MicroRNA-146a-5p alleviates lipopolysaccharide-induced NLRP3 inflammasome injury and pro-inflammatory cytokine production via the regulation of TRAF6 and IRAK1 in human umbilical vein endothelial cells (HUVECs) Jingyuan Hou, Qiaoting Deng, Xunwei Deng, Wei Zhong, Sudong Liu, Zhixiong Zhong

Background: In-stent restenosis (ISR) remains a challenge for coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI) with stents, and risk factors for ISR are controversial. This study aimed to investigate the incidence and risk factors of ISR in patients from southern China. Methods: In this retrospective study, patients diagnosed as acute coronary syndromes (ACS) and underwent successful PCI with drug-eluting stent (DES) and conducted a follow-up coronary angiography in Center for Cardiovascular Diseases of Meizhou People’s Hospital at the period of January 1st, 2016 to January 1st, 2021 were included for analysis. The clinical and angiographic factors were compared between patients in ISR ( +) and ISR (−) groups. The association between variables and ISR was evaluated by multivariate logistic regression model. Result: A total of 341 ACS patients who had been installed at least 1 stent were included in this study. The follow-up time was 34.2 ± 17.2 months. During the follow-up period, 62 (18.2%) patients experienced ISR, and the average time for ISR was 32.8 months; the incidence of ISR for left main coronary artery, left anterior descending coronary artery, left circumflex artery coronary artery and right coronary artery were 6.7%, 20.9%, 19.4% and 14.4%, respectively; left ventricular ejection fraction (LVEF), stent number, stent type, statin therapy, antiplatelet therapy were significantly different between patients in ISR ( +) and ISR (−) group. Multivariate logistic analysis suggested that LVEF and stent number were significantly correlated with ISR. Conclusion: Our study revealed the incidence and risk factors of ISR in patients from southern China. Our data suggested that LVEF and stent number were independent risk factors associated with ISR.

Background: MicroRNAs play a vital role in coronary artery disease. Abnormal expression of microRNAs has been found to be associated with the occurrence of CAD. Methods: We identified significantly differentially expressed microRNAs in plasma between 40 patients with CAD and 10 controls with NCA using RNA sequencing. The differentially expressed microRNAs were analyzed for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Results: Fifty cDNA libraries were constructed and sequenced, and a total of 1871.82 M raw reads were obtained, and 2135 microRNAs were found. Compared to the expressed microRNAs of NCA controls, 159 microRNAs were differentially expressed in CAD patients, including 119 upregulated microRNAs and 40 downregulated microRNAs. The top 10 upregulated miRNAs were miR‐144‐3p, miR‐34a‐5p, miR‐15b‐3p, miR‐22‐3p, miR‐29b‐3p, miR‐1270, miR‐6891‐5p, miR‐106a‐5p, miR‐15b‐5p, and hsa‐miR‐499b‐3p. The top ten downregulated miRNAs were miR‐4437, miR‐6842‐3p, miR‐4664‐3p, miR‐671‐3p, miR‐219a‐1‐3p, miR‐7848‐3p, miR‐664a‐3p, miR‐1284, miR‐361‐3p, and miR‐6780a‐5p. The target genes of differentially expressed microRNAs were related to many basic biological terms, such as biological process, cellular component, and molecular function. According to the KEGG pathway analysis, the most enriched pathways of the differentially expressed microRNAs were endocytosis, focal adhesion, axon guidance, and so on. Furthermore, six upregulated and two downregulated microRNAs were detected by qRT‐PCR (Quantitative Real‐time PCR) and ROC analysis for diagnosing CAD. Conclusion: The results suggest that the expression levels of some microRNAs may play a vital role in the physiological and pathological course of CAD. Our study may provide useful information for the diagnosis and treatment of CAD.

