) aggregation. Growing evidence indicates that impaired autophagy–lysosome pathway (ALP) activity in microglia exacerbates the pathological process; however, the precise regulatory mechanisms involved remain elusive. In this study, we found that Irgm1, a key autophagy regulator, was markedly upregulated in the midbrains of PD mice. Irgm1-deficient mice exhibited accelerated PD progression, more severe motor deficits, greater TH⁺ neuronal loss, increased α-syn deposition and aggravated ALP damage, indicating a neuroprotective role for Irgm1. Moreover, Irgm1 was selectively enriched in the microglia of PD mice, and Irgm1 knockdown amplifiedα-syn-preformed fibril (PFF)-induced ALP impairment: the LC3-II and cathepsin D levels decreased, p62 and α-syn aggregates accumulated, the colocalization of α-syn with Lamp1 declined, lysosomal acidification decreased, and TFEB nuclear translocation was blocked. The TFEB-activating autophagy agonist rapamycin restored TFEB nuclear translocation, reactivated the ALP, accelerated α-syn clearance, and abolished the increased toxicity of Irgm1-deficient microglia toward cocultured SH-SY5Y neurons after PFFs preexposure. Thus, Irgm1 promotes microglial α-syn clearance via the TFEB-ALP axis, and targeting this pathway could be a potential therapeutic strategy for PD.

BACKGROUND AND AIMS:To examine the clinical significance and prognostic value of total coronary artery non-culprit residual lipid burden (RLB) after percutaneous coronary intervention in acute myocardial infarction (AMI) patients. METHODS:A total of 1312 AMI patients who underwent three-vessel optical coherence tomography (OCT) were divided into low RLB group (n = 656) and high RLB group (n = 656) based on median value of OCT-derived RLB (total lipid index of all non-culprit lesions). Patients were followed for up to 5 years (median 4.1 years). Major adverse cardiovascular events (MACE) were recorded. RESULTS:The high RLB group had more frequent multi-vessel disease, non-culprit plaque rupture, thin-cap fibroatheroma (TCFA: 53.8% vs. 11.0%), and other vulnerable plaque features (all p < 0.001) than the low RLB group. After adjusting for clinical risk factors, a high RLB independently predicted non-culprit plaque rupture, TCFA, and vulnerable plaque features. Patients with a high RLB had a significantly greater incidence of 5-year non-culprit lesion-related MACE (8.4% vs. 2.6%, adjusted HR: 3.84, 95%CI: 1.98-7.45) than patients with a low RLB; most events were ischemia-driven revascularization. When a high RLB and non-culprit TCFA were simultaneously added to the model, a high RLB remained predictive (p = 0.002), but non-culprit TCFA was no longer predictive (p = 0.079). When used as a continuous variable, the prognostic value of RLB was attenuated (AUC = 0.63). Moreover, the association of RLB with plaque vulnerability and outcomes was observed in both sexes. CONCLUSIONS:OCT-derived RLB was associated with pancoronary plaque characteristics in AMI patients. A high RLB predicted 5-year adverse events independent of TCFA.

Introduction:Hypertension poses a significant threat to human health through its induction of cardiac damage. The calcium-sensing receptor (CaSR) has been implicated in cardiovascular diseases; however, its specific role in cardiomyocyte injury in spontaneously hypertensive rats (SHRs) remains unclear. This study therefore investigated the effects of Calhex231, a CaSR antagonist, on cardiac damage in SHRs.Methods:Cardiac function and structure were evaluated by echocardiography, histological staining and transmission electron microscopy. To explore the underlying mechanisms, CaSR expression along with markers of mitophagy, autophagy and apoptosis were assessed in rat hearts tissues via Western blotting. Furthermore, mitochondrial membrane potential and intracellular calcium levels were measured in angiotensin II (Ang II)-treated cardiomyocytes at the cellular level.Results:Relative to WKY rats, SHRs showed elevated blood pressure, cardiac injury (hypertrophy, fibrosis, apoptosis), and upregulated CaSR, mitophagy and autophagy. Calhex231 reversed these in-vivo pathologies and, in vitro, protected cardiomyocytes against Ang II-induced apoptosis. This protection was achieved by inhibiting mitophagy/autophagy, lowering [Ca2+]i, and preserving mitochondrial membrane potential. The pivotal role of CaSR was underscored by the fact that its knockdown reproduced the protective effects against Ang II.Conclusion:These findings suggests that Calhex231 protects against cardiomyocyte apoptosis by inhibiting both the PINK1/Parkin-mediated mitophagy pathway and general autophagy. Therefore, targeting the CaSR represents a promising therapeutic strategy to prevent cardiac damage induced by hypertension.

