Role of bisphosphonates in osteoporosis caused by adult growth hormone deficiency

In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.

Effects of different doses of long-acting growth hormone in treating children with growth hormone deficiency

BACKGROUND With the improvement of economy and living standards,the attention paid to short stature in children has been increasingly highlighted.Numerous causes can lead to short stature in children,among which growth hormone deficiency(GHD)is a significant factor.AIM To investigate the long-term efficacy and safety of different doses of long-acting polyethylene glycol recombinant human growth hormone(PEG-rhGH)in the treatment of GHD in children.METHODS We selected 44 pediatric patients diagnosed with GHD who were treated at Wuhu First People's Hospital from 2014 to 2018.Total 23 patients were administered a high dose of long-acting PEG-rhGH at 0.2 mg/kg subcutaneously each week,forming the high-dose group.Meanwhile,21 patients were given a lower dose of long-acting PEG-rhGH at 0.14 mg/kg subcutaneously each week,establishing the low-dose Group.The total treatment period was 2 years,during which we monitored the patients’height,annual growth velocity(GV),height standard deviation score(HtSDS),chronological age(CA),bone age(BA),and serum levels of insulin-like growth factor-1(IGF-1)and insulin-like growth factor-binding protein-3(IGFBP-3)before treatment and at 6 mo,1 year,and 2 years after treatment initiation.We also monitored thyroid function,fasting plasma glucose,fasting insulin,and other side effects.Furthermore,we calculated the homeostatic model assessment for insulin resistance.RESULTS After 1 year of treatment,the GV,HtSDS,IGF-1,BA,and IGFBP-3 in both groups significantly improved compared to the pre-treatment levels(P<0.05).Moreover,when comparing GV,HtSDS,IGF-1,BA,and IGFBP-3 between the two groups,there were no statistically significant differences either before or after the treatment(P>0.05).During the treatment intervals of 0-1.0 years and 1.0-2.0 years,both patient groups experienced a slowdown in GV and a decline in HtSDS improvement(P<0.05).CONCLUSION The use of PEG-rhGH in treating GHD patients was confirmed to be effective,with similar outcomes observed in both the high-dose group and low-dose groups,and no significant differences in the main side effects.

DIAGNOSTIC VALUE OF SERUM INSULIN- LIKE GROWTH FACTOR BINDING PROTEIN- 3 IN CHILDREN WITH OR WITHOUT GROWTH HORMONE DEFICIENCY

OBJECTIVE: To study the value of serum insulin-like growth factor binding protein-3 (IGFBP-3) levels in differential diagnosis of growth hormone deficiency (GHD). METHODS: To measure serum IGFBP-3 levels by RIA in normal children and adolescents, GHD children and short-stature children without GHD. RESULTS: Serum level of IGFBP-3 in 129 children with untreated GHD and with no pubertal development was 1.6 +/- 0.9 mg/L, which was less than that in normal group of the same age, but overlapped with the normal children in Tanner stage I. After six-month treatment with recombinant human growth hormone (rhGH), serum level of IGFBP-3 in 59 GHD significantly increased from 1.3 +/- 0.7 mg/L to 2.7 +/- 0.9 mg/L, accompanied by an increase of body heights, growth velocities and serum level of IGF-1. Serum level of IGFBP-3 in 55 short-stature children without GHD was 3.3 +/- 2.2 mg/L, which was not significantly different from that in normal group. CONCLUSION: Serum IGFBP-3 level can reflect the status of GH secretion in children with GHD and is a useful marker for differential diagnosis of GHD.

