Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Clinical data of a child with acromesomelic dysplasia Maroteaux type (AMDM) treated in the Department of Pediatrics, Tianjin Medical University General Hospital at November 2018 was retrospectively analyzed.The female child aged 3 years and 3 months old with 83 cm height (-3.84 SD) had clinical manifestations of disproportionate short stature, disproportionate shortening of forearms and forelegs, and stubby fingers and toes.Gene sequencing identified compound heterozygous mutations, c.1640T>A(p.Val547Asp)/c.682G>A(p.Gly228Ser), in the NPR2 gene, which have not been reported in the Human Gene Mutation Database.Their protein function was predicted harmful.The child was diagnosed as AMDM.During the follow-up until 4 years and 8 months old, the child was 90 cm tall (-4.35 SD), with a growth velocity of 4.9 cm/year.She was treated with recombinant human growth hormone (rhGH) treatment for 9 months and regularly followed up.The child was now 98.2 cm height (-3.07 SD) and she had a growth velocity of 10.9 cm/year.This case report enriched the gene mutation spectrum of AMDM.Treatment with rhGH can effectively improve the height of the child, but the long-term effect needs further follow-up and observation.

Objective:To study the correlation between umbilical artery blood gas (UABG) and Apgar score of neonates and the risk factors of low base excess (BE) in UABG.Methods:From March 2017 to September 2020, newborns without congenital malformation born in three hospitals were prospectively enrolled and received UABG analysis. According to their Apgar score, the infants were assigned into low Apgar score group and normal Apgar score group. According to BE of UABG, they were assigned into BE<-12 mmol/L group and BE≥-12 mmol/L group. The UABG indexes including abnormal pH and BE between the low Apgar score group and the normal Apgar score group were compared. The risk factors of low BE in UABG were analyzed.Results:A total of 1 351 qualified samples were included including 208 cases in low Apgar score group and 1 143 cases in normal Apgar score group. 115 cases were in BE <-12 mmol/L group and 1 236 cases in BE ≥-12 mmol/L group. The incidences of abnormal pH and BE values in the low Apgar score group were higher than the normal Apgar score group [50.0% (104/208) vs. 13.8% (158/1 143), 34.6% (72/208) vs. 3.8% (43/1 143)]. The pH and BE values of UABG were positively correlated with 1 min Apgar score ( r=0.402, 0.398, P<0.001). Multivariate logistic regression analysis indicated that the risk factors for BE<-12 mmol/L were Ⅲ° contaminated amniotic fluid ( OR= 3.155, 95% CI 1.972~5.025, P<0.001) and placental abruption ( OR = 3.968, 95% CI 1.992~7.874, P <0.001). Conclusions:The pH and BE values of neonatal UABG are positively correlated with 1 min Apgar score. Ⅲ° contaminated amniotic fluid and placental abruption are risk factors of low BE in UABG.