BACKGROUND:This study aimed to investigate plaque characteristics and long-term outcomes associated with long non-culprit lesions (NCLs) in patients with acute myocardial infarction (AMI). METHODS:A total of 1278 AMI patients undergoing three-vessel optical coherence tomography (OCT) were retrospectively enrolled, and 5131 NCLs were identified. A long lesion was defined as an OCT lesion ≥20 mm in length. Patients were followed for up to 5 years, and NCL-related major adverse cardiovascular events (NCL-MACE) were recorded. RESULTS:Both at the patient and lesion level, long NCLs were more stenotic and had more frequent thin-cap fibroatheroma (TCFA) and other vulnerable plaque features than short NCLs (all P < 0.001). During a median follow-up of 4.1 years, patients with ≥1 long NCL had a significantly higher incidence of NCL-MACE than patients without long NCL (7.3% vs. 2.9%, adjusted HR: 2.26, 95%CI: 1.19-4.29). Similar findings were identified when patients were grouped by angiographic lesion length. In the lesion-level analysis, OCT-detected long NCLs remained significantly associated with NCL-MACE after adjustment for TCFA (adjusted HR: 1.97, 95%CI: 1.11-3.52), whereas angiography-detected long NCLs showed no prognostic value. Notably, OCT-detected long TCFA had highest lesion-specific risk (5.4% vs. 1.1%, adjusted HR: 3.69, 95%CI: 1.87-7.27), whereas risk of OCT-detected short TCFA was comparable to that of non-TCFA (1.1% vs. 1.1%, P = 0.986). CONCLUSIONS:Long NCLs were indicative of higher levels of pancoronary plaque vulnerability, irrespective of detection via OCT or angiography. Importantly, OCT-detected long NCLs, especially long TCFA, offered significant predictive value for 5-year adverse events. However, angiography-detected long NCLs lacked prognostic significance.

This study investigated Hippo signaling pathway-related biomarkers in acute myocardial infarction (AMI). First, differentially expressed genes (DEGs) between AMI patients and controls were identified. Consensus clustering then classified AMI subtypes, followed by subtype-specific DEG screening. Candidate genes were derived from intersecting initial DEGs with subtype-associated DEGs. Three machine-learning algorithms prioritized five biomarkers (NAMPT, CXCL1, CREM, GIMAP6, and GIMAP7), validated through multi-dataset analyses and cellular expression profiling. qRT-PCR and Western blot confirmed differential expression patterns between AMI and controls across experimental models. Notably, NAMPT, CXCL1, and GIMAP6 exhibited cell-type-specific expression in endothelial cells and macrophages. We further predicted 179 potential therapeutic agents targeting these biomarkers. Niclosamide and eugenol were observed to mitigate hypoxia-induced injury in neonatal mouse ventricular cardiomyocytes. In vivo experiments demonstrated upregulated NAMPT/CXCL1 and downregulated GIMAP6/GIMAP7 in AMI myocardial tissues, with significant NAMPT protein elevation. These biomarkers show clinical diagnostic potential and provide mechanistic insights into AMI pathogenesis.

