Objective To study the effect of LDYS-14007 on JAK1-STAT3 signaling pathways.Methods MDA-MB-231 cells were treated with 10μmol,1 nmol LDYS-14007, and 10 μmol Tofacitinib,respectively.Western blot assay was used to determine the expression of JAK1,Phospho-JAK1, STAT3 and Phospho-STAT3.Results The absorbance value was linearly related to the concentration of protein C, The linear equation is A=0.0075C+0.0029, r=0.9976, The linear range of 1.08-5.08 mg/mL, With the increased concentration of LDYS-14007, the amount of Phospho-JAK1, Phospho-STAT3 were all gradually decreased.Conclusion LDYS-14007 leads to the levels of Phospho-JAK1 and Phospho-STAT3 decrease, which inhibits JAK1-STAT3 signaling pathway.LDYS-14007 may play an important role in the treatment of rheumatoid arthritis.

Objective: To develop the Chinese version of the Anxiety Sensitivity Index-Revised and examine its replicability, reliability and validity. Methods: This study translated the Anxiety Sensitivity Index-Revised ( ASI-R) and examined the factor analytic structure of anxiety sensitivity in a large sample of middle school students aged 12-18 years (n = 1556) . Factor analysis of the ASI-R items resulted in a hierarchical construct with three lower-order factors loading on a single higher-order factor. Results: after revision, the number of items of the inventory reduced from 36 to 15. Anxiety sensitivity seems to be a hierarchically organized construct with one higher-order factor (anxiety sensitivity ) and three lower-order factors: Physical concern, Cognitive concern (lose of control) , Social concern, which three factors contributed to 52. 29% of total variance. Factor loadings of items were 0. 63 ~ 0. 98 , the internal correlation between items were 0. 37 ~ 0. 53 , the correlation between factors to the total score were 0. 72 ~ 0. 84, internal correlation among factors were 0. 68 ~ 0. 78. internal consistency of each factor 0. 73 ~ 0. 78. the split-half reliability was 0. 71 ~0. 76, that of test-retest was 0. 70 ~0. 78. Conclusion: The questionnaire has satisfying reliability and validity.

Objective To observe the therapeutic effect of sertraline combined with brain function treatment instrument for depressive episodes.Methods According to sequence of hospitalization,80 patients with depression without severe physical disease randomly divided into sertraline with brain function treatment group (40 cases,group A) and only take sertraline group (40 cases,group B),and two groups were given Sertraline 100 mg/day for 8 weeks.24 Hamilton Depression Scale (HAMD-24) and 20 Self-rating Depression Scale (SDS-20) were assessed before and after 1,2,4,6,8 weekend treatment.Results The scores of HAMD-24 and SDS-20 were not significant difference between the two groups before treatment(P＞0.05),but there were statistically significant after treatment (P＜0.05).They were significantly decreased after 8 weeks treatment in group A and were decreased slightly in group B with HAMD-24 and SDS-20.Clinical efficiencies of HAMD of the two groups were 87.2 ％,76.3 ％,respectively,and those of SDS were 89.7 ％,78.9 ％,respectively.Clinical efficacy in group A was significantly better than that in group B (P＜0.05).Conclusion Sertraline with brain function treatment instrument can shorten the onset time and improve its effect.

Objective To analyze influencing factors of physicians' turnover intention at public county hospitals from career stage perspective.Methods Physicians career life was divided into three stages according to professional ranks and titles.The sample was drawn using stratified multistage random methods from public county hospitals in Shandong province and 677 questionnaires were completed,giving a 90.3％ valid response rate.Data were analyzed using multi-group stepwise linear regression.Results The percentage of responders with middle and high-level turnover intention was 23.0％and 6.5％ respectively,and there was no statistically significant difference in turnover intention across three stage subgroups.In physicians at stage 1,the most important factors to predict turnover intention were superiors ' appreciation (r =-0.22,P ＜ 0.05) and payment rationality (r =-0.21,P＜0.05),while in physicians at stage 2,the most important predicting factors were autonomy (r=-0.39,P＜0.05)and learning demand(r=-0.22,P＜0.05),and in physicians at stage 3 were career development(r=-0.31,P＜0.05)and autonomy(r=-0.21,P＜0.05).Conclusion Autonomy and workload are common factors of turnover intention with different predicting power across three career stages.Physicians adjust their career needs to self-actualization with development of career stage,so welltargeted incentives should be taken to stabilize the medical staff of public county hospitals.

