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Background Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader–Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS. Methods A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m2/day for first four weeks, and 1 mg/m2/day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed. Results Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in Conclusion Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients

Background Recent decades have shown a rapid increase in the prevalence of overweight and obesity among Chinese children based on several national surveys. Restrictions due to the coronavirus disease 2019 outbreak have worsened its epidemiology. This review updates the trends in the prevalence of overweight and obesity among Chinese children and adolescents and analyzes the underlying reasons to provide evidence for better policy making. Methods Studies published in English and Chinese were retrieved from PubMed, Google Scholar, China National Knowledge Infrastructure and Wanfang. Results The prevalence of overweight and obesity has been increasing for decades and varies with age, sex and geography but is more pronounced in primary school students. The increase in obesity in boys appeared to be slower, whereas that in girls showed a declining trend. The northern areas of China have persistently maintained the highest levels of obesity with a stable trend in recent years. Meanwhile, the prevalence in eastern regions has dramatically increased. Notably, the overall prevalence of obesity in children has shown a stabilizing trend in recent years. However, the occurrence of obesity-related metabolic diseases increased. The effect of migrants floating into east-coast cities should not be neglected. Conclusions The high prevalence of overweight and obesity among Chinese children and adolescents persists but with varying patterns. Obesity-related metabolic diseases occur more frequently despite a stable trend of obesity. Multiple factors are responsible for the changing prevalence. Thus, comprehensive and flexible policies are needed to effectively manage and prevent the burden of obesity and its related complications.

The outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV) has become a most challenging health emergency. Owing to rigorous quarantine and control measures taken in China, routine neonatal health surveillance and follow-up have become challenging. Without follow-up surveillance, some rapid and progressive newborn diseases, such as bilirubin encephalopathy, may be ignored. The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia. Therefore, we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences. The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.

Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.

To investigate the clinical incidence and characteristics of type 1 diabetes mellitus (T1DM) of children and adolescents at the time of initial diagnosis in China.Data on all pediatric patients with newly diagnosed T1DM were retrospectively collected from 34 medical centers in 25 major cities in China from January 2015 to January 2020. Patients were classified into three age groups:5 years, 5 to10 years, and ≥10 years of age. The same patient population was also categorized into diabetic ketoacidosis (DKA) and non-DKA groups based on clinical criteria.The mean annual clinical incidence of T1DM was 3.16/100,000 from the years 2015 to 2019. A total of 6,544 patients with newly diagnosed T1DM aged 0-16 years (median 7.84 ± 3.8) were studied [ages5 years (29.3%), 5 to10 years (38.7%), and ≥10 years (32%)], 52.4% of them were women. In total, 90.5% of the cases were occurred in individuals without a family history. Patients had lower C-peptide (CP) and body mass index (BMI) z scores when compared with healthy children, 41.8% of them had measurable T1DM-related antibodies and 52.7% had DKA. Among all three age groups, the5 years group had the lowest BMI z score, CP, and glycated hemoglobin (HbA1c) on average, while it had the highest incidence rate of DKA (56.9%). Compared to the non-DKA group, the DKA group was significantly younger, with a lower BMI z score and CP, higher antibody positive rate, HbA1c, and the rate of insulin pump therapy.The clinical incidence of T1DM in children and adolescents in China was 3.16/100,000. Patients with DKA at the first diagnosis of T1DM have a worse β-cell function. Public health measures for the prevention and treatment of T1DM should focus on preschoolers (aged5 years) in particular, considering the severity and the highest frequency of DKA in this age group. More efforts should be dedicated to early screening and diagnosis of the T1DM.

Objective To investigate the role of mannose-binding lectin (MBL) in modulating autophagy and protecting endothelial cells (ECs) from oxidized low-density lipoprotein (ox-LDL) induced injury. Materials and Methods Rapamycin and chloroquine were used to confirm the role of autophagy in ox-LDL induced ECs injury. Dendritic cells (DCs) were co-cultured with ECs, after which inflammatory factors and DCs maturation rate were detected. Autophagy was detected by LC3 and Lamp2a or autophagosomes. Cell viability was analyzed by Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was utilized to analyze cell proliferation and apoptotic rate. ECs transfected with lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)-siRNA or MBL over-expression plasmid were treated with ox-LDL to explore the mechanism of MBL in ECs injury. HE, Oil Red O, TUNEL staining, and immunofluorescence were used to evaluate the atherosclerotic plaque, ECs injury, and autophagy, respectively. Retro-eyeball injections of MBL over-expression adenovirus were conducted every 4 weeks, after which ECs injury, autophagy, the uptake of ox-LDL, and expression of LOX1 were further analyzed. Results ECs treated with 100 ug/mL ox-LDL for 24 h significantly increased the expression of LC3, Lamp2a, and ET1. Rapamycin aggravated, chloroquine alleviated ox-LDL induced ECs autophagy and injury. LOX1-siRNA transfected ECs inhibited the uptake of ox-LDL and reduced ECs autophagy and injury compared with siRNA group. MBL over-expression in vitro decreased the binding of LOX1 and ox-LDL, ameliorated ECs autophagy and injury compared with the control plasmid group. MBL over-expression in vivo alleviated the formation of atherosclerotic plaque in HFD fed ApoE-/- mice, influenced the maturation of DCs, and down-regulated IL-6, IL-12, and TNF-a level compared with the control group. Also, mannan could reverse the protective role of MBL. Conclusion MBL exerts a protective role in ox-LDL induced ECs injury and HFD induced atherosclerosis model by regulating DCs maturation and modulating ECs autophagy via blocking the binding of LOX1 and ox-LDL.

Background A pandemic of SARS‐CoV‐2 infection broke out all over the world, however, epidemiological data and viral shedding in pediatric patients are limited. Methods We conducted a retrospective, multi‐center study, and followed up with all children from the families with SARS‐CoV‐2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS‐CoV‐2 RNA with RT‐PCR method, and epidemiological data between children and adults in the same families was compared. Effect of antiviral therapy was evaluated observationally and fecal viral excretion times among groups with different antiviral regiments were compared with Kaplan Meier plot. Results By February 29, 2020, 1298 cases from 883 families were confirmed with SARS‐CoV‐2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty‐three children had COVID‐19 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS‐CoV‐2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal‐viral‐excreting children. Conclusion Children have lower susceptibility of SARS‐CoV‐2 infection, longer incubation and fecal viral excretion time. Positive results of fecal SARS‐CoV‐2 RNA detection were not used as indication for hospitalization or quarantine. This article is protected by copyright. All rights reserved.

No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population.Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes.Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged 5 years had SID compared to none among patients aged ≥ 11 years.Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.

