Child ; Humans ; Genetic Counseling ; Hypogonadism/genetics*

5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone, which causes abnormal urogenital sinus development. The aim of this study was to analyze the relationship between genotype-phenotype, surgical selections, and postoperative complications of 5α-reductase 2-deficient patients with hypospadias. We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children's Hospital, Capital Medical University (Beijing, China), from April 2007 to December 2021. A total of 69 patients were included in this study; the mean age at surgery was 34.1 months, and the average follow-up time was 54.1 months. Sixty children were treated with preoperative hormone stimulation (PHS) to promote penile growth. The average penis length and glans width were increased by 1.46 cm and 0.62 cm, respectively. The most frequent mutations were p.R227Q (39.1%, 54/138), p.Q6* (15.2%, 21/138), p.G203S (12.3%, 17/138), and p.R246Q (11.6%, 16/138). In 64 patients who were followed up, 43 had a one-stage operation and 21 had a staged operation, and there were significant differences in external masculinization score (EMS) ( P = 0.008) and the average number of operation required to cure ( P < 0.001) between one-stage and staged operations. PHS had a positive effect ( P < 0.001) on penile development. The p.R227Q mutation was associated with higher EMS and less severe hypospadias. One-stage surgery can be selected if conditions permit. The growth and development of children are acceptable in the long term, but penis growth remains unsatisfactory. Long-term complications of hypospadias should be considered during puberty.
Male ; Humans ; Child ; Infant ; Hypospadias/surgery* ; Retrospective Studies ; Oxidoreductases ; Postoperative Complications ; Genetic Association Studies

OBJECTIVES: The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI. METHODS: The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in. RESULTS: Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid. CONCLUSIONS ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.
Humans ; Infant ; Gene Expression Profiling ; Sudden Infant Death/genetics* ; Gene Regulatory Networks ; Protein Interaction Maps/genetics* ; Computational Biology

Humans ; Child ; Metabolic Diseases/therapy*

Objective: To evaluate the consistency of mass spectrometry (MS) and chemiluminescence immunoassay (CLIA) in detecting serum insulin-like growth factor-1 (IGF-1) and IGF-1 standard deviation score (SDS). Methods: This cross-sectional parallel control study prospectively collected the serum samples of 115 children with short stature disorders who were admitted in the Department of Endocrinology, Beijing Children's Hospital, Capital Medical University from February 2020 to December 2021. The serum IGF-1 level was detected by CLIA and MS, and converted to SDS for consistency analysis. Pearson analysis was used to analyze the correlation between the 2 methods, and Deming regression equation was established. Bland-Altman diagram and weighted Kappa coefficient were used to evaluate the consistency of the 2 methods. Results: There were 46 boys (40.0%) and 69 girls (60.0%), aged (8±3) years. Among the 115 cases, 37 were Turner syndrome, 59 were small for gestational age (SGA) at term, 1 was growth hormone deficiency (GHD) and 18 were other diseases. Pearson correlation analysis showed a preferable correlation between IGF-1 measured by the 2 detection methods (r=0.94, P<0.01), and IGF-1 SDS was also significantly correlated (r=0.92, P<0.01). Bland-Altman analysis showed that the consistency of serum IGF-1 levels detected by the 2 methods was poor, and the mean difference between CLIA and MS was 33.38 μg/L. The result detected by CLIA was significantly higher than that by MS, with SDS of 43.51 μg/L (95%CI -51.89-118.7 μg/L). After converting the results to SDS and removing 3 outliers (including 1 GHD patient), the weighted Kappa showed acceptable consistency (κ=0.68). Conclusion: In clinical application, after converting to IGF-1 SDS, IGF-1 detected by MS and CLIA can be used for cross-reference, but too high or too low levels should be cautious about.
Body Height ; Child ; Cross-Sectional Studies ; Female ; Growth Disorders/diagnosis* ; Human Growth Hormone ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I/metabolism* ; Insulins ; Male

Catheter Ablation ; Graves Disease/surgery* ; Humans ; Microwaves/therapeutic use* ; Radiofrequency Ablation ; Treatment Outcome ; Ultrasonography ; Ultrasonography, Interventional

