Graves' disease is a common autoimmune disease triggered by the susceptibility genes and environmental factors.Among the 9 risk genes related to Graves' disease,SCGB3A2 is the first Graves' disease-predisposing gene identified by our group using tagSNPs,strategy of candidate genes,and positional clones.The association between SCGB3A2 and Graves' disease has been confirmed by two independent cohorts from UK and Russia.So far,the geneticists on Graves' disease regard SCGB3A2 as a validated susceptibility gene of that disease.

Thyroid hormones play major roles in the regulation of a wide range of metabolie and physiologic processes.Serum thyroid-stimulating hormone( TSH ) concentration,a sensitive barometer of thyroid function,shows significant individual difference in which genetic variation is a major factor.After using traditional genetic linkage studies and candidate gene association studies to explore the suseeptibility genes of serum TSH,many progresses have been made and new susceptibility genes have been identified by genome-wide association study (GWAS).In this review,we focus on the susceptibility genes of serum TSH levels and also the future prospect that may be obtained from these studies.

[Summary] The genotypes of rs6832151 in the 4p14 were genotyped by Taqman probe technique on FluidigmEPl platform in 617 patients with Graves′disease( GD) and 4 915 health control subjects. The result showed thatRs6832151 Gin4p14wasstronglyassociatedwithGD(OR=1.39,P<0.01),withstatisticalsignificancefor three genetic models according to the locus genotyping ( additive model,dominant model,and recessive model,all P<0.01). There was no statistically significant difference in the sizes of goiter between the genotype subgroups(P>0. 05). The result suggests that rs6832151 G in 4p14 is the susceptibility genes of Graves′ disease in Bengbu population, and is related to the high risk of GD.

Objective To identify the association of thyroid stimulating hormone receptor ( TSHR ) gene intron 1 susceptible loci and 4p14 susceptible locus rs6832151 polymorphisms with Graves’ disease ( GD) in Han Chinese population in Bengbu, Anhui, China. The gene-gene interaction among TSHR intron 1 susceptible loci and 4p14 susceptible locus rs6832151 was also investigated. Methods The genotypes of the single-nucleotide polymorphisms ( SNPs) were analyzed by Taqman probe technique on Fluidigm EP1 platform in 611 patients with GD and 555 control subjects, and linkage analysis, correlation analysis, haplotype analysis, and epistasis analysis with them were performed. Results Six SNPs in two candidate genes(rs12101261, rs4903964,rs179247, rs2284722 and rs17111394 in TSHR, rs6832151 in 4p14) were associated with GD (all P<0. 05). The frequency distributions of haplotypes of SNPs in TSHR intron 1 ( AGTA, GGCG, AATA, and CC) were significantly different between GD and control groups(all P<0. 01). There existed the interactions between rs179247 and rs12101261 in TSHR(P=0. 001) and among rs179247(TSHR),rs4903964(TSHR) and rs6832151(4p14) (P=0. 001). Conclusions rs683215 in 14p14 and rs12101261, rs4903964, rs179247, rs2284722 and rs17111394 in TSHR intron 1 were susceptible loci of GD in the Chinese Han population from Bengbu. The haplotypes in TSHR intron 1 were associated with GD. There exists the interaction between the SNPs in TSHR and 4p14,which may change the risk of GD.

Objective To investigate the association between polymorphisms of thyroid-stimulating hormone receptor(TSHR)gene intron 1(rs179247, rs12101261)and Graves′ disease(GD)in the China Han population from Xuzhou city, Jiangsu Province. Methods Total 1 066 GD patients and 1 107 control subjects were recruited for genotyping by Taqman probe technique on Fluidigm EP1 platform. Meanwhile, serum concentrations of thyroid hormone and TSH receptor antibodies(TRAb)were determined. Results The rs179247_A, rs12101261_T were significantly associated with GD risk(OR=1.35, 95%CI 1.19-1.54, P=5.92×10-6; OR=1.32, 95%CI 1.16-1.50, P=2.22×10-5). Logistic regression identified that rs179247 was an independent susceptibility locus of GD. Serum TRAb concentration showed a significant difference(P=0.015)among rs179247_AA, AG, and GG genotypes. Conclusion rs179247 and rs12101261 in TSHR intron 1 are both associated with GD, and rs179247 may contribute risk to GD independently. The polymorphism is associated with TRAb, but not with serum concentration of thyroid hormones, age of onset, diffused thyroid goiter, ophthalmic signs, and relapse.

Objective To establish a short-term scenario simulation training campus in senior med-ical students before graduation for the sake of a smooth transformation from medical students to residents. Methods There were 101 participants involved in the study . All the participants attended emergency medicine traditional teaching, including 51 fourth-year medical students and 50 fifth-year medical students. The 48 students who took the emergency scenario simulation training course were classified as training camp group while the other 53 students were classified as control group. The control group only participated in the emergency medicine traditional teaching, and the training camp group participated in the emergency sce-nario simulation training course on the basis of control group's routine teaching, including advanced cardiac life support and team collaboration, sepsis and doctor-patient communication, polypnea and crisis manage-ment, disorder of consciousness and interdisciplinary teamwork, multiple injuries and emergency plans, and comprehensive case evaluation. The training camp group was divided into groups and received evaluation of performance on treating emergency simulated case (clinical skills, teamwork, doctor-patient communication) before and after class. The training camp group was received questionnaire survey after class. SAS 9.2 was used to do the t test and descriptive analysis. Results There were no statistically significant differences (P>0.05) between the scores of the performance on clinical skills, teamwork, doctor-patient communication of training camp group and control group before class. The scores of training camp group after class were sig-nificantly better than those of control group (P<0.05). In addition, the course had a high recognition by students. 92% (44/48) students thought the course was contributed to improving the ability of crisis man-agement and clinical practice and were in favor of developing similar courses for senior medical students. Conclusion Scenario simulation training campus can strengthen the cultivation of medical students' com-prehensive thinking, independent clinical decision making, practice skills and communication ability in the final stage of medical education as well as enhancing their self-confidence so as to help them to adapt to the real clinical work.