ABSTRACT:Objective To evaluate the expressions of cell adhesion molecules CD146 and transferrin receptor 1 (TfR1)in ovarian epithelial cancer and investigate their relationship with clinical pathological features of patients with ovarian epithelial cancer (OEC ) so as to further explore the pathogenesis of OEC. Methods Immunohistochemistry was employed to determine the expressions of CD146 and TfR1 in normal,benign and ovarian cancer tissues.Results The immunohistochemical results showed that the positive expressions of CD146 and TfR1 gradually increased with the changes of normal,benign and malignant tissues in OEC.There were significant differences between all the groups (P<0.05).The advanced the clinical stage,the higher the expression rate (P<0 .0 5 ).The lower the histopathological differentiation,the higher the expression rate (P<0 .0 5 ).The expressions of CD146 and TfR1 were not correlated with age or pathological patterns (P>0.05).There was a significant correlation between expressions of CD146 and TfR1 in OEC (P<0.05,rs=0.532).Combined detection sensitivity and specificity were 82.4% and 75.0%.Conclusion The high expressions of CD146 and TfR1 may play a key role in the occurrance,progression and metastasis of OEC.They may be used as potential markers for diagnosis,postoperative follow-up and targeted therapy.

Objective The aim of this study is to study the musical ability,auditory ability and speech intelli-gibility and their relationship in children with artificial hearing devices,and to provide clinical evidence for the hear-ing and speech rehabilitation for children with hearing loss.Methods A total of 27 children (14 boys and 13 girls) with prelingual sensorineural hearing loss from Zibo participated in this study.Their hearing levels were from mod-erate to profound.Their chronological ages at evaluation ranged from 9 to 95 months with a mean of 42 months. Their chronological ages at intervention ranged from 1 to 72 months with a mean of 26 months.Their hearing ages at evaluation ranged from 1 to 60 months with a mean of 16 months.They all wore bilateral aids.Musical Ears, CAP and SIR were used to evaluate their musical ability,auditory ability and speech intelligibility,respectively.A linear and regression analysis was done in the statistic procedure.Results The means and standard deviations of the scores of musical ability,auditory ability,and speech intelligibility were 27.1±16.7,4.4±1.9,2.8±1.4,respec-tively.The scores of musical ability and auditory ability were significantly correlated (r= 0.856,P<0.001).The scores of musical ability and speech intelligibility were also significantly related (r= 0.827,P<0.001).Conclusion The musical ability is closely related to auditory ability in children with bilateral aided hearing.The musical ability is also closely related to speech ability for this group of children.

Objective To explore the risk factors of vascular cognitive impairment (VCI)among Chinese population, and to clarify the scientific evidences for further prevention and treatment.Methods PubMed,CNKI,CBM,VIP and Wangfang databases (from 2002.1 to 2013.1)were searched to collect case-control studies or cohort studies studying risk factors of VCI among Chinese population. Meta-analysis was performed to calculate combined odds ratio (OR)or mean difference (MD)and its 95% confidence interval (95%CI).Results A total of 42 proper papers involving 3 282 cases and 7 815 controls were included in the review.For categorical variables,pooled OR and its 95% CI were as follows:hypertension 2.56 (2.03 - 3.21 ), hyperlipidemia1.79 (1.39 - 2.30 ), hyperglycemia 2.46 (1.90-3.19),Leukoaraiosis 5.46 (2.60-11.46),cerebral infraction multiple foci 4.39 (2.61-7.38),stroke history3.79(2.35-6.11),left hemisphere lesions 2.13(1.42-3.20),smoking 1.51 (1.08-2.11),drinking 0.99(0.73-1.36),basal ganglia lesions 2.15(1.55-2.99),thalamus lesions 2.34(1.57-3.47);for continuous variables,MD and its 95%CI were as follows:level of TG 0.35(0.15-0.55),level of TC 0.44(-0.16-1.04),level of folic acid -4.10(-5.50- -2.69),vitamin B12 -130.44(-225.46--35.41).Conclusion Except for drinking and level of TC, hypertension, hyperlipidemia, hyperglycemia, leukoaraiosis,cerebral infraction multiple foci,stroke history,left hemisphere lesions,smoking,basal ganglia lesions,thalamus lesions,high level of TG,low level of folic acid and vitamin B12 might be the risk factors of VCI among Chinese population.

