Abstract:

Transcription factor EB(TFEB) is a member of the microphthalmia associated transcription factor family. It plays an important role in lipid metabolism and other biological processes by regulating the expression of autophagy and lysosomal related genes. The activity and cellular localization of TFEB can be regulated by posttranslational modifications of proteins. This paper discusses the mechanism of autophagy regulation by TFEB posttranslational modification, aiming to help understand the pathogenesis of related diseases caused by abnormal autophagy, and provides new ideas and feasible intervention targets for the prevention and treatment of corresponding diseases.

Abstract:

Aim To investigate the molecular mechanism of interaction between rheumatoid arthritis (RA) and atherosclerosis (As) based on bioinformatics analysis. Methods The gene expression profiles of As and RA were downloaded from GEO database, differentially expressed genes between RA and As were identified through the test sets, the biological function of common differentially expressed genes was studied by enrichment analysis. Cytoscape software was used to construct the differentially expressed gene protein-protein interaction network and screen the hub genes. Transcriptional regulatory relationship revealed by the TRRUST database predicts transcription factors. Transcription factors were validated by test sets, and hub genes were validated by validation sets and blood samples. Results A total of 198 differentially expressed genes were identified. Functional enrichment analysis showed that differentially expressed genes were mainly concentrated in signaling pathways regulated by cytokines, leukocyte migration, positive regulation of leukocytes, and interaction between cytokines and cytokine receptors. Cytoscape demonstrated the differentially expressed genes and gene clustering modules, obtained the hub genes CCL5, CCR1, CCR2, CCR5, IRF8, ITGAM, ITGB2, LCP2, NCF2 and PTPRC, and the results of validation sets showed that the genes were reliable. qPCR results showed that the expression levels of CCR1 and IRF8 in patients with As combined with RA were significantly higher than those in healthy people. Conclusion The regulatory effect of CCR1 and IRF8 is likely to be the hub factor of RA merging with As.

Abstract:

Aim The key genes for necroptosis in atherosclerosis were screened by bioinformatics methods and verified with the help of in vitro experiments to provide new strategies for the prevention and treatment of atherosclerosis from the perspective of necroptosis. Methods Genes related to atherosclerotic plaques were downloaded from GEO database, and genes related to necroptosis were downloaded from GeneCards database and intersected to obtain atherosclerotic necroptosis genes, and the mechanism of action and signalling pathways of the genes were further analysed by GO and KEGG enrichment analysis, and the protein-protein interaction (PPI) network was constructed and screened for key genes.Finally, macrophages were treated with oxidized low density lipoprotein (ox-LDL) at a final concentration of 100 mg/L, and the expression of key genes was detected by RT-PCR and Western blot. Results A total of 81 atherosclerotic necroptosis genes were obtained. GO and KEGG enrichment analyses revealed that they were mainly enriched in the positive regulation of endopeptidase activity, IκB kinase (IKK)/nuclear factor-κB (NF-κB) signalling, and autophagy signalling pathway. Five key genes including HSPA8, STAT3, HMOX1, SQSTM1 and FAS were obtained by using five computational methods of Cytoscape software cytoHubba plug-in. Compared with the normal control group, the HMOX1 gene was highly expressed in THP-1 macrophages treated with ox-LDL (P＜0.05), while the expression of the HSPA8, STAT3, SQSTM1 and FAS genes showed no significant changes (P＞0.05); the HMOX1 and SQSTM1 genes were highly expressed in RAW264.7 macrophages treated with ox-LDL (P＜0.05), while HSPA8, STAT3 and FAS genes showed no significant changes (P＞0.05). The expression of HMOX1 protein in THP-1 macrophages was also increased. Conclusion HMOX1 may be the key gene of atherosclerotic necroptosis, and it is expected to become a new target for the prevention and treatment of atherosclerosis.

