Objective To evaluate the clinical value of tumor chemosensitivity test in the guidance of the advanced epithelial ovarian carcinoma patients treated with chemotherapy.Methods Women with ovarian cancer were enrolled and fresh tissue samples were collected for chemoresponse testing.Oncologists chose a drug for each patient according to the patient’ s condition by double blind method.Each treatment was classified by the assay as: sensitivity (S); moderate sensitivity (I);resistant (R).Progression-free survival (PFS) and overall survival (OS) were detection.The relationship between treatment response and PFS or OS was analysis.Results 262 patients were enrolled.The PFS and OS were significantly improved in sensitivity patients (S) after chemotherapy,but no significant difference were found in I and R groups.In I+R groups (HR=0.66,P=0.008) , median PFS was 8.9 months, OS was 5.8 months.Chemotherapy response test results was consistent with clinical results cisplatin sensitive and resistant ( HR:0.72 vs.0.66).Multi factor regression analysis showed that tumor chemosensitivity test was independent prognostic factors (HR =0.66, P =0.021).The average OS extended for 14 months (37.6 months for the S group vs.group I +R 23.8 months,HR =0.62, P =0.011).Conclusion Tumor chemosensitivity assay is correlated with the clinical effects and might play an important role in guiding the recurrent epithelial ovarian cancer patients with individualized chemotherapy.

Objective This study aims to investigate the mutation spectrum and frequency of GJB2 , mtDNA12SrRNA,and SLC26A4 genes in Hui people,Tibetan,Tu nationality,and Mongolian patients with non-syndromic hearing loss in Qinghai province.Methods Peripheral blood samples were obtained from a total of 211 minority patients with nonsyndromic hearing loss in Qinghai province to extract genomic DNA.Three genes of GJB2,mitochondrialDNA12SrRNA,and SLC26A4 were screened for mutations in our study cohort using SNPscan technology.Results Among these 211 patients,5 Tu patients and 1 Mongolian patient were found to carry the ho-moplasmic mtDNAA1555G mutation.The GJB2 mutations detection rates were 11.38%,4.55%,5.88%,and 10%in Hui people,Tibetan,Tu nationality,and Mongolian patients,respectively.No statistically significant differences in the GJB2 mutations detection rates were found among all four ethnicities (P>0.05).c.235delC was the most prevalent mutation in both Tu patients and Mongolian patients.The allele frequency was 2.94% and 5%,respec-tively.While for Hui patients,c.299 300delAT was the most prevalent mutation with the allele frequency of 4.47%.The mutations detection rates of SLC26A4 were 6.5%,4.55%and 2.94%in Hui people,Tibetan,and Tu nationality patients,respectively.No statistically significant differences in the SLC26A4 mutations detection rates were found among all three ethnicities (P>0.05).c.235delC was the most prevalent mutation in Hui patients,the allele frequency was 2.44%.While for Tibetan patients,c.1226G>A was the most prevalent mutation with allele frequency of 2.27%.Conclusion A total of 10.9% of deaf patients have inherited hearing impairment caused by GJB2,SLC26A4,and mtDNAA1555G mutations.The mutation spectrum of GJB2 and SLC26A4 genes has the eth-nic specificity in nonsyndromic hearing loss patients of minority ethnicities in Qinghai province.