Background: Recently, lipoprotein(a) [Lp(a)], a genetically determined low-density lipoprotein-like particle, has been recognized as a potential therapeutic target for residual cardiovascular risk. In-stent restenosis remains one of major clinical challenges for patients undergoing stent implantation. This study aimed to investigate the association between Lp(a) level and optical coherence tomography (OCT)-defined ISNA as well as plaque vulnerability in patients with acute coronary syndrome (ACS). Methods: From January 2017 to December 2021, 146 ACS patients with ISR undergoing OCT-guided intervention were enrolled. Baseline serum Lp(a) levels were measured via latex particle-enhanced turbidimetric immunoassay (Roche Diagnostics) and categorized into high (≥75 nmol/L, n=34) and low (<75 nmol/L, n=112) groups. Clinical profiles, angiographic features, and OCT data were compared between groups. Multivariate logistic regression adjusted for covariates was performed to identify independent associations. The primary endpoint was the presence of in-stent neoatherosclerosis (ISNA). Results: The cohort had a mean age of 62.3±8.9 years, with 73.3% (107/146) males. Elevated Lp(a) (≥75 nmol/L) was observed in 23.3% (34/146) of patients. Compared to the low Lp(a) group, the high Lp(a) group exhibited significantly higher rates of ISNA (91.2% vs. 50.9%, P<0.001), thin-cap fibroatheroma (TCFA) (38.2% vs. 8.0%, P<0.001), macrophage accumulation (82.4% vs. 64.3%, P=0.047). Conversely, homogeneous neointima was more prevalent in the low Lp(a) group (41.1% vs. 4.2%, P<0.001). Multivariate analysis confirmed that elevated Lp(a) independently correlated with ISNA (OR: 1.012, 95% CI: 1.004–1.020; P=0.002) and TCFA (OR: 1.010, 95% CI: 1.005–1.016; P<0.001). Conclusion: In ACS patients with ISR, Lp(a) ≥75 nmol/L is independently associated with increased risks of ISNA and vulnerable plaque phenotypes. These findings highlight the potential role of Lp(a) in ISR pathogenesis and suggest its utility in risk stratification and targeted therapeutic strategies.

Diabetes-associated cognitive dysfunction (DACD) is a complication of diabetes mellitus that leads to an increased risk of cognitive impairment and dementia. However, the molecular mechanism underlying DACD has not been elucidated, and a promising therapy for this disease remains to be established. Hydrogen sulfide (H2S), a significant antioxidative and anti-inflammatory gasotransmitter, has emerged as a neuroprotective agent. In this study, we investigated the protective effects of H2S on DACD in a streptozotocin (STZ)-induced diabetic rat model. We applied the Morris water maze to evaluate spatial learning and memory abilities. We used Western blotting and immunohistochemical staining to investigate the expression of the Nrf-2/HO-1 axis and the NLRP3 inflammasome. After NaHS (H2S donor) administration, diabetic rats exhibited improved spatial learning and memory retrieval abilities in the Morris water maze. In STZ-induced diabetic rats, the protein expression levels of the Nrf-2/HO-1 axis, the NLRP3 inflammasome and subsequent inflammatory cytokines in the hippocampal region were elevated compared to those in control rats. Exogenous H2S triggered Nrf-2/HO-1 antioxidant activity and inhibited NLRP3 inflammasome activation and proinflammatory cytokine expression. These findings suggested that exogenous H2S has neuroprotective effects by modulating the Nrf-2/HO-1 axis and the NLRP3 inflammasome pathway, which were found to be associated with DACD. H2S treatment may be a promising therapeutic strategy for preventing the progression of tissue damage caused by DACD.

Respiratory tract infections are the most common triggers for heart failure in elderly people. The healthy respiratory commensal microbiota can prevent invasion by infectious pathogens and decrease the risk of respiratory tract infections. However, upper respiratory tract (URT) microbiome in the elderly is not well understood. To comprehend the profiles of URT microbiota in the elderly, and the link between the microbiome and heart failure, we investigated the oropharyngeal (OP) microbiome of these populations in Heilongjiang Province, located in the North-East of China, a high-latitude and cold area with a high prevalence of respiratory tract infection and heart failure. Taxonomy-based analysis showed that six dominant phyla were represented in the OP microbial profiles. Compared with young adults, the OP in the elderly exhibited a significantly different microbial community, mainly characterized by highly prevalent Streptococcus, unidentified_Saccharibacteria, Veillonella, unidentified_Pre votellaceae, and Neisseria. While unidentified_Prevotellaceae dominated in the young OP microbiome. There was competition for niche dominance between Streptococcus and member of Prevotellaceae in the OP. Correlation analysis revealed that the abundance of unidentified_Saccharibacteria was positive, while Streptococcus was negatively correlated to age among healthy elderly. The bacterial structure and abundance in the elderly with heart failure were much like healthy controls. Certain changes in microbial diversity indicated the potential OP microbial disorder in heart failure patients. These results presented here identify the respiratory tract core microbiota in high latitude and cold regions, and reveal the robustness of OP microbiome in the aged, supplying the basis for microbiome-targeted interventions.IMPORTANCETo date, we still lack available data on the oropharyngeal (OP) microbial communities in healthy populations, especially the elderly, in high latitude and cold regions. A better understanding of the significantly changed respiratory tract microbiota in aging can provide greater insight into characteristics of longevity and age-related diseases. In addition, determining the relationship between heart failure and OP microbiome may provide novel prevention and therapeutic strategies. Here, we compared OP microbiome in different age groups and elderly people with or without heart failure in northeastern China. We found that OP microbial communities are strongly linked to healthy aging. And the disease status of heart failure was not a powerful factor affecting OP microbiome. The findings may provide basic data to reveal respiratory bacterial signatures of individuals in a cold geographic region.

