OBJECTIVETo discuss the effect of taurine (Tau) on the proliferation of hypoxia-induced pulmonary artery smooth muscle cells (PASMCs), and study whether the extracellular signal-regulated kinase 1/2 (ERK1/2) signal pathway participated in the Tau-inhibited PASMC proliferation process and the possible molecular mechanism.

METHODThe primary culture was performed for PASMCs in rats. The second to fifth generations were adopted for the experiment. The Tau concentration was 80 mmol x L(-1). The concentration of ERK1/2 blocker (PD98059) was 50 micromol x L(-1). The drug administration time was 24 h. The effect of Tau on the PASMC proliferation was detected by MTT assay, immunofluorescence staining method and western blot under different conditions. The PASMCs were growing were divided into four groups: the normoxia group, the normoxia + Tau group, the hypoxia group and the hypoxia + Tau group. The Western blot was adopted to detect whether the ERK1/2 signal pathway participated in the Tau-inhibited PASMC proliferation process. Subsequently, the PASMCs were divided into five groups: the normoxia group, the hypoxia group, the hypoxia + Tau group, the hypoxia + Tau + PD98059 group and the hypoxia + PD98059 group.

RESULTHypoxia could induce the PASMC proliferation. Under the conditions of normoxia, Tau had no effect on the PASMC proliferation. Under the conditions of normoxia and hypoxia, Tau had no effect on the expression of the tumor necrosis factor-alpha (TNF-alpha) among PASMCs. Tau could reverse the expression up-regulation of hypoxia-induced proliferative cell nuclear antigen (PCNA) (P < 0.01) and Cyclin A (Cyclin A) (P < 0. 05). Under the conditions of normoxia, Tau had no effect on the expression of phosphoryl extracellular signal-regulated kinase 1/2 (p-ERK1/2). Hypoxia could up-regulate the p-ERK1/2 expression (P < 0.01). Tau could reverse the up-regulation of the hypoxia-induced p-ERK1/2 expression(P < 0.01). Both PD98059 and Tau could inhibit the up-regulated expressions of PCNA, Cyclin A and p-ERK1/2. According to the comparison between the single addition of Tau and PD98059 under conditions of hypoxia, the hypoxia + Tau + PD98059 group showed more significant down-regulation in the expressions of PCNA, Cyclin A and p-ERK1/2.

CONCLUSIONTau could inhibit the hypoxia-induced PASMC proliferation, and may regulate it through ERK1/2 pathway.

Animals ; Cell Hypoxia ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; MAP Kinase Signaling System ; drug effects ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; Oxygen ; metabolism ; Pulmonary Artery ; cytology ; drug effects ; metabolism ; physiopathology ; Rats ; Rats, Wistar ; Taurine ; pharmacology ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

Objective To study the association between serum free fatty acid (FFA) and ankylosing spondylitis (AS).Methods According to the classification criteria,a total of 90 newly diagnosed AS patients,223 healthy individuals and 82 patients with non-inflammatory diseases were divided into three groups,and biochemistry and immunology biomarks were measured in all individuals.One-Way analysis of variance (ANOVA) test was used to compare the difference between the three groups in the serum indexes,and Logistic regression analysis was used to identify AS risk factors associated with AS.Results There were no significant differences in gender,age,body mass index (BMI),white blood cells (WBC),high-level data link control (HDL-C),low-density lipoprotein control (LDL-C),lipoproteins [Lp (a)],alkaline phosphatase (ALP) and TG in the three groups,and our results showed that serum FFA was statistical different between the three groups (F=24.191,P＜0.01),the serum level of FFA in patients with AS was higher compared with patients with noninflammatory diseases and healthy controls [(0.48 ±0.18) mmol/L,(0.28 ±0.09) mmol/L,(0.29±0.16) mmol/L;t=-5.969,P＜0.01;t=5.106,P＜0.01].Seral IgA,IgG,IgM levels,ESR and CRP were statistically different between the three groups (F=14.870,P＜0.01;F=16.464,P＜0.01;F=4.124,P=0.018;F=97.002,P＜0.01;F=22.069,P＜0.01).Gender,age,BMI,serum IgA,IgM,ALP,HDL-C,LDL-C,Lp(a) and TG levels were not associated with AS by logistic regression analysis.However,serum IgG level,ESR and CRP were associated with AS [OR05％CI):1.659(1.032,2.660),P=0.037;OR05％CI):1.340(1.005,1.787),P=0.046;OR05％CI):1.820 (1.025,3.232),P=0.041],and there is an association between FFA and AS was observed in logistic regression analysis (OR=1.132,95％CI:1.014-1.421,P=0.033).Conclusion We suggest that incre-ased FFA is closely associated with AS,and may be an underlying risk factor for AS.