Objective: To analyse the efficacy of recombinant human growth hormone (rhGH) treatment in children born small for gestational age (SGA) with syndormic and non-syndormic short stature. Methods: The clinical data of 59 children born SGA who were diagnosed as short stature and admitted to the Center of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital from July 2012 to June 2021 were collected and analyzed. According to the 2019 consensus on short stature, they were divided into syndromic group and non-syndromic group. Before treatment and 6, 12, 18 and 24 months after treatment, height standard deviation score (Ht-SDS), difference of height standard deviation (∆Ht-SDS) and homeostasis model assessment-insulin resistance index (HOMA-IR) were compared between groups, while Ht-SDS and HOMA-IR were compared before and after treatment. Independent t test or Kruskal-Wallis test were used for comparison between the 2 groups, and paired t test or Mann-Whitney U test were used for the intra-group comparison. Results: Among the 59 cases, 37 were males and 22 females, aged (5.5±2.3) years. There was no significant difference in Ht-SDS after 12 months of treatment between 2 groups (0.9±0.4 vs. 1.2±0.4, t=1.68, P=0.104) or in height SDS after 24 months of treatment (1.4±0.7 vs. 1.9±0.5, t=1.52, P=0.151). After 12 months of treatment, the insulin resistance index of the non-syndromic group was significantly higher than that of the syndromic group (2.29 (1.43, 2.99) vs. 0.90 (0.55, 1.40), Z=-2.95, P=0.003). There were significant differences in Ht-SDS between 6 months and before treatment, 12 months and 6 months in syndromic type (Z=7.65, 2.83 P<0.001, P=0.020), but all were significant differences in non-syndromic type between 6 months and before treatment, 12 months and 6 months, 18 months and 12 months, 24 months and 18 months (Z=11.95, 7.54, 4.26, 3.83, all P<0.001). Conclusion: The efficacy of rhGH treatment in children born SGA is comparable between syndromic and non-syndromic short stature cases, but non-syndromic children treated with rhGH need more frequent follow-up due to the risk of insulin resistance.
Child ; Female ; Humans ; Male ; Body Height ; Gestational Age ; Human Growth Hormone/therapeutic use* ; Infant, Small for Gestational Age ; Insulin ; Insulin Resistance ; Recombinant Proteins ; Child, Preschool

11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics* ; Humans ; Mineralocorticoid Excess Syndrome, Apparent/genetics* ; Pedigree

Objective:To investigate the possible mechanism of Xieheyin in alleviating obese polycystic ovary syndrome with insulin resistance（PCOS-IR）and reducing inflammatory response. Method:Ten of sixty SPF femlae C57BL/6J mice were randomly selected as the normal group，and the rest mice were given letrozole 0.002 g·kg^-1 combined with fecal suspension 2 g·kg^-1 for 28 consecutive days to establish model of PCOS-IR.The mice that were successfully modeled were randomized into the model group，metformin group（0.25 g·kg^-1），and low（10 g·kg^-1），medium（20 g·kg^-1），and high-dose（40 g·kg^-1）Xieheyin groups，and administered with the corresponding drugs by gavage，once a day，for four consecutive weeks. Except the normal control group， the mice in the other groups were continuously given fecal suspension combined with letrozole solution to maintain the model during the treatment. The mice were weighed once a week.Levels of fasting blood glucose （FBG） were detected by blood glucose test strips.And enzyme-linked immunosorbent assay （ELISA） method was used to detect serum testosterone（T），follicle stimulating hormone（FSH），luteinizing hormone（LH），fasting insulin（FINS）level，and LH/FSH and Homeostasis model assesment of insulin resistance （HOMA-IR） were calculated．The uterus and ovaries were weighed and fixed.Hematoxylin-eosin（HE）staining was used to observe ovarian tissue pathology morphology. Western blot was used to detect the expression levels of tight junction key molecular zonula occludens 1（ZO-1），occludin in colon tissues，and the expression levels of Toll-like receptor 4/nuclear factor kappa B/Nod-like receptor protein 3（TLR4/NF-κB/NLRP3）signaling pathway and inflammation associated proteins cysteinyl aspartate specific proteinase-1（Caspase-1） and interleukin-1β（IL-1β） in colon tissues. Result:Compared with normal control group，the body weight of mice in the model control group increased significantly（P<0.01）. Serum FINS，FBG，HOMA-IR，T，LH/FSH were significantly increased（P<0.05，P<0.01）. The uterine organ ratio were decreased significantly（P<0.01），while the ovarian organ ratio were significantly increased（P<0.01）. The number of atresia follicles and cystic dilatation follicles increased significantly，and the number of corpus luteum significantly decreased，the thickness of follicular granulosa cells also decreased，while the white membrane thickness of the ovary increased. Tight junction related ZO-1，occludin proteins in colon tissues were all decreased（P<0.01）.The relative expression levels of inflammation-related protein IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein signaling pathway were significantly increased（P<0.05）.Compared with model control group， the body weight of mice in the low，middle and high dose Xieheyin group decreased significantly（P<0.01）. The serum T，LH/FSH，FINS，FBG，HOMA-IR were significantly decreased（P<0.05，P<0.01）. The uterine organ ratio were increased（P<0.05），while the ovarian organ ratio were decreased（P<0.05）. The number of cystic follicles decreased and corpus luteum increased，the thickness of follicular granulosa cells increased and be arranged normally，while the white membrane thickness of the ovary increased slightly. The expressions of ZO-1，occludin proteins were increased（P<0.01）. The expression levels of IL-1β，Caspase-1 and TLR4/NF-κB/NLRP3 target protein in the high dose group were significantly decreased（P<0.01）. Conclusion:Xieheyin could activate intestinal TLR4/NF-κB/NLRP3 signaling pathway，inhibit pro-inflammatory factor secretion，improve obesity and IR，which was correlated with rebuilding intestinal mucosal barrier and inhibiting intestinal inflammation．