Management of Adult Growth Hormone Deficiency at Peking Union Medical College Hospital:A Survey among Physicians

Objective To evaluate physicians' attitude and knowledge about the management of adult growth hormone deficiency(AGHD) at Peking Union Medical College Hospital and impact factors associated with better decision-making.Methods A 21-question anonymous survey was distributed and collected at Peking Union Medical College Hospital,a major teaching hospital in Chinese Academy of Medical Sciences.Data of physicians' educational background,clinical training,patient workload per year and continuing medical education in AGHD were collected.Factors associated with appropriate answers were further analyzed by multivariate regression models.Results One hundred and eighteen internal medicine residents,endocrine fellows,attending physicians and visiting physicians responded to the survey.Among them,44.9% thought that AGHD patients should accept recombinant human growth hormone replacement therapy.Moreover,56.8% selected insulin tolerance test and growth hormone-releasing hormone-arginine test for the diagnosis of AGHD.Logistic regression analysis of physician demographic data,educational background,and work experience found no consistent independent factors associated with better decision-making,other than continued medical education,that were associated with treatment choice.Conclusions The physicians' reported management of AGHD in this major academic healthcare center in Beijing was inconsistent with current evidence.High quality continued medical education is required to improve Chinese physician management of AGHD.

EFFECTS OF CHINA-MADE RECOMBINANT HUMAN GROWTH HORMONE ON THE TREATMENT OF GROWTH HORMONE DEFICIENCY

To evaluate the therapeutic effect of China-made recombinant human growth hormone (r-hGH) in children with growth hormone deficiency (GHD) and to investigate the utilities of various biochemical parameters in GHD diagnosis and treatment. Methods Our study comprises of 30 normal children and 71 GHD children treated with China-made r-hGH substitution therapy 0.1 IU·kg-1·d-1 for 6 months. Serum insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3), bone turnover markers (Ost, ICTP), and anti-growth hormone antibody (GHAb) were detected before and after r-hGH treatment. Results After the first 3 and 6 months of treatment, growth velocities of GHD children were significantly increased (13.1 ± 3.7 and 12.6 ± 3.6 cm/year) compared with pretreatment values (2.9 ± 0.8 cm/year, P < 0.01). GHD Children had obviously reduced serum levels of IGF-1, IGFBP-3, and bone turnover markers (Ost, ICTP) compared with normal controls (P < 0.01), and these biochemical parameters improved significantly after treatment (P < 0.01). Growth hormone antibodies were positive in 17 of 45 cases after treatment by binding capacity detection. The binding percentage of growth hormone an-tibody which was increased more than 30% after the treatment showed a negative correlation with growth velocity (P < 0.01). Conclusions (1) The growth stimulating effect and safety were confirmed in using China-made r-hGH in the treatment of GHD children for 6 months. (2) The measurements of serum IGF-1 and IGFBP-3 may serve as useful parameters in the diagnosis of GHD. (3) Serum Ost and ICTP are useful laboratory criteria for evaluating the effect of r-hGH therapy in the early stage. (4) It is necessary to monitor serum levels of GHAb during r-hGH therapy.

Growth Hormone Replacement Therapy in Patients without Adult Growth Hormone Deficiency: What Answers Do We Have So Far?

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) have been suggested as “anti-aging” therapies, or for improving quality of life with aging. In this study, we focus on the actions of GH in the main organs and organ systems of the human body, like skeletal muscle, bones and brain, particularly in regard to data and research on the use of GH replacement therapy in adults without growth hormone deficiency, especially elderly patients. Several different studies have been carried out to show what the effects and side effects of GH replacement in healthy people and what would be the impact in quality of life and life span. In this review, we demonstrate what answers we have so far about the effects of GH replacement in many organs and systems in healthy people.

Corneal properties in children with congenital isolated growth hormone deficiency