Objective:To analyze the trends of overweight and obesity prevalence in Chinese children, aged from 6 to 15 years old among 4 provinces and cities from 2009 to 2019.Methods:Reviewed the national multi-center epidemiological survey data of children from the National Key Technology R&D Program of China during the Eleventh Five-Year Plan (2009 to 2010) and the National Key Research and Development Program of China during the Thirteenth Five-Year Plan (2017 to 2019). The participants′ data were selected from four provinces,municipalities and autonomous region,including Beijing, Tianjin (Northern region), Zhejiang (Eastern region), and Guangxi (Southern region). Totally 14 597 pairs of 6-15 year-old children were surveyed. According to the body mass index (BMI) and standard deviation score (SDS) of children among different genders, ages, and regions, t test or chi-square test was used to evaluate the changes in overweight and obesity over a 10-year span. Results:Totally 7 721 pairs of boys and 6 876 pairs of girls were collectted in this study, whose mean age was (10.7±2.5) years. In the past 10 years, the overall BMISDS were 0.39±1.24 and 0.36±1.31 and the overall obesity rate were 11.8% ( n=1 773) anel 12.5% ( n=1 813) of children in the 4 administrative regions did not have statistically significant differences (all P>0.05). However, the overall overweight rate rose from 17.1% ( n=2 496) to 19.1% ( n=2 781) (χ2=18.657, P<0.01), and the average annual growth rate was 0.20%. The BMISDS in the Eastern region increased from 0.10±1.07 to 0.19±1.22 ( t=-4.095, P<0.01), and the overweight rate and obesity rate increased by 3.8% ( n=202) and 3.1% ( n=169) respectively (both P<0.01); the BMISDS in the Northern region and the obesity rate did not have statistically significant differences(all P>0.05), but the overweight rate rose from 20.5% ( n=1 233) to 22.8% ( n=1 365) significantly (χ2=7.431, P<0.01); BMISDS in the Southern region was significantly decreased from 0.30±1.19 to 0.09±1.25 ( t=1.426, P<0.01), and the rate of obesity decreased from 9.8% ( n=315) to7.9% ( n=256) (χ2=6.46, P<0.05), the overweight rate was not stafistically significant ( P=0.10), respectively. The obesity rate of boys had risen from 16.4% ( n=1 265) to 18.2% (1 407) (χ2=8.997, P<0.01) in the past 10 years, and the overweight rate had risen from 18.0% ( n=1 393) to 20.5% ( n=1 579) (χ2=14.26, P<0.01). The overweight+obesity rate rose from 34.4% ( n=2 658) to 38.7% ( n=2 986) (χ2=29.859, P<0.01), and the weight problem in the age group of 8 to 11 years was particularly severe (all P<0.01). The obesity rate of girls dropped from 6.8% ( n=468) to 5.9% ( n=406) (χ2=4.546, P<0.05), the overweight rate rose from 16.0% ( n=1 103) to 17.5% ( n=1 202) (χ2=5.006, P<0.05), and the overall overweight+obesity rate rose from 22.8% ( n=1 571) to 23.4% ( n=1 608) (χ2=0.53, P>0.05). Conclusions:The growth rate of obesity among children in China had slowed down from 2009 to 2019, but the overweight rate was still on the rise. The overall base of overweight and obesity population continued to expand. The weight problem of peri-adolescent boys was particularly prominent. The current status of obesity epidemics in different regions, ages, and genders are significantly different and had their own characteristics. It is necessary to establish a personalized prevention and control strategy.

Objective: This study aims to investigate the menarcheal age of female junior middle school students in Tianjin and associated factors, providing suggestions for further development of adolescence education on physiological and mental health. Methods: A total of 4 127 junior middle school girls in Tianjin area were selected by stratified random sampling method, and investigated by the method of physical examination and questionnaire survey, results were analyzed. Results: There were 1 383 girls reported menarche. Mean age at menarche was(12.68±1.19) years old; One-way ANOVA showed that girls with higher family income, higher parental education had earlier menarcheal age(F=4.97, 9.52, 10.64, P<0.05). It showed that the tendency that obesity group and over-weight group was higher in the rate of menarche than that of normal group and marasmus group(F=4.20, P<0.05). However, different time on watching TV, computer or celephone and sleeping was found to be unrelated with age at menarche(P>0.05). Kruskal Wallis H test showed that girls whose mothers’ AAM was earlier had earlier menarcheal age(H=82.94, P<0.05). According to age, girls were divided into groups of 10-11, 11-12, 12-13 and 13-14 years old. Girls in each age group were divided into the menstruation menarche group and the non-menstruation menarche group. The results showed that the levels of height, weight, BMI, waist circumference, hip circumference, and the skin fold thickness in menstruation group were higher than those in non-menstruation group(t=2.18-10.93, P<0.05). After that, girls of each group were divided into four group：marasmus group, the normal group, the over-weight group and the obesity group according to BMI(χ2=34.66，13.37，11.09，12.60,P<0.05). Conclusion Female junior middle school students’ menarcheal age in Tianjin is related to family income, parents’education, mother’s age at menarche, obesity and physical exercise frequency.

Objective: To investigate the role of neutrophil elastase inhibitor, sivelestat, in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling mechanisms. Methods: A total of forty 4-week-old male C57BL/6J ApoE-/-mice were equally divided into the following four groups: standard chow (SC)+isotonic saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline; and HFHC+sivelestat. These mice were treated with above methods for 12 weeks. Blood and liver tissue samples were collected to measure biochemical parameters, hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score (inflammation) were evaluated by oil red O staining and HE staining, respectively. The mRNA and protein expression levels of hepatic inflammatory cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and immunohistochemistry, respectively. Comparison of means between the four groups was made by one-way analysis of variance, and comparison between any two groups was made by the LSD or SNK method (for data with homogeneity of variance) or the Tamhane or Dunnett method (for data with heterogeneity of variance). Results: Mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH compared with those fed with SC. Compared with mice fed with HFHC diet without sivelestat, those treated with HFHC and sivelestat exhibited the following features: (1) significantly reduced fast blood glucose, blood cholesterol, and hepatic biochemical parameters, as well as increased insulin sensitivity; (2) significantly reduced NAFLD activity score (5.71±1.11 vs 3.16±1.16, P < 0.05); (3) reduced monocyte chemoattractant protein-1 and tumor necrosis factor -α; (4) significantly reduced mRNA levels of CD68 and F4/80; and (5) reduced expression of CD68 in the liver. Conclusion Sivelestat alleviates the hepatic steatosis and inflammation of NASH in mice by inhibiting the activation of Kupffer cells.