Abstract:

Aim To investigate the relationship between carotid artery perivascular fat density and carotid artery stenosis, prognosis. Methods A total of 209 consecutive patients with extracranial internal carotid artery stenosis in Taizhou Central Hospital (Taizhou University Affiliated Hospital) were retrospectively included from January 2017 to January 2021. The carotid artery perivascular fat density in the narrowest axial layer and in the same contralateral axial layer was evaluated by computed tomography angiography. Clinical data of patients were collected. The stenosis was graded according to the guidelines. Symptomatic carotid stenosis was determined according to the medical history. The patients were followed up for one year. Results Carotid artery perivascular fat density was 4.2% higher on the stenosis side than those on the opposite side (P＜0.001). The fat density increased with the stenosis severity. On the stenosis side, carotid artery perivascular fat density was 6.25% higher in symptomatic patients than that in asymptomatic patients (P＝0.015). In asymptomatic patients, perivascular fat density in patients with stenosis related cerebrovascular events occurred within 1 year was 12.4% higher than that in patients without related cerebrovascular events (P＝0.017), and the difference remained after adjusting the clinical parameters by Logistic regression analysis (OR＝1.060,95%CI:1.006～1.117,P＝0.028). Conclusions Carotid artery perivascular fat density is positively correlated with the degree of carotid stenosis. Patients with symptomatic carotid artery stenosis or recurrent related ischemic cerebrovascular outcome events have higher carotid artery perivascular fat density.

Abstract:

Aim To investigate the risk factors of death after acute Stanford type A aortic dissection (ATAAD) complicated with malperfusion syndrome (MPS). Methods 244 patients with ATAAD complicated with MPS who admitted to Nanchong Central Hospital from June 2020 to June 2023 were selected as the study objects. The postoperative survival of the patients was followed up and they were classified into survival group (156 cases) and death group (88 cases). After propensity score matching (PSM) was applied in 1∶1 matching, there were 54 cases in both groups. Univariate and Logistic regression analysis was performed to analyze the risk factors of postoperative death in patients with ATAAD complicated with MPS. Area under curve (AUC) of receiver operating characteristics (ROC) was used to analyze the prognosis of ATAAD complicated with MPS. The prediction model was established by using the regression equation y=1－1/(1+e－z) and the stability of the model was verified by cross-checking method. Results After matching, compared with the survival group (n＝54), in the death group (n＝54), the proportion of sex (male), the proportion of alcohol consumption, acute physiology and chronic health status Ⅱ (APACHE Ⅱ) score, sequential organ failure (SOFA) score, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total serum bilirubin (TSB), cholinesterase, serum creatinine (SCr), blood urea nitrogen (BUN), N-terminal pro-brain natriuretic peptide (NT-proBNP), D-dimer (D-D), white blood cell (WBC), neutrophile granulocyte (NEU), fibrinogen degradation product (FDP), platelet (PLT), fibrinogen (FIB), C-reactive protein (CRP), hypersensitive troponin, operation time, ICU stay time, ventilator stay time, hospital stay, distal extremity hypoperfusion, renal hypoperfusion were significantly increased (P＜0.05). Logistic analysis displayed that gender (male), history of drinking, NT-proBNP≥271.86 ng/L, D-D≥0.74 mg/L and NEU≥13.06×10⁹ L－1 were independent risk factors in ATAAD patients complicated with MPS for postoperative death (P＜0.05). The combination of NT-proBNP, D-D, gender (male), alcohol drinking history and NEU (referred to as “five factors”) had the highest value in predicting ATAAD patients with MPS. The AUC of its ROC curve was 0.979 (95%CI:0.937～0.984), the sensitivity was 94.3%, and the specificity was 91.8%, which was higher than the independent predictor. The best critical value predicted by the five factors was 5.02. The survival rate of the group ＞5.02 was significantly higher than that of the group ≤5.02. Log Rank test P＜0.01. A prediction model was established based on the important factors of postoperative death in ATAAD patients with MPS. The results showed that the model had good prediction accuracy. Conclusion NT-proBNP≥271.86 ng/L, D-D≥0.74 mg/L, gender (male), history of alcohol consumption, and NEU≥×10⁹ L－1 were independent risk factors for long-term prognosis in patients with ATAAD combined with MPS, and their combined application could effectively increase the accuracy of prognosis assessment.