Background Tubularized incised plate (TIP) urethroplasty is the most commonly performed procedure for hypospadias. Several flap procedures have been recommended to decrease the postoperative complication rate in TIP repair, but no single flap procedure is ideal. This study aimed to compare the outcomes of dartos fascia (DF) and tunica vaginalis fascia (TVF) as intermediate layers in TIP urethroplasty. Methods We searched PubMed, EMBASE, the Cochrane Library, Web of Science, clinicaltrials.gov, and other sources for comparative studies up to April 16, 2020. Studies were selected by the predesigned inclusion criteria. The primary outcomes were postoperative complications. The secondary outcomes were functional and cosmetic outcomes. Results The pooled RR with 95% CI were calculated. We extracted the relevant information from the included studies. Only 6 comparative studies were included. No secondary outcomes were reported. The RR of the total complications rate for DF was 2.41 (95% CI 1.42–4.07, P = 0.0001) compared with TVF in TIP repair. For each postoperative complication, the RRs were 6.48 (2.20–19.12, P = 0.0007), 5.95 (1.13–31.30, P = 0.04), 0.62 (0.25–1.52, P = 0.29), and 0.75 (0.23–2.46, P = 0.64) for urethrocutaneous fistula, prepuce-related complications, meatal/urethral stenosis, and wound-related complications, respectively. Conclusions This meta-analysis reveals that compared to DF, TVF is a better option in TIP repair in terms of decreasing the incidence of the total postoperative complications, urethrocutaneous fistula, and prepuce-related complications. However there is limited evidence for functional and cosmetic outcomes. Overall, larger prospective studies and long-term follow-up data are required to further demonstrate the superiority of TVF over DF. Trial registration PROSPERO CRD42019148554.

Since December 2019, the outbreak of coronavirus disease (COVID-19) has become the most serious public health issue. As the special population with immature immune function, newborns with COVID-19 have been reported. Newborns with suspected or confirmed COVID-19 should be transferred to designated hospitals for isolation treatment. An emergency transfer response plan for newborns with COVID-19 has been worked out. This plan puts forward the indications for neonatal COVID-19 transfer, organization management, protection strategies for medical staff, work procedures, and disinfection methods for transfer equipment, in order to provide guidance and suggestions for the inter-hospital transfer of suspected or confirmed neonatal COVID-19.

Additional file 1. Supplemental Table 1. PRISMA Checklist. Supplemental Table 2. Down and Black scale and scores for included studies. Supplemental Figure 1. Sensitivity analysis by changing the model to a random-effect model. (a) total complications, (b) each complication. Supplemental Figure 2. Sensitivity analysis by omitting each study. (a) total complications, (b) urethrocutaneous fistula, (c) meatal/urethral stenosis, (d) wound-related complications, (e) prepuce-related complications.

Background: Despite perceiving their child as being above a healthy weight, many parents do not intervene. Little is known about the factors influencing parental action. We assessed parent...

This study investigated whether respiratory syncytial virus (RSV) infection in children was associated with ambient temperature and air pollutants in Hangzhou, China. A distributed lag non-linear model (DLNM) was used to estimate the effects of daily meteorological data and air pollutants on the incidence of RSV infection among children. A total of 3650 childhood RSV infection cases were included in the study. The highest air pollutant concentrations were in January to May and October to December during the year. The yearly RSV-positive rate was 10.0 % among children with an average age of 4.3 months. The highest RSV-positive rate occurred among patients 0 to 3 months old. Children under 6.5 months old accounted for 80 % of the total patients infected by RSV. A negative correlation was found between ambient temperature and RSV infection, and it was strongest with minimum ambient temperature (r = −0.804, P

Both genetic predisposition and lifestyle factors are associated with the risk for obesity. Multiple obesity loci have been identified using genome-wide association studies mainly in European populations. The aims of this study were to examine the associations of these loci with obesity and gene×dietary behavior interactions among Chinese children and adolescents. Nineteen candidate SNPs were genotyped using Sequenom technology in the Chinese children (N=2977, 853 obese and 2124 controls, aged 7-17). Dietary behaviors were assessed using self-administered questionnaires. After adjusting for age, sex and multiple testing, MC4R rs17782313, SEC16B rs543874, MAP2K5 rs2241423 and KCTD15 rs11084753 were associated with obesity and obesity-related traits (all P

Disorders of sex development (DSD) is defined as a congenital condition or atypical development of the chromosomal, gonadal, or anatomic sex. The diagnosis, gender assignment, and treatment of DSD require the guidance from experienced multidisciplinary teams. So far there has been no consensus about it in China. Due to dysgenetic gonads, defects in sex steroid biosynthesis or action, or gonadectomy during the prepubertal years, those with DSD suffer from hypogonadism. The hormone replacement therapy of DSD aims at general physiological health and long-term prognosis as well as the avoidance of unnecessary genital and gonadal surgery. This review focuses on the advances in the studies of the diagnosis and hormone replacement therapy of 46,XY DSD.性发育异常（DSD）是指先天性的染色体、性腺和解剖性别不典型。DSD的明确诊断、性别分配和治疗，须在有经验的多学科团队（MDT）指导下进行。目前我国对此病尚无统一的诊治指南。过去DSD的治疗只注重男女生殖器外观的要求，由于性腺发育不良、生殖激素合成或作用缺陷、或性腺被切除，导致DSD患者性腺功能低下，现今激素替代治疗不仅提高性生理健康及长期预后，有时还可以避免不必要的生殖器和性腺的手术。本文将对46,XY DSD诊断及激素替代治疗的研究进展进行综述。.

Emerging evidence suggests that microRNA (miRNA) mediated gene regulation influences the maintenance of metabolic homeostasis, particularly the states of obesity and insulin resistance, thereby providing a potential link between miRNAs and nonalcoholic fatty liver disease (NAFLD).Sprague-Dawley rats fed a high-fat diet (HFD) were used to establish a rat model of NAFLD. The miRNA expression profile of liver tissues was evaluated using Illumina HiSeq deep sequencing. Selected miRNAs were then validated by real-time PCR at both 4- and 12-week time points. Furthermore, the expression levels of these miRNAs were assessed in HepG2 cells and human hepatocytes treated with free fatty acids (FFAs) and proinflammatory factors (tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).Our results showed that consumption of a HFD for 4 weeks caused simple steatosis, which progressed to steatohepatitis at 12 weeks. miRNA deep sequencing analysis identified 44 known up-regulated miRNAs (fold change1.5) and 12 down-regulated miRNAs (fold change0.5). Among the abnormally expressed miRNAs, miR-200a, miR-200b, miR-200c, miR-146a, miR-146b and miR-152 were up-regulated both in vitro and vivo. Interestingly, the expression levels of these six miRNAs were increased in HepG2 cells and human hepatocytes after treatment with FFAs and proinflammatory factors.These findings suggest a critical role for miRNAs in the pathogenesis of NAFLD.

