雌激素与C型利尿钠肽介导的青春期线性生长的关系

 目的：探讨青春期女孩雌激素与C型利尿钠肽（C-type natriuretic peptide, CNP）介导的长骨生长的关系,及两者在中枢性性早熟女孩GnRHa治疗相关身高增长减速中的作用。方法：（1）检测56例正常不同青春发育期女孩空腹血清雌二醇（E2）、CNP的N端前肽（N-terminal propeptide of CNP, NT-proCNP）、胰岛素样生长因子1（insulin-like growth factor 1, IGF-1）以及骨形成生化标志物N端中段骨钙素（N-terminal mid-fragment of osteocalcin, N-MID OC）的浓度。（2）检测13例特发性中枢性性早熟（idiopathic central precocious puberty, ICPP）女孩在促性腺激素释放激素类似物（gonadotropin-releasing hormone analogue, GnRHa）治疗开始、治疗6个月末及12个月末时血清E2、NT-proCNP、IGF-1和N-MID OC水平,并计算身高增长速度（height velocity, HV）。结果：(1) 在56例正常不同青春发育期女孩中,与青春前期相比,血清NT-proCNP、IGF-1、E2和N-MID OC浓度均自青春早期开始升高（P<005或P<0.01）;血清NT-proCNP在青春中期维持高水平,至青春后期达峰值（P<005）;血清IGF-1和E2浓度于青春中期继续升高（P<0.01）,亦至青春后期达峰值（P<0.01）;血清N-MID OC浓度于青春中期达到峰值（P<0.05）,青春后期则开始下降（P<0.05）。(2) ICPP女孩GnRHa治疗6个月末HV、血清NT-proCNP和血清N-MID OC均较治疗开始时显著下降（P<0.05）,但与12个月末相比无显著差异;GnRHa治疗开始、治疗6个月末和12个月末后血清IGF-1浓度无显著差异;治疗后血清E2显著下降并回复至青春前期水平（P<0.05）。结论：女孩血清NT-proCNP水平随青春发育进程升高,与血清E2和IGF-1浓度平行,提示女孩青春期升高的雌激素在一定程度上可诱导CNP介导的青春期生长加速。ICPP女孩经GnRHa治疗后,随着雌激素受抑,生长速度减慢,血清NT-proCNP浓度下降,并与生长速度和骨形成平行,提示GnRHa致ICPP女孩生长减速部分缘于雌激素被抑制后CNP介导的长骨生长减慢。     

促性腺激素释放激素治疗改善特发性中枢性性早熟男孩的成年身高

目的 观察缓释型促性腺激素释放激素类似物(GnRHa)治疗后的特发性中枢性性早熟(ICPP)男孩的成年身高.方法 20例ICPP男孩接受GnRHa治疗(20.0±6.1)个月,治疗开始时的年龄和骨龄分别为(11.4±1.0)和(13.0±0.4)岁,当年龄和骨龄达(13.2±1.1)和(13.7±0.6)岁时停止治疗,治疗结束后经随诊(3.3±1.5)年,均已达接近成年身高(FAH).比较预测成年身高(PAH)、FAH和遗传靶身高(THt),探讨GnRHa治疗ICPP男孩对于改善成年身高的远期疗效.结果 成年身高均达遗传靶身高范围,FAH与THt的差异无统计学意义[(169.8±5.8对167.8±4.6)cm,P＞0.05].按骨龄身高SDS预测成年身高(生长曲线法),GnRHa治疗后的PAH较治疗前显著改善[(169.0±5.0对166.2±4.2)cm,P＜0.01];治疗结束时的PAH、FAH和THt差异无统计学意义(P＞0.05);身高净获为(3.62±3.57)cm;剩余生长能力为(11.82±3.99)cm.结论 GnRHa能改善ICPP男孩的成年身高.     

生长激素对于GnRHa治疗中生长过度减速的特发性中枢性性早熟女孩的远期疗效观察

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.     

