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.

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B

AIM: To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS: Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n = 28)and control group (n = 20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk,and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA.RESULTS: Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs40%, P＜0.05). After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1±4.1 vs 30.2±5.3,31.9±5.1 g/L), prealbumin (79.6±28.0 vs 106.6±54.4,108.4±55.0 g/L), cholesterol (76.3±16.7 vs 85.6±32.3,96.1±38.7 mg/dL), and IGFBP1 (56.8±47.2 vs 89.7±50.3ng/mL after 2 wk) were significantly increased compared to control group (P＜0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed.CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.

Altered Nutrition State in the Severe Multiple Trauma Patients Undergoing Adjuvant Recombinant Human Growth Hormone Nutritional Support Therapy

In order to observe the nutrition state in the severe multiple trauma patients undergoing adjuvant recombinant human growth hormone (rhGH) nutritional support therapy, 45 patients with severe multiple traumas (ISS>25) were randomly divided into 3 groups. All the 3 groups had been supplied with nitrogen and caloricity according to the need of patients for 16 days. The rhGH therapy started 48 h after surgery and lasted for 14 days in two rhGH-treated groups in which rhGH was 0.2 and 0.4 U/(kg·d) respectively, and the resting group served as control one. The levels of nitrogen balance, prealbumin and safety variables (blood sugar, Na+, TT3 and TT4) were observed and com- pared among the three groups. The levels of nitrogen balance on the postoperative day (POD) 3 and 5 in the rhGH-treated groups were -1.28±3.19, 5.45±2.00 and -0.18±2.55, 6.11±1.60, respectively, which were significantly higher than those in the control group (-5.17±1.68 and -1.08±3.31, P<0.01). The values of prealbumin on the POD 3 and 5 in the rhGH-treated groups were 180.19±27.15, 194.44±50.82 and 194.94±29.65, 194.11±16.17, respectively, which were significantly higher than those in the control group (117.42±19.10 and 135.63±28.31, P<0.01). There was no sig- nificant difference between the rhGH 0.2 U/(kg·d) group and rhGH 0.4 U/(kg·d) group in both of the levels of nitrogen balance and prealbumin. It is concluded that the nutritional support therapy with adjuvant rhGH which starts 48 h after surgery improves the nutrition state of the patients with severe multiple trauma. It is safe for severe multiple trauma patients who accept rhGH at the dose of 0.2 and 0.4 U/(kg·d).

Effects of recombinant human growth hormone on intestinal translocation of bacteria and endotoxin in rats with obstructive jaundice

Extrahepatic biliary obstruction promotes intestinal translocation of bacteria and endotoxin and this process is an important cause of morbidity and mortality in patients with jaundice. This study was undertaken to investigate the effect and mechanism of recombinant human growth hormone (rhGH) and to alleviate intestinal translocation of bacteria and endotoxin in murine obstructive jaundice. METHODS:A group of 42 Wistar rats were divided into 3 groups:sham operation (SO), bile duct ligation (BDL), and BDL and rhGH treatment (rhGH). By the end of the experiment,on day 7, the animals were killed, and their liver function and serum endotoxin were measured, bacterial cultures of the liver, kidney and mesenchymal lymph were made. Terminal ileum mucosa was observed under an electron microscope. RESULTS:Liver function was improved more significantly in the rhGH group than in the BDL group. The value of endotoxin in the rhGH group was 0.38±0.03 EU/ml, significantly lower than that in the BDL group (0.65±0.04 EU/ml, P【0.01), and similar to that in the SO group (0.30±0.02 EU/ml, P】0.05). The rate of bacteria translocation in the liver, kidney and mesenteric lymph was much higher in the BDL group than in other two groups. The rate of bacteria translocation in mesenteric lymph was 64.29%,significantly higher than that in the SO group and the rhGH group (P【0.05). There was no significant difference in bacteria translocation rate between the SO group and the rhGH group (P】0.05). Under an electron microscope , ileum mucosa epithelial cells in the BDL group were necrotic, and organelle were markedly metamorphic. In the rhGH group, ultrastructural changes were less evident or similar to those in the SO group. CONCLUSION:rhGH has significant protective effects on intestinal mucosa barrier in obstructive jaundice, and reduces intestinal translocation of bacteria and endotoxin.

Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice

AIM： To study effects of recombinant human growth hormone （rhGH） on growth of a human gastric carcinoma cell in vivo. METHODS： Experimental mice were divided into control group, rhGH group, oxaliplatin （L-OHP） group and rhGH＋L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model was established successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen （PCNA）, Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method. RESULTS： Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%, 58.2%, 65.2% and 59.2% in rhGH＋L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH＋L-OHP group （or L-OHP group ） and control group or rhGH group （P 〈 0.05）, whereas there were no significant differences （P 〉 0.05） between L-OHP group and rhGH＋L-OHP group and between rhGH group and control group. CONCLUSION： rhGH does not accelerate the proliferation of human gastric cancer cell in vivo.

Effects of recombinant human growth hormone on enterocutaneous fistula patients

AIM： To explore the effects of recombinant human growth hormone （rhGH） on intestinal mucosal epithelial cell proliferation and nutritional status in patients with enterocutaneous fistula. METHODS： Eight patients with enterocutaneous fistulas received recombinant human growth hormone （10 ug/d） for 7 d. Image analysis and immunohistochemical techniques were used to analyse the expression of proliferating cell nuclear antigen （PCNA） in intestinal mucosal epithelial cells in biopsy samples from the patients who had undergone an endoscopic biopsy through the fistula at day 0, 4 and 7. Body weights, nitrogen excretion, serum levels of total proteins, albumin, prealbumin, transferrin and fibronectin were measured at day 0, 4 and 7. RESULTS： Significant improvements occurred in the expression of PCNA in the intestinal mucosal epithelial cells at day 4 and 7 compared to day 0 （24.93 ± 3.41%, 30.46 ± 5.24% vs 12.92 ± 4.20%, p 〈 0.01）. These changes were accompanied by the significant improvement of villus height （500.54 ± 53.79 um, 459.03 ± 88.98um vs 210.94 ± 49.16 um, P 〈 0.01）, serum levels of total proteins （70.52 ± 5.13 g/L, 74.89 ± 5.16 g/L vs 63.51 ± 2.47 g/L, P 〈 0.01）, albumin （39.44 ± 1.18 g/L, 42.39 ± 1.68 g/L vs 35.74 ± 1.75 g/L, P 〈 0.01） and fibronectin （236.3 4- 16.5 mg/L, 275.8± 16.9 mg/L vs 172.5 ± 21.4 mg/L, P 〈 0.01） at day 4 and 7, and prealbumin （286.38 ± 65.61 mg/L vs 180.88 ± 48.28 mg/L, P 〈 0.05）, transferrin （2.61 ± 0.12 g/L vs 2.41 ±0.14 g/L, P 〈 0.05） at day 7. Nitrogen excretion was significantly decreased at day 7 （3.40 ± 1.65 g/d vs 7.25 ± 3.92 g/d, P 〈 0.05）. No change was observed in the body weight. CONCLUSION： Recombinant human growth hormone could promote intestinal mucosal epithelial cell proliferation and protein synthesis in patients with enterocutaneous fistula.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.

Effects of Exogenous Growth Hormone on Growth Hormone-Insulin-Like Growth Factor Axis of Human Gastric Cancer Cell

Aim: To study effects of recombinant human growth hormone (rhGH) on growth hormone-insulin-like growth factor axis (GH-IGFs) of human gastric cancer cell in vivo in order to reveal part mechanism of growth effects of rhGH on gastric cancer. Methods: Nude mice were randomly divided into control group, cisplatin (DDP) group, rhGH group and DDP + rhGH group after human gastric cancer xenograft model of node mice was successfully founded and drugs were used for 6 days. We investigated volume of tumor, inhibitory rate of tumor and cell cycle by slide gauge and flow cytometry. In addition, We also respectively investigated insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) of blood serum of nude mice, IGF-ImRNA, insulin-like growth factor-I receptor (IGF-IR) mRNA and IGFBP-3 mRNA of xenograft of nude mice by enzyme linked immunosorbent assay (ELISA) and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) on the first day of completing use of drugs later. Results: Tumor grew obviously slowly and tumor inhibitory rate obviously rose in DDP group and DDP + rhGH group compared with control group and rhGH group (p p p < 0.05). Expressions of IGF-I mRNA and IGF-IR mRNA were not obviously different in all groups. But expression of IGFBP-3 mRNA obviously increased in rhGH group, DDP group and DDP + rhGH group compared with control group;meanwhile, expression of IGFBP-3 mRNA also obviously increased in DDP + rhGH group compared with control group, DDP group and rhGH group. Conclusion: Our results indicated rhGH in short-time use did not improve proliferation of human gastric cancer cells and its mechanism was possible that rhGH in short-time use raised simultaneously IGF-I and IGFBP-3 of blood serum and increased IGFBP-3 mRNA, but degraded ratio of IGF-I and IGFBP-3 of blood serum in human gastric cancer cells.