Objective To explore the diagnosis and treatment of a rare case of methylmalonic aciduria combined with congenital adrenal hyperplasia. Methods The clinical and laboratory data of the first case of methylmalonyl CoA mutase deifcient methylmalonic aciduria combined with 21-hydroxylase deifciency in China were analyzed. Results The male patient with age of onset at 3 months presented with feeding dififculty, diarrhea, metabolic acidosis, and psychomotor retardation after polio vaccination or high protein diet. At one year and 8 months of age, methylmalonic aciduria was diagnosed, and the patient was clinically improved after treatment. At 5 years of age, precocious puberty was noticed, and virilizing form of 21-Hydroxylase deifciency was diagnosed. Genetic testing conifrmed 2 known mutations in MUT gene (c.866G?>?C, c.2179C?>?T) and 2 known mutations in CYP21A2 gene (c.188A?>?T, c.518T?>?A). Conclusions The clinical manifestations of inherited metabolic disorders and endocrine diseases are complex and it is rare that multiple disorders occurred simultaneously in one patient. This male patient has two rare diseases, methylmalonic aciduria and 21-hydroxylase deifciency.

Objective To investigate the characteristics of plasma glucose, insulin secretion and changes of insulin resistance (IR) after a glucose load in obese children, and to predict islet β-cell function. Methods A total of 635 obese children were classified into normal glucose tolerance (NGT) group (n=483), impaired glucose regulation (IGR) group (n=112) and type 2 diabetes mellitus (DM) group (n=40) based on their glucose levels. Subjects were also divided into G1 group (23 kg/m2≤BMI<30 kg/m2, n=393) and G2 group (BMI≥30 kg/m2, n=242) based on their different BMI levels. Level of fast plasma glucose (FPG, 0.5 h-PG, 1 h-PG, 2 h-PG and 3 h-PG) and insulin (FINS, 0.5 h-INS, 1 h-INS, 2 h-INS and 3 h-INS) were measured 0 h, 0.5 h, 1 h, 2 h and 3 h after a glucose load. Insulin resistance index (HOMA-IR), whole body insulin sensitivity index (WBISI), function of pancreatic beta-cell (HOMA-β), first-phase insulin secretion index (ΔI30/ΔG30) and area under curve of insulin (AUCI) were calculated and compared between groups. Results The value of insulin at each time point was significantly higher in IGR group than that of NGT group. The values of insulin at 0.5 h, 1 h, and 2 h were significantly lower in DM group than those of IGR group, respectively (all P<0.05). Compared with NGT group, AUCI, HOMA-IR and HOMA-β increased, but WBISI and ΔI30/ΔG30 decreased in IGR group (all P<0.05). HOMA-IR increased but WBISI, HOMA-βandΔI30/ΔG30 decreased in DM group (all P<0.05). Compared with IGR group, AUCI, HOMA-βandΔI30/ΔG30 decreased in DM group (all P<0.05). Values of FINS, AUCI, HOMA-IR, 2h-PG and HOMA-βwere significantly higher in G2 group than those of G1 group, but WBISI decreased (all P<0.05). There were no significant differences in FPG and ΔI30/ΔG30 between these two groups. Conclusion From NGT, IGR to DM, the peak of insulin secretion is postponed, insulin resistance is getting heavier and the compensation of insulin secretion after a glucose load is increased first and then decreased.