Abstract:

Aim To analyze the predictive value of plasma ApoB/ApoA ratio and D-dimer (D-D) levels for left ventricular thrombosis (LVT) after PCI in patients with acute ST-segment elevation myocardial infarction (STEMI), and establish a column chart model. Methods 187 STEMI patients admitted to Fuyang Sixth People's Hospital from January 2021 to December 2022 were selected. According to the follow-up results 28 days after surgery, the patients were divided into LVT group and non LVT group. The study conducted univariate and binary Logistic regression analysis on clinical data such as plasma ApoB/ApoA1 ratio and D-D in the two groups of patients, identified independent risk factors for LVT formation in STEMI patients after PCI, established a column chart model, and evaluated the diagnostic efficacy of the column chart model. Results The results showed that an increase in the ApoB/ApoA1 ratio (OR＝1.0,5%CI:1.057～1.648), an increase in D-D levels (OR＝1.1,5%CI:1.020～1.042), a preoperative TIMI of 0 (OR＝4.1,5%CI:1.018～16.849), and a decrease in LVEF (OR＝0.6,5%CI:0.853～0.963) were independent risk factors for LVT formation after PCI (P＜0.05), and the AUC predicted by the above indicators for LVT formation were 0.2,0.0,0.623 and 0.726, respectively. Based on the above indicators, a column chart model was established. ROC curve analysis showed that the consistency index of the model was 0.926, and the calibration curve showed that the model had good discrimination and consistency. Conclusions The increase in plasma ApoB/ApoA1 ratio and D-D levels in STEMI patients is closely related to the formation of LVT after PCI. The column chart model established based on the above indicators has high diagnostic efficacy in predicting LVT, which is beneficial for clinical medical staff to identify high-risk patients.

Abstract:

Aim To study the distribution of CYP2C19, ABCB1, and PON1 genotypes and their correlation with clopidogrel resistance in patients with coronary heart disease in Tai'an. Methods A total of 594 patients with coronary heart disease who were treated with clopidogrel during hospitalization in Tai'an Central Hospital from January 2019 to March 2020 were selected. Fluorescence in situ hybridization was used to detect CYP2C19*2 (rs4244285), CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), ABCB1 (rs1045642) and PON1 (rs662) gene types. Results CYP2C19*2, CYP2C19*3, CYP2C19*17 genotypes in patients with coronary heart disease in Taian were mainly with homozygous (GG). The frequencies of CYP2C19*2 GG, CYP2C19*3 GG, CYP2C19*17 CC, ABCB1 CT and PON1 AG were 48.0%, 89.6%, 97.0%, 46.8% and 47.1% respectively. There was no significant difference in CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1, PON1 genotype distribution and allele distribution between male and female patients (P＞0.05). Significant regional differences in the frequency of CYP2C19 alleles and the distribution of metabolic types were found in patients with coronary heart disease in Tai'an. Among 594 patients included in the study, there were 287 patients with a risk level of clopidogrel resistance ≥ 2 in the composite evaluation of patients, approximately 48.3% of the total number of patients. This indicated that clopidogrel resistance was present in 48.3% of patients on the regular dose of clopidogrel. Of the 287 people with a risk level ≥ 2,6 had a normal CYP2C19 metabolic type, representing approximately 7.7% of the total number of patients. Conclusion There were gene polymorphisms observed in CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1 and PON1 distribution in patients with coronary heart disease in Tai'an, and ABCB1 and PON1 gene polymorphisms would had an impact on the outcome of medication guidance in approximately 7.7%.

Abstract:

Aim To investigate the serum levels of thrombin-antithrombin complex (TAT), tissue type plasminogen activator-inhibitor complex (t-PAIC) and thrombomodulin (TM) in patients with intracranial atherosclerotic stenosis (ICAS), and their correlations with the degree of stenosis. Methods A total of 196 ICAS patients (ICAS group) who underwent treatment in Cangzhou People's Hospital from January 2021 to February 2023 were enrolled as research subjects. Based on the degree of vascular stenosis, they were separated into three groups:mild group (n＝78), moderate group (n＝64), and severe group (n＝54). A group of 196 healthy outpatient with similar clinical basic data to ICAS patients was selected as controls. The serum levels of TAT, t-PAIC, and TM in each group were compared; Spearman method was applied to analyze the correlation between serum levels of TAT, t-PAIC, TM and stenosis severity in ICAS patients; Multivariate Logistic regression was applied to analyze the influencing factors of severe stenosis in ICAS patients; ROC curve was applied to analyze the predictive value of serum TAT, t-PAIC, TM and total cholesterol (TC) levels for severe stenosis in ICAS patients. Results Compared with the control group, the serum levels of TAT, t-PAIC, and TM were significantly increased in the ICAS group (P＜0.05); the levels of serum TAT, t-PAIC, TM, and TC in the mild, moderate, and severe groups increased accordingly (P＜0.05). Spearman analysis showed that the serum levels of TAT, t-PAIC, and TM in ICAS patients were positively correlated with the degree of stenosis (r＝0.4,0.5,0.628; all P＜0.05). Multivariate Logistic regression analysis showed that TAT, t-PAIC, TM, and TC were independent risk factors for severe stenosis in ICAS patients (P＜0.05). The ROC curve showed that the AUC of severe stenosis in ICAS patients predicted by combination of TAT, t-PAIC, TM, and TC was 0.927, with a sensitivity of 83.33% and a specificity of 86.62%, which was superior to the independent prediction of TAT, t-PAIC, TM and TC(Z_combined detection-TAT=4.617, Z_combined detection-t-PAIC=4.024, Z_combined detection-TM=4.004, Z_combined detection-TC=7.078, all P＝0.000). Conclusion The serum levels of TAT, t-PAIC, and TM in the ICAS group were significantly increased, and were positively correlated with the severity of stenosis. The combination of the three and TC has a high predictive value for the occurrence of severe stenosis in ICAS patients.