China is gradually taking its place as one of the world's economic giants and concurrently learning to cope with the burden of diseases that are more common in the developed world, such as paediatric type 2 diabetes mellitus. The prevalence of type 2 diabetes has been recently observed among children and adolescents in China; hence, there is a lack of information about the incidence, prevalence, pathogenesis, and pathophysiology of the disease. Diagnosis, treatment, and management have been standardized to a large degree, but there is still a need for data regarding optimal management protocols and how to achieve the best control over current state of the disease. The objective of this review is to consolidate the available information about paediatric diabetes, with a focus on the increasing prevalence of type 2 diabetes in Chinese youth. Here we emphasize the prevention strategies and have included literature with respect to pathogenesis, diagnosis, and treatment published in English and Chinese within the past 10 years.

A novel configuration of compound-cavity multi-wavelength Brillouin erbium fiber laser is proposed and experimentally demonstrated. With an incident optical carrier power of 8 dBm, at least 14 lasing lines are obtained with a wavelength spacing of ∼0.08 nm. Stability and power uniformity of the multi-wave-length lasing are ensured by the flat hybrid gain of Brillouin and erbium, the compound-cavity structure, and the four-wave mixing suppression using a long (10 km) single-mode fiber. A stable and frequency-switchable microwave can be achieved by incorporating a fiber Bragg grating filter to select the desired nth-order Stokes wave and beating it with the optical carrier at a photodetector. In our experiment, the 1st-4th-order Stokes waves are filtered respectively and hence a high-quality microwave with a switchable frequency from ∼10 to ∼40 GHz and a tuning step of ∼10 GHz is achieved. The signal-to-noise ratio is measured to be >25 dB.

A novel quasi-distributed fiber Bragg grating (FBG) sensor system based on Fourier domain mode locking (FDML) fiber laser is proposed and demonstrated. The low reflectivity FBGs with the same Bragg wavelength are connected cascaded in a long fiber working as the sensing elements of the sensor system as well as the wavelength and cavity length selecting elements of the FDML laser. By adjusting the driving frequency of the FDML fiber laser, lasing with different selected cavity lengths will be achieved correspondingly. When the wavelength of the working FBG shifts which includes the sensing information, FBG interrogation can be realized both in wavelength and time domain.

Aim: To investigate the role of ghrelin and obestatin in obesity mechanisms. Methods: A total of 88 obese children and 25 normal children were enrolled. Moreover, 46 obese children took part in a summer camp for weight reduction. Fasting ghrelin, obestatin and other biochemical parameters were measured in all subjects and re-measured in 45 obese children finishing the camp. Results: The ghrelin levels in the control and obese groups were 67.26 ± 23.41 pmol/L and 56.53 ± 15.97 pmol/L with a significant difference (p = 0.039), while the obestatin levels (89.41 ± 23.63 vs. 83.13 ± 17.21 pmol/L) were not significantly different (p = 0.083). The ghrelin/obestatin ratio in the controls was significantly higher than that in the obese group (p = 0.014). In the latter, fasting insulin and alanine aminotransferase were independent factors for ghrelin; fasting insulin, weight and gender were independent factors for obestatin and alanine aminotransferase was an independent factor for ghrelin/obestatin. Moreover, ghrelin, obestatin and ghrelin/obestatin increased after weight reduction (p < 0.05, respectively), and the increment in ghrelin and obestatin was associated with a decrement in insulin resistance. Conclusion: These data suggest that ghrelin, obestatin and/or the ghrelin/obestatin ratio are associated with obesity in childhood.

To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP).Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis.There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P0.05), and positively correlated with the levels of leptin and neurokinin B (P0.05).The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.

Copy number variants (CNVs) have been implicated as an important genetic marker of obesity, and gene-environment interaction has been found to modulate risk of obesity. To evaluate the associations between CNVs and childhood obesity, as well as the interactions between CNVs and dietary behaviors, we recruited 534 obese children and 508 controls from six cities in China and six candidate CNVs were screened through published genome-wide studies (GWAS) on childhood obesity. We found three loci (10q11.22, 4q25 and 11q11) to be significantly associated with obesity after false discovery rate (FDR) correction (all the p ≤ 0.05). Cumulative effect of the three positive loci was measured by the genetic risk score (GRS), showing a significant relationship with the risk of obesity (Ptrend &lt, 0.001). The OR of obesity increased to 21.38 (95% CI = 21.19–21.55) among the 10q11.22 deletion carriers who had meat-based diets, indicating prominent multiplicative interaction (MI) between deletions of 10q11.22 and preference for a meat-based diet. Simultaneous deletions of 5q13.2 and duplications of 6q14.1 had significant MI with a preference for salty foods. Our results suggested that CNVs may contribute to the genetic susceptibility of childhood obesity, and the CNV-diet interactions modulate the risk of obesity.

Purpose According to the developmental origins of health and disease theory, fetal nutrition is associated with obesity and chronic diseases in children and adults. However, previous findings regarding the association between birth weight and childhood obesity have been inconsistent. The aim of the present study was to investigate the relationship between birth weight and childhood obesity in China. Methods The 16,580 subjects (8477 boys and 8103 girls) aged 7–17 years, who participated in this study were recruited from a cross-sectional study in six cities in China. Epidemiological data, including birth information, were collected through face-to-face interviews, and anthropometric indices were measured by trained physicians. Overweight and obese cases were defined using sex-specific and age-specific 85th and 95th percentile body mass index (BMI) cutoffs for Han children and adolescents. Central obesity was defined using sex-specific waist-to-height ratio (WHtR) cutoffs (WHtR ≥0.48 in boys and WHtR ≥0.46 for girls). Results The overall rate of overweight status and obesity was 20.3% in the Chinese children and adolescents and that of central obesity was 18.9%. Subjects were stratified into eight groups according to weight at birth. J-shaped relationships were observed between birth weight and BMI for age Z-score and WHtR. After adjusting for confounders such as gender, gestational age, parental factors, and dietary factors, the risk of overweight and obese status was still higher in the children with higher birth weights than in children with birth weights of 3000–3499 g (3500–3999 g: odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.02–1.28; 4000–4499 g: OR = 1.39, 95% CI = 1.19–1.63; and 4500–4999 g: OR = 1.36, 95% CI = 1.06–1.76). Moderately high birth weight also increased the risk of central obesity. Relative to the children with normal birth weights (3000–3499 g), the adjusted OR and 95% CI were 1.33 (1.13–1.56) in children with birth weights of 4000–4499 g. Children with very low birth weight (lower than 1500 g) had the highest risk of central obesity. The adjusted OR was 2.30 (95% CI: 1.03–5.14) relative to children with birth weights of 3000–3499 g. Conclusions Birth weight was associated with obesity in Chinese children and adolescents. J-shaped relationships were observed between birth weight and BMI and WHtR in childhood, and very low birth weight was associated with a mild increase in the risk of central obesity in Chinese children and adolescents.

