Abstract:Atherosclerosis (As) is a pathological process caused by a complex set of factors, including endothelial dysfunction, lipid deposition in the arterial vessel wall, macrophage infiltration, smooth muscle cell dysfunction, and foam cell formation, in which inflammatory response plays an indispensable role. NOD-like receptor protein 3(NLRP3) inflammasomes are transducers of inflammatory cells, and NLRP3 inflammasome activation mediates the inflammatory response and activates downstream interleukin-18 and interleukin-1β, thereby participating in the occurrence and development of As. Therefore, specific inhibitors targeting NLRP3 inflammasome and downstream inflammatory factors are potential targets for current clinical drug research and are expected to be a new therapeutic measure for treating As. In this article, the mechanism of NLRP3 inflammasome and the relationship with As are discussed, and drugs targeting NLRP3 inflammasome and downstream inflammatory factors are also described.

Abstract:Adipose tissue fibrosis is caused by improper remodeling of the extracellular matrix, which leads to abnormal deposition in adipose tissue. As the hallmark of adipose tissue dysfunction, adipose tissue fibrosis has a close relationship with metabolic dysfunction such as obesity and insulin resistance. Therefore, reversing adipose tissue fibrosis can restore the function of adipose tissue, enhance the sensibility of insulin and then improve patients metabolic abnormalities such as obesity. This review summarizes the latest research progress in the pathological mechanism of adipose tissue fibrosis and the potential drug targets for reversing adipose tissue fibrosis, in order to provide a greater insight into this pathological process and provide the direction of drug development.

Abstract:Cardiovascular disease is one of the major diseases that seriously threaten the health of Chinese residents, and the fatality rate stands first in the disease spectrum in China for a long term. With the rapid development of population aging, the prevalence and mortality of cardiovascular diseases remain on the rise, and the current treatment effect on and prognosis of heart failure are not satisfactory. It is particularly important to explore the potential pathogenic mechanisms of heart failure and identify new therapeutic targets. This article reviews the research advances in targeted therapy for heart failure in recent years, which may provide new ideas for delaying the progress of heart failure.

Abstract:Aim To explore the association between mammalian target of rapamycin (mTOR) gene polymorphism and genetic susceptibility to coronary heart disease in Han population in South China, and provide new ideas for early prevention and intervention of coronary heart disease. Methods Polymerase chain reaction-ligase detection reaction (PCR-LDR) technology was used to classify mTOR gene polymorphisms in 804 patients with coronary heart disease and 979 control subjects. The genotypes of rs2295079 and rs1883965 of mTOR gene were detected. The association between each polymorphic site and susceptibility to coronary heart disease was analyzed by unconditional Logistic regression. Results There was no statistical difference in the distribution of alleles and genotype frequencies of rs2295079 and rs1883965 between the coronary heart disease group and the control group (P＞0.05); the distribution frequencies of the haplotype rs2295079C-rs1883965A constructed by these two loci in the coronary heart disease group and the control group were 8.3% and 6.5%, respectively, and the coronary heart disease group was significantly higher than the control group; individuals carrying rs2295079C-rs1883965A haplotype had a significantly increased risk of developing coronary heart disease (OR＝1.29, P＝0.047), this haplotype had a more significant risk of developing coronary heart disease in people aged ≤60 years old (OR＝1.73, P＝0.009). Conclusion The haplotype rs2295079C-rs1883965A of the mTOR gene is closely related to the genetic susceptibility to coronary heart disease, and is more obvious in the population aged ≤60 years old, suggesting that this haplotype may be an important rick factor in increasing the risk of coronary heart disease in the Han population in South China.