Abstract:

Atherosclerosis is the main pathological basis for the occurrence and development of cardiovascular and cerebrovascular diseases. Macrophage efferocytosis deficiency exists in the formation of atherosclerosis. Defective efferocytosis leads to the accumulation of uncleared apoptotic cells and secondary necrosis, leading to characteristic formation of necrotic core and plaque instability in atherosclerosis. The complete process of efferocytosis includes recognition(“find me”)stage, phagocytosis(“eat me”)stage, and the post-processing reaction (digestion) stage. It has been reported that miRNA is involved in the regulation of key signal transduction and lipid homeostasis in atherosclerotic efferocytosis. This paper discussed the important role of efferocytosis in the process of atherosclerosis and the influence of efferocytosis defect on atherosclerosis. This review focuses on the regulatory effects of “eat me”and “don't eat me”signals of efferocytosis in the overall inflammation of atherosclerosis, and meanwhile the regulation of miRNA on lipid metabolism and inflammation regression in atherosclerosis, and the fine tuning of miRNA targeting macrophage efferocytosis in the process of atherosclerosis.

Abstract:

Atherosclerosis is the pathological basis of a variety of cardiovascular diseases, which are still the leading cause of human death worldwide. Ferroptosis is a kind of iron dependent non-apoptotic cell death mode, which is closely related to various physiological mechanisms. Recent studies have found that ferroptosis in macrophages plays an important role in the occurrence and development of atherosclerosis. Based on the imbalance of iron metabolism in macrophages, this paper reviews the correlation between ferroptosis in macrophages and atherosclerosis in terms of the interaction between ferroptosis in macrophages and lipid peroxidation, inflammation, oxidative stress, etc., in order to provide new ideas for the study of the pathogenesis of atherosclerosis.

Abstract:

Heart failure is a fatal stage of end-stage cardiovascular disease, which brings a huge medical burden to the society because of its high mortality and re-hospitalisation rates. Intestinal microecology is the largest and most complex microecosystem of human body. It is inhabited by tens of thousands of microorganisms in human gastrointestinal tract. In recent years, with the deepening of the study of intestinal flora, more and more studies have found that the imbalance of intestinal microecology can cause changes of metabolites in heart failure patients, which is one of the key triggers for the development of heart failure, therefore, using the intestinal microbial homeostasis as a new entry point for the treatment of heart failure will be a hotspot in medical research. However, the theory of Chinese medicine, “the spleen is the guardian”, covers the physiological functions of the spleen, such as the spleen's main function of transporting, spleen's main function of ascending and clearing, and its main function of hiding camping, etc., and the functions of intestinal flora and the “spleen is the guardian” are similar to a certain extent. Therefore, this paper starts from a holistic viewpoint and takes the theory of “spleen as the guardian” in Chinese medicine as an entry point to elaborate on the pathogenesis of intestinal microecological imbalance and heart failure, so as to provide a reference for Chinese medicine treatment or drug research.

Abstract:

Myocardial infarction with non-obstructive coronary artery (MINOCA) is a common acute coronary syndrome in clinical practice. Its diagnosis is more difficult than general acute coronary syndrome, and may be difficult to distinguish from other non ischemic diseases that can cause similar symptoms and myocardial damage. Delayed treatment timing can have a significant detrimental effect on patients. This article provides a review of the clinical diagnosis and treatment progress of MINOCA, with the aim of providing guidance for clinical practice.