Analysis of clinical features and related genes variation in 41 girls with McCune-Albright syndrome / 中华内分泌代谢杂志

Objective To investigate the clinical characteristics and molecular pathological mechanism of McCune-Albright syndrome ( MAS) in order to provide a guidance for the precision medicine of MAS. Method The clinical data and genetic findings of 41 patients with MAS were analyzed retrospectively. Results (1) MAS girls had the phenotype of peripheral precocious puberty with premature sexual development and high estradiol, low LH and FSH, and the increased volume of uterus and ovary. ( 2 ) In 41 MAS cases, there were 17 cases with GNAS1 gene mutation, and the total positive rate was 41. 5%, of which the classic triad was 66. 7%, two signs 56. 3%, and 12. 5% in only one classic sign. GNAS1 gene mutation was found in 78. 6% of patients with polyostotic fibrous dysplasia of bone, while only 55. 0% in patients with cafe au lait skin spots. Children with precocious puberty and fibrous dysplasia of bone is an important basis for clinical diagnosis of MAS, but cafe au lait skin spots does not seem to be the specifical manifestation of MAS. Conclusion Clinically MAS was lack of typical clinical manifestations, and the most important clinical weight factor for the diagnosis of MAS was peripheral precocious puberty with fibrous dysplasia of bone. GNAS1 gene screening may be helpful to improve the clinical accurate diagnosis of MAS.

The use of the increased IL-27 expression as a diagnostic marker in the serum of hepatocellular carcinoma patients / 中国医师杂志

Objective To investigate the clinical significance of IL-27 in hepatocellular carcinoma ( HCC) in the early stage , and to compare it with alpha-fetoprotein ( AFP) in diagnostic performance .Methods Enzyme-linked immunosorbent assay was used to detect the serum level of IL-27 in the HCC group and control group .Receiver operator characteristic ( ROC) curve was used to ana-lyze two indicators and the logistic regression model predicted value ( PRE) was obtained .Results The study indicated the concentra-tion of IL-27 in HCC group [(364.19 ±177.55)pg/ml] was significantly higher than the control group [(255.49 ±94.33)pg/ml], the area under the curve (AUC) of IL-27 and AFP were (0.804) and (0.818), respectively.Logistic regression obtained the regres-sion model PRE that contains AFP and IL-27, with a predicted area under the ROC curve for HCC (0.901), while the diagnostic sen-sitivity (84.8%) and specificity (96.7%) were significantly higher than the capability of individual diagnosis of each indicator .Con-clusions In this study we obtained the model which can be used for clinical diagnosis of hepatocellular carcinoma in future .

Changes of amino-terminal propeptide of C-type natriuretic peptide and growth velocity in patients with idiopathic short stature or isolated growth hormone deficiency after recombinant human growth hormone treatment / 中华内分泌代谢杂志

Objective To explore the value of amino-terminal propeptide of C-type natriuretic peptide (NTproCNP) in evaluating the efficacy of therapy with recombinant human growth hormone ( rhGH ) in patients with idiopathic short stature (ISS) and isolated growth hormone deficiency ( IGHD ).Methods Forty-eight prepubertal children( IGHD n=25,ISS n=23 ) treated for at least 1 year with rhGH were included.Serum insulin-like growth factor- Ⅰ ( IGF- Ⅰ ) and NTproCNP levels were measured before starting treatment and 6 months later.Twelve months after starting treatment,all patients were assessed and annual growth velocity ( GV ),height standard deviation score ( HTSDS),and gained HTSDS (△HTSDS) were recorded.Results In GHD group,positive relationships between GV and change of IGF- ISDS( △IGF- ISDS ),GV and change of NTproCNP concentrations(△NTproCNP) were found( r=0.407,P=0.044 ;r=0.490,P=0.013 ).GH peak value was also positively associated with IGF- ISDS and NTproCNP before therapy ( r =0.558,P =0.004; r =0.630,P =0.001 ).△IGF- ISDS and △NTproCNP were positively associated after therapy ( r =0.466,P =0.019 ).In ISS group,GV was associated with △NTproCNP ( r=0.845,P＜ 0.01 ).Conclusions NTproCNP is a novel biomarker of growth as its level increases during growth-promoting treatment.Furthermore,IGF- Ⅰ is also valuable in evaluating the efficacy of rhGH therapy in short stature patients.