Fanconi-Bickel综合征临床特征分析

【目的】 总结一种少见的、由葡萄糖转运子2(GLUT2)基因突变引起的遗传病：Fanconi-Bickel综合征(FBS)的临床特征,提高临床医生对该病的诊治水平。【方法】 在国内首次报道两例FBS,并与文献报道的病例进行比较,总结FBS的临床特征。【结果】 两例FBS患儿均经GLUT2基因检测确诊,临床上呈显著的生长迟缓、腹胀、肝大,伴低血糖、肝脏糖原堆积,与糖原累积症I型(GSD-I)类似;但FBS患儿存在餐后血糖增高、糖尿且程度重于其他小管功能障碍。早期即可有较严重的低血磷性佝偻病、Ⅱ型肾小管酸中毒以及无高乳酸和高尿酸血症等特征有别于GSD-I。与文献报道不同的是,本文两例FBS均为出生小于胎龄儿,其中1例存在较明显的肝功能损害,对目前FBS的临床特征谱进行了补充。【结论】 临床上FBS需与GSD-I和糖尿病等鉴别;熟悉和掌握FBS的临床特征,有助于提高临床医生的诊断水平。     

推拿联合妈咪爱治疗小儿腹泻临床观察

目的观察推拿结合妈咪爱治疗小儿腹泻的临床效果。方法选取68例腹泻患儿,将其按照随机数字表法分为对照组和治疗组,每组各34例。对照组给予西医常规治疗,采取对症的方法及时补液、纠正脱水及水电解质紊乱。治疗组采用推拿结合妈咪爱(枯草杆菌二联活菌颗粒)口服治疗。连续治疗1周后评定疗效。结果治疗后,治疗总有效率为94.1%,对照组为76.5%,比较后有显著性差异(0.05);比较两组大便次数复常时间及出院时间,治疗组大便次数复常时间及出院时间均优于治疗组,有显著性差异(0.05)。结论推拿联合妈咪爱口服治疗小儿腹泻疗效可靠,且安全性高,具有一定的推广运用价值。     

生长激素对于GnRHa治疗中生长过度减速的特发性中枢性性早熟女孩的远期疗效观察

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.     

生长激素对于GnRHa治疗中生长过度减速的特发性中枢性性早熟女孩的远期疗效观察

目的 观察重组人生长激素(rhGH)对于促性腺激素释放激素类似物(GnRHa)治疗中生长过度减速的特发性中枢性性早熟(ICPP)女孩的最终成年身高(FAH)的影响.方法 49例ICPP女孩接受GnRHa治疗,当身高增长速度减慢至4 cm/年以下时,其中26例联用rhGH治疗为联合治疗组,23例拒绝加用rhGH但继续使用GnRHa为单用组.比较2组治疗前后的预测成年身高(PAH)和FAH.结果 联合治疗组联用rhGH前半年,身高增长速度均小于4 cm/年[(3.2±1.0)cm/年],PAH无明显改善[联用rhGH前半年和rhGH开始时PAH分别为(152.5±4.0)cm和(152.6±3.7)cm];联用rhGH(11.4±5.4)个月后,身高增长速度增加至(6.7±2.0)cm/年,PAH增加至治疗结束时的(157.1±4.7)cm(均P<0.01);FAH[(157.5±4.5)cm]显著高于GnRHa开始时的PAH[(148.1±4.6)cm]和遗传靶身高[(154.4±4.6)cm,均P<0.01].单用组治疗结束时的PAH[(153.9±6.3)cm]较拒绝联用rhGH时的PAH[(153.1±6.2)cm]无差异;FAH[(154.7±5.5)cm]高于治疗开始时的PAH[(150.3±6.0)cm,P<0.01],但与遗传靶身高[(155.6±4.3)cm]无差异.结论 联用rhGH能够显著加快GnRHa治疗中生长过度减速的ICPP女孩的身高增长速度,进一步改善PAH和FAH.

Abstract：

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.     

C型利钠肽和长骨生长

C型利钠肽(CNP)是长骨生长重要的局部调节因子,与受体NPR-B结合后催化cGMP的合成,激活下游因子调节长骨生长.CNP信号系统的调节机制尚未完全阐明,目前已知CNP信号系统与成纤维细胞生长因子受体3(FGFR-3)信号通路存在交联对话.NPR-B基因突变的杂合子可能是引起特发性矮小的原因之一.CNP可作为线性生长的生物标记,用于生长监测及生长障碍性疾病的诊断和治疗.对CNP信号系统与长骨生长关系的深入研究,有助于为今后骨骼发育障碍疾病的药物治疗开辟新途径.