Protective effect of perioperative recombinant human growth hormone application on intestinal mucosal barrier function in patients with intestinal obstruction and the assessment of immune inflammatory response

Objective:To study the protective effect of perioperative recombinant human growth hormone (r-hGH) application on intestinal mucosal barrier function in patients with intestinal obstruction and the influence on the immune inflammatory response.Methods:60 patients with intestinal obstruction who underwent surgical treatment in our hospital between February 2013 and July 2016 were selected as the research subjects and divided into the control group (n=34) who received conventional surgical treatment and the observation group (n=26) who received surgery combined with perioperative r-hGH treatment. The serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of intestinal mucosal barrier indexes, immunoglobulin and inflammatory response indicators were not statistically significant between the two groups of patients. After treatment, serum intestinal mucosal barrier indexes Endotoxin, D-Lactate and DAO levels in observation group were lower than those in control group, immunoglobulin IgA, IgM and IgG levels were higher than those in control group, and inflammatory response indicators IL-1, IL-6, PCT and TNF-α levels were lower than those in control group patients. Conclusion:Perioperative r-hGH application in patients with intestinal obstruction can protect the intestinal mucosal barrier, also optimize the humoral immunity and suppress the systemic inflammatory response.

Improved Cardiac Contractility of Human Recombinant Growth Hormone on the Congestive Heart Failure of Pig

The enhanced cardiac contractility effect of human recombinant growth hormone (hr-GH) on the congestive heart failure (CHF) was studied on the pig. To build a pig model of congestive heart failure, a temporary artificial cardiac pacemaker was implanted in the pig’s body and paced at 220 beats to 240 beats per minute for 1 week. After the model of congestive heart failure was successfully set up, the frequency of the pacemaker was changed to 150 beats to 180 beats per minute to maintain the CHF model stable. Pigs were divided into three groups: The hr-GH group in which 0.5 mg/kg per day of hr-GH was administrated intramuscularly for 15 days, the injection control group in which an equal amount of physiological saline was injected intramuscularly, and a normal control group. The left ventricular diastolic end pressure was (10.60±2.41) mmHg in the hr-GH group, but (19.00±3.81) mmHg in the saline control group (P<0.01); Cardiac output was (1.86±0.13) L/min in the hr-GH group, but (1.56±0.18) L/min in the saline control group (P<0.05); Peripheral vascular resistance was (56.88±7.51) mmHg·(L/min) -1 in the hr-GH group, whereas (70.30±11.59) mmHg·(L/min) -1 in the saline control group (P<0.05); +dp/dt max was (2900±316.23) and (2280±286.36) in the hr-HG group and the saline control group respectively (P<0.05). The results show that hr-GH enhances myocardial contractility of CHF, and the CHF model built by a temporary artificial cardiac pacemaker at a high rate of stimulation is reasonable and applicable.

Growth-Promoting Effect of Recombinant Human Growth Hormone and Stanozolol in Girls with Turner Syndrome

Summary: Ten girls with Turner syndrome were treated with a combination therapy of recombinant human growth hormone (R hGH) and low dose stanozolol for a period of 8 to 36 months. The results showed that when compared with the growth rate before the treatment, the growth rates after treatment with R hGH and stanozolol showed a sustained increase, reaching 9.0±1.9 cm/year during the first year of treatment; the height age increase by 2.5±0.8 years while the bone age increase were 1.0±0.7 years; and the predicted final adult height at the end of the first year of the treatment increased to 149.4±6.1 cm compared to their original mean of 142.8±4.2 cm. We are led to conclude that therapy with R hGH in combination with stanozolol can increase the growth velocity and significantly increase the predicted adult height of children with Turner syndrome.