To clarify the impact of body mass index (BMI) on luteinizing hormone (LH) secretion in response to gonadorelin (GnRH) stimulation testing in girls diagnosed with idiopathic central precocious puberty (ICPP).Retrospective single-center cohort study was carried out in 865 confirmed ICPP girls who underwent GnRH stimulation tests. Pubertal development according to Tanner, sex hormone parameters, and LH secretion in response to GnRH-stimulation was compared.Around 609 girls were of normal weight (70.4%), while 168 children (19.4%) were overweight, and 88 (10.2%) were obese. Peak LH levels after GnRH were much higher in the normal-weight group, with a median of 9.1 mIU ml(-1) (interquartile 5.2-13.1), compared with the median peak LH in the overweight and obese groups (8.5 mIU ml(-1), interquartile 5.3-11.6, and 6.2 mIU ml(-1), interquartile 5.3-11.0, respectively P 0.001 for all comparisons). Peak LH/FSH ratio was also lower in the obese group (median 0.6, interquartile 0.68-0.90) compared with the normal-weight (median 0.8, interquartile 0.61-1.11) and overweight (median 0.8, interquartile 0.64-0.92) groups.Higher BMI is associated with lower LH response to GnRH-stimulation testing in girls with ICPP. It is recommended that BMI should be considered when interpreting GnRH-stimulation tests.

To evaluate the sensitivity and specificity of hepatic ultrasonography (US) for the diagnosis of hepatic steatosis in obese children, using ¹H magnetic resonance spectroscopy (¹H MRS) as the reference standard.A total of 162 obese children with age of 10.5 ± 2.2 years and BMI of 28 ± 4 were enrolled in this study. They accepted hepatic US and (1)H MRS examinations. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of US were calculated for the overall presence of hepatic steatosis by comparison with ¹H MRS results.Using quantitative criteria of liver fat content (LFC)5% determined by (1)H MRS, 95 children(58.6%)were diagnosed as having hepatic steatosis. The sensitivity and specificity of US in diagnosing steatosis were 91.6% (87/95) and 50.7% (34/67) respectively, with PPV of 72.5% (87/120), and NPV of 81.0% (34/42). Considerable overlap in LFC measured by ¹H MRS was observed between different grades from US findings: absent (LFC interquartile range: 1.3%-3.9%), mild (2.4%-10.7%), moderate (7.1%-20.2%) and severe (7.6%-28.8%) steatosis.The US can yield a high sensitivity and low specificity in the diagnosis of hepatic steatosis in obese children, suggesting it can be used as a screening tool for hepatic steatosis. To improve diagnostics, ¹H MRS is needed to determine LFC.

We aimed to evaluate the current status of sexual maturation of Chinese children, to examine the association between obesity and early sexual maturation in boys and compare it with girls and to test the hypothesis that the associations differ by gender. Cross-sectional study. A representative sample involving 9812 boys and 8895 girls aged 6–18 years who participated in the Chinese Children and Adolescent Metabolic Syndrome Epidemiologic Study (July 2009– July 2010) were surveyed. All subjects had complete anthropometry and sexual maturation data. Subjects who reached Tanner stage 2 or more (5601 boys and 6538 girls) were divided into tertiles based on the timing of sexual maturation. The subjects in the earliest tertile were included into the early-maturing group, and the middle tertile and the latest tertile into the not early-maturing group. Overweight was defined as a body mass index (BMI) ⩾85th percentile and obesity ⩾95th percentile. Logistic regression analysis was used to test how early maturation affected the risk of overweight. Multiple linear regression was used to examine the association between fatness (BMI Z-score) and sexual maturation. Slightly more boys were obese than girls (P

The association of the rs9939609 single nucleotide polymorphism in FTO gene with obesity has been extensively investigated in studies of populations of European, African, and Asian ancestry. However, inconsistent results have been reported in Asian populations, and the relationship of FTO variation and dietary behaviors has only rarely been examined in Chinese children and adolescents. The aim of this study was to assess the association of rs9939609 with obesity and dietary preferences in childhood in a Chinese population. Epidemiological data including dietary preferences were collected in interviews using survey questionnaires, and rs9939609 genotype was determined by real-time PCR. The associations of rs9939609 genotypes with obesity and dietary preferences were analyzed by multivariate logistic regression using both additive and dominant models. The results showed that subjects with a TA or AA genotype had an increased risk of obesity compared with the TT participants; the odds ratios (ORs) were 1.47 (95% CI: 1.25-1.71, P = 1.73×10-6), and 3.32 (95% CI: 2.01-5.47, P = 2.68×10-6), respectively. After adjusting for age and gender, body mass index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, and low-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol was lower in TA and AA participants than in those with the TT genotype. After additionally controlling for body mass index, the association remained significant only for systolic blood pressure (P = 0.005). Compared with TT participants, those with the AA genotype were more likely to prefer a meat-based diet (OR = 2.81, 95% CI: 1.52-5.21). The combined OR for obesity in participants with TA/AA genotypes and preference for a meat-based diet was 4.04 (95% CI: 2.8-5.81) compared with the TT participants who preferred a plant-based diet. These findings indicate the genetic variation of rs9939609 is associated with obesity and dietary preferences in Chinese children and adolescents.

To investigate the role of non-high density lipoprotein cholesterol (non-HDL-C) in the assessment of cardiovascular disease (CVD) risk factors such as hypertension, pre-diabetes and diabetes in obese children.According to the presence of complications (hypertension, pre-diabetes and diabetes), 810 children with central obesity were divided into two groups: one group with complications (n=499) and one group without complications (n=311). One hundred and sixty-four age- and sex-matched children served as the control group. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to analyze the detection of non-lipid CVD risk factors by seven lipid markers.The prevalence rates of hypertension and pre-diabetes were significantly higher in obese children with high non-HDL-C concentrations (≥3.76 mmol/L). After adjusting for waist circumference Z-scores, the area under the ROC curve for non-HDL-C was 0.680 to detect non-lipid CVD risk factors, while the areas for low-density lipoprotein cholesterol, total cholesterol and apoprotein B were 0.659, 0.669 and 0.647 respectively.Compared with the other lipid markers, non-HDL-C is a better predictor for non-lipid CVD risk factors in obese children. Measurement of non-HDL-C concentations is recommended for obese children.

