Growth Disorders

生长障碍
  • 文章类型: Journal Article
    The prevalence of short stature among prepubertal children in China is relatively high. Early identification of the cause and timely intervention can bring greater benefits to children with short stature. This paper provides an overview of early diagnosis, intervention measures, and personalized medication dosage for prepubertal short stature children, aiming to provide references for clinical doctors.
    我国青春期前儿童矮身材的发生率较高。尽早明确病因,及时进行干预,可为矮身材儿童带来更好的获益。该文对青春期前矮身材儿童的早期诊断、干预措施、个体化用药剂量等进行了概述,以期为临床医生提供参考。.
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  • 文章类型: Journal Article
    不同原因的儿童侏儒症的治疗结果差异很大,并且没有关于治疗的经济负担与结果相关的研究。本文比较了重组人生长激素(rhGH)治疗生长激素缺乏症(GHD)和特发性身材矮小(ISS)的疗效和单位身高的医疗保健成本,以期为儿童提供更具成本效益的治疗选择。我们回顾性分析了在2019.1年至2022.1年间首次到潍坊市人民医院就诊并接受rhGH治疗1至3年的117例(GHD66例,ISS51例)矮小儿童,以追踪治疗效果,并使用配对t检验进行统计学分析,非参数检验,和卡方检验,评估rhGH治疗GHD和ISS儿童的疗效和药物成本。GHD和ISS患儿的年生长速度(GV)在治疗后的3至6个月内增长最快,然后逐渐减慢。GHD组患儿治疗后0~36个月GV高于ISS组(3、6、9、12个月P<0.05);GHD组和ISS组患儿身高标准差评分(HtSDS)随治疗时间的增加逐渐升高,GHD组的身高标准差评分(ΔHtSDS)的变化较ISS组更为显著(3、6、9、12个月时P<0.05)。(2)青春期组儿童身高增加1cm的医疗费用高于青春期前组儿童在同一阶段的医疗费用(3至24个月P<0.05)。同组治疗时间越长,增加1cm身高的医疗费用越高。RhGH可有效治疗儿童侏儒症,促进身高增长,GHD患儿的疗效优于ISS患儿;治疗时间越早,医疗费用越低,综合效益越高。
    Treatment outcomes for different causes of childhood dwarfism vary widely, and there are no studies on the economic burden of treatment in relation to outcomes. This paper compared the efficacy and healthcare costs per unit height of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency (GHD) and idiopathic short stature (ISS) with a view to providing a more cost-effective treatment option for children. We retrospectively analyzed 117 cases (66 cases of GHD and 51 cases of ISS) of short-stature children who first visited Weifang People\'s Hospital between 2019.1 and 2022.1 and were treated with rhGH for 1 to 3 years to track the treatment effect and statistically analyzed by using paired t tests, non-parametric tests, and chi-square tests, to evaluate the efficacy of rhGH treatment for GHD and ISS children and the medicinal cost. The annual growth velocity (GV) of children with GHD and ISS increased the fastest during 3 to 6 months after treatment and then gradually slowed down. The GV of the GHD group was higher than that of the ISS group from 0 to 36 months after treatment (P < .05 at 3, 6, 9, and 12 months); the height standard deviation scores (HtSDS) of the children in the GHD and ISS groups increased gradually with the increase of the treatment time, and the changes in the height standard deviation scores (ΔHtSDS) of the GHD group were more significant than those of the ISS group (P < .05 at 3, 6, 9, and 12 months). (2) The medical costs in the pubertal group for a 1-cm increase in height were higher than those of children in the pre-pubertal group at the same stage (3 to 24 months P < .05). The longer the treatment time within the same group, the higher the medical cost of increasing 1cm height. RhGH is effective in treating children with dwarfism to promote height growth, and the effect on children with GHD is better than that of children with ISS; the earlier the treatment time, the lower the medical cost and the higher the comprehensive benefit.