Vascular remodeling is the main pathological process that causes the damage of the target organ of hypertension. Perivascular adipose tissue (PVAT) surrounds blood vessels and plays a key role in the pathogenesis of various cardiovascular diseases. This study aimed to investigate the effects of renal denervation (RDN) on hypertensive vascular remodeling and to elucidate the role of PVAT in this process. Male spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat were selected. Aortic vascular remodeling was evaluated using hematoxylin and eosin (H&E) staining and Masson's trichrome staining. Morphological changes in the PVAT were observed through H&E and Oil Red O staining. Dihydroethidium was used to measure oxidative stress levels in PVAT, while western blot analysis was used to determine the expression levels of proteins associated with vascular remodeling. The results showed that the aortic medial thickness, media thickness/lumen diameter, collagen volume fraction, and reactive oxygen species (ROS) level in PVAT were significantly higher in the SHR group than in the WKY group. The indexes mentioned above were lower in the SHR-RDN group than in the SHR group. H&E staining revealed that fat droplets in PVAT in the SHR-RDN group became smaller and browning occurred. Moreover, the protein expression of uncoupling protein-1 (UCP-1) and neuregulin 4 (Nrg4) was significantly increased in the SHR-RDN group. In addition, the expression of adiponectin increased and the expression of leptin decreased in the SHR-RDN group compared to the SHR group. In conclusion, RDN can relieve hypertensive vascular remodeling, which may be associated with PVAT.

BACKGROUND AND PURPOSE:Reducing hypertensive myocardial fibrosis is the fundamental approach to preventing hypertensive ventricular remodelling. C1q/TNF-related protein-3 (CTRP3) is closely associated with hypertension. However, the role and mechanism of CTRP3 in hypertensive myocardial fibrosis are unclear. In this study, we aimed to explore the effect of CTRP3 on hypertensive myocardial fibrosis and the potential mechanism. METHODS AND RESULTS:WKY and SHR rats were employed, blood pressure, body weight, heart weight, H/BW were measured, and fibrotic-related proteins, CTRP3 and Collagen I were tested in myocardium at 12 and 20 weeks by immunohistochemical staining and Western blotting, respectively. The results showed that compared with the WKY, SBP, DBP, mean arterial pressure and heart rate (HR) were all significantly increased in SHR at 12 and 20 weeks, while heart weight and H/BW were only increased at 20 weeks. Meanwhile, CTRP3 decreased, while Collagen I increased significantly in the SHR rat myocardium at 20 weeks, which compared to the WKY. Moreover, the expression of α-SMA increased from 12 weeks, Collagen I/III and MMP2/9 increased and TIMP-2 decreased until 20 weeks. In order to explore the function and mechanism of CTRP3 in hypertensive fibrosis, Angiotensin II (Ang II) was used to induce hypertension in primary neonatal rat cardiac fibroblasts in vitro . CTRP3 significantly inhibited the Ang II induced activation of fibrotic proteins, purinergic 2X7 receptor (P2X7R)-NLRP3 inflammasome pathway. The P2X7R agonist BzATP significantly exacerbated Ang II-induced NLRP3 inflammasome activation, which was decreased by the P2X7R antagonists A43079, CTRP3 and MCC950. CONCLUSION:CTRP3 expression was decreased in the myocardium of SHR rats, and exogenous CTRP3 inhibited Ang II-induced fibrosis in cardiac fibroblasts by regulating the P2X7R-NLRP3 inflammasome pathway, suggesting that CTRP3 is a potential drug for alleviating myocardial fibrosis in hypertensive conditions.

