Adult ; Ataxin-1 ; Ataxins ; Female ; Humans ; Mutation ; Nerve Tissue Proteins ; genetics ; Nuclear Proteins ; genetics ; Spinocerebellar Ataxias ; genetics ; Trinucleotide Repeats

Objective To investigate the role of miR-592 in the Glioma.Methods We first analyzed the expression of miR-592 in Glioma tissues from patients by quantitative PCR.We transfected U251 cells with miR-592 mimics and then detected the growth of cells by MTT assay.We performed dual-luciferase reporter assay and western blot assay to examine whether Runx2 was the direct target of miR-592 in U251 cells.In order to test whether Runx2 was the functional target of miR-592,we determined the cell growth curve by down-regulating the level of Runx2.Moreover,we also detected the apoptosis of U251 after Runx2 knockdown.Results The expression of miR-592 was significantly reduced in glioma tissues (t=2.752,P--0.013).Over-expression miR-592 remarkably increased the apoptotic rate of U251 cells compared with the control group (t=2.127,P=0.031;t=2.284,P=0.026).Flow cytometry analysis showed that MiR-592 significantly promoted apoptotic cell death of U251 cells Apoptosis rate was 7.2％±0.68％ in miR-592 group and 17.47％±1.45％ in control group (t=3.294,P=0.007).The results of double luciferase assay and Western blot assay showed that miR-592 directly targeted the 3'Runx2 of-UTR to inhibit the level of Runx2 protein.The effect of down-regulation of Runx2 on the growth of U251 cells was detected,the results showed that growth was significantly slower in the cells transfected with Runx2 siRNA than in those without Runx2 siRNA (t=3.124,P=0.O11).Detection of cycle by flow cytometry showed that runx2 down-regulated the apoptosis rate of U251 cells.Tumor growth curve showed that overexpression of miR-592 significantly inhibited tumor growth and the down regulation of Runx2 expresssion also significantly inhibited tumor growth.Conclusion miR-592 suppresses the growth and promotes the apoptotic rate of U251 cells by targeting Runx2.

Objective To investigate the metabolite changes in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric symptoms using magnetic resonance spectroscopy (MRS) and explore the associations between image findings and clinical variables. Methods Twenty-two SLE patients with neuropsychiatric symptoms (NPSLE), twenty-one SLE patients without neuropsychiatric symptoms (non-NPSLE) and twenty healthy controls (HCs) underwent routine MRI scan and multivoxel magnetic reson-ance spectroscopy (MVS). The absolute metabolite concentrations were measured bilaterally in the posterior cingulate gyrus (PCG), dorsal thalamus (DT), lentiform nucleus (LN) and posterior paratrigonal white matter (PWM) using LCModel and SAGE software. The relationships between metabolite con-centrations and cognitive function scores were analyzed by Spearman rank correlation. Single-factor Chi-square analysis and t-test were used for analysis. Results ① Compared to control subjects, NPSLE patients had significantly lower N-acetylaspartate (NAA) values in bilateral PCG and DT, with the mean differences of -1.504 [95% confidence interval ( CI) (-2.335, -0.672), P=0.001], -1.460 [95%CI (-2.349, -0.570), P=0.002], -1.259 [95%CI (-1.894, -0.625), P=0.000] and -1.022[95%CI (-1.688, -0.356), P=0.003] for RPCG, LPCG, RDT and LDT, respectively. The concentration of total creatinine were observed to decline in RPCG and RDT, with the mean differences of-1.094 [95%CI (-1.845, -0.342), P=0.003], -0.955 [95%CI (-1.630, -0.280), P=0.006], -1.259 [95%CI (-1.894,-0.625), P=0.006] respectively. Glutamine and glutamate-values decreased significantly in RDT [mean difference=-2.586, 95%CI (-4.139, -1.033), P=0.002]. ② Compared to non-NPSLE patients, NPSLE patients had a lower NAA level in LPCG [mean difference=-1.256, 95%CI (-2.146, -0.367), P=0.006]. Positive correlations between mini-mental state examination scores [RPCG: rs=0.312, P<0.05; LPCG: rs=0.355, P<0.01], Montreal cognitive assessment scores (RPCG: rs=0.362, P<0.01; LPCG: rs=0.285, P<0.05) and NAA values in bilateral PCG were detected. Conclusion Both NPSLE and non-NPSLE patients may have metabolite dysfun-ctions in different brain regions. The cognitive disorder in SLE patients may be interpreted by neuronic damage of PCG.

