Abstract:Abnormalities in lipid metabolism induce myocardial structural and functional disorders, leading to the development of diabetic cardiomyopathy (DCM), which has become a hotspot in current DCM research. The transmembrane glycoprotein CD36 is a multifunctional membrane protein that facilitates fatty acid transport, which is involved in the regulation of cardiac lipid metabolism. CD36 signaling plays a key role in the pathogenesis of DCM mediated cardiac injuries. This article summarizes the structure of CD36 and its role in specific cell types, and further explores the pathophysiological role of CD36 in DCM, proposing that targeting CD36 may prove to be a potential pharmacological strategy in the prevention and treatment of DCM.

Abstract:Aim To investigate the mechanism of perilipin 2 (PLIN2) increasing lipid accumulation in macrophages. Methods The experiments were divided into oxidized low density lipoprotein (ox-LDL) group, different PLIN2 expression groups, and different activity Rab18 groups, the levels of Rab18 and acyl-CoA long chain synthetase 3 (ACSL3) protein in high expression and silent expression of PLIN2 macrophages were measured, and the levels of PLIN2, Rab18, and ACSL3 protein expression in high expression PLIN2 macrophages with different activity Rab18 were measured.Western blot was used to detect protein expression levels, immunofluorescence was used to observe the localization of intracellular related proteins, and oil red O staining was used to observe intracellular lipid accumulation. Results The expression levels of Rab18 and ACSL3 in cells with high expression of PLIN2 were increased significantly (P＜0.05), and there was an intracellular phenomenon of co-localization of PLIN2 with Rab18 and ACSL3. The expression level of ACSL3 in high expression macrophages of PLIN2 after transfection with the Rab18 dominant mutant Q67L plasmid (Rab18 activity increased) was increased significantly (P＜0.05), and the number of intracellular lipid droplets was also increased significantly (P＜0.05). Conclusion PLIN2 promotes macrophage lipid accumulation through Rab18 by up-regulating ACSL3.

Abstract:Aim To investigate the effects of astragalus polysaccharide and hirudin combined intervention on lipid accumulation, mitochondrial membrane potential and apoptosis-related proteins in macrophages induced by oxidized low density lipoprotein (ox-LDL). Methods RAW264.7 cells were incubated with 100 mg/L ox-LDL for 24 h to establish a foam-cell model, which were treated by astragalus polysaccharide and hirudin after dose optimization. The control group, model group, astragalus polysaccharide group, hirudin group and the combined intervention of the two drugs group were established. Oil red O staining and oxidase method were used to detect the cholesterol contents in macrophages induced by ox-LDL, flow cytometry was used to detect the early apoptosis rate, late apoptosis rate and total apoptosis rate of macrophages, the changes of mitochondrial membrane potential were detected by laser confocal microscopy, Western blot was used to detect the expression levels of anti-apoptotic protein Bcl-2, proapoptotic protein Caspase-3 and Bax. Results The contents of cholesterol in macrophages of the astragalus polysaccharide and hirudin combined intervention group were decreased than those in the hirudin group or astragalus polysaccharide group significantly (P＜0.05). Compared with the model group, the astragalus polysaccharide and hirudin combined intervention could reduce the early apoptosis rate and total apoptosis rate of macrophages induced by ox-LDL (P＜0.01), increase the mitochondrial membrane potential of macrophages (P＜0.01), reduce the expressions of Caspase-3 and Bax, and increase the expression of Bcl-2 protein (P＜0.05) significantly. Conclusions The astragalus polysaccharide and hirudin combined intervention in reducing lipid accumulation in macrophages is superior to drug treatment alone. The combined treatment of the two drugs can reduce the apoptosis rate of macrophages induced by ox-LDL. Its mechanism may be related to regulate mitochondrial membrane potential and regulate the expressions of proapoptotic protein Caspase-3, Bax and anti-apoptotic protein Bcl-2.