BackgroundCortistatin (CST), an endogenous bioactive polypeptide, has been acknowledged for its protective effect against several cardiovascular diseases, but its relationship with hypertension remains unclear. Therefore, we aimed to investigate changes in plasma CST in hypertensive patients and further analyze correlations with blood pressure, metabolic parameters and left ventricular structure and function.MethodsIn this hospital-based study, basic information and plasma samples for evaluating clinically relevant indicators such as total cholesterol (TC), triglycerides (TGs), fasting blood glucose (FGB), serum creatinine (Scr) and CST were collected from 81 essential hypertension patients and 75 normotensive subjects. Plasma CST levels were examined by enzyme-linked immunosorbent assay (ELISA).ResultsCompared with normotensive subjects, plasma CST was significantly lower in hypertensive patients. Plasma CST levels in hypertensive patients without blood pressure control was significantly lower than those of hypertensive patients with blood pressure control. Plasma CST levels were significantly negatively correlated with SBP and serum creatinine (Scr) in the overall population. Furthermore, multivariate logistic regression analysis showed that the OR of CST for hypertension was 0.64 using the unadjusted model, and there was still statistical significance using the four-adjusted model.ConclusionsThe circulating concentration of CST was significantly lower in hypertensive patients and was higher after blood pressure control, suggesting that CST may be a new endogenous protective target for hypertension.

Background:In recent years, a mass of studies have shown that pyroptosis plays an important role in the proliferation of vascular smooth muscle cells (VSMCs). We investigated whether angiotensin II (Ang II) induces the pyroptosis of rat aortic VSMCs and the role of NOD-like receptor family pyrin domain containing 3 (NLRP3) in this process. Additionally, we explored the effect and related mechanism of recombinant tissue factor pathway inhibitor (rTFPI) in Ang II-induced VSMC pyroptosis. Methods:Cultured VSMCs were divided into five groups: control group, Ang II group (1×10-5 mol/L), MCC950 group (NLRP3 inhibitor, 15 nmol/L), Ang II + MCC950 group and Ang II + rTFPI (50 µg/L) group. Cell viability was measured by cell counting kit-8 (CCK8) assays and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Propidium iodide (PI) staining and immunofluorescence were performed to determine the pyroptosis of VSMCs. Changes in VSMC ultrastructure were evaluated through transmission electron microscopy. The expression levels of NLRP3, pro-caspase-1, gasdermin D-N (GSDMD-N), and interleukin-1β (IL-1β) were determined by western blot analysis. Results:The cell viability, the positive rate of PI staining, and the expression level of GSDMD detected by immunofluorescence in the Ang II group were higher than that in the control group, whereas they all decreased in Ang II + MCC950 group and Ang II + rTFPI group compared with Ang II group (P<0.05). Electron microscopy analysis revealed less extracellular matrix, increased myofilaments, and decreased endoplasmic reticulum, Golgi complex, and mitochondria in Ang II + rTFPI-treated VSMCs than in Ang II-treated VSMCs. The protein expression levels of the pyroptosis-related molecules NLRP3, pro-caspase-1, GSDMD-N, and IL-1β in Ang II group showed an increasing trend compared with those in control group (P<0.05); however, these expression levels in Ang II + MCC950 and Ang II + rTFPI groups were significantly lower than those in Ang II group (P<0.05). Conclusions:Ang II may induce pyroptosis in VSMCs by activating NLRP3. rTFPI can inhibit Ang II-induced VSMC pyroptosis. Furthermore, rTFPI might exert this effect by inhibiting the NLRP3 pathway and therefore play an important role in the treatment of vascular remodeling induced by hypertension.