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  • 文章类型: Journal Article
    这项研究的目的是探讨生长激素(GH)治疗对特发性身材矮小女孩青春期发作和进展的影响。
    这项研究包括541名年龄在4.5至10.6岁之间接受GH治疗的女孩,在22年的随访期间进行监测。其中,对126名女孩进行了月经初潮随访。参与者分为两组:ISS对照组(n=66)和一组接受0.15iu/kg剂量的每日GH治疗(n=60)。我们每三个月评估这些女孩的青春期发育和GH使用情况。
    (1)生长激素(GH)治疗组与对照组之间的青春期开始没有显着差异;但是,与对照组相比,治疗组的平均青春期持续时间更长。(2)在青春期,治疗组与未治疗组之间的身高增长没有显着差异。(3)GH治疗时间与治疗组女性性腺发育开始年龄和初潮年龄呈显著负相关。
    GH治疗似乎不会加速青春期的开始,但可能会延长其持续时间,在青春期没有显着影响身高增长。此外,较长的GH治疗时间与女性性腺发育和初潮有关。
    UNASSIGNED: The aim of this study was to explore the impact of growth hormone (GH) therapy on the onset and progression of puberty in girls with idiopathic short stature.
    UNASSIGNED: This study included 541 girls aged between 4.5 and 10.6 years who were receiving GH treatment, monitored over a 22-year follow-up period. Of these, 126 girls have been followed up to the onset of menarche. The participants were divided into two groups: a ISS control group (n = 66) and a group receiving daily GH treatment at a dose of 0.15 iu/kg (n = 60). We assessed the pubertal development and GH usage of these girls every three months.
    UNASSIGNED: (1) There was no significant difference in the onset of puberty between the growth hormone (GH) treatment group and the control group; however, the average duration of puberty was longer in the treatment group compared to the control group. (2) During puberty, there were no significant differences in height growth between the treated and untreated groups. (3) The duration of GH treatment showed a significant negative correlation with the age at onset of gonadal development and the age at menarche in females within the treatment group.
    UNASSIGNED: GH treatment does not seem to accelerate the onset of puberty but may extend its duration, without significantly impacting height growth during puberty. Additionally, longer GH treatment duration is linked to earlier gonadal development and menarche in females.
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  • 文章类型: Journal Article
    患儿 男,8岁4月龄,因“发现身高落后同龄儿5年余”就诊于河南中医药大学第一附属医院儿科医院,主要表现为言语延迟、身材矮小、行走姿势异常、脊柱侧弯和运动发育迟缓,生长激素激发试验示生长激素峰值>10 μg/L,影像学检查示脑垂体顶部膨隆,基因检测结果显示患儿有新发的FOXP4基因杂合性致病变异NM_001012426:c.1618G>A,P.E540K,与已报道的4个FOXP4错义变异均位于叉头DNA结合域上。FOXP4基因杂合变异与以言语延迟和生长发育障碍等临床表型有关。.
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  • 文章类型: Journal Article
    目的:探讨生长激素胰岛素样生长因子(GH-IGFs)与支气管哮喘患儿生长迟缓的关系。
    方法:研究了112例支气管哮喘患儿和50例健康儿童。血清GH,通过ELISA评估IGF-1和胰岛素样生长因子结合蛋白3(IGFBP3)。比较了GH-IGFs相关参数,并分析各参数与支气管哮喘严重程度的相关性。将支气管哮喘组分为生长迟缓组和非生长迟缓组,分析GH-IGFs对生长迟缓的诊断价值以及GH-IGFs与生长迟缓的关系。
    结果:GH,IGF-1和IGFBP3在支气管哮喘组中较低。GH,IGF-1和IGFBP3水平随着支气管哮喘的严重程度而降低。GH,生长迟缓组的IGF-1和IGFBP3低于非生长迟缓组。GH-IGFs联合检测的AUC高于GH和IGFBP3单独检测。GH<9.27μg/L和IGF-1<179.53mmoL/L是支气管哮喘患者生长迟缓的危险因素。
    结论:GH-IGFs相关参数对儿童生长迟缓有诊断价值,GH和IGF-1水平下降是儿童生长迟缓的危险因素。
    To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma.
    112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation.
    GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 μg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma.
    GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.