AIM:To compare the corneal parameters of children with congenital isolated growth hormone deficiency and healthy subjects.METHODS:In this cross-sectional,prospective study,50 cases with growth hormone(GH)deficiency treated with recombinant GH and 71 healthy children underwent a complete ophthalmic examination.The corneal hysteresis(CH),corneal resistance factor(CRF),Goldmann-correlated intraocular pressure(IOPg)and corneal-compensated intraocular pressure(IOPcc)were measured with the Ocular Response Analyzer(ORA).Central corneal thickness(CCT)was measured by a ultrasonic pachymeter.RESULTS:The mean age was 13.0±3.0 years in the GH deficiency group consisting of 21 females and 29 males and 13.4±2.4 years in the healthy children group consisting of 41 females and 30 males.There was no statistically significant difference between the groups for gender or age(Chi-square test,P=0.09;independent ttest,P=0.28,respectively).The mean duration of recombinant GH therapy was 3.8±2.4y in the study group.The mean CH,CRF,IOPg and IOPcc values were 11.0±2.0,10.9±1.9,15.1±3.3,and 15.1±3.2 mm Hg respectively in the study group.The same values were 10.7±1.7,10.5±1.7,15.2±3.3,and 15.3±3.4 mm Hg respectively in the control group.The mean CCT values were 555.7±40.6,545.1±32.5μm in the study and control groups respectively.There was no statistically significant difference between the two groups for CH,CRF,IOPg,IOPcc measurements or CCT values(independent t-test,P=0.315,0.286,0.145,0.747,0.13 respectively).CONCLUSION:Our study suggests that GH deficiency does not have an effect on the corneal parameters and CCT values.This observation could be because of the duration between the beginning of disease and the diagnosis and beginning of GH therapy.

Growth Hormone Replacement Therapy in Adult Growth Hormone Deficiency and Risk of Cancer: A Meta-Analysis

The growth hormone (GH) replacement therapy in adult growth hormone deficiency (AGHD) is now well developed, nevertheless, the safety of GH replacement, especially the incidence of cancer in these patients remains to be further clarified. To summarize the evidence on the safety of using GH in AGHD, we conduct this meta-analysis to assess the relationship between the risk of cancer and GH replacement therapy. Randomized controlled trials and cohort studies involved in GH therapy for AGHD were selected. Meta-analysis was performed and risk ratio (RR) was pooled with 95% confidence interval (CI) to investigate the relationship between GH replacement and the risk of cancer. The result indicated that there was no evidence to draw a conclusion that GH replacement therapy will increase the risk of cancer (P = 0.001, RR = 0.77, 95% CI [0.65, 0.90]). Meanwhile, according to the calculated analysis, the replacement therapy might even reduce the risk of cancer. Furthermore, subgroup analysis demonstrated that there was no correlation between replacement therapy of GH and the risk of cancer both in prospective and retrospective cohort design research, and in prospective group, the risk of cancer even decreased (P = 0.0002, RR = 0.71, 95%CI [0.59, 0.85]). In conclusion, our study corroborates evidence from previous studies showing that GH replacement therapy in AGHD patients would not increase the risk of cancer;instead, it might be even decrease cancer risk. The results suggested that GH replacement therapy in AGHD patients was safe.

Changes in Serum Leptin Levels during r-hGH Treatment in Growth Hormone-Deficient Children

To observe the effect of growth hormone on serum leptin levels, serum leptin concentrations were measured by enzyme immunoassay in 12 prebutal children with growth hormone deficiency 1, 3 and 6 months before and after the treatment with recombinant human growth hormone (r hGH). For comparison, 34 normal prepubertal children were also investigated. Relationship between leptin levels and body mass index (BMI) was observed at the same time. Our results showed that serum leptin level in normal prepubertal children was 1.22±0.34 ng/ml; the pretreatment serun leptin levels in GHD children was 3.08±2.41 ng/ml, which was significantly different from those 1, 3 and 6 months after GH treatment (i.e. 1.64±1.37 ng/ml,1.57±1.40 ng/ml and 1.35±0.89 ng/ml respectively) (all P <0.001). Our results suggested that r hGH has a suppressive effect on leptin expression.

