Type-B RAF (BRAF) gene is one of the most popular genes of thyroid carcinoma in recent studies,and its mutation has significant relationships with the occurrence,development,treatment,and prognosis of papillary thyroid carcinoma(PTC).The influence of BRAFV600E mutation on the expression of iodine uptake relative proteins in PTC cells and the value of molecular targeted therapy with BRAFV600Einhibitors in the clinical treatment of PTC in the future were summarized in this review.

Aim To screen out the antigenic sequences from HCV core protein random peptide libraries displayed on phage and to explore a new way to screen the viral antigens. Methods The anti-HCV core antibody-positive serum was used to screen antigenic peptides from the HCV core protein random peptide libraries displayed on phage for 4 rounds. Detection of numbers of positive clones, positive rate of insertion of HCV random DNA and positive rate of hybridization with HCV core probes were used to evaluate the screening effects. The DNA sequences of 7 selected clones with positive hybridization were determined and analysed. Results Six out of 7 sequences are HCV core protein sequences, in which 5 were perfectly displayed,and one was possibly displayed. These sequences included several major HCV core antigenic epitopes. The remaining one was E.coli nrfa gene. Conclusion The phage display technique can be applied to study the viral antigenic peptides with the advantages of simple, accuracy and rapidity.

[Objective] To observe the efficacy of metformin treatment on non-alcoholic fatty liver disease (NAFLD) in obese children.[Methods] A retrospective analysis was performed of 10 patients over 10 years old with NAFLD from July 10,2013 to August 23,2016.These patients were treated with metformin in pediatric endocrinology outpatient department of the First Affiliated Hospital of Sun Yat-sen University.The changes of liver ultrasonography,hepatic enzymes,blood lipids,blood glucose,insulin,HOMA-IR,BMI,and waist circumference height ratio were compared before and after treatment with metformin.[Results] There were 10 cases of NASH,including 5 boys and 5 girls.The short-term treatment of metformin reduced the levels of ALT,AST,and HOMA-IR for all 10 patients (P ＜ 0.01).ALT,gradually decreased with the course of treatment.Fasting insulin and waist circumference to height ratio also improved with the treatment (P ＜ 0.05);the changes of TG,BMI,and fast glucose were not obvious (P ＞ 0.05).[Conclusion] Metformin can effectively reduce liver enzymes and improve insulin sensitivity in children with NASH in short term,the improvement of TG and BMI in short term is not obvious.

[Objective] We assessed in a retrospective unicenter study the state of metabolism and gonadal axis of early menarche girls and girls who treated with Gonadotropin-releasing hormone analogs (GnRHa).[Methods] Thirty-nine early menarche girls and 58 girls who had been treated with GnRHa were enrolled in our study and 19 normal menarche girls were enrolled as control group.Data were collected in height,weight,gonadal hormone,blood glucose,insulin,blood lipid,leptin,adiponectin and the size of uterus and ovary.[Results] Both BMI SDS for chronological age (CA) and for bone age (BA) of early menarche girls were significantly higher than normal menarche girls (P ＜ 0.05).The ratio of insulin resistance in early menarche girls (20.5％) was also significantly higher than normal girls (0％).No significant difference in lipid metabolism and gonadal axis between two groups.In girls treated with GnRHa,BMISDS,insulin,HOMA-IR and the ratio of insulin resistance (20.7％) were all significantly higher than normal group (P ＜ 0.05).Meanwhile,DHEAS,androstenedione and testosterone of GnRHa treated girls were significantly higher than early menache girls,and DHEAS was higher than normal girls.The size of uterus in treated group was larger than the other two groups.[Conclusion] Early menarche and GnRHa treatment may take negative effect to BMI and glucose metabolism.Androgen was higher in GnRHa treated group.Therefore,suggestion was that BMI,insulin,blood glucose and androgen should be monitored in early menarche girls and girls treated with GnRHa.

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.

[ ABSTRACT] AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue ( GnRHa) and growth hormone ( GH) on the linear growth in mid-and late pubertal girls at great bone ages with central precocious puberty ( CPP) or early and fast puberty ( EFP) , and to determine the relation between C-type natriuretic pep-tide ( CNP) signaling pathway and the accelerative effect of GH on long bone growth in these girls.METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height ( PAH) , and divided into GnRHa treatment group ( treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group ( treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc) .The height, weight and pubertal stage were determined every 3 months.At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide ( NT-proCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity ( HV) , height SD score for bone age ( HtSDSBA ) , PAH and the serum indexes mentioned above were com-pared at the beginning and the end of the treatment.RESULTS: After 6 months of the treatment, HV, ΔHtSDSBA andΔPAH of the girls treated with GnRHa +GH were statistically higher than those of the girls given GnRHa alone ( P <0.01).Serum concentrations of NTproCNP, P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment.The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION:In the CPP or EFP girls who are in mid-and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height.This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.

Objective To assess the efficacy and impact factors of treatment with Gonadotropin-releasing hormone analogs (GnRHa) in central precocious puberty (CPP) or early and fast puberty (EFP) girls in a retrospective unicenter study.Methods One hundred and two girls (75 CPP and 27 EFP) were treated with GnRHa alone and were followed up to their final adult hight (FAH).Results FAH was (158.0 ± 4.8) cm,being significantly higher than pretreatment predicted adult height [(151.1 ±5.1) cm,P＜0.01].There was no significant difference between CPP [(7.3 ± 4.4) cm] and EFP [(5.5 ± 4.5) cm] in net height gain.There was no significant improvement in FAH and pretreatment PAH for the patients who had menarche before treatment or whose growth velocity was less than 4 cm during the first year.Conclusion GnRHa treatment improves FAH efficiently for both CPP and EFP girls.Nevertheless,those who had menarche before treatment or whose growth velocity was less than 4 cm during the first year can hardly improve FAH by GnRHa treatment alone.

