Objective To investigate the interference effects of orexin A on cell proliferation of the insulin?secreting beta?cell line(INS?1 cells) through the orexin receptor 1(OX1R)and the AKT/PKB signaling pathway. Methods INS?1 cells were exposed to different concentrations of orexin A in vitro,and treated with OX1R antagonist(SB334867),PI3K antagonist(wortmannin),or AKT antagonist(PF?04691502). The INS?1 cell proliferation and apoptosis,insulin secretion,OX1R protein activity and AKT phosphorylation level were determined. Results Orexin A(10-10 to 10-6 mol/L)stimulated the proliferation and activation of INS?1 cells,prevented apoptpsis,and increased insulin secretion. Additionally,AKT phosphorylation was stimulated by orexin A(10-10 to 10-6 mol/L). The OX1R antagonist SB334867(10-6 mol/L),the PI3K antagonist wortmannin (10-8 mol/L)and the AKT antagonist PF?04691502(10-6 mol/L)weakened the effects of orexin A. Conclusion Orexin A activated the AKT sig?naling pathway through the mediation of orexin A?OX1R,and promoted cell proliferation in INS?1 cells.

Objective To systematically evaluate the effects of glucagon?like peptide?1(GLP?1)analogues exenatide and liraglutide on body weight in patients with type 2 diabetics mellitus. Methods Such databases as PubMed,Embase,CNKI and CMFD(1987?2014)were searched for randomized controlled trials. The meta?analysis was performed on the extracted related data using the software STATA 11. Results Totally 31 RCTs (7 036 patients)were included. The meta?analysis on body weight in these patients showed the following findings:compared to controls,liraglutide (1.8 mg)effectively decreased body weight(WMD=-0.45,95%CI:-0.59,-0.31);compared to positive controls,liraglutide(1.2 mg and 1.8 mg) also effectively decreased body weight(WMD=-0.91. 95%CI:-1.07,-0.75;WMD=-0.78,95%CI:-1.02,-0.54). Compared to controls,exena?tide(5μg and 10μg)effectively decreased body weight(WMD=-0.36,95%CI:-0.64,-0.09;WMD=-0.99,95%CI:-1.27,-0.72);compared to positive controls,exenatide(10μg)also effectively decreased body weight(WMD=-1.14,95%CI:-1.46,-0.82). Conclusion As novel intes?tinal pancreatotropic hormone analogues,exenatide and liraglutide can effectively reduce body weight,providing new alternatives of hypoglycemic agents for patients with type 2 diabetics mellitus.

Objective To investigate the value for the level mensuration of von Willebrand factor antigen (vWF:Ag) in stroke risk assessment in the patients with non-valvular atrial fibrillation (AF).Methods 180 non-valvular AF patients were selected from the Tianjin medical university general hospital from the 2009 to 2011 for retrospective cohort study,112 males and 68 females in the group,age 61-87 years.Using the IL ACL-9000 blood coagulation instrument assay the level of vWF:Ag.Using ROC curve to analyze the diagnosis performance of vWF:Ag,using Cox regression analysis model to evaluate the of vWF:Ag effect on prognosis,using x2 test to analyze the relevance between vWF:Ag and clinical pathological factors.Compared the patients group with CHADS2 score with the patients group with CHA2DS2VASc score date using t test.Results vWF:Ag levels were control group (112 ± 34)％,paroxysmal AF group (119 ±31)％,the persistent AF group (179 ± 47)％,permanent AF group (217 ± 56)％,atrial fibrillation associated with stroke group (235 ± 104)％ respectively.There was no difference between the paroxysmal AF group and control group (q =1.75,P ＞ 0.05) ; vWF:Ag level was higher in persistent atrial fibrillation group than in paroxysmal AF group (q =10.10,P ＜ 0.01); permanent atrial fibrillation group was higher than that of the persistent AF group (q =5.21,P ＜ 0.01).The optimum cut-off point with vWF:Ag for stroke diagnosis was 188.5％,the area under ROC curve =O.843 (95％ confidence interval:0.785-0.901).In Cox regression multianalysis,the vWF:Ag (HR =0.405; 95％ CI =0.268-0.716; P =0.026),the congestive heart failure(HR =2.901 ; 95％ CI =1.837-3.951 ; P =0.001),stroke/transienl ischemic attack (HR =4.665 ; 95 ％ CI =2.837-7.291 ; P =0.000),age (HR =0.474 ; 95 ％ CI =0.211-0.765; P =0.039),the Cox analysis showed that vWF:Ag was the independent prognosis factor for stroke in AF patients.Inx2 analysis,there was the relationship between the level of the vWF:Ag and the congestive heart failure/LVdysfunction (x2 =8.227,P ＜ 0.01),hypertension (x2 =3.305,P ＜ 0.05),age (x2 =7.581,P ＜ 0.01),diabetes mellitus (x2 =6.730,P ＜ 0.01),stroke/ transient ischemic attack/thromboembolism (x2 =4.825,P ＜ 0.05),vascular disease (x2 =4.126,P ＜ 0.05).Compared the subjects with CHADS2 (score =1) with the CHA2DS2VASc(score =1),the level of the vWF:Ag was higher in patients with CHADS2 score =1 (t =4.283,P ＜ 0.01).Conclusion There was relationship between the level of vWF:Ag and main pathologic factors in patients with AF,and changed with the condition,high vWF:Ag level was an independent predictor of stroke risk,and had superior reference value for in assessment of stroke in patients with atrial fibrillation.