Objective To analyse a novel splice mutation in EXT1 gene of hereditary multiple osteochondroma, and study its pathogenic mechanism.Methods In April of 2013, the proband was hospitalized from the outpatient department with multiple joint deformity for more than 20 years, peripheral blood of the proband and his parents were collected and genomic DNA was extracted .Coding regions and adjacent intron sequences of EXT1/EXT2 genes in genomic DNA of the family members were amplified and sequenced.Bioinformatics was used to analyze the mutation from sequencing .cDNA from peripheral blood of the proband ,the mother and normal control was made respectively as a template for amplifying coding regions of EXT1 gene, and the product was T-A cloned and sequenced.The abnormal transcripts of each group were counted and analyzed using chi square test to study the pathogenic mechanism of the mutation .Results Sequencing results of family members revealed that there was a heterozygous deletion mutation ( c.1284 +2del) in the 5′splice site of intron 4 in EXT1 gene of the proband and his mother .Bioinformatics predicted that exon 4 of EXT1 gene was skipping or spliced aberrantly due to the mutation .T-A clone and sequencing results as well as the statistical analysis suggested that there was a significantly higher proportion of transcripts with skipping exon 4 in the proband and his mother compared with the normal control (P=0.000, P<0.01).Conclusions c.1284+2del in EXT1 gene is reported for the first time internationally , which results in a considerable number of abnormal transcripts with skipping exon 4 in EXT1 gene, thereby influences the normal transcription and translation of EXT1 gene.

Objective To investigate the effects of a miRNA family member, let-7e, and a combi-nation of miR-106b and miR-20a on the expression of cytokines by THP-1 cells with Luminex xMAP technol-ogy.Methods The efficiency of transfection was evaluated by immunofluorescence assay after transfecting THP-1 cells with micrONTM mimic negative control (Cy3) for 24 h, 36 h and 48 h.The three miRNA mim-ics (let-7e, miR-106b and miR-20a) were respectively used to transfect the THP-1 cells for 24 h, 36 h and 48 h and the expression of each miRNA was analyzed by qRT-PCR analysis for screening out the optimal transfection time.The transfected THP-1 cells were stimulated with1 mg/L of LPS for 1 h.The Luminex xMAP technology was used to detect the expression of IL-8, interferon-inducible protein-10 (IP-10), mono-cyte chemotactic protein 1 (MCP-1), IL-1α, IL-6, IL-10, TNF-α, IFN-αand IFN-βin the supernatants of cell culture.A statistical analysis was performed to analyze the data obtained by using SPSS16.0 software. Results More than 90% of the transfected THP-1 cells were labeled with red fluorescence.The optimal transfection times for let-7e mimic and miR-106b/miR-20a mimics were 48 h and 24 h, respectively.Com-pared with the corresponding negative control (NC), the expression of IL-8, IP-10 and MCP-1 by THP-1 cells were enhanced after the transfection with let-7e mimic, but were inhibited after the co-transfection with miR-106b and miR-20a mimics.Conclusion The expression of IL-8, IP-10 and MCP-1 were enhanced in let-7e transfected THP-1 cells, but were inhibited in miR-106b and miR-20a co-transfected THP-1 cells.

Glycogen synthase kinase-3β( GSK-3β) is a serine-threonine kinase,which was originally identified as a key regula-tor of glycogen metabolism. In nervous system, GSK-3β partici-pates in many central and peripheral nervous system physiological processes through transcription,cell proliferation and differentia-tion. The abnormal activity of GSK-3βinduces downstream signa-ling molecules and gene expression abnormalities,which are in-volved in some neuropsychiatric disorders such as schizophrenia, bipolar disorder,Alzheimer's disease,and pain. In recent years, lots of basic and clinic researches focus on GSK-3β,which might gradually become critical theraptic target of many diseases. The article mainly reviews the mechanisms involved in abnormal acti-vation of GSK-3β related neuropsychiatric disorders.