Objective To investigate the effects of intensive antihypertensive treatment and guidelinerecommended standard blood pressure control on early reperfusion and outcomes after intravenous recombinant tissue plasminogen activator (rtPA) thrombolysis in patients with acute ischemic stroke.Methods A total of 50 patients with acute ischemic stroke (systolic blood pressure,150-185 mmHg;1 mmHg=0.133 kPa) and received intravenous rtPA therapy were enrolled prospectively.They were randomly divided into either a intensive antihypertensive treatment group or a guideline antihypertensive treatment group.In the the intensive antihypertensive treatment group,systolic blood pressure was decreased to 140-150 mmHg in 60 min for at least 72 h.In the guideline antihypertensive treatment group,systolic blood pressure was decreased to the target value ＜ 180 mmHg according to the guideline recommendation.Multi-mode MRI was completed at 24 h before and after thrombolysis.The primary endpoints were the modified Rankin Scale (mRS) score at day 90 and the mortality at day 90;the secondary endpoints were the early reperfusion rate in ischemic brain tissue,recanalization rate,and incidence of symptomatic intracranial hemorrhage.Results There was no significant difference in demographics and baseline data between the 2 groups.Within 24,48,and 72 h after thrombolysis the mean systolic blood pressure in the intensive antihypertensive treatment group was significantly lower than those in the guideline antihypertensive treatment group,while there was no significant difference in diastolic blood pressure.There were no significant differences in favorable outcome rate at day 90 (mRS score 0-2:68％ vs.64％;x2 =0-089,P=0.765),mortality (4％ vs.12％;x2 =1.087,P=0.297),incidence of symptomatic intracranial hemorrhage (4％ vs.8％;x2 =0.355,P =0.552),reperfusion rate after thrombolysis (76％ vs.68％;x2 =0.397,P =0.529),and recanalization rate (56％ vs.52％;x2 =0.081,P =0.777) between the intensive antihypertensive treatment group and the guideline antihypertensive treatment group.Conclusions Early intensive antihypertensive treatment in patients with acute ischemic stroke received intravenous rtPA thrombolysis does not have adverse effect on reperfusion rate,and does not increase the risk of death or disability either.

Objective To intestate the effect of different doses of atorvastatin on early neurological deterioration and short-term outcomes in patients with acute ischemic stroke.Methods The patients with acute ischemic stroke were enrolled prospectively.They were randomly assigned to either a standard therapy group (atorvastatin 20 mg/d) or an intensive treatment group (atorvastatin 40 mg/d).The primary outcomes were early neurological deterioration within 1 week of treatment and the good outcome of evaluation at 1 month after treatment (the modified Rankin Scale score 0-2); the secondary outcomes were the National Institutes of Health Stroke Scale (NIHSS) score and adverse events at 1 month.Results A total of 125 patients with acute ischemic stroke were enrolled,including 62 in the standard therapy group and 63 in the intensive treatment group.The incidence of early neurological deterioration at 1 week after treatment in the standard therapy group was significantly higher than that in the intensive treatment group (16.13％ vs.4.76％;x2=4.333,P=0.038); the proportion of good outcome in the standard therapy group was significantly lower than that in the intensive treatment group at 1 month after treatment (53.23％ vs.71.43％ ;x2 =4.413,P=0.036).During the treatment,no significant liver damage,muscle toxicity and other adverse events of causing atorvastatin reduction or withdrawal occurred in the patients of both groups.Conclusions Using high-dose atorvastatin in the acute phase of ischemic stroke may decrease the incidence of early neurological deterioration compared with the conventional dose,and improve short-term clinical outcomes.

AIM: To investigate whether rs7903146 polymorphisms in transcription factor 7-like 2 (TCF7L2) gene are associated with susceptibility to type 2 diabetes mellitus (T2DM) in Chinese Uygur population.METHODS: In this case-control study, 935 cases of T2DM patients were recruited in T2DM group, and 971 healthy examination individuals were selected as normal control.The TCF7L2 gene polymorphism was detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrum.RESULTS: Significant differences in the frequencies of CC, CT and TT genotypes and the frequencies of C and T alleles on TCF7L2 rs7903146 were found between T2DM group and control group(P<0.05).As compared with C allele, the patients with T allele had a significantly higher risk of T2DM with OR of 1.190 (95% CI: 1.034~1.371).As compared with CC genotype, the patients with CT genotype had a significantly higher risk of T2DM with OR of 1.374 (95% CI: 1.122~1.683), and the patients with CT+TT genotype had a significantly higher risk of T2DM with OR of 1.307 (95% CI: 1.090~1.567).The levels of fasting plasma glucose, serum creatinine and blood urea nitrogen were higher in all participants with CT+TT genotype of rs7903146 than those with CC genotype, which showed a significant difference (P<0.05).CONCLUSION: The polymorphisms of rs7903146 in TCF7L2 gene may be associated with T2DM in Uygur population from Xinjiang region.The T allele and CT genotype of rs7903146 are the risk factors for T2DM.