Systemic Effects of Growth Hormone in Growth Hormone Deficient Adults: A Meta-Analysis of 48 Prospective Studies

Introduction: The use of growth hormone (GH) treatment in GH deficiency (GHD) continues to increase. However, individual controlled trials of the efficacy and safety of GH have involved relatively few patients and yielded variable results. We seek to analyze the overall effect of GH treatment on various parameters by performing a contemporary meta-analysis of the efficacy and safety of GH administration. Methods: Meta-analysis of 48 blinded, placebo controlled, randomized clinical studies of GH treatment in GHD adults published up to June 2011 was performed. Analyzed variables included anthropomorphic measurements (waist-hip ratio (WHR), lean body mass (LBM)/fat free mass (FFM), trunk fat (TrF), total body water (TBW), fat mass (FM), and body mass index (BMI));cardiovascular (CV) parameters (systolic/diastolic blood pressure (SBP, DBP), heart rate (HR), stroke volume (SV), LDL, HDL, total cholesterol (TChol), triglycerides (TG), apolipoprotein B (ApoB), C-reactive protein (CRP));and diabetes parameters (fasting insulin and glucose, hemoglobin A1c (HgbA1c)). Effect sizes (ES) were used to determine significance and weighted mean differences between GH and control were used to quantify size of effect. Results: 2231 adults with growth hormone deficiency were included. Significant beneficial changes resulting from GH administration were observed in the following variables: anthropomorphic—WHR, FM, LBM, FFM, TBW;cardiovascular—LDL, HDL, TChol, ApoB, CRP;significant adverse changes were seen in diabetic parameters—fasting insulin, fasting glucose, and HgbA1c. Compared to prior meta-analyses, larger ESs were observed for LDL, HDL, total cholesterol, fasting insulin and fasting glucose levels. Conclusions: GH administration in GHD adults results in improvement in anthropomorphic parameters, as well as CV parameters, but with worsening of diabetes markers. Data on long-term safety, including on CV effects and malignancy, as well as data assessing the role of GH replacement in combination with testosterone replacement continue to be sparse.

Benefit of Growth Hormone Replacement in Adults Older than 60 Years

Objective: Benefits of replacement therapy in growth hormone deficiency (GHD) are well documented in younger and middle-aged patients. The aim of our investigation was to prove the benefit of GH replacement for patients older than 60 years especially in terms of health-related quality of life (HRQoL) of age as well. Design: Data of 743 consecutively recruited patients (394 men, 349 women) with GHD aged 20 - 49 (n = 606) and 60 - 69 (n = 137) years enrolled from KIMS Germany (Pfizer International Metabolic Database) were compared. Treatment effects over the 12 months dose-finding and the subsequent phase up to three years were analysed using mixed models. Serum insulin-like growth factor I (IGF-I), fasting blood glucose, fasting serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) as well as body mass index (BMI) at baseline and at last visit were studied. HRQoL was assessed using the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). Results: For both age groups and genders the IGF-I level and standardized IGF-I increased over the dose-finding phase. In women, the overall QoL-AGHDA score at the baseline examination was 8.7 (95% CI: 7.7 - 9.7) and decreased to 6.3 (95% CI: 5.1 - 7.6) at the end of the dose-finding phase (p < 0.001). In men, the corresponding values were 8.8 (95% CI: 7.8 - 9.8) and 6.4 (95% CI: 5.1 - 7.6;p < 0.001) without differences between the age groups. The therapy benefit for elderly was supported by the non-impairment after the dose-finding phase. In total cholesterol, LDL-C and fasting blood glucose, no significant changes were detected, whereas an increase in BMI did not differ between age groups. Conclusion: We could show positive effects of GH replacement on HRQoL in patients older than 60 years of age. Therefore, GH replacement should be considered in elderly GHD adults without difference compared to younger age groups.