Objective To analyze the pattern of early catch-up growth In children with prepubertal short stature and various secretory forms of growth hormone(GH)following recombinant human growth hormone (rhGH)treatment and to explore the mechanism. Methods Sixty-two children with prepubertal short stature and various GH secretory forms were analyzed retrospectively, 27 with complete growth hormone deficiency (cGHD), 23 with partial growth hormone deficiency (pGHD)and 12 with idiopathic short stature(ISS). According to the GH peak value in GH provocative test, the group of pGHD was divided into pGHD-1(5.0-6.9μg/L)and pGHD-2(7.0-9.9μg/L). Height velocity, increase in height standard differentiation score (SDS), was calculated; serum levels of somatotrophic axis hormone were detected and bone age was determined. Results The quick early catch-up growth in different groups were similar in the initial 6 months. While that in the ISS group persisted for shorter period and was correlated with lower level in serum GH-binding protein(r=0.526,P=0.025)and Δinsulin-like growth factor-binding protein-3 (IGFBP-3) SDS (r=0.532,P=0.034) after rhGH treatment. The same doses of rhGH were applied to children with cGHD and pGHD. Children with pGHD-1 showed similar response to rhGH,regarding height velocity and ΔIGFBP-3 SDS, as compared with those of cGHD. However, children with pGHD-2 presented similar response with ISS, being worse than cGHD. Conclusion Downregulation of GH receptor and decrease in post-receptor effect seem to be the mechanism leading to early retardation in ISS. The incomplete catch-up growth in pGHD-2 may be caused by relatively inadequate rhGH dose. The cut-off value of GH provocative test in diagnosing GHD is more reasonable to be 7μg/L.

Objective To explore the relationship between adrenarche and gonadarche.Methods Total 49 idiopathic central precocious puberty(ICPP)girls,whose serum dehydroepiandrosterone sulfate(DHEAS)Z scores for chronological age were higher than+2 s at diagnosis.were enrolled.Physical examinations during pubertal stage were repeated at 3-6 months intervals,and serum DHEAS levels were monitored yearly within an average period of 4.08 years.Of them,16 girls were followed up until more than one year after discontinuation of gonadotropin-releasing hormone analogue(GnRHa)treatment.Results Before GnRHa treatment,these49 girls presented a younger average age at attainment of pubic hair stage2(PH2)and pubic hair stage3(PH3)than normal(8.07 years vs 11.16 years,8.82 years vs 12.40 years respectively).During GnRHa treatment,the intervals between PH2 and PH3,PH3 and pubic hair stage4(PH4),breast stage 2(B2),and PH2 were longer than normal(1.69 years vs 0.83 years,1.64 years vs 0.60 years,and3.62 years vs 0.76 years respectively).The intervals between PH2 and PH3,as well as B2 and PH2 during GnRHa treatment were also longer than that before GnRHa treatment(1.69 years/35 0.88 years,3.62 years vs 1.13 years respectively).The serum DHEAS Z scores decreased during GnRHa treatment,and increased significantly after GnRHa cessation.Conclusion Gonadarche after age of 6-year-old may lead to earlier adrenarehe.GnRHa treatment might slow down the progression of adrenarche and suppress the hypothalamuspituitary-gonadal axis.

Objective To analyze the clinical characters of childhood adrenocortical tumors, and to enhance the knowledge of diagnosis of this disease. Methods A retrospective analysis of clinical characters,laboratory tests,and imaging findings in 31 cases of childhood adrenocortical tumors was carried out. Results 16 cases of adenoma and 15 cases of carcinoma were included. The average age was (4.49±3.51) years old, and 67.7% of the patients were younger than 5 years old. The ratio of male to female was 1.0: 1.4. 12 patients presented only precocious sexual development, 4 patients presented only Cushing syndrome, 10 patients showed sexual precocity combined with Cushing syndrome, and 5 patients did not have any endocrine abnormalities. Raised testosterone level in 92.3% of these patients was the most common finding in laboratory tests. Only 12.5% of ultrasound images and 20.8% of CT images were consistent with pathologic diagnosis. Conclusions The clinical manifestations of adrenocortical tumors in childhood are precocious sexual development, Cushing's syndrome, or nonfunctional. The common laboratory findings are elevation of sex hormone and disorder of cortisol circadian rhythm. Precocious sexual development and elevation of androgens are more common in childhood adrenocortical tumor than those in adults. Imaging usually cannot give proper diagnosis. Final diagnosis should be established by clinical features, laboratory tests, imaging, and pathologic results.