Objective To study the significance of thyroid stimulating antibody (TSAb) and thyroid stimulating-blocking antibody (TSBAb) in children with Graves' disease (GD) or Hashimoto's thyroiditis (HT).Methods Five hundred and twenty-seven cases of serum from 180 children with autoimmune thyroid disease (AITD) children were divided into 282 cases of GD and 245 cases of HT.According to the status of thyroid function,they were divided into 157 cases of hyperthyroidism,91 cases of hypothyroidism and 279 cases of normal thyroid.GD group was subdivided into 127 GD hyperthyroidism and 155 GD remission;HT group was subdivided 30 HT hyperthyroidism,124 HT remission and 91 HT hypothyroidism.Seventy-nine healthy children were taken as the healthy control group.Free triiodothyronine(FT3),free thyroxine(FT4) and sensitive thyroid stimulating hormone(TSH) were detected by chemoluminescence.Serum TSAb and TSBAb were detected by serum TSAb or TSBAb enzyme linked immunosorbent assay (ELISA),respectively.The differences in TSAb and TSBAb among each group were compared and analyzed of find out the relationship between TSAb and TSBAb was performed.Beside,the correlation between TSAb and TSBAb with FT3,FT4,and TSH were analyzed.Results (1) TSAb levels were significant (F =11.995,all P =0.000):the GD group (0.727 ± 0.157) ＞ HT group (0.605 ± 0.148) ＞ healthy control group (0.350 ± 0.105);the difference was significant(F =109.165,P =0.000) among hyperthyroidism group (0.745 ± 0.169) ＞ normal thyroid group (0.647 ± 0.153) ＞hypothyroidism group(0.612 ±0.144) ＞healthy control group (0.350 ±0.105);the difference was significant(F=156.712,P =0.000) in the GD hyperthyroidism group(0.747 ±0.17) ＞ GD remission group (0.640 ± 0.16) ＞ healthy control group (0.350 ± 0.105);the difference was significant (F =109.165,P =0.000) in the HT hyperthyroidism group(0.739 ±0.140) ＞HT remission group(0.655 ±0.135) ＞ HT hypothyroidism group(0.612 ± 0.140) ＞healthy control group (0.350 ±0.105).(2) TSBAb levels were significantly different(F =15.610,P =0.000):the HT group(0.704 ±0.633) ＞ GD group(0.567 ±0.178) ＞ healthy control group (0.334 ±0.104);the difference was significant(F =13.311,P =0.000) in the hypothyroidism group (0.693 ± 0.125) ＞ remission group (0.648 ±0.446) ＞hyperthyroidism group(0.562 ±0.181) ＞healthy control group(0.334 ±0.104);the difference was significant(F =19.269,P =0.000) in the GD remission group (0.672 ±0.572) ＞ GD hyperthyroidism group (0.550 ± 0.187) ＞ healthy control group (0.334 ± 0.104);HT hypothyroidism group (0.693 ± 0.725) was higher than HT hyperthyroidism group(0.618 ±0.142) and HT remission group (0.619 ±0.199),the difference was not significant between HT hyperthyroidism group and HT remission group(F =12.208,P =0.000).(3) TSAb level was positively correlated with TSBAb,FT3 and FT4(r =0.162,0.091,0.194,all P ＜ 0.05) and was negatively correlated with TSH (r =-0.224,P ＜ 0.05).TSBAb levels were negatively correlated with FT3 (r =-0.155,P ＜ 0.05) and was positively correlated with TSH (r =0.131,P ＜ 0.05).Conclusions Thyroid function was related to the serum levels of TSAb and TSBAb.TSAb and TSBAb could be regarded as an important predictive index for children with AITD during the treatment period.

Objective To investigate the possible association of circulating components of GH-IGFs-IGFBPs system with the GHR-exon 3 genotype in idiopathic short stature (ISS) children. Methods Genomic DNA was extracted and isolat-ed from peripheral leukocytes in 108 ISS children. GHR-exon 3 polymorphism was analyzed with multiplex poly-merase chain reactions (PCR) assay. According to the results of genotype, ISS children were divided into GHRfl group and GHRd 3 group. The height and weight were recorded in two groups. The body mass index (BMI) and BMI standard deviation score (SDS) were measured. The serum levels of insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGF-1 SDS and IGFBP3 SDS were calculated. GH stimulation test was used to measure the serum GH peak value. Fifty-five ISS chil-dren were treated with recombine human GH [0.15 IU/(kg·d)] for three months to analyse the association of IGF-1 response of GH treatment and genotypes. Results There were 63 GHRfl and 45 GHRd3 in 108 ISS children. There were no signifi-cant differences in BMI, IGF-1, IGFBP3, GH peak, IGF-1 SDS and IGFBP3 SDS between two groups (P>0.05). Multiple stepwise regression analysis showed that age, IGFBP3, lg (BMI) and lg (GH peak) were influencing factors of lgIGF-1 (P<0.05). In 55 ISS children treated with rhGH, there were 34 cases of GHRd3. The differences of △IGF-1 and △IGF-1 SDS were higher in GHRd3 group than those of GHRfl group (n=21). Conclusion The GH sensitivity may be a risk factor in ISS children, which may not be related with GHR polymorphism.