Rheumatoid arthritis(RA),a systemic,inflammatory autoimmune disorder characterized by inflammation of the lining or synovium of the joints,is a complex polygenic disease with a complicated inheritance mode.Both genetic and environmental factors determine the development and progression of RA.Study on susceptible genes of RA provides a theoretic basis for clinical diagnosis and treatment.As a novel high-throughput screening method,genome-wide association study(GWAS) is a powerful approach for mapping susceptible genes of polygenic disease like RA.GWAS can not only verify the well-established susceptible loci,but also identify novel genetic loci candidates.Great improvement has been made in using GWAS to screen for novel genes,which casts new lights on the mechanism and treatment of RA.This review summarizes the progress in using GWAS for screening of RA susceptible genes.

ObjectiveTo determine the allele frequency and genotypic distribution of plateletactivating factor acetylhydrolase (PAF-AH) gene polymorphism in the patients with sepsis. Methods Ala379Val,Val279Phe site genotypes were determined in patients (n=66) and healthy controls(n=68) by means of restriction fragment length polymorphism analysis of polymerase chain reaction products,DNA sequencing was used to detect the PCR product containing allele gene polymorphism.SPSS13.0 statistical software was use to analyze.Results All the samples by PCR-RFLP analysis of the PAF-AH gene in the Ala379Val site have three kinds of genotypes: in 66 cases of sepsis group there were 1 homozygous Val/Val type,19 heterozygous Val/Ala type,46 homozygous Ala/Ala type.In 68 cases of control group there were 2 Val/Val type,22 Val/Ala type,44 Ala/Ala type.The Ala379Val allele frequency and genotypic distribution in the patients with sepsis was not significantly different from those in the healthy controls.No statistically significant difference was observed between the survival group and the death group ( P＞0.05 ).PAFAH gene of Va1279Phe polymorphism could have three kinds of genotypes.All 66 patients in the sepsis group were the homozygous Val/Val type.Control group 68 cases,only one case was homozygous Phe/Phe type,and the others were homozygous Val/Val type,not found heterozygous Val/Phe type.The Val279Phe genotypic distribution and allele gene frequency in the patients with sepsis was not significantly different from those in the healthy controls; no statistically significant difference was observed no statistically significant difference was observed between the survival group and the death group ( P＞0.05 ).ConclusionNo associations were found between PAF-AH gene Ala379Val and Val279Phe polymorphisms and sepsis susceptibility,prognosis and severity.

OBJECTIVE To investigate the repressor SmeT and other sequences of efflux pump SmeDEF in the clinic isolates of Stenotrophomonas maltophilia to involve in antibiotic resistance. METHODS The mRNA level of smeD examined the resistance profile of the clinical strains to antimicrobials was by agar dilution and their reaction to pump inhibitor was investigated by RT-PCR,and the smeD-smeT fragment was amplified by PCR,and then sequenced.Adding poly(A) to 3′ end of RNA,applying 3′RACE,nested PCR,then sequence-analysis. RESULTS The amino acid sequences of the forepart of SmeT were conservative in all the 7 strains.In antibiotic-resistant strains with positive reaction to pump inhibitor,the intergenic sequences of smeD-smeT were different from those in sensitive ones.The variations in(-165 to-82)nt of smeT and several nucleic acids before the start codon of smeT,possibly involved in antimicrobial resistance.All isolates didn′t have Leu166Gln mutation within the SmeT protein of D457R,which was reported possibly associated with antibiotic resistance.The resistant strains with efflux positively inhibited had Asp218Glu substitution,different from the negatively-inhibited ones. CONCLUSIONS The expression level of SmeDEF is related with the antibiotic resistance of S.maltophilia.The possible resistance mechanism includes the variations in the intergenic smeD-smeT and/or smeT codon sequence.

Objective To obtain the gene coding for the group 5 allergens from Dermatophagoides farinae ( Derf5 ) and predict its molecular characteristics. Methods The total RNA of D. farinae were extracted, and the gene Derf5 was amplified by RT-PCR with the primers designed according to previous sequence published in GenBank. The target gene was linked into pMD19-T Simple plasmid, sequenced and analyzed by bioinformatics software. Results The sequence homology reached to 97.8% between our sequenced result with one complete open reading fragment (ORF) and the reference. The gene encode an extracellular hydrophobic protein with 132 amino acid resides, one signal peptide from 1 to 19 position and one transmembrane domain from 1 to 19 position. The secondary structure was composed of extended strand (1. 52% ), random coil (7.58%) and alpha helix (90.91%). The encoded protein was deduced to have two Casein kinase Ⅱ phosphorylation sites. The similarity of the amino acid sequence of the group 5 allergens were 78% between D. farinae and D. pteronyssinus. Conclusion The gene Derf5 was cloned successfully, and its characteristics was primarily predicted.