OBJECTIVETo detect the relationship between point mutations on exon 2 of parkin gene and sporadic early-onset Parkinson's disease.

METHODSThe point mutations on exon 2 of parkin gene were detected using polymerase chain reaction(PCR), agarose electrophoresis, single strand conformation polymorphism(SSCP), DNA sequencing and analysis of restrict enzyme in DNA of 60 Parkinson's disease patients with an onset age under 50 and 120 normal controls.

RESULTSOne homozygous mutation (G(237)-->C) on exon 2 was found by sequencing and verified by analysis of restrict enzyme, whereas no mutation was found in normal controls.

CONCLUSIONPoint mutations on exon 2 of parkin gene are likely to be related to sporadic early-onset Parkinson's disease.

Adult ; Aged ; Aged, 80 and over ; Exons ; Female ; Humans ; Ligases ; genetics ; Male ; Middle Aged ; Parkinson Disease ; genetics ; Point Mutation ; Polymorphism, Single-Stranded Conformational ; Sequence Analysis, DNA ; Ubiquitin-Protein Ligases

Objective To study the changes of immune function of endotoxin tolerant dendritic cell (ETDC) and to observe its effect on sepsis in mouse model.Methods ETDC were prepared by pretreated bone marrow dendritic cells derived from BALB/c mice with lipopolysaccharide stimulation.The cells were collected and the expressions of surface markers including major histocompatibility complex ( MHC)Ⅱ, CD86 and CD11c were detected by flow cytometry.The proliferation rate of T lymphocytes was evaluated by cell counting kit-8 and the concentrations of cytokines in the supernatant were detected by enzyme linked immuno sorbent assay.Afterwards, 36 mice were randomly assigned into 4 groups.The blank control group did not receive any treatment, the sham-operated group underwent simple incision suture, the sepsis group and ETDC reinfusion group underwent cecal ligation and puncture to establish sepsis.Before sepsis model establishment, 0.9% sodium chloride solution or suspension of ETDC and 0.9%sodium chloride were reinfused by tail vein.The serum levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), tumor necrosis factor (TNF)-α, interleukin(IL)-6 and IL-10, and the proportion of help T cell ( Th) 17/regulatory T cell ( Treg) in spleen of each group were detected.The pathological manifestations of liver, kidney and ileum in each group were observed.T test and χ2 test were used for comparisons between groups.Results The results of flow cytometry showed that MHCⅡ, CD86 and CD11c of ETDC were 70.4%, 43.1%, and 73.1%, respectively, which were significantly lower than those of mature dendritic cell (mDC) (96.1%, 89.5%, and 84.6%, respectively) (χ2 ＝56.47, 83.78, and 23.29, respectively, all P＜0.01).The concentrations of IL-10, TNF-αand IL-6 in the supernatant of ETDC were (978.04 ±56.70), (980.34 ±111.96) and (12 743.03 ±865.81) ng/L, respectively, and those of mDC were (741.35 ±99.23), (1 703.11 ±117.00) and (19 052.28 ±1 145.84) ng/L, respectively.The differences were all statistically significant (t＝5.073, 10.93, and 10.76, respectively, all P＜0.01).The proliferation rates of T lymphocytes co-cultured with ETDC in 1∶5 and 1∶10 ratio group were (676.95 ±85.99)%and (514.00 ±106.39)%, respectively, which were lower than those of the mDC group (956.25 ±127.12)%and (772.07 ±214.08)%, respectively.The pathological injuries of liver, kidney and ileum in ETDC treatment group were significantly lighter than those in sepsis group.Serum ALT and AST levels in the ETDC reinfusion group were (299.71 ±36.91) and (690.39 ±154.92) U/L, respectively, and TNF-α, IL-6 and IL-10 were (0.067 ±0.005), (0.428 ±0.051) and (0.058 ±0.005) ng/L, respectively.Serum ALT and AST levels in the sepsis group were (620.67 ±69.27) and (1 430.17 ±134.05) U/L, respectively, and TNF-α, IL-6 and IL-10 were (0.085 ±0.007), (0.774 ±0.088) and (0.036 ±0.005) ng/L, respectively.The differences were all statistically significant (t＝11.60, 10.96, 5.991, 8.657, and 8.04, respectively, all P ＜0.01).The proportion of Treg/Th17 in the ETDC reinfusion group was 23.4%, and that in the sepsis group was 60.8%(χ2 ＝28.69, P＜0.01).Conclusion The reinfusion of ETDC has a protective effect on sepsis in mouse model, which may play a negative immune regulatory role by regulating the differentiation of T cells.