MEASUREMENTS OF URINARY HUMAN GROWTH HORMONE IN SUBJECTS WITH NORMAL AND ABNORMAL GROWTH:A CRITICAL OF ITS POTENTIAL CLINICAL UTILITY

Ovrmight urinary human growth hormone (HGH) levels in 53 normal growthprepuberty children,38 primary short stature chjildren ahildren them 11 cases with GH defi-ciency (GHD), 27 cases with normal GH reset to the conveatnd pharmacutical provocative tests diagnosed as idiopathic growth failure or non-GHD short children and 3adults with acromegaly were measured by the LAB-ELISA technique,The levelsdemonstrated stable in normal growth prepubertal children,but significantly rasised inacromegaly,and decreased in GHD,and in non=GHD short children,Thus,the resultsshow that measurement of urinary HGH being useful for Jiagnosis of GHD and forscreening the non-GHD growth failure.

Application of human growth hormone to patients with polycystic ovary syndrome during in vitro fertilization

Objective:To observe the effect of applying human growth hormone during in vitro fertilization to patients with polycystic ovary syndrome(PCOS) Methods:One hundred and twenty-one cycles of in vitro fertilization and embryo transfer in PCOS patients with anovulation from Dec.2008 to Nov.2010 were studied retrospectively.Of these 121 cycles,48 were with treatment of growth hormone(GH group),73 without GH treatment(control group).The dose of gonadotropin(Gn),the number of retrieved oocytes,good-quality embryo rate,implantation rate,frozen embryo rate,and pregnancy rate were compared. Results:The dosage of Gn was slightly higher in GH group than that in control group(29.18±8.33 vs.23.43±8.68 ampoullas,4U/ampoulla) and the number of retrieved oocytes in GH group were slightly less than that in control group(10.73±6.0 vs.14.0±8.57),but there were no significant differences(P>0.05).The good-quality embryo rate(59.1%vs.33.3%),frozen embryo rate(87.5%vs.58.9%),pregnancy rate(56.5%vs. 35.3%) and implantation rate(35.3%vs.20.4%) in GH group were all significantly higher than those in control group(P<0.05). Conclusion:Early usage of GH in the ovarian hyperstimulation in PCOS patients could significantly improve good-quality embryo rate,implantation rate and pregnancy rate.

Growth hormone abolishes the negative effects of everolimus on intestinal wound healing

AIM: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3 mg/kg po; III: everolimus 3 mg/kg po + hGH 2.5 mg/kg sc). Animals were pre-treated with hGH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical (Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological (cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with hGH resulted in considerably higher values (I: 134 &#x000b1; 19 mmHg, II: 85 &#x000b1; 25 mmHg, III: 114 &#x000b1; 25 mmHg; P &#x0003c; 0.05,&#x02005;I&#x02005;vs II; P = 0.09,&#x02005;I&#x02005;vs III and II vs III) Hydroxyproline concentration was significantly increased by hGH compared to everolimus alone (I: 14.9 &#x000b1; 2.5 &#x003bc;g/mg, II: 8.9 &#x000b1; 3.6 &#x003bc;g/mg, III: 11.9 &#x000b1; 2.8 &#x003bc;g/mg; P &#x0003c; 0.05,&#x02005;I&#x02005;vs II/III and II vs III). The number of MPO-positive cells was reduced significantly by hGH compared to everolimus alone (I: 10 &#x000b1; 1 n/mm&#x000b2;, II: 15 &#x000b1; 3 n/mm&#x000b2;, III: 9 &#x000b1; 2 n/mm&#x000b2;; P &#x0003c; 0.05,&#x02005;I&#x02005;vs II and II vs III), while the number of PCNA-positive cells were increased by hGH (I: 28 &#x000b1; 3 /mm&#x000b2;, II: 12 &#x000b1; 3 /mm&#x000b2;, III: 26 &#x000b1; 12 /mm&#x000b2;; P &#x0003c; 0.05,&#x02005;I&#x02005;vs II and II vs III). Corresponding to these biochemical findings, HE-histology revealed significantly increased amount of granulation tissue in hGH-treated animals.CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with hGH. Both inflammation as well as collagen deposition is influenced by hGH.

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.