Abstract:Aim To study the expression and biological significance of microRNA-499 (miR-499) and high mobility group protein 1 (HMGB1) in carotid atherosclerotic plaque. Methods Patients with carotid atherosclerosis diagnosed in Sanmenxia Central Hospital of Henan Province from January 2018 to December 2020 were enrolled in the carotid atherosclerosis group, and healthy people were enrolled in the control group. The expression level of miR-499 in peripheral blood and the content of HMGB1 in serum were detected. Apolipoprotein E (ApoE) knockout mice were divided into groups and fed with high cholesterol diet to establish carotid atherosclerotic plaque model. miR-NC, miR-499, NC lentivirus (lenti-NC) and HMGB1 lentivirus (lenti-HMGB1) were given by tail vein injection. Then the pathological changes, the expression levels of miR-499 and HMGB1 in carotid atherosclerotic plaque were determined. Human umbilical vein endothelial cells (HUVEC) were cultured and double luciferase reporter gene was used to verify the targeted binding of miR-499 and HMGB1. Results The expression level of miR-499 in peripheral blood of carotid atherosclerosis group was lower than that of control group, and the content of HMGB1 in serum was higher than that of control group, and the expression level of miR-499 was negatively correlated with the content of HMGB1 in serum (P＜0.05). The expression level of miR-499 in carotid atherosclerotic plaque of model group was lower than that of control group, and the expression level of HMGB1 was higher than that of control group; the pathological changes of carotid atherosclerotic plaque in miR-499+model group were better than those in miR-NC+model group, the expression level of miR-499 in carotid atherosclerotic plaque was higher than that of miR-NC+model group, the expression level of HMGB1 was lower than that of miR-NC+model group. The pathological changes of carotid atherosclerotic plaque in lenti-HMGB1+miR-499+model group were more severe than those in lenti-NC+miR-499+model group, and the expression level of HMGB1 was higher than that in lenti-NC+miR-499+model group. The fluorescence value of wild-type HMGB1 reporter gene in miR-499 group was significantly lower than that in miR-NC group (P＜0.05). Conclusion miR-499 targeting HMGB1 is involved in the formation of carotid atherosclerotic plaque.

Abstract:Aim Single nucleotide polymorphisms (SNP) occurring in the precursor or mature sequences of microRNA or in their binding sites on 3′ untranslated region of target genes may participate in the occurrence and development of many diseases, such as tumor, nervous system diseases, muscle hypertrophy, cardiovascular diseases and so on. In this study, bioinformatics technology was used to analyze the biological processes and signal pathways that may be affected by SNP rs386585341 A＞G located at the fourth position of miR-499a-3p seed sequence. Methods RNAfold database was used to predict whether rs386585341 A＞G would affect the secondary structure of pre-miR-499a. Pre-miR-499a-A and pre-miR-499a-G overexpression plasmids were constructed respectively to detect whether rs386585341 A＞G would affect the expression of mature miR-499a. Gene expression microarray and bioinformatics were used to analyze the effect of rs386585341 A＞G on the function of miR-499a-3p, then take the intersection of differential gene expression profile and TargetScan target gene, and analyze the divergence of target genes of miR-499a-3p with different alleles of rs386585341A＞G.Results rs386585341 A＞G did not affect the secondary structure of pre-miR-499a, nor the expression levels of mature miR-499a-5p and miR-499a-3p, but affected the target gene network regulated by mature miR-499a-3p. The results of GO and pathway analysis of differentially expressed genes (DEG) showed that miR-499a-3p-A and miR-499a-3p-G showed different biological functions. The downstream gene network of miR-499a-3p-A was mainly enriched in immune regulation, while the downstream gene network of miR-499a-3p-G was mainly enriched in angiogenesis. The 4 target genes of miR-499a-3p-A including Spry2, Pcnx, Ndufa5 and Tcf7l2, were obtained by intersect analysis of down-regulated genes and TargetScan target genes, but the direct target genes of miR-499a-3p-G were not obtained. It indicated that after the miR-499a-3p seed region fourth was converted from A to G by rs386585341, the target gene formula of miR-499a-3p could be transformed from the degradation of target gene mRNA to the protein translation that only inhibits target genes.Conclusion rs386585341 A＞G may play important roles in immune differentiation and angiogenesis by affecting the downstream network of miR-499a-3p.

Abstract:Aim To study the health effects of road traffic noise on rats and the effects on their metabolite levels in vivo, and to investigate the possible mechanism. Methods Twelve Wistar rats (half male and half female) were randomly divided into noise group and control group according to sex. The noise group was exposed to road traffic noise at a mean of 75 dB from 23:00 daily to 7:00 the next day for 2.5 months. Blood pressure was measured, and feces were collected for LC-MS non-targeted metabolomics analysis. Results The systolic and diastolic blood pressure were higher in the noise group (P＜0.001). The mean systolic and diastolic blood pressure were (176.67±27.07) mmHg and (93.93±21.54) mmHg in noise exposed group, as well as (150.38±17.98) mmHg and (67.72±24.67) mmHg in control group. Metabolomic analysis identified 41 significant metabolites, including 2-hydroxyphenylacetic acid, N-formylmethionine, 3-hydroxyphenylalanine, etc., which mainly involved in the amino acid metabolic pathway. Conclusion Road traffic noise exposure was associated with a high blood pressure in rats. N-formylmethionine and 2-hydroxyphenylacetic may play roles in this association.

