Shexiang tongxin dropping pill alleviates myocardial injury induced by coronary microembolization by down-regulating APOC1 to inhibit STAT3 signaling pathway.

AIM: This study determines to validate the mechanism of Shexiang Tongxin dropping pill (STDP) in attenuating coronary microembolization (CME) induced myocardial injury. METHODS: CME rat models were established and underwent corresponding treating. Gene chip analysis was performed in rat myocardial tissues for GO and KEGG enrichment analysis. The differentially expressed genes were detected by qRT-PCR. H&E staining and ELISA were used for pathological analysis and detection of troponin (cTnI) and Creatine Kinase Isoenzyme (CK-MB). Lipopolysaccharide (LPS) treated primary cardiomyocytes were used to mimic inflammatory in vitro models. Cell viability and apoptosis of cardiomyocytes were determined by MTT and flow cytometry. The expressions of inflammatory cytokines, apoptotic proteins and proteins related to the STAT3 signal pathway were detected by western blot. APOC1 mRNA expression was detected by qRT-PCR. Immunofluorescence (IF) was used for subcellular localization of p-STAT3 and the binding of APOC1 with STAT3 was verified using Co-IP. RESULTS: STDP can attenuate myocardial injury in CME rat models, and lead to decreased expression of APOC1 and suppressed STAT3 signal pathway. In vitro models found STDP can suppress the cell viability and cell apoptosis of primary cardiomyocytes, in addition to suppressing the secretions of IL-6, IL-1ß and TNF-α, while the protective effect of STDP can be reversed by overexpression of APOC1. Co-IP found that APOC1 can bind STAT3 directly. APOC1 can increase p-STAT3 expression in the nucleus to activate the STAT3 signal pathway. CONCLUSIONS: STDP can suppress APOC1 and STAT3 signal pathway to inhibit inflammation and cell apoptosis of cardiomyocytes. APOC1 may be one of the key regulatory factors in CME-induced myocardial injury.

Do medical alliances truly work? Perspectives on health service utilisation among outpatients with chronic diseases in Shanghai, China.

BACKGROUND: To achieve proper health utilisation among various health institutions and improve primary care capacity, China implemented medical alliance (MA) reform as part of healthcare reforms in 2009. With chronic disease management as the focus and priority of primary health institutions, this study aimed to analyse the specific distribution and trends of outpatient visits to various levels of health institutions (community health centres (CHCs) vs hospitals) in MAs. METHODS: All outpatient data were extracted from the Chuansha MA in Pudong New Area, Shanghai, between 2016 and 2020, and submitted to descriptive analysis, Chi-Square tests and correlation analysis. RESULTS: This article found that outpatients aged >60years visited CHCs more than hospitals for some chronic diseases. The adjusted average costs of outpatients presented upward trends both in hospitals and in CHCs. CONCLUSIONS: The Chuansha MA worked in guiding older outpatients to visit CHCs, but did not control the increasing medical costs. The Shanghai government should further improve medical capability of CHCs to attract all community-dwelling residents at all ages to implement hierarchical diagnosis and treatment systems, as well as make more efforts to control increasing medical costs.

Expression of microRNAs differed in the omental adipose tissue of obese rats.

OBJECTIVE: To establish obese rat models by high-fat diet, screen microRNAs by microarray in the omental adipose tissue, and find out differential expression of microRNAs in obese rats, for further understanding the role of microRNAs as regulating molecules in obesity-induced lipid metabolism disorders. METHODS: 40 male SD rats were randomly divided into normal diet group and high-fat diet group, respectively. After fed for 8 weeks, rats were weighted, measured length and other characteristics were observed. Eye blood was taken to test blood glucose level, blood lipids level, insulin level and other indicators. The omental adipose tissue was measured by electronic analytical scales and saved at -80°C liquid nitrogen. Fat cells were stained by oil red to observe their morphology under microscopy. The expression of microRNAs was screened by microarray, and verified by Real-Time PCR. RESULTS: After high-fat diet for 4 and 8 weeks, some fatty indicators changed, including increased body weight, omental fat weight, triglycerides, total cholesterol, low-density lipoprotein, blood glucose level and insulin level, and decreased high-density lipoprotein, and differential phenotype of fat cells. Besides, by microarray techniques and Real-Time PCR, 13 differential expression microRNAs were identified, including 7 up-regulated microRNAs (microRNA30a, microRNA7e, microRNA30c, microRNA335, microRNA103, microRNA107, microRNA139-5p), and 6 down-regulated microRNAs (microRNA494, microRNA140, microRNA342-5p, microRNA382, microRNA17-1-3p, microRNA92a). CONCLUSION: Changes in the expression of microRNAs contribute to the pathogenesis of many diseases, including obesity disorders. These alterations can be due to various mechanisms, such as cell proliferation, apoptosis, migration, and differentiation, providing new therapies for diseases.

Clinical and procedural predictors of no-reflow in patients with acute myocardial infarction after primary percutaneous coronary intervention.