Objective To evaluate the effects of propofol on the proliferation of hippocampal neurons in fetal rats in vitro.Methods Pregnant Sprague-Dawley rats at 16-18 days of gestation,were sacrificed and the fetal rats were taken out from the abdominal cavity.The hippocampal neurons of the fetal rats were isolated and seeded in culture plates.After being cultured for 9 days,the neurons were divided into 7 groups using a random number table(n =36 each):control group (C group),intralipid group (I group) and propofol 0.1,1.0,10.0,100.0,1 000.0 μmol/L groups (P1-5 groups).In group I,10％ intralipid was added to the culture media until the final concentration reached 100 μmol/L.In P1-5 groups,propofol was added to the culture media until the final concentration reached 0.1,1.0,10.0,100.0 and 1 000.0 μmol/L,respectively.The neurons were then incubated for 3 h.The proliferation of hippocampal neurons was determined by MTT assay at 12,24,36,48,60 and 72 h after the end of incubation with propofol.Results Compared with group C,the proliferation of hippocampal neurons was significantly decreased in P1-5 groups (P ＜ 0.05),while no significant change was found in group I (P ＞ 0.05).Compared with group P1,the proliferation of hippocampal neurons was significantly decreased in group P5 (P ＜ 0.05),while no significant change was found in P2-4 groups (P ＞ 0.05).Conclusion Propofol can decrease the proliferation of hippocampal neurons in fetal rats in vitro.

Objective To study the expression of active efflux pump AdeABC,AdeIJK,AdeFGH,AbeM,AbeS,CraA,MdtL in clinical Acinetobacter baumannii isolates and whether the efflux pumps confers resistance to antibiotics.Methods Thirty-two multi-drug resistant Acinetobacter baumannii islates and 10 sensitive isolates were collected.Genes of the exporter protein were amplified by PCR.The expression of adeB,adeJ,adeG,abeM,abeS,craA,mdtL were examined by real-time fluorescence quantitative RT-PCR.The controlling genes adeRS and adeL were amplified by PCR and sequenced.Results The positivity rates of adeB,adeJ,adeG,abeM,abeS,craA,mdtL were 100％,100％,100％,96.88％,100％,100％ and 93.75％ respectively in 32 multi-drug resistant Acinetobacter baumannii isolates,and all 100％ in 10 sensitive isolates.The difference of expression of adeB,abeM and mdtL were significant( P＜0.001,P =0.001,P=0.013) between 21 multi-drug resistant isolates of C clone and 10 sensitive isolates.The mutations of adeRS existed in 2 multi-drug resistant isolates,no point mutation of adeL.Conclusion The expression of AdeABC,AbeM and MdtL may involved in the resistant mechanisms of the clinical Acinetobacter baumannii islates.

Objective To understand the status of soil?transmitted nematode infections in rural residents so as to provide the evidence for formulating the guidance for prevention and control of the diseases. Methods The national surveillance sites of soil?transmitted nematode infections were established in Shuyang County,Suqian City,Jiangsu Province from 2006 to 2015. At least 1 000 fecal samples of residents aged 3 years or above were collected in every autumn,and the intestinal helminth eggs were detected with the Kato?Katz technique and the Enterubius vermicularis eggs were detected by the cellophane tape method for children aged 3-12 years. The soil samples were collected from vegetable fields,lavatories,courtyards and kitchens to exam?ine Ascaris lumbricoides eggs and larvae of hookworm. Results The infection rates of soil?transmitted nematodes in residents and E. vermicularis in children reduced from 1.81%(19/1 049)and 4.72%(5/106)in 2006 to 0.25%(3/1 180)and 0(0/263) in 2015,respectively,in the surveillance sites. The infection intensity was mild in all the infected cases. The soil samples were negative for detecting A. lumbricoides eggs and hookworm larvae. Conclusion The infection rates of soil?transmitted nema?todes in the residents and E. vermicularis in the children show a decreasing trend and keep at a low level of prevalence in Shuy?ang County.