To investigate the clinical status and natural course of premature thelarche (PT) in infants under 2 years of age and to analyze the predictive factors for regression of thelarche.The clinical and laboratory data of 863 infants under 2 years of age, who visited the department of endocrinology in our hospital due to PT between October 2009 and September 2010, were analyzed. A a longitudinal follow-up study was performed.Of the infants under 2 years of age with isolated PT, 89.3% showed a regression before the age of 3 years (mean 17±5.6 months), 10.7% had recurrent or persistent thelarche, with no regression after the age of 3 years, and some even developed into central precocious puberty. The independent predictive factors for regression of thelarche were Tanner stage at the first visit and whether baseline estradiol level had increased.PT in infants under 2 years of age is not rare in the clinical setting, and it usually runs a self-limited course, subsiding before the age of 3 years. However, regular follow-ups should be performed for infants aged over 2 years with persistent thelarche.

To investigate the lipid levels of Han ethnicity Chinese children at school-age, to provide objective data for the formulation of prevention and management strategy regarding dyslipidemia among children and adolescents.20 191 children (with 10 669 boys and 9522 girls) aged 7 to 16 years old from 6 representative geographical areas, including Beijing, Tianjin, Hangzhou, Shanghai, Chongqing and Nanning, were surveyed in a randomly selected clustered sample in China. Data on fasting blood triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured. Non-high-density lipoprotein cholesterol (non-HDL-C) levels were calculated with data collection, entry, and collation were under the same criteria.(1) In the 7 - 16 year-old group, TG (P(95)) fluctuated between 1.26 mmol/L and 1.88 mmol/L, while TC (P(95)) was between 4.80 mmol/L and 5.46 mmol/L. LDL-C (P(95)) was between 2.67 mmol/L and 3.27 mmol/L while non-HDL-C (P(95)) was between 3.36 mmol/L and 3.91 mmol/L, suggesting that age did not seem to be an affecting factor for the lipid level (P0.05). The level of HDL-C (P(5)) fluctuated between 1.08 mmol/L and 0.83 mmol/L, and the dependability analysis on HDL-C and age showed statistically significant difference (P0.01, r = -0.274). (2) In the 7 - 9 year-old group, the levels of TG, TC, LDL-C and non-HDL-C of boys were lower but the HDL-C level was higher than in girls. However, in the 10-16 year-old group, the levels of five lipids of boys were all lower than in girls, with all the differences statistically significant (P0.05). (3) The levels of TG, TC, LDL-C and non-HDL-C in the obese group were significantly higher than those in non-obesity group, as HDL-C was significantly lower than in non-obese group (P0.01). Incidence rates of single and multiple dyslipidemia in obese group were significantly higher than in non-obese group (P0.01). (4) Grouped by region, the abnormal rates of TG were descending, with the ranking as North (10.4%), Midwest (9.7%) and East (8.3%), while the abnormal rates of TC were descending with the ranking as Midwest (6.0%), North (5.2%) and East (4.8%). The abnormal rates of LDL-C were descending as the ranking of North (3.1%), East (2.6%) and Midwest (0.9%), with the abnormal rates of non-HDL-C were descending as Midwest (6.5%), North (4.2%) and East (3.6%). The abnormal rates of HDL-C were descending as Midwess (14.2%), North (5.7%) and East (5.5%). All the differences in the above-said items were statistically significant (P0.05). (5) According to the standards of hyperlipidemia formulated by the American Academy of Pediatrics, the incidence rates of abnormal TG, TC, LDL-C, non-HDL-C, HDL-C were 9.4%, 5.4%, 2.2%, 4.8%, 8.6% respectively.(1) Levels of lipids were affected by many factors, but age was not one of them in children and adolescents. However, HDL-C was declining along with the increase of age, to some extent. (2) Girls had a relatively protective tendency through the increasing HDL-C level when they entered the puberty years. (3) Lipids levels in non-obese group were significantly better than the obese group. (4) The lipids levels of children and adolescents in the Eastern region of the country were better than that in the northern and mid-western areas.

Childhood diabetes has become a growing concern. We conducted a study to evaluate the status and trend of diabetes from 14 medical centers in China. Pre-diabetic status among obese children was also noted.Hospital medical records were reviewed, and data of diabetes were collected from 1995 through 2010. We took every five years as a calculation unit to analyze the trend of new-onset diabetes. Data on obesity were collected in the recent five years.A total of 4 337 836 patients aged 0-18 years were discharged from the 14 centers. The prevalence (per 100 000 persons) of new-onset type 1 diabetes, type 2 diabetes and other types of diabetes were 96.8, 8.0, and 3.3, respectively. The prevalence of type 1 diabetes increased from 90.9 to 92.9 and 101.4, while type 2 diabetes increased from 4.1 to 7.1 and 10.0 in every five years (P0.0001). The increasing trend was significant from Southwest to East and North China (type 1 diabetes from 59.76 to 80.02 and 120.45, type 2 diabetes from 2.52 to 3.77 and 15.64 (per 100 000 persons) (all P0.0001). Well developed areas in China had a higher prevalence compared to less developed areas [type 1 diabetes: 151.51 vs. 32.2 (per 100 000 persons); type 2 diabetes: 15.16 vs. 1.64 and others: 7.54 vs. 0.42 (per 100 000 persons)]. Of the 3153 obese children, 18.24% had impaired fasting glucose (IFG), 5.99% had impaired gulose tolerance (IGT), and 4% had combined IFG and IGT.The prevalence of childhood diabetes in China has increased dramatically, with type 2 diabetes exceeding type 1 diabetes. The incidence rate of abnormal glucose metabolism in obese children has reached 28.26%.

To quantitatively evaluate clinical significance of intrahepatic fat (IHF) content in children and adolescents with non-alcoholic fatty liver disease (NAFLD).Ninety-three obese children were enrolled in this study. Physical parameters, liver function, serum lipids, glycemic and insulin related parameters were measured. Liver B-mode ultrasound (US) examination was performed. IHF content was quantified by 1H magnetic resonance spectroscopy (1H MRS). Three subgroups were classified according to the conditional diagnostic criteria for obese children: simple obesity (n=31), NAFLD-1 (US fatty liver and normal alanine aminotransterase, n=33) and NAFLD-2 (US fatty liver and elevated alanine aminotransterase, n=29). Twenty healthy age- and sex-matched children served as a control group. IHF content among the four groups was compared. The relationship of IHF content with other common clinical laboratory parameters and independent factors influencing increased IHF content were investigated.IHF content measured by 1H MRS was 0.80% (0.4%-1.0%), 2.9% (1.7%-4.30%), 14.0% (7.2%-17.5%) and 18.8% (14.0%-29.1%) respectively in the control, simple obese, NAFLD-1 and NAFLD-2 groups. There were significant differences in IHF content between the groups. Univariate correlation analysis demonstrated that IHF content was positively correlated with waist circumference, hip circumference, waisttohip ratio, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminoreansferase, γ-glutamic acid transtetase, triglyceride, low-density lipoprotein, OGTT 2-hour plasma glucose, fasting insulin, 2-hour insulin and insulin resisfence, and negatively correlated with high-density lipoprotein. Multivariate linear regression analysis demonstrated three independent risk factors for increased IHF content: increased waist circumference, increased 2-hour plasma glucose and decreased high-density lipoprotein levels.IHF content determined by 1H MRS can reflect early hepatic fatty infiltration and is closely related to the occurrence and progress of NAFLD in obese children and adolescents. There is a significant correlation between most of common clinical laboratory parameters and IHF content, and waist circumference, high-density lipoprotein and OGTT 2-hour plasma glucose are independent factors impacting IHF content.