Background: Apolipoprotein E (APOE) is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The aim of the present study was to investigate the possible association between APOE gene polymorphism and the risk of CAD in postmenopausal Hakka women in southern China. Methods: The APOE genotypes of 653 CAD patients and 646 control participants were determined by the polymerase chain reaction (PCR) and hybridization to a Sinochip. Results: The prevalence of each APOE genotype differed between CAD patients and control participants (P = 0.011). The E3/E3 genotype was the most common and the E2/E2 genotype was the least common in the study sample. Moreover, the presence of ε4 allele was associated with higher serum concentrations of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), and lower concentration of high-density lipoprotein-cholesterol (HDL-C). Multiple logistic regression analysis revealed that participants with ε4 allele have a significantly higher risk of CAD after adjustment for the presence of diabetes mellitus and hypertension, and their serum uric acid, TC, and LDL-C concentrations (adjusted odds ratio (OR) 1.50, 95% confidence interval (CI) 1.10–2.05, P = 0.010). Conclusions: The present results suggest that APOE polymorphism is associated with a higher risk of CAD in postmenopausal Hakka women in southern China.

Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to chemotherapy-related adverse events. In the present study, we purposed to assess the impact ofDPYDandGSTP1variants on the toxicity of adjuvant chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment.Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drug-based chemotherapy regimen by direct sequencing ofDPYDandGSTP1polymorphisms. ThreeDPYDvariants including *2A, *5A, *9A, andGSTP1c.313A>G were analyzed and clinical outcomes were assessed.Results: The data suggest that the incidence ofDPYD*5A,DPYD*9A, andGSTP1c.313A>G variants were 38.4%, 24%, and 32.7%, respectively.DPYD*2Avariant was not found. A total of 23 patients (22.1%) suffered severe vomiting and 19 patients (18.3%) suffered severe anemia.DPYD*5Apolymorphism was found significantly associated with grade 3/4 ulceration (p= 0.001).GSTP1was determined to be an independent risk factor for severe vomiting and skin ulceration (p= 0.042 andp= 0.018, respectively). Patients withGSTP1c. 313A>G mutant type contributed to a higher risk for grade severe toxicity compared with wild genotype (p= 0.027). Nevertheless, no significant difference was found between patients withDPYD*2A,*5A, and*9Afor chemotherapeutic toxicity.Conclusions: The results demonstrated thatGSTP1polymorphisms were useful predictors of severe events. Screening of single-nucleotide polymorphisms ofGSTP1in colorectal cancer patients before chemotherapy may help to realize personalized therapy.

T cells are key regulators of immunity and one of the cells recruited in atherosclerosis and participated in various stages of the development of atherosclerosis. Characterizing T-cell receptor (TCR) repertoires is a priority of great scientific interest and potential clinical utility for the early diagnosis, risk stratification and prognostic evaluation of acute myocardial infarction (AMI). The TCR repertoires in 21 subjects including 7 patients with non-ST-segment elevation myocardial infarction (NSTEMI), 6 patients with ST-segment elevation myocardial infarction (STEMI) and 8 subjects with normal coronary artery (NCA) as control were characterized by using high-throughput sequencing. Bioinformatics analysis were performed. Patients with NSTEMI displayed more diverse TCR sequences than NCA controls, but they had lower percentage of top 200 TCR sequences. However, no significant differences were observed between the patients with STEMI and NCA controls, but STEMI group had lower percentage of top 200 TCR sequences. T cells from patients with AMI and NCA controls showed a differential V and J gene usage, especially, significant difference was observed in frequencies of V gene (TRBV2, TRBV29-1, TRBV30 and TRBV12-3) and J gene (TRBJ2-1) usage. Furthermore, significantly differences in average overlap was observed in groups of AMI and NCA control. The results showed that patients with AMI had distinct TCR repertoires which revealed the association between cardiovascular condition and T-cell clonotypes. Our findings revealed the differences of TCR repertoires between patients with AMI and NCA controls, which might be potential biomarkers for evaluating risk stratification or diagnosis of acute coronary syndrome.