Amygdala plays a crucial role in emotion. This article introduces several problems of the current study of amygdala: the relationship between amygdala and basic emotions and social emotions; whether activity of amygdala is elicited by valence or by arousal; the contribution of awareness to the activation of amygdala; the functional asymmetries of the left and right amygdala. In addition, some possible reasons of the disputes are discussed mainly concerning the constructional complexity of amygdala and the differences among research paradigms. The purpose of the article is to summarize the amygdala research in emotion and provide some useful references for the future study.

OBJECTIVETo study the effect of ozonized saline on the activation of the Keap1-Nrf2-ARE signaling pathway in rat liver cells.

METHODSTwenty male Sprague-Dawley rats were randomly divided into ozonized saline (OS) group, model group, ozonized saline control (OSC) group and normal control (NC) group. The rats in OS group and model group were intravenously administered with OS or oxygen saline (5 ml/kg) respectively, once a day for 15 days, and then intraperitoneally injected with CCl4 dissolved in oliver oil. The rats in OSC group were pretreated with OS for 15 days. The rats in NC group were fed normally for 15 days. On the 16th day, the rats in OSC group and NC group were intraperitoneally injected with oliver oil (2 ml/kg) without CCl4. After 24 hours of CCl4 or olive oil intraperitoneal injection, the serum levels of alanine transaminase (ALT) and aspertate aminotransferase (AST) were measured. The liver tissues were also collected for detection of total anti-oxygen capability (TAOC), glutathione (GSH), catalase (CAT), Glutathione peroxidase (GPx). Western Blot was used to detect Nrf2 and immunofluorescence staining assay to display intracelluar distribution of Nrf2.

RESULTSCompared with the rats in model group,the serum ALT and AST levels of rats in OS group were significantly lower (P < 0.01) ,which were (1240.4 ± 188.2) U/L and (1245.4 ± 176.9) U/L vs (539.8 ± 175.3) U/L and (546.0 ± 130.2) U/L, and the TAOC, CAT, GPx and GSH activity of rats in OS group were significantly higher, which were (0.72 ± 0.24) U/mg, (1.05 ± 0.21) mg/g, (676.9 ± 115.1) U/mg and (45.2 ± 14.3) U/mg vs (1.37 ± 0.19) U/mg, (2.23 ± 0.55) mg/g, (1024.6 ± 162.9) U/mg and (68.2 ± 9.9) U/mg, respectively. In contrast with NC group, pretreatment of OS in OSC group elevated TAOC, CAT, GPx and GSH activity (P < 0.01 or P < 0.05). Ozonized saline can strengthen the Nrf2 expression in liver cells.

CONCLUSIONPreconditioning injection of ozonized saline can reduce rat's liver injury induced by CCl4. The ozonized saline, as a novel Nrf2 activator, can reduce the oxidative damage of radical oxygen species (ROS) and the deleterious substance by activating the Keap1-Nrf2-ARE signaling pathway and its downstream genes expression.

Alanine Transaminase ; metabolism ; Animals ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Hepatocytes ; drug effects ; metabolism ; Intracellular Signaling Peptides and Proteins ; Kelch-Like ECH-Associated Protein 1 ; Liver ; metabolism ; Male ; Malondialdehyde ; metabolism ; NF-E2-Related Factor 2 ; metabolism ; Oxidative Stress ; Ozone ; pharmacology ; Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Superoxide Dismutase ; metabolism

Objective We aimed to investigate the expression of IRF4 and apoptosis of the histone deacetylase inhibitor LBH589 against MM cells in vitro,and study the mechanism of apoptosis when LBH589 alone or/and combined with lenalidomide in RPMI8226 cell so as to provide a new strategy for the treatment of multiple myeloma.Methods The cell viability on the growth of RPMI8226 cell were assessed by CCK8 assay.Apoptosis were measured by flow cytometry,The Grandpad software analyzes the statistical significance and evaluates the synergistic effect of the drug.The expression level of the related transcription factor and apoptotic gene protein were determined by western blot.The cell viability on the growth of RPMI8226-R cell were assessed by CCK8.Results LBH589 combined with lenalidomide have significant effect on inhibit cell proliferation and induce apoptosis in a dose-dependent manner.Apoptosis induced by LBH589/lenalidomide alone or combination was shown to involved PARP activation,decreased Bcl-2 and Bcl-xl expression.significantly down regulated transcriptional related factors of IRF4 and c-MYC expression compared with either agent alone.Conclusion LBH589 and lenalidomide alone or combination decrease the expression of transcription factor IRF4 and c-MYC,and have a significant synergistic effect,and highly expression of IRF in RPMI8226-R reduce proliferation inhibition.

Objective To evaluate the nutritional status and nursing nutritional guidance in maintenance of hemodialysis patients(MHD).Methods 48 cases of MHD were selected and randomly divided into two groups:experimental group(n=23)and control group(n=25).Control group was siven routine nursing.Experimental group waft given routine nursing plus nutritional guidance.Results After six months nutritional guidance,the nutritional status of the experimental group are better significantly than that of the control group(P<0.05).Conclusions Nutritional guidance Call significantly improve the nutritional status of the MHD.