Objective To assess the clinical value of lung ultrasound (LUS) B-lines in diagnosis of rheumatoid arthritis (RA) associated interstitial lung diseases (RA-ILD).Methods Forty-five consecutive patients with RA who underwent a high resolution computed tomography (HRCT) scan of the chest,were also examined by LUS for detection of B-lines(within 1 month independently in all patients).The B-lines score was obtained by summing the number of total 50 inter-costal spaces (ICSs) of chest wall.Pulmonary fibrosis was quantified by HRCT as previously described by the 30-point Warrick score.Results B-lines score significantly correlated with the Warrick score [(r=0.778,95％CI(0.627,0.872),P＜0.05].Receiver operating characteristic (ROC) curve confirmed that B-lines cut-off point 77[sensitivity of 100％,specificity of 64.3％ respectively,area under curve [AUC] =0.86,95％CI(0.724,0.945)] and 108[sensitivity of 90％,specificity of 88.6％ respectively,AUC=0.879,95％CI(0.747,0.957)] had an optimal power to discriminate mild (Warrick score＜8) and severe fibrosis (Warrick score＞15):Conclusion The data confirm that LUS is a useful technique to identify ILD in RA.In RA-ILD,B-lines correlate significantly with HRCT and are able to identify mild and severe degree of fibrosis.LUS is a promising non-invasive and non-ionizing strategy for screening RA-ILD.

OBJECTIVETo assess the association of CYP2C19 gene polymorphisms with the incidence of ischemic stroke among patients receiving clopidogrel therapy following coronary stenting for coronary artery disease.

METHODSClinical data of patients receiving clopidogrel therapy after coronary stenting were retrospectively studied. For a case-control study, 137 patients with acute cerebral infarction and 122 non-stroke patients were selected. Based on the variants of the CYP2C19 gene detected by a DNA microarray assay, the patients were further divided into the wild-type group(CYP2C19*1/*1) and mutant group(defined by the presence of at least one loss-of-function allele, including CYP2C19*1/*2, CYP2C19*1/*3, CYP2C19*2/*2, CYP2C19*2/*3 and CYP2C19*3/*3). The incidences of ischemic stroke in the two groups were compared through a chi-square analysis. The influence of CYP2C19 gene polymorphisms and clopidogrel therapy on the incidence of ischemic stroke was analyzed through multivariable logistic regression.

RESULTSA total of 259 patients were enrolled. The case and control groups showed no difference in terms of gender and age. There were 123 cases (47.5%) in the CYP2C19 wild-type group and 136 cases (52.5%) in the mutant group. The incidence of ischemic stroke of mutant group was significantly higher than that of wild-type group (59.9% vs. 44.3%, X2=6.398, P=0.042). Multivariate analysis revealed that loss-of-function polymorphisms of the CYP2C19 gene carried a 1.13 times greater risk for ischemic stroke compared to wild-type genotype (OR=2.13, 95%CI: 1.23-3.71).

CONCLUSIONThe efficacy of clopidogrel for the prevention of ischemic stroke in post-coronary stent patients may be reduced by the insufficiency of the CYP2C19 gene. The dosage of clopidogrel therapy should be adjusted based on its polymorphisms.

Brain Ischemia ; prevention & control ; Cytochrome P-450 CYP2C19 ; genetics ; Genotype ; Humans ; Percutaneous Coronary Intervention ; adverse effects ; Platelet Aggregation Inhibitors ; therapeutic use ; Polymorphism, Genetic ; Stents ; adverse effects ; Stroke ; prevention & control ; Ticlopidine ; analogs & derivatives ; therapeutic use