Objective To understand how serum DHEAS levels change with sex,age and stage of sexual maturation in children and adolescents and explore the relationship between adrenarche and pubertal maturatiotL Methods Serum samples from 120 healthy boys,198 healthy girls and 152 girls with idiopathic central precocious puberty (ICPP) were examined for DHEAS.Referenee ranges for healthy children and adolescents and statistical difierences between heahhy girls and ICPP girls were analyzed with respect to sex,age and stage of sexual maturation.Results Both healthy children and ICPP girls showed extremely low levels of serum DHEAS and they were not related to sex.age or tanner stages in the individuals below age of 6 years.Serum DHEAS levels were positively related to both age (above age of 6 years)and tanner stage in healthy groups(r=0.69 and 0.71 respectively,P＜0.01).After the onset of puberty,serum DHEAS levels appeared to be higher in boys than that in girls within the same tanner stage(P＜0.05).Within the individusis in the same age group with same sex.serum DHEAS levels increased along with pubertal development.While within the individuals in same tanner stage group with salne sex after puberty onset.serum DHEAS levels showed no significant difference among different age groups.For example.there was no difference in serum DHEAS levels of healthy girls in tanner stage Ⅲ among different age subgroups(age of8-9;age of 10-11,age of 12-13)and the mean vallie of serum DHEAS was 532.0-557.8μg/L(F=0.21,P=0.98).In different age subgroups above age of 6 years,Z scores for serum DHEAS in ICPP girls were highher than them healthy ones with advanced tanner stages(0.97us-0.1 and 1.39us-0.08,JP≤0.01)In different tanner stage subgroups.Z scores for serum DHEAS showed no difierence between healthy and ICPP girls despite apparent different age ranges(0.00 us-0.31-0.18,P＞0.05).Conclusions Serum DHEAS level increased along with both age (above 6 years) and tanner stage in healthy children and adolescents.There was no gender difference until the onset of puberty.It was demonstrated that adrenache and gonadarche were related to each other.Reference ranges for adolescents should be interpreted according to sex.age and tanner stage simultaneously.

Objective To study the significance of antibody to double-stranded DNA (anti- dsDNA) in autoimmune hepatitis(AIH). Methods Anti-dsDNA were detected by immunological blotting. According to the anti-dsDNA, the patients were separated two groups: anti-dsDNA positive group and anti-dsDNA negative group. The clinical characteristics were compared between anti-dsDNA positive AIH group and negative group. Results Among the 43 serum samples, 13 (30.23%) eases with anti-dsDNA positive were found. The average level of AST(aspartate aminotransferase) and TBIL(total bilirubin) were (647.56 ±529.77) IU/L and (10.81± 8.08) rag/L, respectively, which was higher than that of the control group (P < 0.05). PTA (prothrombin activity) was 75.72%± 30.23 %, lower than that of the control group(P < 0.05). The liver cirrhosis rate in the anti-dsDNA positive AIH group was 61.5% (8/13), ,significantly higher than that of the control group. The time from the onset to liver cirrhosis was significantly shorter in an- ti-dsDNA positive AIH group than that of control group by the survival analysis and log rank test (P = 0. 0074). Conclusion AIH patients with anti-dsDNA positive generally associate with the serious liver damage, and prognosis is worse.