To provide data as age-gender dependent mean, standard deviation and percentile on height, weight, waist circumference (WC), hip circumference (HC), body mass index (BMI), waist hip ratio (WHR), waist to height ratio (WHtR) among 7-16 year-olds Chinese children and adolescents, towards setting up diagnostic criteria on metabolic syndrome for them.A representative sample involving 22,197 children and adolescence aged 7 to 16 years were randomly surveyed and they were from 6 representative geographical areas, including Beijing, Tianjin, Hangzhou, Shanghai, Chongqing and Nanning. A total of 21 858 had available data, with male/female ratio as: 11,460/10,398. Using the standard methods, we measured height, weight, WC, HC, BMI, WHtR and other data in all age groups. Physique indexes among different geographic regions (North, Mid-west and East) were compared.(1) Both male and female showed an increasing trend of height, weight, waist circumference, hip circumference and BMI along with the increase of age. WHR of girls decreased gradually from 0.84 to 0.76 went from 7 to 16 years old while WHR of boys changed from 0.87 to 0.81 accordingly. (2) WHtR was rarely affected by age. It fluctuated between 0.42-0.43 in all girls and 0.44-0.45 in boys less than 11 years. WHtR of boys older than 12 years showed a slight decline from 0.45 to 0.42 of WHtR. (3) The average height, weight, BMI of children and adolescents from the northern regions (Beijing, Tianjin) were significantly higher than that of the mid-western (Chongqing, Nanning) and the eastern regions (Shanghai, Hangzhou) (P0.001), while those from the mid-western region were slightly higher than that of the eastern region (P0.05) in each of the age group.Reference values and percentile curves for WC and WHtR of Chinese children and adolescents were provided. For the assessment of central obesity. WHtR had the advantages of relative stability and small degree of variation and rarely affected by age and gender, when compared with WC, and could be used as an simple index to reflect the central obesity of children and adolescents.

To investigate the role of serum cholesterol and triglyceride in the assessment of cardiovascular disease risk factors in children and adolescents.Case-control study.Childrens Hospital of Zhejiang University School of Medicine, Hangzhou, China.Children from 6 years to 17 year old. 188 with simple obesity, and 431 with obesity and metabolic abnormalities. 274 age and gender-matched healthy children as controls.Receiver operating characteristic curves were used to analyze the detection of cardiovascular disease risk factors by cholesterol and triglyceride in children and adolescents.The ranges of areas under receiver operating characteristic curves (AUC) for triglyceride and non-high-density lipoprotein cholesterol were 0.798-0.860 and 0.667-0.749, respectively to detect cardiovascular disease risk factors. The ranges of AUC for low-density lipoprotein cholesterol, total cholesterol, and high-density lipoprotein cholesterol were 0.631-0.718, 0.596-0.683, and 0.292-0.376, respectively.Triglyceride and non-high-density lipoprotein cholesterol are better than low-density lipoprotein cholesterol as predictors of cardiovascular disease risk factors in Chinese Han children and adolescents.

To investigate the prevalence of positive thyroid antibodies in children with type 1 diabetes mellitus (T1DM) and its influencing factors.The clinical data of T1DM children who were treated in the Children's Hospital of Zhejiang University from May 2005 to April 2011 were retrospectively studied. The relationships of thyroid globulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) with cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ were evaluated, and the percentages of CD3+, CD4+ and CD8+ T-lymphocytes in peripheral blood were examined.A total of 186 T1DM children with complete data of both TGAb and TPOAb were included in the study, among whom 143 with normal TGAb and TPOAb levels and 43 (23.1%) presented with positive thyroid antibody (including 21 cases with both positive TGAb and positive TPOAb). Eighteen cases (9.7%) were diagnosed as autoimmune polyglandular syndrome type 3 variant (APS3v). Significantly more patients in the positive thyroid antibody group had a family history of diabetes than in the negative thyroid antibody group (27.9% vs 14.7%; P0.05). The average age of the positive thyroid antibody group was 10.1±3.2 years, which was significantly greater than that in the negative thyroid antibody group (8.1±4.0 years) (P0.05). The IL-2 level (4.48 ±1.27 pg/mL vs 2.82 ±0.84 pg/mL, P0.05) and the percentage of peripheral CD3+ T-lymphocyte[(61±11)% vs (66±11)%; P0.05] were also different between the positive and negative thyroid antibody groups.Genetic background and abnormal function of T-lymphocytes (especially higher IL-2 level) may be involved in the elevated prevalence of positive thyroid antibody in T1DM children.