BACKGROUND: Compared to adult studies, studies which involve the treatment of pediatric congenital hypogonadotropic hypogonadism (CHH) are limited and no universal treatment regimen is available. The aim of this study was to evaluate the feasibility of human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) therapy for treating male adolescents with CHH. METHODS: Male adolescent CHH patients were treated with hCG/hMG (n = 20) or a gonadotropin-releasing hormone (GnRH) pump (n = 21). The treatment was divided into a study phase (0-3 months) and a follow-up phase (3-12 months). The testicular volume (TV), penile length (PL), penis diameter (PD), and sex hormone levels were compared between the two groups. The TV and other indicators between the groups were analyzed using a t-test (equal variance) or a rank sum test (unequal variance). RESULTS: Before treatment, there was no statistical difference between the two groups in terms of the biochemistry, hormones, and other demographic indicators. After 3 months of treatment, the TV of the hCG/hMG and GnRH groups increased to 5.1 ± 2.3 mL and 4.1 ± 1.8 mL, respectively; however, the difference was not statistically significant (P > 0.05, t = 1.394). The PL reached 6.9 ± 1.8 cm and 5.1 ± 1.6 cm (P < 0.05, t = 3.083), the PD reached 2.4 ± 0.5 cm and 2.0 ± 0.6 cm (P < 0.05, t = 2.224), respectively, in the two groups. At the end of 6 months of treatment, biomarkers were in normal range in the two groups. Compared with the GnRH group, the testosterone (T) level and growth of PL and PD were significantly greater in the hCG/hMG group (all P < 0.05). While the TV of both groups increased, the difference was not statistically significant (P > 0.05, t = 0.314). After 9 to 12 months of treatment, the T level was higher in the hCG/hMG group. Other parameters did not exhibit a statistical difference. CONCLUSIONS: The hCG/hMG regimen is feasible and effective for treating male adolescents with CHH. The initial 3 months of treatment may be a window to optimally observe the strongest effects of therapy. Furthermore, results from the extended time-period showed positive outcomes at the 1-year mark; however, the long-term effectiveness, strengths, and weaknesses of the hCG/hMG regimen require further research. TRIAL REGISTRATION ClinicalTrials.gov, NCT02880280; https://clinicaltrials.gov/ct2/show/NCT02880280.
Adolescent ; Adult ; Child ; Chorionic Gonadotropin/therapeutic use* ; Gonadotropin-Releasing Hormone ; Humans ; Hypogonadism/drug therapy* ; Male ; Menotropins/therapeutic use* ; Spermatogenesis ; Testosterone