Objective To analyze the feature of SLA specific T cell response in AIH. Methods Thirtyone cases of AIH were enrolled by investigating T-cell reactivity against chemically synthesized peptides spanning the full SLA protein using ELISpot. The 31 cases of AIH included 10 anti-SLA/LP positive cases and 21 negative cases. The control groups included 30 PBC patients, 29 chronic viral hepatitis patients and 30 healthy cases. The secretion of IFN-γ after PBMC stimulated by SLA peptides was observed. Results Eighteen of 31 cases with AIH [56. 08 % ( 18/31 ) ] showed the positive response to SLA peptide pools, and only 1 of 30 patients with primary biliary cirrhosis (3.34%) and 1 of 29 patients with virus hepatitis ( 3.44% ), could be elicited responses by SLA peptide pools. There wasn't positive response in healthy eases. The response frequency to SLA peptides in AIH group was significantly higher than those in PBC cases, chronic viral hepatitis cases and healthy cases (X2 = 21. 295, 20. 655, 15.988, P < 0. 01 ). Amongst 18 AIH patients with positive responds to SLA pool, 8 antigen clusters including aa 1-44, aa 57-132, an 129-180,aa 177-196, aa 193-244, aa 241-268, aa 281-308 and aa 321-428 were highlighted. The mean number of recognized peptides was 6 (2-17), indicating the polyclonal feature. Fourteen of 18 AIH patients with positive response to SLA peptides were subjected to live function test simultaneously when PBMC were collected. There was significant correlation between the breadth of recognized poptides and AST ( logarithm, r = 0. 539, P = 0. 045). Conclusions SLA peptides can induce PBMC in peripheral blood of AIH patients to secrete IFN-γ and it is polyclonal response. The breadth of recognized peptides may reflect the degree of liver inflammation.

Objective To compare the different efficacies of recombinant human growth hormone (rhGH) alone and rhGH combined with low-does stanozolol on growth velocity (GV) of girls with Turner syndrome (TS). Methods 51 girls with TS were divided into two groups: Group 1 (n = 23) were treated with rhGH alone and group 2 (n = 28) with rhGH combined with low-does stanozolol both for more than six months. The two groups were compared in terms of GV, height standard deviation score for chronologic age (HtSDSCA), HtSDS for bone age (HtSDSBA), HtSDS (ΔHtSDS) and the ratio of ΔBA/ΔCA. Results In the first year, the GV was (6.29 ± 1.44) and (8.13 ± 1.87) cm/a in Group 1 and Group 2, respectively. HtSDSCA changed from (-3.51 ± 0.99) to (-3.19 ± 1.09) and (-4.21 ± 1.19) to (-3.43 ± 1.06), and ΔBA/ΔCA was (0.60 ± 0.39) and (0.77 ± 0.56) in Group 1 and Group 2, respectively. The GV and ΔHtSDS in Group 2 were significantly better than Group 1 (P < 0.05). The GV was negatively correlated with the age. Conclusion Compared with the therapy with rhGH alone, the one with rhGH combined with low-dose stanazolol is more effective in improving GV without accelerating bone maturation among the girls with Turner syndrome.

Objective To study the effect on body mass index ( BMI ) caused by treatment with Gonadotropin-releasing hormone analogs ( GnRHa) in girls with central precocious puberty ( CPP) or early and fast puberty ( EFP ) . Methods The BMI in 318 girls ( 227 CPP and 91 EFP ) treated with GnRHa alone was analyzed. Among them 89 were followed up to their final adult height. Results Before GnRHa treatment was started, thegirlswithCPPandEFPhadameanBMIstandarddeviationscore(SDS)forchronologicalage(BMISDSCA)of0.39 ±0.84andforboneage(BMISDSBA)of-0.11±0.69. Attheendoftreatment,themeanBMISDSCAwas0.59±1.01 and BMISDSBA was 0. 24 ± 0. 89, both were significantly higher than those at initiation. The increment in BMISDSBA (0.38±0.50)wasgreaterthanthatinBMISDSCA(0.21±0.56). Moreover,theratioofoverweight(BMI>85%)was significantly elevated. BMISDSCA of 89 girls who were visited at their final adult height was 0. 17 ± 1. 15, which was similar with BMISDS at initiation and in normal population. Conclusion The mean BMISDSCA of CPP and EFP was significantly higher than the general population, while BMISDSBA was significantly lower. During GnRHa treatment, BMISDS tended to be elevated. But it was reversible, for the mean BMISDS was back to normal at final adult height.