Objective:To observe and analyze the therapeutic effect and safety of tirofiban combined large dose statin in patients with acute myocardial infarction (AMI),and evaluate its influence on myocardial perfusion and cardiac function.Methods:A total of 97 consecutive AMI patients visited to our hospital from May 2011 to January 2013, who were beyond the emergency PCI time window (≥12h),their chest pain was remissive or not further aggravated were studied.All patients were pumped with tirofiban for 48h continuously;according to combined rosuvastatin dose,they were divided into large dose group (n = 52,20mg,once/d,until one month after infarction,then changed to routine dose of 10mg,once/d)and routine dose group (n=45,10mg,once/d).All patients received se-lective PCI after 7 ~ 10d conservative treatment.Myocardial perfusion level,left ventricular ejection fraction (LVEF)on one week after PCI and 30d after AMI,enzymology changes [creatine (CK),lactate dehydrogenase (LDH)]and major adverse cardiovascular events (MACE)during hospitalization were compared between two groups.Results:Compared with routine dose group,there were significant reductions in thrombus scores in infarct related artery (IRA)[(1.32±1.01)scores vs.(0.81±0.78)scores]and corrected TIMI frame [(32.4±4.73)vs. (26.8±2.34)]in large dose group (P =0.021,P <0.001);after selective PCI,TIMI flow of large dose group was significantly better than that of routine dose group (P =0.024).On one week after PCI,LVEF:(51.4±8.9)% of large dose group was significantly higher than that of routine dose group (47.7±8.7)%,P =0.021;there were no significant difference in levels of CK and LDH between two groups on 7d and 30d after PCI (P >0.05).There was no MACE in both groups during hospitalization and 30d after PCI.Conclusion:Tirofiban combined large dose statin is safe and effective in patients with acute myocardial infarction,it can reduce intra-coronary thrombus burden,im-prove myocardial tissue perfusion and cardiac function without increasing MACE.

Objective To explore the potential relationship between ubiquitination of transforming growth factor kinase 1(TAK1)/nuclear factor-κB(NF-κB)signaling pathway mediated by ring finger protein 99(RNF99)and septic acute respiratory distress syndrome(ARDS).Methods Plasmid and siRNA transfection were conducted to overexpress or knock down RNF99 in MLE12,and expressions of p65 phosphate and p65 protein were analyzed.The protein interaction between RNF99 and TRAF6 or TAK1 was analyzed by immunoprecipitation assay.Forty mice were randomly divided into WT plus PBS,WT plus LPS,RNF99 specific expression(TG)plus PBS,and TG plus LPS groups,with 10 mice in each group.Sepsis was induced by intraperitoneal injection of 30 mg/kg LPS.Results As compared with vector group,protein expression levels of TRAF6 and TAK1 in MLE12 cells decreased significantly in RNF99 group(P<0.05).Ubiquitinated TRAF6 protein increased in MLE12 cells with RNF99 knockdown.As compared with LPS plus vector group,phosphorylation level of p65 in MLE12 cells was signifi-cantly lower in LPS plus RNF99 group(P<0.05).As compared with si-NC group,protein expression levels of RNF99 and IκBα in si-RNF99 group decreased significantly(P<0.05).As compared with LPS plus si-NC group,phosphorylation level of p65 in LPS plus si-RNF99 group increased significantly(P<0.05).The staining percentage of CD68 macrophages in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Phosphorylation level of p65 in lung tissues was significantly lower in TG plus LPS group than in WT plus LPS group(P<0.05).Conclusion RNF99 regulates NF-κB signaling pathway by interacting with the key regulator of NF-κB signaling pathway(TRAF6/TAK1),and improves lung injury after intraperitoneal injection of LPS in mice.

Objective: To investigate the protective effect of neurotrophic factor(MANF) derived from midbrain astrocytes on myocardial injury induced by sepsis by activating SIRT1/AMPK signaling pathway. Methods: 48 mice were randomly divided into 4 groups: control group, recombinant mouse MANF(rmMANF) group, cecal ligation and puncture(CLP) group and CLP+rmMANF group, with 12 mice in each group.The survival rate, sepsis score, anal temperature, blood biochemical indexes, pathological indexes of myocardial injury and the expression of endoplasmic reticulum stress(ERS) related proteins were detected 8 h after CLP.H9C2 cells were divided into control group(Con),LPS group, LPS+rmMANF group, LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group.The cells were collected after 24 h treatment with LPS,and the expression of ERS protein and apoptosis in cells were analyzed. Results: Compared with CLP group, the sepsis score and serum Lactate dehydrogenase(LDH),creatine kinase(CK),aspartateaminotransferase(AST) and blood urea nitrogen(BUN) levels in CLP+rmMANF group decreased significantly(P<0.01),and the anal temperature and serum albumin(ALB) levels increased significantly(P<0.05).Compared with CLP group, the expression of MANF in CLP+rmMANF group increased significantly(P<0.01),and the expression of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP) and the percentage of TUNEL positive cells decreased significantly(P<0.05).In vitro, LPS stimulation down-regulated the expression of SIRT1 and AMPK in H9C2 cells, while rmMANF further increased the expression level of SIRT1 and AMPK.Compared with LPS+rmMANF group, the expression of GRP78 and CHOP protein and the apoptosis rate of H9C2 cells in LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group increased significantly(P<0.05). Conclusion rmMANF inhibits ERS related to sepsis-induced myocardial injury by activating SIRT1/AMPK signaling pathway, thereby protecting myocardial injury.