Effects of recombinant human growth hormone on final adult height in children with Turner′s syndrome and analysis of the influencing factors / 中华内分泌代谢杂志

Objective To observe the final adult height (FAH) outcome and influencing factors in Turner′s Syndrome(TS) children treated with recombinant human growth hormone ( rhGH ).Methods Thirty TS children treated with rhGH were compared with 16 TS children without rhGH treatment and were followed up to achieve their FAH.Comparisons were made regarding predicted adult height (PAH),height standard deviation score for chronological age( HtSDScA ),height SDS for BA( HtSDSRA ),and growth velocity ( GV ) between rhGH treatment and without treatment groups and between the onset and by the end of rhGH treatment group.The factors determining FAH were also evaluated.Results FAH in rhGH treatment group was obviously improved as compared with untreatment group[ ( 149.5±6.3 vs 142.4±5.2) cm,P＜0.01 ].FAH in treatment group was positively correlated with height standard deviation score for chronological age ( Ht0 SDSCA ),Hto SDS for BA ( Hto SDSBA ),height age ( HA0 ) at preliminary diagnosis,and correlated with duration of rhGH therapy,duration of estrogen-free rhGH therapy,and PAH0SDS at preliminary diagnosis.Stepwise regression analysis indicated that duration of estrogen-free rhGH therapy and PAH0 SDS were the variables with the greatest identified influence on FAH (F =11.56 and F =86.91,P＜ 0.01 ).FAH in the 45,XO group was significantly different from the mosaicism group (45,XO/46,XX ) [ ( 147.2 ± 6.3 vs 153.3±6.4) cm,P =0.038].Conclusion rhGH treatment is efficacious in improving FAH of TS children,but a variability in the magnitude of the response to rhGH is recognized.Duration of estrogen-free rhGH therapy and PAH0SDS are the variables with the greatest identified influence on FAH,and karyotype may be one of the influence factors.rhGH treatment should be initiated as early as possible and sufficient course of estrogen-free rhGH therapy is needed to yield a satisfactory FAH.

Efficacy of treatment with gonadotropin-releasing hormone analogue alone or combined with recombinant human growth hormone in pubertal short children / 中华内分泌代谢杂志

Objective To assess the efficacy of gonadotropin-releasing hormone analogue(GnRHa)with or without recombinant human growth hormone(rhGH)treatment in Chinese short pubertal children with non-growth hormone deficiency.Methods Of 42 short pubertal children(14 males,28 females)without growth hormone deftcieney,the average age was(11.6±0.8)year.30 children were treated with slow release GnRHa with initial dose (100μg·kg-1·d-1,28d)and maintenance dose(60-80μg·kg-1·d-1,28d)labd rgGH with initial dose(0.15IU·kg-1·d-1)and maintenance dose(0.10-0.15IU·kg-1·d-1)for at least 1year.16 of them were still ongoing till the end of the second year.12 children were treated with GnRHa alone by initial dose(100μg·kg-1·d-1,28d)and maintenance dose (60-80μg·kg-1·d-1,28d),and 7 of them remained on it for 2 years.Dynamic changes including annual growth velocity(GV),bone age(BA)/chronologic age(CA)ratio,Tanner stage,height SDS for CA (HtSDSCA),height SDS for BA(HtSDSBA),and predicted adult height (PAHSDS)were observed.Results By the end of the first year tretment with combination therapy,the following parameters:GV,HtSDSCA,HtSDSBA,and PAHSDS all increased significantly(all P<0.05).Treatment with GnRHa alone did not yield significant changes in GV,HtSDSCA,HtSDSBA,and PAHSDS(all P>0.05).Changes in GV,HtSDSBA,and PAHSDS between these two groups were statistically significant(all P<0.05).By the end of the second year treatment,in the combination group,GV slowed from 6.7 to 5.5 cm/year(P<0.05).HtSDSCA,HtSDSBA,PAHSDS increased(all P<0.05).In the group with GnRHa treatment alone,GV slowed from 4.0 to 3.6 cm/year(P>0.05).HtSDSCA,HtSDSBA,PAHSDS increased(all P>0.05).Changes in GV,HtSDSCA,HtSDSBA,and PAHSDS between these 2 groups were statistically significant respectively(all P<0.05).Conclusion This combined treatment regimen significantly impreved the growth by increasing growth rate and delaying bone matumtion in pubertal chidren without growth hormone deficiency.Further study is needed to verify beneficial effects on the final height gain.