Optimizing growth in pediatric renal transplant recipients: An update

Growth retardation is a significant complication observed in pediatric renal transplant recipients,originating from a multifactorial etiology.Factors contributing to growth impairment encompass pre-transplant conditions such as primary kidney disease,malnutrition,quality of care,growth deficits at the time of transplantation,dialysis adequacy,and the use of recombinant human growth hormone.Additionally,elements related to the renal transplant itself,such as living donors,corticosteroid usage,and graft functioning,further compound the challenge.Although renal transplantation is the preferred renal replacement therapy,its impact on achieving final height and normal growth in children remains uncertain.The consequences of growth delay extend beyond the physi-ological realm,negatively influencing the quality of life and social conditions of pediatric renal transplant recipients,and ultimately affecting their educational and employment outcomes.Despite advancements in graft survival rates,growth retardation remains a formidable clinical concern among children undergoing renal transplantation.Major risk factors for delayed final adult height include young age at transplantation,pre-existing short stature,and the use of specific immunosuppressive drugs,particularly steroids.Effective management of growth retardation necessitates early intervention,commencing even before transplantation.Strategies involving the administration of recombinant growth hormone both pre-and post-transplant,along with protocols aimed at minimizing steroid usage,are important for achieving catch-up growth.This review provides a comprehensive outline of the multifaceted nature of growth retardation in pediatric renal transplant recipients,emphasizing the importance of early and targeted interventions to mitigate its impact on the long-term well-being of these children from birth to adolescence.INTRODUCTION Children with chronic kidney disease(CKD)endure frequent hospitalizations and ongoing treatment,which significantly affect their quality of life.One of the most noticeable effects of CKD in children is poor growth,with stunted height being a common sign of chronic malnutrition.Growth assessment involves regularly measuring weight and height/length and comparing these against z-score charts,along with other anthropometric indicators like head circumference and mid-upper arm circumference.Data from the North American Pediatric Renal Trials and Collaborative Studies(NAPRTCS)registry shows that over 35%of children enrolled had stunted growth at the time of admission,with growth impairment being more severe in younger children(58%in those aged under 1 year,compared to 22%in those aged over 12 years).Additionally,the same data revealed that growth impairment worsens as the severity of the disease increases.Although recent advances in science have enabled better outcomes for children with CKD,in resource-limited settings,numerous children are still deprived of achieving optimal growth owing to the disease and its related factors.Stunting is a key indicator of chronic growth impairment in children.A study by Wong et al[1]in the United States Renal Data System found that each SD decrease in height among children with stage V CKD is linked to a 14%increase in the risk of death[1].Similarly,research by Furth et al[2]using data from the NAPRTCS indicated that children with a height standard deviation score(SDS)of-2.5 face a relative hazard of death of 2.07.Stunting also correlates with increased hospitalizations.A study in the United States followed 1112 pediatric patients with end-stage renal disease from 1990 to 1995.It showed that children with severe or moderate growth failure had higher hospitalization rates compared to those with normal growth.Specifically,the relative risk for hospitalization was 1.14(95%CI:1.1-1.2)for those with moderate growth failure and 1.24(95%CI:1.2-1.3)for those with severe growth failure,even after adjusting for age,sex,race,cause,and duration of end-stage renal disease,and treatment type[2](dialysis or transplant).The growth of a child significantly affects his/her psychological and overall well-being as an adult.Short children are often embarrassed by peers,and it has been observed that height influences employment status,with unemployment being more prevalent among stunted individuals.Further,marital opportunities can be fewer among stunted individuals[3].Hence,all measures to achieve adequate growth should be attempted in children with CKD,regardless of whether they undergo transplantation.

Effects of Recombinant Human Growth Hormone on Corneal Healing, Epithelial Nerve Regeneration and Tear Inflammatory Factors in Rabbits