Abstract:Aim To analyze the efficacy and safety of bioabsorbable polymer-coated drug-eluting stents in patients with coronary heart disease and diabetes mellitus. Methods The study searched database both at home and abroad, and retrieved the clinical randomized controlled trial (RCT) of comparison of bioabsorbable polymer-coated drug-eluting stent (BP-DES) and durable polymer-coated drug-eluting stent (DP-DES) in patients with coronary heart disease and diabetes mellitus. The efficacy and safety were evaluated by target lesion failure rate, target vessel revascularization rate, target lesion revascularization rate and cardiogenic mortality rate. Results A total of 14 RCT were included, of which 3 855 patients were treated with BP-DES and 2 916 patients with DP-DES, with a mean follow-up of 2.9 years. The overall target lesion failure rate of BP-DES versus DP-DES was 13.5% versus 12.8% (RR:1.7,5% CI:0.88～1.29, P=0.50). The overall cardiac mortality rate of BP-DES versus DP-DES was 6.2% versus 5.4% (RR:1.0,5%CI:0.90～1.34, P=0.35), and the overall target lesion and target vessel revascularization rates were not statistically different. There were no statistically significant differences in subgroup analysis according to follow-up time. Conclusion In patients with coronary heart disease and diabetes, BP-DES has a similar safety and efficacy profile to DP-DES.

Abstract:Aim To investigate the mechanism of Chuanxiong in the treatment of atherosclerosis (As) based on network pharmacology and molecular docking. Methods TCMSP database was used to screen the active components of Chuanxiong, and Swiss target prediction was used to predict the drug targets. The relevant targets of As were screened in the databases of DrugBank and DisGeNET. The target protein interaction network was constructed by STRING, and the network was drawn by Cytoscape and analyzed by topology. Omicshare was used for GO enrichment analysis and KEGG enrichment analysis. DockThor was used for molecular docking. Results 167 related therapeutic targets were obtained. 46 targets, including CASR and MAPK3 etc. were found to be the core targets by network topology analysis. GO enrichment analysis showed that Chuanxiong could affect the occurrence and development of As in biological process, molecular function and cell composition. KEGG pathway enrichment analysis showed that Chuanxiong might play a role in the treatment of As by regulating multiple metabolic pathways such as neuroactive ligand receptor interaction and calcium signaling pathway etc. Conclusions By using network pharmacology method, it was confirmed that Chuanxiong had the characteristics of multi-channel and multi-target action in the treatment of As. The possible mechanism of Chuanxiong in the treatment of As was predicted, which provided a reference and theoretical basis for its subsequent basic research.

Abstract:Aim To compare the efficacy and safety of bare metal stent (BMS), drug-coated balloon (DCB) and drug-eluting stent (DES) in coronary heart disease patients with high bleeding risk (HBR). Methods Domestic and international electronic databases were searched to collect randomized controlled clinical trials of DCB or DES vs. BMS in coronary heart disease patients with HBR, Meta-analysis was performed using Revman 5.3 software. The primary endpoints of this study were to compare the target lesion revascularization (TLR) rate, recurrent myocardial infarction rate, cardiogenic mortality rate and bleeding rate of DCB and DES vs. BMS in coronary heart disease patients with HBR. The secondary endpoints were to indirectly compare the TLR rate, recurrent myocardial infarction rate, cardiogenic mortality rate and bleeding rate of DCB and DES, so as to compare the clinical effect of the three. Results In coronary heart disease patients with HBR, compared with BMS group, DCB group and DES group had lower TLR rate (RD＝－0.4,5%CI:－ 0.05～0.03, P＜0.05), lower cardiogenic mortality rate (RD＝－0.2,5%CI:－0.04～－0.01, P＜0.05), and lower recurrent myocardial infarction rate (RD＝－0.3,5%CI:－0.05～0.01, P＜0.01). Compared with DES group, DCB group had lower TLR rate (0% vs. 5.5%, RR＝0.6,5%CI:0.00～0.98, P＝0.05) and recurrent myocardial infarction rate (0% vs. 5.8%, RR＝0.6,5%CI:0.00～0.93, P＜0.05). Patients in the three groups were treated with very short dual antiplatelet therapy (DAPT) program, and there was no significant difference in bleeding rate among the three groups. Conclusion In coronary heart disease patients with HBR, DCB and new generation DES combined with short-term DAPT have higher efficacy and safety than BMS.