音乐疗法干预联合综合性健康管理对GHD患儿精氨酸联合可乐定激发试验不良反应发生率的影响

目的:探讨音乐疗法干预联合综合性健康管理对生长激素缺乏症(GHD)患儿精氨酸联合可乐定激发试验不良反应发生率的影响。方法:选取2021年1月—2022年5月于新余市妇幼保健院接受精氨酸联合可乐定激发试验的GHD患儿100例,将其从1编号,根据随机数字表法分为观察组和对照组,两组均50例,对照组接受综合性健康管理的干预方式,观察组在对照组的基础上联合音乐疗法进行干预。比较两组生理指标、护理满意度及不良反应发生情况。结果:干预后,两组收缩压、舒张压、呼吸频率、心率和血糖均低于干预前,脉搏次数少于干预前(P<0.05),观察组收缩压、舒张压、呼吸频率、心率和血糖均高于对照组,脉搏次数多于对照组(P<0.05);观察组的护理总满意度(96.00%)高于对照组(84.00%)(P<0.05);观察组不良反应发生率(2.00%)低于对照组(14.00%),差异有统计学意义(P<0.05)。结论:音乐疗法干预联合综合性健康管理相比于单独应用综合性健康管理对接受精氨酸联合可乐定激发试验的GHD患儿在试验中所产生的不良反应具有更好的减轻效果,其对于患儿的血压及血糖水平的调节作用更好。

MAGNETIC RESONANCE IMAGES OF THE HYPOTHALAMIC-PITUITARY AREA IN IDIOPATHIC GROWTH DEFICIENCY

In order to describe the magnetic resonance imaging (MRI) findings in hypothalamic-pituitary area and its clinical relevance in patients with idiopathic growth hormone deficiency (IGHD), the MR imagings of 26 patients with IGHD were analyzed. On MRI, 24 out of 26 cases (92. 3%) showed apparent pituitary upper margin depression; 8 out of 26 cases (30. 8%) showed definite pituitary stalk transection; 22 out of 26 cases (84. 6%) showed absence of the normal posterior pituitary bright spot. The bright lipidlike signal on T1W1 images at the median eminence distal to the breaking point (so-called ectopic posterior lobe) was found in 4 out of 26 cases (15. 4%). According to the MRI findings of the pituitary stalks, the 26 cases were divided into three groups; group A of 8 cases (31%) characterized by the definite transaction of stalk; group B of 13 cases (50%) defined by the possible stalk transection; and group C of 5 cases (19%) with no definite stalk transection.MRI findings were consistent with the clinical and endocrine tests. The stalk transection was statistically significantly difference in insulin test, L-dopa/p test, and height standard deviation score (P< 0.05). The MRI of hypothalamic-pituitary area may differentiate partial IGHD form stalk-transected, doubtful transection and without transection.

矮小症儿童骨密度与25羟维生素D相关性分析

目的:探讨矮小症儿童的骨密度,分析骨密度与25羟维生素D的相关性。方法:将88例矮小症儿童列为观察组,与88例身高正常儿童的骨密度比较;分析观察组骨密度与25羟维生素D的相关性。根据是否生长激素缺乏、是否青春发育、维生素D营养状态将观察组进行分类,比较各类状态的骨密度。结果:观察组儿童的骨密度Z值低于对照组(P=0.004)。矮小症儿童基线骨密度Z值与25羟维生素D无相关性(r=0.007,P=0.947)。生长激素缺乏症组的骨密度Z值低于特发性矮身材组,但差异无统计学意义(P=0.321)。青春期组儿童的骨密度Z值低于青春期前组,差异有统计学意义(P=0.001)。维生素D不足组的矮小儿童骨密度与年龄、骨龄呈负相关(r=-0.579、-0.573,P<0.001),与25羟维生素D无相关性(P=0.436)。结论:矮小症儿童骨密度Z值低于身高正常儿童,青春发育者尤明显;25羟维生素D值不能反映矮小症儿童的骨密度水平,骨量积累不足需考虑时间累积效应。

补肾运脾方联合生长激素治疗脾肾不足型生长激素缺乏症患儿的临床效果

目的 探讨补肾运脾方联合生长激素治疗脾肾不足型生长激素缺乏症患儿的临床效果。方法 选取2021年9月至2023年3月仪征市中医院收治的100例脾肾不足型生长激素缺乏症患儿,按照随机数字表法分为对照组(n=50)与观察组(n=50)。对照组采用生长激素治疗,观察组采用补肾运脾方联合生长激素治疗。比较两组临床疗效、生长发育情况和代谢指标。结果 观察组总有效率高于对照组(P <0.05)。治疗后,观察组生长发育情况优于对照组(P<0.05)。治疗后,观察组生长激素、胰岛素样生长因子-1水平均高于对照组(P<0.05)。结论 补肾运脾方联合生长激素治疗脾肾不足型生长激素缺乏症患儿的临床效果较好,可促进患儿生长发育,改善代谢指标,值得临床推广。