目的 探究组织因子途径抑制物（TFPI）对大鼠心肌缺血再灌注（I/R）及心肌细胞缺氧复氧（H/R）损伤的影响，并从心肌细胞凋亡的变化探索其机制。方法 在体内实验中，通过SD大鼠心脏原位结扎法可逆阻断前降支建立大鼠心肌I/R模型。将大鼠随机分为对照组、I/R组和I/R+rTFPI组，再灌注后3天采用HE染色观察大鼠心肌组织形态学变化，TTC染色法评估心肌梗死区范围，扫描透射电镜观察心肌超微结构损伤情况，Western-Blot法检测各组大鼠心肌组织中Bcl-2、Bax和cleaved-caspase-3蛋白的表达。在体外实验中，采用胰酶消化法及差速贴壁法培养SD乳鼠原代心肌细胞，用MIC101系统模拟心肌细胞I/R损伤，缺氧2小时、复氧12小时后建立体外心肌细胞缺氧/复氧（H/R）模型。将心肌细胞分为对照组、H/R组和H/R+rTFPI（10μg/L）组，用CCK8法检测心肌细胞活力，TUNEL法检测心肌细胞凋亡率，Western-blot方法检测心肌细胞中Bax、Bcl-2及cleaved-caspase-3蛋白的表达水平。结果 体内实验中，成功建立大鼠在体心肌I/R模型。HE染色结果显示I/R组较对照组心肌细胞坏死程度加重，I/R+rTFPI组较I/R组心肌细胞坏死程度减低；TTC染色示I/R+rTFPI组较I/R组心肌梗死范围减少了39.76%（P＜0.05）；扫描透射电镜观察显示I/R组凋亡及损伤程度较对照组加重，I/R+rTFPI组凋亡及损伤较I/R组减轻；Western-Blot结果示，再灌注3天后I/R组心肌组织Bcl-2的表达较对照组降低了53.43%（P＜0.05）、Bax和cleaved-caspase-3（P＜0.05）的表达较对照组分别增加了29.05%和73.25%（P＜0.05），而I/R+rTFPI组Bcl-2的表达水平较I/R组升高了55.01%（P＜0.05），Bax和cleaved-caspase-3的表达水平较I/R组分别降低了13.77%和24.25%（P＜0.05）。在体外实验中，CCK8检测结果显示H/R组细胞活力较对照组下降了29.70%（P＜0.05），H/R+rTFPI组细胞活力较H/R组升高了19.77%（P＜0.05）。TUNEL结果显示H/R组较对照组凋亡率增加了56.76%，H/R+rTFPI组细胞凋亡率较H/R组降低了24.55%（P＜0.05）。Western-blot结果示：H/R组细胞Bcl-2表达较对照组降低了46.92%，Bax表达较对照组增加了41.90%（P＜0.05），cleaved-caspase-3表达较对照组升高了2.68倍（P＜0.05）。H/R+rTFPI组Bcl-2表达较H/R组增加了28.24%（P＜0.05），Bax及cleaved-caspase-3表达较H/R组分别降低了26.34%和57.60%（P＜0.05）。结论 TFPI可显著拮抗心肌I/R和心肌细胞H/R损伤，此效应与其抑制心肌细胞凋亡有关。

我国高血压(HTN)患者人数较多,知晓和控制率较低.HTN相关动脉粥样硬化性心血管疾病(ASCVD)对患者健康负担较重,是致死和致残的重要原因.本文就HTN引起ASCVD的病理生理机制、临床意义及HTN合并ASCVD的诊疗进展作一综述,旨在为HTN合并ASCVD的临床治疗提供参考.

Diabetes,as a major medical problem of this century,causes damage to major organs,including kidneys,heart,eyes,nerves,and blood vessels,eventually leading to diabetic complications,posing a serious threat to individual health.Epigenetics has an important impact on the occurrence and progression of diabetes mellitus through various mechanisms and promotes the generation and maintenance of metabolic memory,thus ultimately leading to a poor prognosis.Substantial studies have explored the relationship between DNA and protein modification in epigenetic regulation and diabetes,but research on RNA modification in diabetes remains limited.N6-methyladenosine(m6A)-mediated regulation of gene expression is essential for both normal physiological and pathophysiological states.Several recent studies have shown that m6A methylation modification is involved in the occurrence and development of diabetes and its complications,making it a potential disease-specific therapeutic target.An in-depth investigation of the biological functions of m6A methylation modification in diabetes and its complications can provide a therapeutic reference for the future application of m6A methylation modification in the treatment of diabetes and its complications.