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  • 文章类型: Journal Article
    背景:来曲唑中很少有关于女孩身高提升的数据。本研究旨在阐明重组人生长激素联合治疗的有效性和安全性。GnRHa和来曲唑在改善身材矮小和骨龄晚期女孩身高方面的作用。
    方法:这是一项基于记录的回顾性研究。对接受rhGH的身材矮小的女孩进行了随访,GnRHa和来曲唑在我们医院门诊治疗。治疗组包括总共29名参与者。治疗前,患者的平均年龄为11.17岁,平均治疗时间为17.31个月。对照组由29名接受rhGH/GnRHa治疗的矮小女孩组成,平均年龄为12.43岁,平均治疗时间为16.59个月。
    结果:治疗前预测的成人身高(PAH)为155.38cm,治疗后PAH为161.32cm(p<0.001)。治疗组的ΔPAH比对照组高4cm(5.85cmVS1.82cm,P<0.001)。治疗前后骨龄身高SDS差异有统计学意义(P<0.001)。年龄的身高SDS差异有统计学意义(P=0.003)。治疗期间BMI增加(P=0.039)。高度增益为8.71±4.46cm,生长速率为每年6.78±3.84cm。
    结论:GH联合治疗,GnRHa和来曲唑可以提高身材矮小女孩的成年身高(AH)和PAH,并且没有明显的副作用。
    OBJECTIVE: There have been rare data on letrozole for height improvement in girls. This study aimed to clarify the efficacy and safety of combination therapy with recombinant human growth hormone (rhGH), GnRHa, and letrozole in improving the height of girls with short stature and advanced bone age.
    METHODS: This was a hospital record-based retrospective study. Follow-up was conducted on girls with short stature who received treatment with rhGH, GnRHa, and letrozole in our hospital. The treatment group included a total of 29 participants. Before treatment, the mean age of the patients was 11.17 years, and the mean treatment duration was 17.31 months. The control group consisted of 29 short-statured girls who received rhGH/GnRHa treatment, with the mean age and treatment duration of 12.43 years and 16.59 months, respectively.
    RESULTS: The predicted adult heights (PAHs) before and after treatment were 155.38 and 161.32 cm (P < .001). The ΔPAH in the treatment group was 4 cm higher than that in the control group (5.85 vs 1.82 cm, P < .001). Significant differences were noted in the height standard deviation scores of bone age (P < .001) and chronological age (P = .003) before and after treatment. There was an increasing body mass index during therapy (P = .039). The height gain was 8.71 ± 4.46 cm, and the growth rate was 6.78 ± 3.84 cm per year.
    CONCLUSIONS: Combined treatment with GH, GnRHa, and letrozole can enhance the adult height and PAH in short-statured girls, and no significant side effects have been reported.
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  • 文章类型: Journal Article
    特发性身材矮小(ISS)是一种常见的儿童疾病,其基本原因未知。最近的研究强调了循环外泌体在各种疾病发病机理中的作用,但他们与国际空间站的联系仍未被探索。在实验中,人软骨细胞与ISS患者的血浆外泌体共培养,导致软骨细胞生长和骨形成受损。特定的长链非编码RNA(lncRNA)的水平升高,ISSRL,被确定为国际空间站的一个区别因素,具有很高的特异性和敏感性。在ISS血浆外泌体中沉默ISSRL逆转了软骨细胞增殖和骨形成的抑制。相反,ISSRL在软骨细胞中的过度表达阻碍了它们的生长和骨形成,通过miR-877-3p/GZMB轴揭示其作用机制。随后,具有精确软骨靶向能力的外泌体(CT-Exo-siISSRL-oeGH)加载ISSRL和生长激素的定制siRNA。这种创新的方法提供了一种治疗策略,通过纠正生长板软骨中异常的非编码RNA表达并精确递送生长激素以促进骨骼生长来解决ISS。这项研究为ISS的诊断和治疗提供了有价值的见解,突出工程外泌体的潜力。
    Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.