Objective To investigate the epidemiological pattern of Borna disease virus (BDV)infection in horses and to analyze the phylogenetic tree of derived BDV in Yili, Xinjiang. Methods We established a modified nested RT-PCR (nRT-PCR) to detect BDV p24 segment in peripheral blood mononuclear cells (PBMCs) and brain tissues of 120 horses in Yili, Xinjiang. Positive products were analyzed by sequencing and homology analysis. Results The positive rate of BDV infection was 2.5% in both PMBCs and brain tissues at the same time. The gene sequence revealed in positive PCR samples was more than 93 % ,identical to that of BDV derived from horses in other countries. We also noticed a high degree of identity ( >98 % ) to standard strain He/80 in gene sequence of positive PCR samples. Conclusion Our study found the presence of BDV natural infection in horses in Yili. The endemic BDV had a high degree of identity to standard strain He/80.

Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia (AML). The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 (pLKB1) on the senescence of acute myeloid leukemia (AML) stem cells. The protein expressions of pLKB1 and Sirtuin 1 (SIRT1), a regulator of pLKB1, were measured in CD34(+)CD38(-) KG1a cells treated with resveratrol (40 μmol/L) or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase (SA-β-gal) staining, cell proliferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34(+)CD38(-) KG1a cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34(+)CD38(-) KG1a cells. It was concluded that resveratrol-downregulated pLKB1 is involved in the senescence of AML stem cells.
Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Leukemia, Myeloid, Acute ; enzymology ; genetics ; pathology ; Neoplastic Stem Cells ; drug effects ; Phosphorylation ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; Sirtuin 1 ; genetics ; metabolism ; Stilbenes ; pharmacology

Objective To investigate the risk factors for reduced renal function in patients with ischemic stroke.Methods The medical records of patients with ischemic stroke were analyzed retrospectively.They were divided into normal renal function group and reduced renalfunction group.Reduced renal function was defined as estimated glomerular filtration rate (eGFR) ＜60 ml/(min·1.73 m2).Multivariate logistic regression analysis was used to identify the risk factors for reduced renal function in patients with ischemic stroke.Results A total of 805 patients with ischemic stroke were enrolled in the study.8.8％ of patients had a reduced renal function.There was no significant differences in the proportion of patients with mild and moderate neurological deficit between the reduced renal function group and the normal renal function group (all P ＞ 0.05),however,the proportion of patients with severe neurological deficit was significantly higher than that in the normal renal function group (8.4％vs.2.6％,x2 =5.573,P =0.017).The proportion of small artery occlusion in the reduced renal function group was sigaificantly higher than that in the normal renal function group (66.2％ vs.46.5％,x2 =9.962,P =0.002),and the proportion of large artery atherosclerosis was significantly lower than that in the normal renal function group (19.7％ vs.43.5％,x2 =15.045,P =0.000).Multivariate logistic regression analysis indicated that old age (odds ratio [ OR] 3.301,95％ confidence interval [ CI],1.575 to 6.918; P=0.002) was the most important independent risk factor for reduced renal function,then was female (OR,2.291,95％ CI 1.355to 3.872; P=0.002) and hyperlipidemia (OR,2.527,95％ CI 1.095 to 5.831; P=0.030).Conclusions Reduced renal function in patients with ischemic stroke is strongly associated with old age,female,and hyperlipidemia.

BACKGROUNDMost indices for evaluating a diagnostic test can be expressed as functions of sensitivity (SEN) and specificity (SPE). Practically, all existing methods suffer from the inability to weight sensitivity and specificity relative to their importance. In this paper, we developed a novel index, the weighted Youden index, that allows Youden index to be a combination of sensitivity and specificity with user-defined weights.

METHODSThe weighted Youden index Jw is defined as Jw = 2(w×SEN + (1-w)SPE)-1 (0 ≤ w ≤ 1). It has three properties: (1) the sum of the weights which are attached to sensitivity and specificity should be equal to 1; (2) the range of Jw should be within [-1, 1], which is the range of the Youden index J; (3) Jw should be equal to J when sensitivity and specificity have equal weights. According to the central limit theorem, we obtain the standard error of Jw, and propose a statistical inference method to compare two weighted Youden indices. The monotonicity of the test statistic was discussed.

RESULTSAn example of comparing two diagnostic tests for pheochromocytoma was used to demonstrate the weighted Youden index method. Weighted Youden index, the confidence interval for each test and the hypothesis test of comparing two independent diagnostic tests were presented. Assigning the weights is essential to the weighted Youden index approach.

CONCLUSIONThe weighted Youden index can broaden its applications in diagnostic test development and motivate further research in weighting sensitivity and specificity explicitly.

Diagnostic Tests, Routine ; Humans ; Models, Theoretical ; Sensitivity and Specificity