Objective To observe the final adult height of 20 boys with idiopathic central precocious puberty (ICPP) treated with slow-releasing gonadotropin-releasing hormone analogue(GnRHa).Methods Twenty boys with ICPP were treated with GnRHa for( 20.0 ± 6.1 ) months.At the beginning of therapy,mean chronological age and bone age was( 11.4 ± 1.0 ) years and ( 13.0 ± 0.4 ) years,respectively,GnRHa was discontinued when the boys reached the chronological age and bone age of( 13.2 ± 1.1 ) years and ( 13.7 ± 0.6 ) years,respectively.After the end of treatment,all the boys had been followed up for( 3.3 ± 1.5 ) years and had achieved adult height.Comparisons were made among their predicted adult height ( PAH ),final adult height ( FAH ),and target height ( THt ).The long-term outcome of final adult height in boys with ICPP was investigated after GnRHa treatment.Results All the boys reached target height range.Final height was similar to the target height [ ( 169.8 ± 5.8 vs 167.8 ± 4.6 ) cm,P＞0.05 ].The height gain,defined as the difference between predicted adult height at the start of treatment using the height SDS for bone age and actual adult height was( 3.62 ± 3.57 ) cm with the residual growth capacity of ( 11.82 ±3.99)cm,PAH significantly improved after GnRHa treatment compared with before treatment [ ( 169.0 ± 5.0 vs166.2 ± 4.2 ) cm,P＜0.01 ].There were no differences among PAH,FAH,and THt.Conclusion GnRHa treatment improves final height within the range of target height in boys with central precocious puberty.

Forty girls with Turner's syndrome (TS),aged (12.6 ± 1.9) years,were treated with daily subcutaneous injection of recombinant human growth hormone (rhGH,1.0 ～ 1.1 IU · kg-1 · w-1) and oral stanozolol (0.02 ～ 0.04 mg · kg-1 · d-1) for 1 ～ 5 years.Growth velocity (GV),height standard deviation score (SDS) by reference of healthy Chinese girls (HtSDSNor) and height SDS by reference of untreated Chinese TS girls (HtSDSTs)were evaluated regularly.Of the forty girls studied,thirteen had discontinued the treatment after a mean duration of (2.9 ± 1.2)years when GV was less than 2 cm/year or when patients were satisfied with the achieved height.Final adult height (FAH) or near-final height,which was defined as the most recent available height after discontinuation of treatment,and the height gained in the thirteen girls were evaluated.Estrogen therapy was started at the age of(16.0 ± 1.1) years.HtSDSNor increased from-4.2 ± 1.0 to-3.4 ± 1.0 in the first year,and-2.8 ± 1.0,-2.4 ± 0.8,-2.5 ± 0.5,-2.3 ±0.3 respectively in the 2nd,3rd,4th,and 5th year.The change in HtSDSTs was similar to HtSDSNor.It was increased from 0.1 ± 0.9 to 1.0 ± 0.9 in the first year,and to 1.5 ± 0.8,1.9 ± 0.6,1.7 ± 0.4,1.7 ± 0.2 in the subsequent 4 years.The predicted adult height (PAH) in 13 girls was (142.8 ± 4.2) cm before treatment.FAH was (151.7 ± 4.1) cm,which was significantly higher than PAH (P＜0.01),and the mean height gain was (8.9 ± 2.8) cm (5.1 ～ 12 cm).FAHSDSNor was increased to-1.6 ± 0.8 from-3.8 ± 0.8.For girls with TS around 9 years of age,combined therapy with rhGH and low dosage of stanazolol may significantly increase growth velocity and improve final adult height.

Objective To summarize the prevalence,risk factors,and characteristics of testicular adrenal rest tumors(TART) in children and adolescent males with congenital adrenal hyperplasia(CAH) due to 21-hydroxylase deficiency (21-OHD).Methods During past 4 years,there were 44 males with CAH caused by 21-OHD undergone testicular ultrasound scan in our clinic.We have diagnosed 13 cases of TART and summarized the characterizations.Results The prevalence of TART in our group was 29.5％ with 11 cases of salt wasters and 2 cases of simple virilizers.The median age of TART diagnosis was 10.2 years.The median follow-up period of TART was 3.0 years.History of poor control of CAH was found in every case before diagnosis of TART.The doses of hydrocortisone were increased in 5 cases of TART who refused operations or had small TART,resulting in tumor regression in two of those five patients.Testis-sparing surgeries were performed in 8 patients with symptoms relieved; 7 of those eight patients presented elevated FSH and LH after operations.Conclusions Prevalence of TART in our CAH children and adolescent males was 29.5％.Testicular ultrasound was useful in TART screening.TART should be considered when a CAH patient with poor control,especially in post-pubertal one.Delayed management of TART may lead to impaired testicular function.Increased doses of glucocorticoid may be effective in TART of small size.Testis-sparing surgery should be also considered if necessary.