Abstract:Aim To investigate the clinical predictive value of free thyroid hormone (FT4)/free triiodothyronine (FT3) ratio for the risk of all-cause death in hospital in acute myocardial infarction (AMI) patients. Methods The clinical data of AMI patients who underwent coronary angiography or percutaneous coronary intervention (PCI) in the Department of Cardiology of the Second Affiliated Hospital of Dalian Medical University from January 2016 to December 2022 were collected retrospectively, a total of 63 patients with complete medical history and died during hospitalization were selected, 180 AMI patients who did not die during hospitalization in the same period were selected as the control group. Results Age, ST elevation myocardial infarction (STEMI), renal insufficiency, atrial fibrillation, heart rate, KillipⅢ/Ⅳ, multi-vessel disease, cardiac troponin I and brain natriuretic peptide (BNP) in the in-hospital death group were higher than those in the survival group, while ejection fraction (EF) was lower than that in the survival group, the difference was statistically significant (P＜0.05). FT4 and FT4/FT3 ratio in the in-hospital death group was higher than those in the survival group, and the FT3 was lower than that in the survival group, the difference was statistically significant (P＜0.05). Multivariate Logistic regression analysis showed that the FT4/FT3 ratio was associated with the risk of all-cause death in hospital in AMI patients (OR＝1.4,5% CI:1.193～2.850, P＜0. 05). In addition, age, heart rate, KillipⅢ/Ⅳ grade, STEMI, renal insufficiency and low EF were also positively correlated with the risk of all-cause death in hospital in AMI patients (OR＝1.4,1.1,2.7,2.8,4.5,4.407, P＜0.05). The results of the ROC curve analysis showed that the FT4/FT3 ratio (AUC＝0.4,5%CI:0.708～0.839, P＜0.001) predicted the risk of all-death in hospital better than FT4 (AUC＝0.0,5%CI:0.561～0.719, P＝0.001) or FT3 (AUC＝0.9,5%CI:0.647～0.790, P＜0.001) alone. The difference in area under the ROC curve was statistically significant (P＝0.001 and P＝0.042). Conclusions FT4/FT3 ratio is related to the risk of all-cause death in hospital in AMI patients, which can predict the risk of all-cause death in hospital in AMI patients. Compared with FT3 or FT4 alone, FT4/FT3 ratio has better clinical predictive value for all-cause death in hospital in AMI patients.

Abstract:Aim To discuss the construction of the nomogram model of coronary atherosclerotic plaque (CAP) shown on chest computed tomography (CT) and the influencing factors of plaque stability. Methods The data of patients at high risk of cardiovascular disease that received CT examination from January 2020 to October 2021 were collected for a retrospective cross-sectional study. Basic information (including gender and age), medical history, complications, blood pressure, blood biochemical indicators, etc. of the patients were collected. According to their coronary artery conditions shown by CT imaging, the patients were divided into CAP group and CAP-free group. The data were then reduced by using LASSO regression cross-validation. The nomogram model was built and validated, and its application value was evaluated by the decision curve. In the end, the influencing factors of CAP-CT value were evaluated by optimal scaling regression. Results There were 240 patients with CAP and 52 patients without CAP included in the research. After adjusting the parameter (λ＋1se), age, uric acid, estimated glomerular filtration rate (eGFR) were non-zero variables. The statistically significant age and eGFR were used to build the nomogram model. Area under ROC curve was 0.759(95%CI:0.691～0.828), sensitivity was 73.8%, specificity was 71.2%. Hosmer-Lemeshow test indicated good model fit (χ²＝11.846, P＝0.158). The prediction accuracy was 82.2%. Mean absolute error of Bootstrap resampling internal verification was 0.029. The calibration curve basically fits the ideal curve. According to the decision curve, the nomogram model shows good net benefits within the risk threshold of 0.10～0.40. Combined diabetes mellitus and β2-microglobulin (β2-MG) were independent risk factors for CAP-CT values (both P＜0.05), with the importance of 0.121 and 0.564, respectively. Conclusion Emphasis on the protection of renal function and glycemic compliance will help to reduce the formation of CAP and increase CAP stability. In particular, more attention should be paid to renal function when selecting medications.