To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet.Male SD rats (n = 36) were randomly divided into three groups with 12 rats in each and treated with different diet and drugs: group I: ordinary diet, group II: high-fat diet, group III: high-fat diet and metformin. Ten weeks later, the rats were sacrificed and their body weight and liver weight were obtained, serum lipid metabolic indexes, insulin resistance indexes and secretory phospholipase A2 (sPLA2), lysophosphatidylcholine (LPC) levels and other parameters were measured. Phospholipase A2 mRNA expression levels were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). In addition, the histological changes of liver tissue were analyzed.Compared to ordinary diet group, the rat's liver weight (g) (16.92 ± 2.49 vs. 12.16 ± 0.82), hepatic exponent (0.034 ± 0.004 vs. 0.026 ± 0.002), serum alanine aminotransferase (U/L) (45.43 ± 9.73 vs. 29.42 ± 6.73), triglyceride (mmol/L) (1.22 ± 0.24 vs. 0.85 ± 0.19), cholesterol (mmol/L) (2.00 ± 0.37 vs. 1.49 ± 0.33), lipoprotein(a) (mmol/L) (743.86 ± 32.19 vs. 648.42 ± 78.87), low-density lipoprotein (mmol/L) (1.31 ± 0.35 vs. 0.65 ± 0.22), insulin (mmol/L) (22.16 ± 5.16 vs. 16.86 ± 5.35), insulin resistance index(5.10 ± 1.45 vs. 3.59 ± 0.99), free fatty acid (mEq/L) (0.57 ± 0.10 vs. 0.35 ± 0.07), sPLA2 [µmol/(min·ml)] (0.130 ± 0.016 vs. 0.098 ± 0.024), lysophosphatidylcholine (µmol/L) (707.26 ± 92.48 vs. 508.87 ± 96.50), leptin (pg/ml (80.08 ± 17.73 vs. 65.11 ± 14.09), liver triglyceride (mg/g) (13.57 ± 0.65 vs. 12.03 ± 1.14), cholesterol (mg/g) (2.19 ± 0.15 vs. 1.94 ± 0.12) (P0.05) were significantly increased in high-fat diet group. Moreover, degree of hepatic steatosis was significantly higher and sPLA2 mRNA expression was also significantly increased. Secondly, in comparison with high-fat diet group, early metformin treatment significantly reduced the rat's body weight (g) (394.40 ± 33.10 vs. 491.86 ± 26.45), liver weight (g) (13.24 ± 1.16 vs. 16.92 ± 2.49), serum alanine aminotransferase (U/L) (30.40 ± 4.50 vs. 45.43 ± 9.73), triglyceride (mmol/L) (0.75 ± 0.19 vs. 1.22 ± 0.24), cholesterol (mmol/L) (1.61 ± 0.38 vs. 2.00 ± 0.37), insulin (mmol/L) (16.96 ± 5.60 vs. 22.16 ± 5.16), insulin resistance index (3.75 ± 1.41 vs. 5.10 ± 1.45), sPLA2 [µmol/(min·ml)] (0.101 ± 0.009 vs. 0.130 ± 0.016), lysophosphatidylcholine (µmol/L) (549.92 ± 90.78 vs. 707.26 ± 92.48), liver triglyceride (mg/g) (11.23 ± 1.70 vs. 13.57 ± 0.65), cholesterol (mg/g) (1.97 ± 0.20 vs. 2.19 ± 0.15) (P0.05). Moreover, degree of hepatic steatosis was significantly lower and sPLA2 mRNA expression was also significantly decreased by metformin. Thirdly, when compared to ordinary diet group, metformin could also significantly increase hepatic exponent (0.034 ± 0.004 vs. 0.026 ± 0.002) and low-density lipoprotein level (mmol/L) (0.96 ± 0.34 vs. 0.65 ± 0.22) (P0.05). However, it had no impact on hepatic steatosis and sPLA2 expression (P0.05).It was indicated that metformin has potent effects on improving lipid metabolism and insulin resistance in high-fat diet induced non-alcoholic fatty liver disease rat model. The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function.

The Wilms' Tumour gene is thought to have tumour suppressor activity and to play an important role in nephrogenesis, genitourinary development, haematopoiesis and sex determination. WT1 mutations will impair gonadal and urinary tract development and have been demonstrated to cause syndromes of WAGR, Denys-Drash and Fraiser.To elucidate the role of constitutional mutations of WT1, in the expression of the different clinical feature, we describe a 14-year-9-month nonmosaic XY sex-reversed woman with pure gonadal dysgenesis (46, XY karyotype, completely female external genitalia, normal Mullerian ducts, absence of Wolffian ducts, streak gonads) who had right kidney removed at 7 months of age because of Wilms' tumour and was diagnosed as secondary thrombocytopenia (Plt 60-80 × 10(9) /L) since she was 4 years old. We sequenced the genomic DNA of all the 10 exons of the WT1 in which mutations may occur in proposita.A new de novo insertion mutation in the first exon was found. A 'GCCGCCTCACTCC' is inserted between codon 138 and 139, resulting in the creation of a stop codon and a truncated protein.The present data provide further evidence to support the role of WT1 in diverse cellular functions.

To review the incident status of childhood type 1 diabetes mellitus hospitalized in the Children's Hospital of Zhejiang University School of Medicine from 1999 to 2009 and to explore the clinical value of IL-10 in diabetic ketoacidosis.The clinical data of 263 children with type 1 diabetes mellitus hospitalized in the Children's Hospital of Zhejiang University School of Medicine from January 1999 to February 2009 were retrospectively reviewed. Serum lipid levels were measured in 48 children with type 1 diabetes mellitus and in 24 healthy children. The diabetic children were classified into two subgroups, with or without ketoacidosis. Serum lipid and cytokines levels were compared.Childhood type 1 diabetes mellitus was common in females (56.3%). The peak incident age of the disease was between 6 and 11.9 years. Diabetic ketoacidosis was as the presenting symptom for the first visit in 86 cases (32.7%). The levels of serum lipid, blood glucose and HbA1c in diabetic children with ketoacidosis were significantly higher than those without ketoacidosis (P0.05). Logistic analysis demonstrated that the increased levels of blood glucose, serum lipid and HbA1c were risk factors for diabetic ketoacidosis. The level of serum IL-10 in diabetic children with ketoacidosis was significantly higher than that in patients without ketoacidosis (P0.01), while there were no differences in serum levels IL-2, IL4, IL-6, TNF-α and IFN-γ between them. Serum levels IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in diabetic children were significantly higher than those in healthy children (P0.01).Ketoacidosis is a common acute complication of type 1 diabetes mellitus. The disorders of glucose and lipid metabolism are the risk factors for ketoacidosis in diabetic children. IL-10 may be a sensitive index of diabetic ketoacidosis in children with type 1 diabetes mellitus.

