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.

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 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 evaluate the long-term final adult height outcome of combined treatment with gonadotropin-releasing hormone analogue(GnRHa)and recombinant human growth hormone(rhGH)in girls with idiopathic central precocious puberty(ICPP).Methods Out of 49 sirls with ICPP[treated with GnRHa at a dose of 60-80 μg/kg every 4 weeks for at least 6 months,whose height velocity fell below 4 cm/year and showed no improvement of predicted adult height(PAH)in 6 months],26 received(rhGH-combined group),in addition to chronological age,and duration of GnRHa treatment,who showed the same growth pattern but refused rhGH treatment,served to evaluate the efficacy of rhGH in addition.At the conclusion of the smdy,all the girls had been followed up for(3.3±1.9)years,and(3.2±0.9)years in rhGH-combined group and control group,respectively;and had achieved adult heisht.To compare the PAH with the final adult height(FAH)before and after treatment in the two groups.Results During rhGH treatment, height velocity of the rhGH-combined girls increased significantly[(6.7±2.0 vs <4)cm/year baseline],RhGH-combined gids showed an adult height far higher than pretreatment PAH [(157.5±4.5 vs 148.1±4.6)cm,P<0.01],and target height[(154.4±4.6)cm] was,significantly excceded.The control group reached an adult heisht also significandy higher than pretreatment PAH[(154.7±5.5vs 150.3±6.0)cm,P<0.01],while target height[(155.6±4.3)cm]was just reached but not significantlyexcceded.The gain in height obtained,calculated between pretreatment PAH and final heisat,(9.4±4.9)cm in rhGH-combined group was much more than that(4.3±4.2)cm in the control group(P<0.01).Conclusion RhGH may accelerate the linear growth and improve adult height of GnRHa-treated ICPP girls.

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.