Abstract:Aim To explore the association between serum neutrophil percentage to albumin ratio (NPAR) level and coronary artery layered plaque in patients with acute coronary syndrome (ACS). Methods 222 patients who underwent coronary angiography (CAG) and optical coherence tomography (OCT) examination of culprit vessels immediately after angiography at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University from January 2018 to January 2023 and diagnosed with ACS were selected as the study subjects, and they were classified into 111 cases of layered plaque and 111 cases of non-layered plaque according to the OCT image results. Serum NPAR level was compared between the layered plaque group and the non-layered plaque group, and the influencing factors of coronary artery layered plaque were analyzed by multivariate Logistic regression analysis. Results Comparing the clinical and biochemical index data between the layered plaque group and the non-layered plaque group, the history of alcohol consumption, lumen stenosis rate, neutrophil percentage level, NPAR level was higher in the layered plaque group than that in the non-layered plaque group, and the albumin level was lower than that in the non-layered plaque group, the differences were statistically significant (P＜0.05). Comparison of the OCT characteristics showed that lipid arcs were larger and fibrous cap thickness was thinner, macrophage infiltration rate was higher, vulnerable plaques, plaque rupture, cholesterol crystals, microvessels, thrombus, calcified nodules, calcified plaques were detected at a higher rate, and fibrous plaques were detected at a lower rate in the layered plaque group, and the differences were all statistically significant (P＜0.05). Spearman correlation analysis showed that the serum NPAR a positive correlation with the rupture of plaques, and the TCFA (r＝0.436 and r＝0.622, respectively, both P＜0.05). Multivariate Logistic regression analysis showed that high level of NPAR was an independent risk factor for the development of layered plaque in culprit vessels in ACS patients (OR＝10.6,5%CI:3.242～31.999, P＜0.001). Conclusion Layered plaque is associated with plaque vulnerability characteristics, and serum NPAR level is elevated in patients with layered plaque in culprit vessels with ACS, which is an independent risk factor for coronary layered plaque in ACS patients.

Abstract:Aim To determine the relationship between remnant cholesterol (RC) and long-term cardiovascular risk in young patients with coronary artery disease (CAD). Methods 3 200 patients with CAD hospitalized from May 2013 to November 2015 were analyzed retrospectively. They were divided into three groups according to age:young group (＜45 years old), middle-aged group (45～70 years old) and elderly group (≥70 years old); They are divided into high group and low group according to RC levels. The incidence of major adverse cardiovascular event (MACE) was statistically analyzed. KM method was used to evaluate the survival rate without MACE event, and Cox regression was used to evaluate the predictors of clinical endpoint. The dose-response relationship between RC and MACE risk was demonstrated using a restricted cubic spline (RCS) model. Results A total of 3 112 patients were followed up (97.25%), including 160 in young group, 2 390 in middle-aged group, and 562 in elderly group. The median follow-up time was 7.36 years. Among them, 864 cases (27.8%) experienced MACE events. KM curve showed that RC was not a predictor of long-term MACE in patients with CAD of all ages (P＞0.05), nor was it a predictor of MACE in middle-aged and elderly groups (P＞0.05). KM curve and Cox regression showed that RC was an independent predictor of long-term MACE in premature CAD patients, and the risk of MACE increased by 1.07 times for every 1 mmol/L increase in RC (HR=2.7,5%CI:1.35～3.17, P＜0.01). Through calculation and verification, it was found that the optimal cutoff value of RC for predicting the occurrence of MACE in premature CAD patients was 0.94 mmol/L, and the risk of MACE in premature CAD patients with RC＞0.94 mmol/L increased by 1.98 times (HR=2.8,5%CI:1.41~6.32, P＜0.01); Conversely, the risk of MACE was reduced by 66% in premature CAD patients with RC＜0.94 mmol/L (HR=0.4,5%CI:0.16～0.71, P＜0.01). Conclusion RC is an independent predictor of long-term MACE occurrence in premature CAD patients (7.36 years). The optimal cutoff value of RC in this population is 0.94 mmol/L. Controlling RC below 0.94 mmol/L is able to reduce the risk of MACE by 66% in premature CAD patients.

