Objective To investigate the long-term effects of GnRHa treatment on final height gain,gonadal function,and body mass index（BMI） in children with central precocious puberty （CPP） or early and fast puberty （EFP）,and to explore the influencing factors of height gain and early predictors.Methods Fifty patients with CPP and 44 patients with EFP who were treated with GnRHa for more

目的:探讨肾动脉血流量对经皮肾动脉去交感神经术(RDN)治疗慢性收缩性心力衰竭患者的疗效评估作用.方法:本研究是一项前瞻性研究.纳入的18例患者皆被诊断为慢性收缩性心力衰竭,接受双侧RDN治疗.术前及术后即刻用基于X射线造影的三维重建血流量计算方法评估患者肾动脉血流的变化,并进行6个月的随访,观察患者6 min步行距离、超声心动图指数、NYHA分级及脑钠肽等生化检查.并观察手术前、后肾血流量的变化与相关指标的关系.结果:6个月随访发现,RDN术后患者的6 min步行距离(247.33±93.34)m∶(355.06±119.14)m,P=0.002]和NYHA分级改善明显(P=0.006).相关性分析发现,肾动脉血流量与左室射血分数(LVEF)、6 min步行距离有相关性(P＜0.05).结论:RDN可能是一种有效的治疗慢性心力衰竭的新技术,可有效改善心功能,并且通过监测手术前后的肾动脉血流量变化可即刻评估RDN治疗的有效性.

BACKGROUND:Dwarfism is a common severe growth disorder, but the etiology is unclear in the majority of cases. Recombinant human growth hormone may be a treatment option, but it has limited efficacy. The currently known laboratory assays do not meet the precision requirements for clinical diagnosis. Here, we have constructed a targeted next-generation sequencing (NGS) panel of selected genes that are suspected to be associated with dwarfism for genetic screening.METHODS:Genetic screening of 91 children with short stature of unknown etiology was performed with the help of the NGS panel. All the coding regions and exon-intron boundaries of 166 genes were included in the panel. To clarify the pathogenicity of these mutations, their clinical data were reviewed and analyzed.RESULTS:The assay identified p.A72G, p.I282V, and p.P491S variants of the PTPN11 gene and a p.I437T variant of the SOS1 gene in 4 cases with Noonan syndrome. A frameshift mutation (p.D2407fs) of the ACAN gene was identified in a case of idiopathic short stature with moderately advanced bone age. A p.R904C variant of the COL2A1 gene was found in a patient, who was accordingly diagnosed with Stickler syndrome. Severe short stature without limb deformity was associated with a p.G11A variant of HOXD13. In addition, we evaluated evidence that a p.D401N variant of the COMP gene may cause multiple epiphyseal dysplasia.CONCLUSIONS:Our findings suggest that syndromes, particularly Noonan syndrome, may be overlooked due to atypical clinical features. This gene panel has been verified to be effective for the rapid screening of genetic etiologies associated with short stature and for guiding precision medicine-based clinical management.

PTPN11 is the most common mutation gene of RAS disease, which is located in the upstream of RAS/MAPK pathway and participates in signal transduction. Because the molecular mechanism of RAS's disease involves the same pathway, it may present a certain commonality in clinic, but the different genotypes with PTPN11 mutation may also express different phenotypes. Therefore, it is not easy to identify and diagnose this disease early in clinic. The present article aims to analyze the correlation between the clinical phenotype and genotype of 4 patients with RAS disease.

Objective To detect pathogenic genes of short stature with unknown etiology by a targeted next generation sequencing panel to analyze the correlation between genotypes and clinical phenotypes.Methods A total of 77 children diagnosed with unexplained short stature were enrolled for the study.These children were treated in Ruijin Hospital of Shanghai Jiao Tong University from 2007 to 2015.To search for genetic variation in 187 candidate genes which were associated with growth,we constructed a targeted next generation sequencing panel encompassing the coding regions of 187 genes.According to ACMG Guidelines,the sites of variation were determined.Sanger sequencing was used to verify the suspected pathogenic genes variation.The relationship between genotype and clinical phenotype was analyzed.Results Including 5 pathogenic variants,one likely pathogenic variant and one variant of uncertain significance,we identified 7 heterozygous variants of 7 cases in 77 cases of short stature with unknown etiology.A pathogenic variant p.D2407fs of ACAN gene was found in a case with advanced bone age.There were 3 reported pathogenic variants,including p.A72G,p.I282V and p.P491S of PTPN11 gene,which were diagnosed as Noonan syndrome.A case carrying known pathogenic variant COL2A1 (p.R904C) was diagnosed as Stickler syndrome.We still got one likely pathogenic variant COMP (p.D401 N),which could cause multiple epiphyseal dysplasia.There was a familial short stature of delayed bone age carrying a variant (p.S289Y) of uncertain significance,in which the genotype was in accordance with the clinical phenotype.Conclusion The ACAN gene defection is associated with the idiopathic short stature with advanced bone age.The likely pathogenic variant COMP(p.D401N) may cause multiple epiphyseal dysplasia.The newly-found heterozygous varians(p.S289Y) of GHSR gene may result in short stature,which needs further function verification.

原发性肾上腺皮质功能减退(primary adrenal insufficiency,PAI)指肾上腺不能产生足够的糖皮质激素和(或)盐皮质激素,也称艾迪生病(Addison disease).PAI在成人有90％是自身免疫性,而儿童主要是遗传因素引起,国外报道显示,儿童PAI的病因72％是由先天性肾上腺皮质增生症(congenital adrenal hyperplasia,CAH)引起,其他遗传因素占6％,自身免疫疾病则占13％[1].儿童PAI症状为非特异性,因此对诊断提出了挑战.本文主要概述儿童PAI分子发病机制,以期进一步协助临床诊断.