Amyotrophic Lateral Sclerosis ; genetics ; Animals ; Biological Transport, Active ; Bipolar Disorder ; genetics ; Glucose Transporter Type 4 ; metabolism ; Hepacivirus ; physiology ; Humans ; Neoplasm Metastasis ; Neoplasms ; metabolism ; Point Mutation ; Polymorphism, Single Nucleotide ; R-SNARE Proteins ; metabolism ; Tissue Distribution ; Transport Vesicles ; physiology ; Vesicular Transport Proteins ; chemistry ; genetics ; metabolism ; physiology ; Virus Replication

Objective In order to study the value of drug treatment for leukemia, quercetin was delivered to the cultured NB4 cell line. MethodsUsing RT- PCR and western blot, we studied the expression of mutant p53 gene and protein after inducing 24, 48, 72, 96 and 120h by the quercetin with different concentrations (30, 60, 90μmol/L). Results We verified the results that quercetin with concentration of 30 ～90μmol/L could successfully inhibit the expression of mutant p53 protein, but the mutant p53 gene did not have. ConclusionThat data suggested that quercetin would be an effective method for the therapy of leukemia.

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Clostridium difficile is a gram-positive,anaerobic spore-forming bacillus commonly found in the environment and human gut.Excessive use of antibiotics,immunosuppressive agents and chemotherapy drugs may lead to overgrowth of the toxic strain of Clostridium difficile with high resistance,which are supposed to be the major contributing factors leading to Clostridium difficile associated diarrhea(CDAD).The globally increasing incidence of CDAD,especially the outbreak of nosocomial infection caused by the hypervirulent strain in North America,arouse worldwide attention.For providing new ideas to the early diagnosis and treatment of CDAD,this review summarize the latest development on pathogenesis and rapid laboratory diagnosis of Clostridium difficile.

Objective To investigate the ch an ges of gastric intramucosal pH (pHi) during orthotopic liver transplantation (OL T) without venovenous bypasss. Methods Twenty patients (14 males and 6 females) aged (46.7 ?4.6) years, undergoing orthotopic liver transplantation without venovenous byp asss, were included in this study. A gastric tube technique was used to draw gas tric juice 3～5 mL to determine pHi and PiCO 2 before OLT, at 20 min preanhep atic phase, 30 min anhepatic phase, 30 min new hepatic phase and at 2 h and 2 4 h after operation. The arterial blood samples collected taken for the measure ments of PaCO 2, PO 2, pH, BE and HCO 3- at the same time point s as above. pHi was calculated through Henderson-Hasselbach equation. Results The gastric intraumucosal pH (pHi) was decreased significant ly at the time points of 30 min anhepatic phase and 30 min new hepatic phase c ompared with before operation (P

Objective To observe the curative effect in patients with systemic lupus erythematosus(SLE) complicated by moderate or severe thrombocytopenia with a blood platelet count(BPC) of under 50 × 109/L and analyze its related factors. Methods We retrospectively analyzed the clinical data on 109 SLE patients with mod-erate or severe thrombocytopenia. Results Of the 109 patients,82(75.2%)had complete response(CR),15 (13.8%)had partial response(PR),and 12(11.0%)had no response(NR),respectively. As compared with the CR+PR group,the NR group had a higher incidence rate of decreased bone marrow megakaryocyte(P < 0.05). However,there were no significant differences between the two groups in SLEDAI scores,rates of positive PAIg and ACA,and levels of C3 and C4(P>0.05 for all comparisons). The total effectiveness rate did not differ signifi-cantly between MP pulse therapy and high-dose corticosteroid therapy. Conclusions A decrease in bone marrow megakaryocytes can be an adverse factorfor affecting the efficacy in patients with SLE complicated by moderate or severe thrombocytopenia.

Background Increase in ophthalmic optical medical instruments and microsurgical applications leads to retinal photochemical damage and other problems delivery of a variety of devices,so the in-depth study and understanding of its pathogenesis after retina light damage can provide a reference for the clinical treatment of related diseases.Objective This study was to investigate the therapeutic effect and relative mechanism of erythropoietin (EPO) on mouse retina photic injury by studying the expression of matrix metalloproteinases-2 (MMP-2)and MMP-9.Methods Fifty-two SPF BALB/c mice were randomized into normal control group,simple light-induced group and EPO pretreatment group by balloting method.The mice of simple light-induced group and EPO pretreatment group were continuously irradiated with 6000 lx diffuse light for 4 hours in a home-made box to establish the models of light-induced damage;while recombinant human EPO (rhEPO)of 5000 U/kg was intraperitoneally injected prior to the light exposure in the EPO pretreatment group.The expressions of MMP-2 and MMP-9 were examined at 6,12,36,72,96 hours and 7 days following light-exposure by immunohistochemistry.Results Edema and structural disorder of RPE cells appeared inthe simple light-induced group after light-exposure and aggravated with lapse of light-exposure time,but no similar change was seen until 7 days in the EPO pretreatment group.The immunohistochemistry findings showed that the expression of MMP-2(A value)in RPE cells was less in the normal mice.However,a large quantity of positive cells appeared in RPE layer 36 hours after light-exposure.Compared with the simple light-induced group,the positive expression of MMP-2 protein in EPO pretreatment group was significantly decreased,showing statistically significant differences among these three groups and different time points (Fgroup =3.68,P =0 04; Ftime =9.13,P=0.00).There was hardly any MMP-9 expression in the retina of the normal mice.In simple light-induced group,a few of positive cells appeared in RPE layer 6 hours after light-exposure and reached its peak 12 hours following light-exposure.The gradually down-regulation of MMP-9 expression happened 96 hours later following light-irradiation.The expression tendency of MMP-9 in EPO pretreatment group was similar to the simple light-induced group.Significant differences in expressions of MMP-9 were found among different groups and time points (Fgroup=3.61,P =0.04;Ftime =16.91,P=0.00).Conclusions MMP-2 and MMP-9 may be involved in the mechanism of retina photic injury by down-regulating the expression of MMP-2 and MMP-9 in RPE cells.