MicroRNAs (miRNAs) are noncoding RNAs that play an important role in the mechanisms of diabetic cardiomyopathy (DCM); however, whether human recombinant relaxin-3 (H3 relaxin) inhibits myocardial injury in DCM rats and the underlying mechanisms involving miRNAs remain unknown. miRNA expression profiles were detected using miRNA microarray and bioinformatics analyses of myocardial tissues from control, DCM, and H3 relaxin-administered DCM groups, and the regulatory mechanisms of the miRNAs were investigated. A total of 5 miRNAs were downregulated in the myocardial tissues of DCM rats and upregulated in H3 relaxin-treated DCM rats, and 1 miRNA (miRNA let-7d-3p) was increased in the myocardial tissue of DCM rats and decreased in H3 relaxin-treated DCM rats as revealed by miRNA microarray and validated by real-time polymerase chain reaction. Important signaling pathways were found to be triggered by the differentially expressed miRNAs, including metabolism, cancer, Rap1, PI3K-Akt, and MAPK signaling pathways. The study revealed that H3 relaxin improved glucose uptake in DCM rats, potentially via the regulation of miRNA let-7d-3p.

Autophagy plays various roles at different stages of ischemia reperfusion (I/R) injury in cardiomyocytes. It has been reported that tissue factor pathway inhibitor (TFPI) has a protective effect on I/R injury. This study aimed to determine the roles of TFPI in autophagy during the I/R injury process in cardiomyocytes and the possible mechanisms. An isolated hypoxia/reoxygenation (H/R) pattern of cardiomyocytes was established by the MIC101 system. The cell viability and oxidative stress of cardiomyocytes were detected by an MTT assay and ROS assay, respectively. The autophagy level was measured by Ad-mCherry-GFP-LC3B and MDC. We detected the expression levels of autophagy-related proteins by western blotting. After 2 h of hypoxia and 12 h of reoxygenation, the cardiomyocyte viability in the H/R group was significantly lower than that in the control group (p < 0.05) than in the H/R group. According to intracellular ROS production, the fluorescence intensity in the H/R group was enhanced compared with that in the negative control group, and it was weaker in the H/R + rTFPI group compared with the H/R group. The level of autophagy and the expression levels of autophagy-related proteins (LC3-II/LC3-I, Beclin-1 and PI3K) were markedly increased in the H/R group compared to the control group (p < 0.05) whereas the levels were markedly decreased in the H/R + rTFPI group compared to the H/R group (p < 0.05). TFPI could relieve cardiomyocyte injury by inhibiting the Class III PI3K/Beclin-1 pathway and oxidative stress; thus, TFPI decreased autophagy and protected cardiomyocytes induced by H/R injury. In conclusion, TFPI may be a new direction for the prevention of myocardial I/R injury.

目的 调查哈尔滨市老年慢性心力衰竭(CHF)患者自我管理水平现状,探讨其与自我效能的相关性.方法 采用随机分层抽样抽取2018年1月 ～2018年6月哈尔滨市7个区12个医院CHF患者560例.均行心力衰竭自我管理量表、自我效能量表评估;Pearson相关分析患者自我管理水平与自我效能的相关性.结果 患者总体自我管理水平得分率为64.96％,其中药物管理、 饮食管理得分率较高(69.85％、67.92％),心理和社会适应管理得分率居中(63.65％),症状管理得分率较低(61.14％);在不同病程、文化程度、居住情况、人均月收入、自理能力、NYHA心功能分级及是否合并抑郁状态方面,CHF患者总体自我管理水平比较差异均有统计学意义(P<0.05);自我效能总分为(36.34±5.17)分,得分率为60.57％,自我效能良好125例(22.32％),一般319例(56.96％),差116例(20.72％);Pearson相关分析结果显示,560例CHF患者自我管理各维度及总体自我管理评分与自我效能各维度及总体自我效能评分均呈正相关.结论 哈尔滨市老年慢性心力衰竭患者自我管理、 自我效能水平均处于中等水平,二者呈正相关.可通过综合干预来增强患者自我效能,提高自我管理水平.