Long-term follow up of childhood-onset primary growth hormone deficiency: clinical analysis of 80 cases / 中华内分泌代谢杂志

Objectives To evaluate final adult height(FAH), lipid profile, sexual development, and quality of life in individuals with childhood-onset growth hormone deficiency (CO-GHD) during the transition from childhood to adulthood, to reassess the function of GH-IGF-I axis, and to explore effective managements for different types of GHD in each period. Methods Totally 80 CO-GHD patients were divided into 2 groups; 22 patients with isolated growth hormone deficiency ( IGHD) and 58 patients with multiple pituitary hormone deficiencies (MPHD); 62 male (age ≥18 years) and 18 female ( age ≥ 16 years) patients. The clinical and biochemical parameters, education and occupation, rhGH, and other hormones therapy in the past were followed up. Results rhGH replacement improved FAH of patients with GHD. The incidences of either hyperlipidemia (39.0% , 47.4%) or fatty liver disease (26.8%, 31.6%) showed no statistically significant changes between 2 groups with and without rhGH replacement. Mean value of IGF-I SDS was significantly higher in IGHD group than that in MPHD group (-1.43±0. 31,-3. 01 ±0. 66) ,and also IGFBP3(-2. 10±0. 33,-3. 17±0. 19,all P< 0.05 ). Patients with IGHD had normal sexual development, but the incidence of sexual dysfunction accounted for 79.7% in MPHD group. Conclusions rhGH improves FAH of individuals with CO-GHD. Patients with CO-GHD should be followed during the transition period; GHD patients carry a high risk of metabolic abnormalities in the adulthood; IGHD female can give birth to offsprings; patients with MPHD have gonadotrophin deficiency of varying degrees.

Detection of fibroblast growth factor receptor 3 gene mutation at nucleotide 1138 site in congenita achondroplasia patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>[corrected] To investigate the mutation at the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) nucleotide 1138 site for identifying the major pathologic mechanism of achondroplasia (ACH) and to evaluate the efficacy of denaturing gradient gel electrophoresis(DGGE) method for screening the point mutations.</p><p><b>METHODS</b>The genomic DNA from 17 clinically diagnosed ACH patients where analysed by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) with Sfc I and Msp I restriction endonucleases and by PCR-DGGE technique for screening.</p><p><b>RESULTS</b>G to A transition mutation at nucleotide 1138 was detected in 14/17 of the ACH patients as heterozygotes by PCR-RFLP with Sfc I digestion. No 1138 G to C transition was detected by Msp I digestion. All of the 14 samples with G to A mutation were also found to be positive for point mutation by PCR-DGGE. No mutation was detected in 3 negative samples by PCR-RFLP, implying that there was actually no point mutation in this amplified region.</p><p><b>CONCLUSION</b>Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot point for mutation in ACH and hence its major pathologic cause. PCR-DGGE is a sensitive and reliable technique for point mutation screening, especially for the heterozygotes.</p>

Inhibitory effects of sorafenib combined with cisplatin on hepatocellular carcinoma cells HepG2 in vitro / 解放军医学杂志

Objective To explore the inhibitory effects of sorafenib combined with cisplatin (DDP) on human hepatocellular carcinoma cells HepG2 in vitro, and the possible underlying mechanisms. Methods The HepG2 cells were divided to 4 groups as control group, sorafenib group, cisplatin group and sorafenib-cisplatin group. Sorafenib and cisplatin were used in single agent or in combination against HepG2 in vitro. The inhibitory effects of sorafenib and/or cisplatin on proliferation of HepG2 were determined by MTT assay at 24h, 48h, 72h and 96h after the addition of the drugs to HepG2 culture. Cell cycle at 24h time point and apoptosis at 48h time point were examined by flow cytometry (FCM). At 24h time point, cells were labeled by Rhodamine123 and mitochondrial transmembrane potential (??m) was determined by FCM, while caspase-3 activity was assessed by caspase-3 colorimetric assay. Results MTT assay showed that sorafenib and cisplatin, when used as a single agent or in combination, could inhibit the growth of HepG2 cells and induce apoptosis in vitro, while synergistic effect was noted when lower doses of sorafenib and DDP were used in combination. It was also found that combined use of sorafenib and cisplatin arrested HepG2 cells at G0/G1 and G2 phase as shown by cell cycle analysis, and the highest apoptosis rate appeared in sorafenib-cisplatin combination group (P