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  • 文章类型: Journal Article
    背景:现代家禽业中的脂肪肝出血性综合征(FLHS)主要由营养引起。尽管FLHS取得了令人鼓舞的进展,在表观遗传学方面,营养影响FLHS易感性的机制仍然缺乏。
    结果:在这项研究中,我们通过染色质免疫沉淀测序(ChIP-seq)分析了组蛋白H3(H3K27me3)富集的三甲基化赖氨酸残基27的全基因组模式,并检查了其与健康和FLHS母鸡转录组的关联。研究结果表明,FLHS母鸡的H3K27me3水平在全基因组范围内增加。此外,发现H3K27me3占据整个基因和远处的基因间区域,可以起到类似消音器的调节元件的作用。对高甲基化峰中的转录因子(TF)基序的分析表明,有23种TF参与了肝脏代谢和发育的调节。转录组分析表明,差异表达基因(DEGs)在脂肪酸代谢中富集,氨基酸,和碳水化合物代谢。从PPI网络中鉴定出的hub基因是脂肪酸合成酶(FASN)。联合ChIP-seq和转录组分析显示,增加的H3K27me3和下调的基因在ECM-受体相互作用中有显著的富集,紧密连接,细胞粘附分子,附着者接合处,和TGF-β信号通路。
    结论:总体而言,H3K27的三甲基化修饰已被证明在FLHS中具有显著的调节功能,介导与ECM-受体相互作用途径相关的关键基因的表达。这突出了H3K27me3的表观遗传机制,并为探索FLHS的核心调控目标和营养调控策略提供了见解。
    BACKGROUND: Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics.
    RESULTS: In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways.
    CONCLUSIONS: Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.
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  • 文章类型: Journal Article
    国际发展工作涉及外部伙伴带来专业知识,资源,以及对低收入国家地方干预措施的管理,但是对相关的当地共同价值观的理解往往存在差距。人们普遍需要更好地设计适应当地文化相关元素的干预措施,正如最近全球卫生研究中有关新殖民主义的讨论所强调的那样。最近的一项创新是生产“文化协议”的概念,以指导和指导社区参与或干预设计,但没有生成它们的建议。这项研究探索并证明了从另一个领域采取的方法的潜力,名为WeValueInSitu,生成当地文化知情协议。WeValueInSitu使利益相关者团体参与意义制定过程,这些过程将其本地共享价值的包络“具体化”,使他们能够与外人交流。我们的研究背景是理解和减少儿童发育迟缓,包括制定干预措施,在塞内加尔和印度尼西亚的UKRIGCRF行动中心进行。每个国家研究小组都涉及从微观营养到表观遗传学的八个健康学科,广泛收集样本和问卷。当地文化知情协议通常对预先告知参与和干预设计很有价值。在这里,我们探索通过以下方式立即生成它们WeValueInSitu结晶过程,并进行专门的焦点小组讨论,探索:当地的生活实践可能对影响儿童发育迟缓的环境产生重大影响,以及他们强调哪些文化元素是相关的。讨论将以共同的价值观为框架,并揭示与他们的联系。在这项研究中,像父亲这样的利益相关者团体,母亲们,教师,市场交易者,管理员,招募了农民和卫生工作者,共有20组83名参与者。与当地可接受的食品干预措施的文化知情协议相关的主题包括:特定的性别角色;社会等级制度;卫生服务获取挑战;关于营养不良的传统观念;以及接受外部帮助的态度。基于文化的协议的概念,以及使用WeValueInSitu来生成它,因此在这里得到了证明。未来的工作范围与演绎文化研究相比的优势和局限性,使用其他形成性研究方法现在将是有用的。
    International development work involves external partners bringing expertise, resources, and management for local interventions in LMICs, but there is often a gap in understandings of relevant local shared values. There is a widespread need to better design interventions which accommodate relevant elements of local culture, as emphasised by recent discussions in global health research regarding neo-colonialism. One recent innovation is the concept of producing \'cultural protocols\' to precede and guide community engagement or intervention design, but without suggestions for generating them. This study explores and demonstrates the potential of an approach taken from another field, named WeValue InSitu, to generate local culturally-informed protocols. WeValue InSitu engages stakeholder groups in meaning-making processes which \'crystallize\' their envelope of local shared values, making them communicable to outsiders.Our research context is understanding and reducing child stunting, including developing interventions, carried out at the Senegal and Indonesia sites of the UKRI GCRF Action Against Stunting Hub. Each national research team involves eight health disciplines from micro-nutrition to epigenetics, and extensive collection of samples and questionnaires. Local culturally-informed protocols would be generally valuable to pre-inform engagement and intervention designs. Here we explore generating them by immediately following the group WeValue InSitu crystallization process with specialised focus group discussions exploring: what local life practices potentially have significant influence on the environments affecting child stunting, and which cultural elements do they highlight as relevant. The discussions will be framed by the shared values, and reveal linkages to them. In this study, stakeholder groups like fathers, mothers, teachers, market traders, administrators, farmers and health workers were recruited, totalling 83 participants across 20 groups. Themes found relevant for a culturally-informed protocol for locally-acceptable food interventions included: specific gender roles; social hierarchies; health service access challenges; traditional beliefs around malnutrition; and attitudes to accepting outside help. The concept of a grounded culturally-informed protocol, and the use of WeValue InSitu to generate it, has thus been demonstrated here. Future work to scope out the advantages and limitations compared to deductive culture studies, and to using other formative research methods would now be useful.