AGHD患者血清妊娠相关蛋白A水平变化及影响因素

目的:比较成人生长激素缺乏症(Adult growth hormone deficiency,AGHD)患者与健康成人血清妊娠相关蛋白A(Preg-nancy-associated plasma protein A,PAPP-A)水平及其与糖脂代谢、血压、游离脂肪酸、C反应蛋白等的关系。方法:采用酶联免疫吸附法检测20例AGHD患者和20例健康成人的血清妊娠相关蛋白A水平,同时检测空腹血糖、血脂谱、空腹胰岛素、游离脂肪酸、C反应蛋白等,计算体重指数,并以稳态模型评估胰岛素抵抗指数(Homeostasis model assessment index for insulin resis-tance,HOMA-IR)和胰岛素分泌指数(Homeostasis model assessment ofβ-cell function,HOMA-β)。结果:AGHD患者血清妊娠相关蛋白A高于对照组[7.57(6.59～8.96)与6.20(5.78～6.96)比较,P<0.05]。AGHD患者血清PAPP-A与年龄、体重指数、腰围、腰臀比、收缩压、餐后2 h血糖、空腹胰岛素、HOMA-IR正相关r(值依次为0.451、0.878、0.813、0.605、0.489、0.549、0.503、0.487;均P<0.05);在调整腰围、腰臀比、餐后2 h血糖、甘油三酯后,AGHD患者血清妊娠相关蛋白A与体重指数、空腹胰岛素正相关r(值依次为0.728、0.433;均P<0.05)。多元回归分析提示,体重指数、餐后2 h血糖、空腹胰岛素、HOMA-IR是AGHD患者血清PAPP-A的独立相关因素。结论:AGHD患者血清PAPP-A升高,并与体重指数、餐后2 h血糖、空腹胰岛素、HOMA-IR相关。提示在AGHD患者中,血清PAPP-A可能与动脉粥样硬化及糖代谢有联系。

特发性矮小患儿的眼部生物学参数研究

目的研究特发性矮小(ISS)患儿的眼部生物学参数,并与生长激素缺乏症(GHD)患儿及正常儿童进行比较,探究该群体眼部生物学参数的特点,为ISS患儿视力的筛查及使用生长激素治疗的安全性提供参考依据。方法选取15例5~14岁ISS患儿作为观察组,32例GHD患儿作为GHD组,并选取47名进行常规视力筛查的正常身高儿童作为正常对照,所有受试对象均接受眼科检查,包括裸眼视力、眼轴、眼压、角膜曲率、轴率比等参数。研究ISS患儿的眼部生物学参数,比较上述三组儿童视力相关参数的差异,分析影响ISS患儿视力发育的影响因素。结果ISS轴率比明显大于GHD组及正常儿童,ISS组眼压明显高于GHD组及正常儿童。ISS组的眼轴与GHD组、正常儿童比较,差异无统计学意义(P>0.05),但GHD组眼轴明显短于正常儿童的眼轴。ISS的角膜曲率明显大于正常儿童。ISS组的轴率比与生长激素激发试验的峰值、角膜曲率均呈正相关关系(β=1.052,P<0.05;β=0.004,P<0.05)。结论ISS患儿可能存在眼压高、近视风险大的问题,较高的生长激素激发试验峰值结果及较大的角膜曲率可能是其近视的高危因素。