[Summary] The activities of 17α-hydroxylase and 17,20 lyase of cytochrome P450c17 were evaluated by ELISA in NCI-H295R cells after treatment with palmitate and oleate. The results showed that 0. 75 mmol/L plamitate did not influence the activity of 17α-hydroxylase, but increased the activity of 17, 20 lyase by 74. 3% ( P<0. 05). Oleate at the same concentration did not change the activity of 17,20 lyase. There were no significant changes in the protein expressions of P450c17, P450 oxidoreductase, and cytochrome b5 after treatment with palmitate and oleate. However,reactive oxygen species in cells were elevated by palmitate. The results suggest that exposure to palmitate may increase androgen production by inducing 17, 20 lyase activity of P450c17 in NCI-H295R cells, which is related with oxidative stress-mediated post-translational regulation of the enzyme.

Objective To prepare rabbit antibody against mouse AD-004 by AD-004 expressed in the prokaryotic expression system and to identify its distribution in the testis and adrenal. Methods The full-length cDNA of mouse AD-004 was cloned into PET28 plasmid, and the protein was induced in E. coli BL21 bacteria by adding IPTC and then purified by Ni2+ -NTA column. The purified protein was used as an immunogen to prepare polyclonal antibody ( pAb) of AD-004. The specificity of the antibody was detected by Western blotting. Immunohistochemical staining was performed in the mouse adrenal and testis via pAb of AD-004. Results Hisfused AD-004 was expressed efficiently in the prokaryotic system. Western blot analysis showed that the polyclonal antibody was duly bound to purified AD-004 with high specificity and sensitivity. AD-004 could be abundantly identified in the adrenal medulla and mainly expressed in the Leydig cells of testis. Conclusion The mouse protein of AD-004 is obtained from the prokaryotic expression system. The rabbit anti-AD-004 antibody has been prepared successfully. AD-004 protein is mainly localized in the interstitium of testis, suggesting that AD-004 may play a role in the synthesis of sex-steroid hormone.

Objective:To investigate the clinical features and treatment outcome of Kallmann syndrome(KS) caused by fibroblast growth factor receptor-1(FGFR1) gene mutation in 4 patients.Methods:Targeted next-generation sequencing(NGS) was performed on thirty KS and normosmic idiopathic hypogonadotropic hypogonadism(nIHH) patients. FGFR1 mutation was identified in four KS patients. The clinical data, laboratory and imaging examinations, and treatment outcome were retrospectively analyzed.Results:Four male patients, aging from 11 to 22 years old, presented as micropenis, and with olfactory dysfunction. Among them, two had history of cryptorchidism, three had history of cleft lip and palate repair surgery. The most severe patient presented with short stature, left microtia and dental agenesis. FGFR1 heterozygous mutation was identified in all four patients, two were point mutation(p.Y374X; p. E670K), and the other was frameshift mutation(p.S346Yfs*61; p.S723*fs*1). One patient, who started treatment of the pulsatile GnRH pump during his youth, succeeded in having two babies.Conclusion:Patients with Kallmann syndrome caused by FGFR1 mutation presents complex clinical manifestations. Besides dysosmia, micropenis, microrchidia, and delayed pubertal development are the main clinical manifestations in male patients. Symptoms such as cleft lip and palate are helpful for early recognition. Genotyping analysis is crucial to confirm the diagnosis. The pulsatile GnRH pump can produce satisfactory therapeutic effect, but the age of initiating therapy should be carefully considered.

Objective To investigate the effects of the genetic polymorphisms in osteoporosis-related genes and the gene-gene interaction on bone mineral density (BMD) and osteoporotic fractures.Methods Thirty-nine single nucleotide polymorphism (SNP) sites in 23 genes that related to bone mineral density ( BMD ) and osteoporotic fractures were scanned in 683 Shanghai Han postmenopausal women.TaqMan SNP Genotyping Assay or Sequenom Mass ARRAY System were applied for genotyping analysis.The relation of these SNP sites with BMD and osteoporotic fractures were analyzed.Results Altogether,12 SNPs in 9 candidate genes ( rs7524102 and rs6696981 in ZBTB40 gene,rs9479055 in ESR1 gene,rs6993813,rs6469804,and rs11995824 in OPG gene,rs3736228 in LRP5 gene,rs1107748 in SOST gene,rs87938 in CTNNB1 gene,rs1366594 in MEF2C gene,rs7117858 in SOX6 gene,and rs10048146 in FOXL1 gene) were associated with BMD at lumbar spine(L1-L4) or total hip.In addition,rs11898505 in SPTBN1 gene was related to osteoporotic fractures ( OR 0.522,95％ CI 0.326-0.838,P =0.007 ).Gene-gene interaction involving rs1038304 in ESR1 gene,rs1366594 in MEF2C gene,and rs10048146 in FOXL1 gene was associated with osteoporotic fractures ( P =0.010 7 ).Conclusions ( 1 ) SNPs in gene ZBTB40,ESR1,OPG,LRP5,SOST,CTNNB1,MEF2C,SOX6,FOXL1,and SPTBN1 are associated with BMD of lumbar spine or total hip,as well as osteoporotic fractures.(2) Gene-gene interaction involving rs1038304,rs1366594,and rs10048146may contribute to the risk of osteoporotic fractures.