Objective:The goal of this study is to investigate the effects of recombinant human growth hormone(rh GH)on corneal healing,epithelial nerve regeneration and tear inflammatory factor levels in rabbits.Methods:After corneal epithelial injury models were established,fifty adult clean New Zealand white rabbits were randomly divided into two groups,normal saline was administered to the control group,while recombinant human growth hormone was administered to the observation group.The healing rate of corneal epithelial injury,the regeneration ability of corneal epithelial nerve and the level of inflammatory factors in tears were observed and compared between the two groups of rabbits before and 24,48,72 and 96 h after modeling.Results:There were significant differences in corneal epithelial healing rate,time and interaction between the two groups(P<0.05).The experimental group exhibited a superior healing rate of corneal epithelium at 24,48,72,and 96 h compared to the control group(P<0.05).There were significant differences in central cornea sensitivity between the two groups,along with variations in time and interaction(P<0.05).There was no significant difference in the central corneal sensitivity between the two groups before modeling and at 24,72 and 96 h after modeling(P>0.05),whereas the experimental group exhibited a higher central corneal sensitivity compared to the control group at 48 h after modeling(P<0.05).There were significant differences in IL-1α,TNF-α,IL-17a and IL-21 between the two groups(P<0.05).There were significant differences in IL-17a and IL-21 between the two groups(P<0.05).The experimental group exhibited a significant decrease in IL-1αlevels compared to the control group between 24 and 72 h after modeling(P<0.05),the experimental group exhibited a substantial increase in IL-17a levels compared to the control group at 72 h after modeling(P<0.05),and the level of TNF-αin the experimental group was significantly lower than that of the control group between 24 and 96 h after modeling.Conclusion:Recombinant human growth hormone aids in expediting the healing process of the healing of rabbit corneal epithelial injury,facilitating the restoration of epithelial nerve,and mitigating the inflammatory response.

重组人生长激素临床应用的安全性思考

重组人生长激素(recombinant human growth hormone,rhGH)是改善身材矮小的有效治疗药物,目前rhGH可应用于包含生长激素缺乏症在内的多种原因导致的身材矮小,临床应用的扩展使其安全性问题备受关注。基于现有证据,当rhGH规范应用于生理性替代治疗时,其安全性较好。临床中,应用rhGH进行治疗期间可结合文献证据和临床经验重点关注短期安全性,长期安全性由于rhGH治疗时间不足尚无准确定论。该文梳理了在rhGH治疗过程中有可能出现的不良事件及其风险控制措施,旨在帮助临床医生了解rhGH治疗的整体安全性,改善临床规范化应用。

枇杷叶三萜酸联合重组人表皮生长因子对激素依赖性皮炎豚鼠皮肤屏障功能的修复及免疫失衡的影响

目的 观察枇杷叶三萜酸(TAL)联合重组人表皮生长因子(rh-EGF)对激素依赖性皮炎(HDD)豚鼠模型皮肤屏障功能修复及免疫失衡的影响。方法 选取40只无特定病原(SPF)级豚鼠,随机分为对照组、模型组、rh-EGF组、TAL组和联合组,每组各8只。除对照组外,其他各组涂抹0.05%卤米松乳膏,连续45 d,构建HDD模型。构建成功后,rh-EGF组涂抹rh-EGF凝胶,TAL组涂抹TAL溶液,联合组涂抹TAL和rh-EGF凝胶,对照组和模型组涂抹生理盐水,共15 d。记录各组临床症状并打分;检测经皮水分丢失(TEWL)、角质层含水量(WCSC)和皮脂量(SC);HE染色观察各组豚鼠皮肤组织病理变化;采用酶联免疫吸附测定(ELISA)法检测总免疫球蛋白E(IgE)、白细胞介素-4(IL-4)、干扰素-γ(IFN-γ)水平。结果 与对照组比较,模型组症状明显、皮肤组织损坏严重,TEWL增加,WCSC和SC减少;免疫因子Ig E和IL-4水平升高、IFN-γ水平降低(P<0.05)。与模型组比较,rh-EGF组、TAL组和联合组用药后临床症状减轻、皮肤组织损伤不明显;TEWL减少,WCSC和SC增加,免疫因子IgE和IL-4水平降低、IFN-γ水平升高(P<0.05)。且联合组与rh-EGF组和TAL组比较,作用效果更加明显(P<0.05)。TAL组和联合组各指标比较,差异无统计学意义(P>0.05)。结论 TAL联合rh-EGF可有效缓解HDD豚鼠的临床症状,改善皮肤细胞损伤,修复皮肤屏障功能,提升免疫能力。

青春期矮身材儿童身高改善的药物治疗

青春期矮身材可严重影响青少年的身心健康。青春期由于性激素导致的骨龄持续加速进展,限制了生长所需的时间,是矮身材治疗的巨大挑战,至今仍无标准化的治疗方案。青春期也是改善成年终身高的最后机会。目前临床常用治疗药物主要有重组人生长激素、促性腺激素释放激素类似物和第三代芳香化酶抑制剂。近年来,以改善成年终身高为目的的个体化治疗成为临床关注的重点。该文对青春期矮身材儿童身高改善的药物治疗相关研究进行梳理总结,为临床医生提供参考.