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  • 文章类型: Systematic Review
    这项研究的目的是比较长效生长激素(LAGH)作为生长激素替代疗法在患有生长激素缺乏症(GHD)的青春期前儿童中的相对疗效和安全性。我们搜查了PubMed,Embase,CNKI,和万方数据库从成立到2023年7月,并确定了11项相关研究。PEG-LAGH对高度速度的影响(平均差[MD]:-0.031,95%可信区间[CrI]:-0.278,0.215)比somatrogon(MD:0.105,95%CrI:-0.419,0.636)更好,与每日生长激素(DGH)相比,索马帕西坦(MD:0.802,95%CrI:-0.451,2.068)和lonapegsomatropin(MD:1.335,95%CrI:-0.3,2.989)。此外,就身高标准差得分而言,PEG-LAGH表现出比somatrogon(MD:-0.055,95%CrI:-1.3,0.51)和somapacitan(MD:0.22,95%CrI:-0.91,1.3)更好的改善(MD:-0.15,95%CrI:-1.1,0.66)。PEG-LAGH(风险比[RR]:1.00,95%CrI:0.82,1.2)与其他LAGH(somatrogon,RR:1.1,95%CrI:0.98,1.2;索马帕西坦,RR:1.1,95%CrI:0.96,1.4;lonapegomatropin,RR,1.1,95%CrI:0.91,1.3),与DGH相当。这是第一项通过网络荟萃分析间接比较LAGH的研究,并提供了各种LAGH特别是PEG-LAGH在青春期前GHD儿童中的最佳疗效和可接受的安全性的证据。
    The purpose of this study is to compare the relative efficacy and safety of long-acting growth hormone (LAGH) as a growth hormone replacement therapy in prepubertal children with growth hormone deficiency (GHD). We searched the PubMed, Embase, CNKI, and Wanfang databases from inception to July 2023 and identified eleven relevant studies. PEG-LAGH showed better effect on height velocity (mean difference [MD]: - 0.031, 95% credibility interval [CrI]: - 0.278, 0.215) than somatrogon (MD: 0.105, 95% CrI: - 0.419, 0.636), somapacitan (MD: 0.802, 95% CrI: - 0.451, 2.068) and lonapegsomatropin (MD: 1.335, 95% CrI: - 0.3, 2.989) when compared with daily growth hormone (DGH). Furthermore, in terms of height standard deviation score, PEG-LAGH demonstrated better improvement (MD: - 0.15, 95% CrI: - 1.1, 0.66) than somatrogon (MD: - 0.055, 95% CrI: - 1.3, 0.51) and somapacitan (MD: 0.22, 95% CrI: - 0.91, 1.3). PEG-LAGH (risk ratio [RR]: 1.00, 95% CrI: 0.82, 1.2) reduced the risk of adverse events compared with other LAGH (somatrogon, RR: 1.1, 95% CrI: 0.98, 1.2; somapacitan, RR: 1.1, 95% CrI: 0.96, 1.4; lonapegsomatropin, RR, 1.1, 95% CrI: 0.91, 1.3) and was comparable with DGH. This is the first study to indirectly compare the LAGH thorough a network meta-analysis and provide evidence of the optimal efficacy of various LAGH specifically PEG-LAGH and acceptable safety profile in prepubertal children with GHD.
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