BACKGROUND: The treatment of acute myocardial infarction (AMI) is thought to restore antegrade blood flow in the infarct-related artery (IRA) and minimize ischemic damage to the myocardium as soon as possible. The present study aimed to identify possible clinical predictors for no-reflow in patients with AMI after primary percutaneous coronary intervention (PCI). METHODS: A total of 312 consecutive patients with AMI who had been treated from January 2008 to December 2010 at the Cardiology Department of East Hospital, Tongji University School of Medicine were enrolled in this study. Inclusion criteria were: (i) patients underwent successfully primary PCI within 12 hours after the appearance of symptoms; or (ii) patients with ischemic chest pain for more than 12 hours after a successful primary PCI within 24 hours after appearance of symptoms. Exculsion criteria were: (i) coronary artery spasm; (ii) diameter stenosis of the culprit lesion was <50% and coronary blood flow was normal; (iii) patients with severe left main coronary or multivessel disease, who had to require emergency revascularization. According to thrombolysis in myocardial infarction (TIMI), the patients were divided into a reflow group and a no-reflow group. The clinical data, angiography findings and surgical data were compared between the two groups. Univariate and multivariate logistic regressions were used to determine the predictors for no-reflow. RESULTS: Fifty-four (17.3%) of the patients developed NR phenomenon after primary PCI. Univariate analysis showed that age, time from onset to reperfusion, systolic blood pressure (SBP) on admission, Killip class of myocardial infarction, intra-aortic balloon pump (IABP) use before primary PCI, TIMI flow grade before primary PCI, type of occlusion, thrombus burden on baseline angiography, target lesion length, reference luminal diameter and method of reperfusion were correlated with no-reflow (P<0.05 for all). Multiple logistic regression analysis identified that age >65 years [OR=1.470, 95% confidence interval (CI) 1.460-1.490, P=0.007], long time from onset to reperfusion >6 hours (OR=1.270, 95%CI 1.160-1.400, P=0.001), low SBP on admission <100 mmHg (OR=1.910, 95%CI 1.018-3.896, P=0.004), IABP use before PCI (OR= 1.949, 95%CI 1.168-3.253, P=0.011), low (≤1) TIMI flow grade before primary PCI (OR=1.100, 95%CI 1.080-1.250, P<0.001), high thrombus burden (OR=1.600, 95%CI 1.470-2.760, P=0.030), and long target lesion (OR=1.948, 95%CI 1.908-1.990, P=0.019) on angiography were independent predictors of no-reflow. CONCLUSION: The occurrence of no-reflow after primary PCI for acute myocardial infarction can predict clinical, angiographic and procedural features.

Frequency of TLR 2, 4, and 9 gene polymorphisms in Chinese population and their susceptibility to type 2 diabetes and coronary artery disease.

Toll-like receptors (TLRs) are pivotal components of the innate immune response. Activation of the innate immune system and subsequent chronic low-grade inflammation are thought to be involved in the pathogenesis of atherosclerosis and type 2 diabetes. In the study, we genotyped TLRs gene polymorphisms, including TLR2 Arg677Trp and Arg753Gln, TLR4 Asp299Gly and Thr399Ile, TLR9-1486T/C and -1237T/C. The frequencies of TT, TC and CC genotype of TLR9-1486T/C mutation were 39.6%, 45.8% and 14.6%, respectively; the frequencies of T allele and C allele were 62.5% and 37.5%. However, neither of these parameters was statistically significant among study groups. In addition, we were surprised to find that the commonly reported TLR SNPs in the Western countries, like TLR2 Arg677Trp or Arg753Gln, TLR4 Asp299Gly or Thr399Ile and TLR9-1237T/C, were not polymorphic at all in all study subjects. In conclusion, our data suggests that TLR2 Arg677Trp or Arg753Gln, TLR4 Asp299Gly or Thr399Ile and TLR9-1237T/C polymorphisms have low frequency and TLR9-1486T/C polymorphism may not be a suitable marker in predicting the susceptibility to type 2 diabetes or coronary artery disease in the Chinese Han population.

Modified clopidogrel loading dose according to platelet reactivity monitoring in patients carrying ABCB1 variant alleles in patients with clopidogrel resistance.

OBJECTIVES: The aim of the present study was to investigate the impact of a adjusted clopidogrel loading dose (LD) according to platelet reactivity index in carriers of ABCB1 mutant allele undergoing percutaneous coronary intervention (PCI). METHODS: All patients met the inclusion criteria were recruited in the present study. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index. High treatment platelet reactivity (HTPR) was determined by a cut-off value of >50%. The genetic polymorphism of ABCB1 was determined by allele-specific polymerase chain reaction (PCR). In patients carrying ABCB1 and HTPR after a first 300-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 300-mg LDs to obtain a VASP index<50%. The rate of major adverse cardiovascular events (MACE) and major or minor bleeding in one month were recorded. RESULTS: 536 patients were included in the present study. One hundred seventy-two patients (32%) carried ABCB1 mutant allele (11 homozygotes [2%] and 161 heterozygotes [30%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild allele (65.5±13.8% vs. 47.6±21.8%; p<0.001). Of the 172 ABCB1 mutant allele carriers, 130 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (66.9±12.8% vs.50.2±18.3%; <0.001). Finally, dose adjustment according to platelet reactivity monitoring enabled 88% of ABCB1 mutant allele carriers and 91% of wild allele carriers exhibiting HTPR to reach a VASP index<50%. The rate of MACE and major or minor bleeding in one-month follow-up between the wild allele carriers and the mutant allele carriers didn't differentiate significantly. CONCLUSIONS: Increased and adjusted clopidogrel loading dose according to platelet reactivity monitoring attenuated clopidogrel resistance in carriers of ABCB1 mutant allele.