生长激素治疗前后GHD儿童维生素D变化的研究

【目的】探讨生长激素缺乏症(growth hormone deficiency,GHD)患儿、非GH缺乏性矮身材(non-GHdeficient short stature,NGHDSS)患儿及GHD患儿应用生长激素治疗3个月后的25-羟维生素D3[25-(OH)D3]、1,25-二羟维生素D3[1,25-(OH)2D3、]的变化。【方法】20例GHD患儿在治疗前及治疗3月后分别测血清25-(OH)D3、1,25-(OH)2D3水平并观察他们的身高变化,与20例NGHDSS患儿和20例正常儿童进行对照。放射免疫分析法测定血清25-(OH)D3、1,25-(OH)2D3水平。多组均数比较采用单因素方差分析,治疗前后均数间较采用配对t检验。【结果】GHD患儿治疗前血清25-(OH)D3水平低于正常对照组(P<0.05),治疗3个月后血清25-(OH)D3、1,25-(OH)2D3水平较治疗前增加(P值均<0.05),并高于对照组(P值均<0.05)。NGHDSS患儿血清25-(OH)D3水平高于GHD组(P<0.05),与正常对照组差异无显著性(P>0.05)。NGHDSS患儿血清1,25-(OH)2D3水平与正常对照组及GHD组差异均无显著性(两者P>0.05)。【结论】GHD患者血清25-(OH)D3低于正常,治疗后血清25-(OH)D3、1,25-(OH)2D3水平上升,推测GH通过直接或间接作用增强α羟化酶活性,促进维生素D的代谢。

侏儒症动物模型研究进展

侏儒症(Dwarfism)是一种全球范围内罕见的生长发育障碍性疾病,通常由遗传或疾病导致,最突出表型是身材矮小。动物模型是研究其发病机制、预防、治疗方案及鉴定潜在治疗靶点及生物标志物的重要工具。随着基因工程技术的发展,基因编辑动物模型越来越多地被用于侏儒症的相关研究。本文将从理论依据、模型特点以及研究应用等方面对现有侏儒症动物模型进行总结与讨论,供科研和临床人员参考使用,以便更好地开展对侏儒症的发病机制和防治方法的研究。

Ghrelin水平及基因多态性与GHD患儿心脏病变的相关性研究

目的分析生长激素缺乏症(GHD)患儿的Ghrelin的水平及基因多态性与患儿心脏病变的相关性。方法收集65例GHD患儿为GHD组,50例健康体检儿童为对照组。经三维斑点追踪成像超声技术(3D-STI)检测2组的心脏结构和功能指标,包括整体纵行应变(GLS)、整体径向应变(GRS)、整体圆周应变(GCS)、整体扭转角度(GTA)和左室体质量(LVM));ELISA法检测2组血浆的acyl-Ghrelin、desacyl-Ghrelin水平,计算总Ghrelin及acyl-Ghrelin/desacyl-Ghrelin(A/D)值;PCR-RFLP法检测C408A和G346A位点单核苷酸多态性。结果与对照组比较,GHD组的GLS、GRS、GCS、LVM均明显降低(P<0.05或P<0.01),但2组的GTA比较差异无统计学意义(P>0.05);GHD组的acyl-Ghrelin、desacyl-Ghrelin、总Ghrelin水平及A/D值均高于对照组(均P<0.01);GHD组的acyl-Ghrelin、desacyl-Ghrelin水平、总Ghrelin水平与GLS、GRS、GCS均呈负相关(r=-0.548,P=0.001;r=-0.481,P=0.003;r=-0.411,P=0.014;r=-0.520,P=0.001;r=-0.444,P=0.007;r=-0.381,P=0.024;r=-0.536,P=0.001;r=-0.464,P=0.005;r=-0.397,P=0.018),而与GTA、LVM均无相关性(P>0.05);A/D值与GLS、GRS、GCS、GTA、LVM均无相关性(P>0.05);与对照组比较,GHD组GG基因型分布较对照组高(χ2=8.851,P=0.003),GT基因型分布较对照组低(χ2=11.523,P=0.001),CC、CT、TT比较差异均无统计学意义(均P>0.05);GHD组不同基因型对应的GLS、GRS、GCS、GTA、LVM检测值比较差异均无统计学意义(均P>0.05)。结论GHD患儿存在心脏的结构和功能改变,且acyl-Ghrelin、desacyl-Ghrelin、总Ghrelin的水平与心脏的功能改变相关;Ghrelin的C408A基因多态性与GHD的发病相关。