Abstract:Aim To systematically evaluate the effect of non-vitamin K antagonist oral anticoagulants (NOAC) on liver function. Methods The PubMed, Embase, Cochrane Library, Wanfang, CNKI and VIP databases were searched to collect randomized controlled trials (RCT) related to non-vitamin K antagonist oral anticoagulant treatment published openly before June 0,3. Data were extracted according to the inclusion criteria. The quality of the included studies was evaluated. Meta-analysis was performed on the related data using R language. Results A total of 22 RCT studies were included, with 64 063 patients receiving non-vitamin K antagonist oral anticoagulant treatment. Compared with the control group, non-vitamin K antagonist oral anticoagulants did not increase the risk of abnormal liver function (alanine transaminase (ALT)＞3 ULN) (RR＝0.2,5%CI:0.61～0.84, I²＝59%, P＜0.01), or the risk of severe liver injury (ALT＞3 ULN combined with total bilirubin (TBIL)＞2 ULN) (RR＝0.8,5%CI:0.80～1.19, I²＝0%, P＝0.01). When used for preventing deep vein thrombosis after orthopedic surgery, compared with the control group, non-vitamin K antagonist oral anticoagulants reduced the risk of abnormal liver function (RR＝0.9,5%CI:0.61～0.79, I²＝0%, P＜0.01). Conclusions Non-vitamin K antagonist oral anticoagulants have high liver safety. The occurrence of non-vitamin K antagonist oral anticoagulant-associated liver injury may be dose-dependent. Regular monitoring of liver function is recommended when applying non-vitamin K antagonist oral anticoagulants clinically to patients with a history of liver disease.

Abstract:Heart failure with preserved ejection fraction (HFpEF) is a syndrome with high heterogeneity in pathophysiology, and its proportion in heart failure is increasing with the aging of the population. Importantly, there are few effective treatments for HFpEF, so the search for new treatments for HFpEF has become a hot topic in the current heart failure research field. In recent years, new progress has been made in the study of the pathogenesis and treatment of HFpEF, which will be reviewed in this article.

Abstract:This review focuses on the structural characteristics of mitoNEET and its various biological functions as a key protein in regulating mitochondrial function, maintaining cellular iron homeostasis, and participating in energy metabolism. The aim is to provide new intervention methods and therapeutic targets for the prevention and treatment of diseases closely related to inflammation, oxidative stress damage, lipid metabolism disorders, such as obesity diabetes and atherosclerosis-related diseases.

Abstract:Macrophage is a kind of immune cell which is closely related to atherosclerosis (As). With the change of internal environment, macrophage can polarize into different phenotype. Under the physiological environment, the polarization of macrophages is in dynamic balance. In the As state, the polarization balance is destroyed and the corresponding phenotypic macrophages are differentiated, which play different roles in each stage of As. The debate between Zheng and Xie exists in the whole process of As formation and development, while macrophage polarization runs through the whole stage of As syndrome differentiation and change. On account of this, this paper discusses the relationship between macrophage polarization and As based on the theory of Zheng and Xie, and propose that attention should be paid to the combination of macro and micro in the clinical prevention and treatment of As, and it can control the inflammatory response and stabilize plaque by regulating the macrophage polarization, thus providing an emerging target for the treatment of As with traditional Chinese medicine.

Abstract:The cardiovascular system, a complicated and delicate closed circulatory system, is regulated by various protein post-translational modifications, in which N-glycosylation plays a crucial role. N-glycosylation of nascent peptide chains is a co-translation or post-translational modification. Inrecent years, increasing investigations have demonstrated that N-glycosylation is implicated in the regulation of cardiovascular function by affecting the location and function of numerous essential proteins, further participates in the incidence and progression of various cardiovascular-related diseases, including hypertension, arrhythmia, atherosclerosis, etc. This review focuses on the role of protein N-glycosylation and its potential therapeutic implications in diverse cardiovascular diseases.

Abstract:Vascular calcification is age dependent and a risk factor for cardiovascular all-cause mortality. Recently, growing evidences have shown that novel forms of programmed cell death including ferroptosis, pyroptosis, and autophagy play an important role in the development of vascular calcification. This review introduces the molecular mechanism of programmed cell death and its relationship with vascular calcification, elucidates the evidence of anti-vascular calcification by regulating the cell death pathway key molecules.