Objective To investigate the memory monitoring ability in patients with idiopathic generalized epilepsy (IGE) and explore the mechanism of the memory impairment.Methods The feeling of knowing (FOK) paradigm of episodic memory (EM) and semantic memory (SM) were established and subsequently administered in 31 patients with IGE (IGE group) and 30 healthy controls (HC group) participants who were matched in age,sex and educational level.Results Compared with HC group (feeling of knowing of episodic memory (FOK-EM) FOK accuracy (85.29± 16.84) ％;feeling of knowing of sematic memory (FOK-SM) recall (76.61± 18.66) ％),the FOK-EM FOK accuracy ((64.03± 22.10) ％) and FOK-SM recall ((53.27±26.91) ％) in IGE group were significantly decreased(t=-4.215,P＜0.01;t=-3.677,P＜0.01).The correct judgment and correct recognition of FOK-EM ((51.16±32.93) ％) and the false judgment and correct recognition ((21.07±24.38) ％) of FOK-EM in the IGE group were significantly different with the HC group (the correct judgment and correct recognition of FOK-EM:(79.34±27.26)％ and the false judgment and correct recognition of FOK-EM:(2.45±5.38) ％;t=-3.634,P＜0.01;t=4.149,P＜0.01).Most importantly,the false judgment and correct recognition of FOK-EM were correlated with the Digital Span Test,Vocabulary Fluency Test and the Stroop effect in IGE group (r=-0.309,P＜0.05;r=-0.355,P＜0.01;r=-0.354,P＜0.05;r=0.602,P＜0.01).Conclusion The results show that the IGE group made less accurate metamemory monitoring than the HC group by underestimating their memoU performance on FOK-EM,whereas the semantic metamemory monitoring is not impaired in IGE group.More importantly,the impairment of memory monitoring was correlated with the deficit of executive function,indicating that this mechanism can be an influential factor of memory disorder in IGE.It also indicates that the episodic and semantic metamemory monitoring depend on different neural networks.

Objective To study the expression of active efflux pump AdeABC in clinical Acineto-bacter baumannii islates and whether this efflux pump confers resistance to antibiotics. Methods The anti-biotic susceptibility and the function of efflux pump inhibitor were tested by micro-dilution broth method. The expression of adeB was examined by RT-PCR. The controlling gene adeRS was amplified by PCR and se-quenced. Results Thirty multidrug resistance Acinetobacter baumannii isolates and 5 sensitive isolates for PCR were both abtained the expected products of adeB and adeRS. The mRNA expression of adeB in 15 multidrug resistance(MDR) isolates were positive, but there was no expression of adeB in 5 sensitive iso-lates. The mutations of adeRS existed in 2 MDR isolates. Conclusion The expression of AdeABC may in-volved in the resistant mechanisms of the clinical MDR Acinetobacter baumannii isolates.

Objective To investigate antimicrobial resistance and ceftriaxone resistance mechanisms in clinically isolated nontyphoidal Salmonella(NTS),and provide evidence for the prevention and control of NTS infection and rational use of antimicrobial agents.Methods 108 NTS isolates were isolated from stool specimens of outpatients with acute diarrhea in the Second Hospital of Tianjin Medical University and Tianjin Medical University General Hospital from May to October of 2014,NTS were performed antimicrobial susceptibility testing;non-ceftriaxone-susceptible isolates were typed by serological,multilocus sequence (MLST),and pulsed-field gel electrophoresis (PFGE)methods,extended-spectrumβ-lactamase (ESBL)detection and AmpC genes were detection.Results Among 108 NTS isolates,mono-drug resistance rate to 11 antimicrobial agents was 49.07% (n= 53),multidrug resistance rate was17.59% . Susceptibility rates to nalidixic acid,levofloxacin,ciprofloxacin,ceftriaxone,and ertapenem were 61.11% ,66.67% ,68.52% ,97.22% ,and 100.00% respectively. Three non-ceftriaxone-susceptible NTS isolates were detected,2 were ST11 Salmonellaenterica serotype (Sa8709,Sa8771),1 was ST34 Salmonellatyphimurium serotype(Sa8763). Cluster analysis of PFGE revealed that Sa8709 was highly similar to Sa8771 strains(91 .70% ), but the similarity to Sa8763 was low(55.80% );Sa8709 strain carried CTX-M gene,Sa8771 strain carried CTX-M and TEM genes,Sa8763 strain carried OXA gene. Conclusion Clinically isolated NTS in this area are low resistant to fluoroquinolones,multidrug resistant strains carrying ESBLs have emerged.