Obese children and adolescents are often complicated with the abnormalities of lipid and glucose metabolism, which are often associated with adulthood hypertension, diabetes and cardiovascular disease. In this study, the blood lipids, blood pressure and carotid arterial intima-media thickness (IMT) in obese children and adolescents were measured to investigate the relationship between the dyslipidemia and early vascular lesions.A total of 580 obese children and adolescents aged from 7 to 17 years of age were enrolled from 3 hospitals from Jan. 2008 to Sept. 2009. They were divided into 2 groups according to their blood lipoid levels. Ortholiposis group included 100 males and 52 females with a mean age of 10.47 years and a mean body mass index (BMI) of 28.28 kg/m(2). Dyslipidemia group included 305 males and 123 females with a mean age of 10.83 years and a mean BMI of 27.60 kg/m(2). Physical examination, and measurement of blood lipid, glucose and liver enzyme were taken. Carotid IMT was measured for 285 subjects.(1) Hypertension was found in 12.5% (19/152) and 20.1% (86/428) patients in ortholiposis and dyslipidemia groups, respectively, with a significant difference (χ(2) = 4.362, P = 0.037). The OR was 1.760 with 95% confidence interval of 1.030 - 3.008. Higher prevalence of hypertension was found in patients with dyslipidemia. (2) The left, right and mean common carotid IMTs of dyslipidemia group were higher than those of ortholiposis group without significant difference (all P0.05). The left, right and mean internal carotid IMTs in dyslipidemia group were (0.66 ± 0.15) mm, (0.65 ± 0.15) mm and (0.65 ± 0.15) mm, respectively while these in ortholiposis group were (0.62 ± 0.13) mm, (0.60 ± 0.13) mm and (0.61 ± 0.12) mm, respectively (P0.05 for all). (3) Bivariate correlation analysis showed that systolic blood pressure was positively correlated with age, BMI, BMI Z score, waist circumference, hip circumference, uric acid, alanine transaminase, triglyceride, fasting insulin and insulin resistance index (P0.05 for all). Moreover, mean carotid and internal carotid IMTs were positively correlated with age, BMI, waist circumference, hip circumference, and triglyceride (all P0.05). Multiple linear regression analysis showed that hip circumference and insulin resistance index were independent determinants of systolic pressure. Waist circumference was independent determinant of mean common and internal carotid IMT and triglyceride was independent determinants of mean internal carotid IMT.(1) Vascular lesions, including hypertension and thicker tunica intima are common in obese children and adolescents. (2) Vascular lesions are closely related with dyslipidemia, and waist circumference and hypertriglyceridemia are the risk factors.

To analyze the clinical characteristics of the patients with pituitary stalk interruption syndrome (PSIS), and to achieve better comprehension of this disease.Data of 13 patients with PSIS were retrospectively analyzed for the clinical, laboratory and imaging features.All the 13 patients (9 male, 4 female) had the chief complaint of growth retardation, 81.5 - 135.0 cm in body height, which were minus two standard deviations below the average of the normal children of same age and same sex. GH stimulated peak levels were all below 5 microg/L; Among them, one was accompanied by delayed sexual development, one by central diabetes insipidus, one was complicated with central hypothyroidism and one was accompanied by central adrenocortical hypofunction.The most remarkable clinical manifestations of patients with PSIS were growth retardation, partial or complete adenohypophyseal dysfunction. MRI revealed absence of pituitary stalk or anterior pituitary hypoplasia with ectopic posterior pituitary gland.

To study the relationship between nonalcoholic fatty liver disease (NAFLD) and the development of cardiovascular disease (CVD) in children with obesity.Two hundred and thirty-one obese children and 24 non-obese children as control were enrolled. Body mass index (BMI), serum triglyceride, blood pressure, liver function, and carotid artery intima-media thickness (IMT) were examined. The obese children were classified into two subgroups according to the diagnosis criteria: group 1 without liver disorder (OCWLD group, n=75) and group 2 with NAFLD (NAFLD group, n=156). The incidences of hyperlipidemia and hypertension, carotid artery intima-media thickness (IMT) and biochemical indicators were compared in the three groups.The NAFLD group showed significantly greater carotid IMT (0.066+/-0.021 cm) than the OCWLD (0.060+/-0.011 cm) and control groups (0.037+/-0.007 cm) (P0.05). The OCWLD group had also thicker IMT than the control group (P0.05). The incidences of hyperlipidemia and hypertension were 39.7% and 40.4%, respectively in the NAFLD group, which were significantly higher than those in the OCWLD (22.7% and 29.3% respectively)and control groups (4.2% and 12.6% respectively) (P0.05). The liner stepwise regression analysis showed that the IMT was positively correlated with BMI, NAFLD and ALT (adjusted R2=0.316, P0.01).NAFLD may be not only an early marker but also an early state of CVD in obese children. Early diagnosis and treatment of NAFLD is crucial for the prevention of the occurrence and development of CVD.

To investigate the relationship between sleep duration and metabolic syndrome in obese children.Sleep time was recorded and metabolic syndrome (MS) diagnostic criteria as blood pressure, body mass index (BMI) were measured among 311 obese children. The children were divided into 4 groups by sleep time while normal-weight children served as the control group. A disorderly multi-classification logistic regression method was used.Statistically, significant differences were found in the levels of BMI, blood pressure, fasting blood glucose and postprandial 2 h glucose and the incidence rates of abnormality on MS, blood pressure, fasting insulin, and BMI/= 30 kg/m(2) between the group with daily sleep time less than 8 h and the group with daily sleep time no less than 10 h (P0.05). Date from logistic regression analysis revealed that the reduction of sleep time was the risk factor of MS in obese children.Insufficient sleep could greatly contribute to the occurrence of MS in obese children.

The incidences of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are very high in obese children, and insulin resistance may be the key point linking them together. Debates still remain as to whether NAFLD could be a component of MS. Some researchers reported that NAFLD was a composition of MS, while the others stated that NAFLD was an independent predicting factor of MS. Here we analyzed the prevalence of NAFLD and MS in 308 obese children who came to our endocrinology department from June 2003 to September 2006, and we also evaluated the relationship between NAFLD and MS in this group of obese children.Totally 308 obese children aged from 9 to 14 years with mean age of (10.7 +/- 2.6) years were enrolled. Two hundred and thirty one were males, and 77 were females. Body mass index (BMI), waist circumference (WC), biochemical indicators, liver B-mode ultrasound examination, oral glucose tolerance test (OGTT) and insulin releasing test were performed for all of the cases. The incidences of NAFLD including simple nonalcoholic fatty liver (SNAFL) and nonalcoholic steatohepatitis (NASH) as well as MS were calculated. Three subgroups were selected according to the diagnostic criteria: Group 1: OCWLD (obese children without liver disorder), Group 2: SNAFL and Group 3: NASH. The prevalence of MS, components of MS, free insulin, whole body insulin sensitivity index (WBISI), homeostasis model of insulin resistance (HOMA(IR)) were compared among these three subgroups.(1) Among all the obese children, the prevalence of NAFLD, SNAFL, NASH and MS was 65.9% (203), 45.5% (140), 20.5% (63) and 24.7% (76) respectively. Among all the MS children, the prevalence of NAFLD was 84.2% (64/76). The prevalence of MS was 29.3% (41/140) in SNAFL group and 36.5% (23/63) in NASH group, which was significantly higher than that of OCWLD group 11.4% (12/105) (P0.05), but no significant difference was found between SNAFL group and NASH group (P0.05). Moreover, there were significantly higher incidences in NASH group concerning every component of MS (hypertension, hyperlipidemia, hyperglycemia) compared with that of OCWLD group. The incidence of hypertension in SNAFL was significantly higher than that of OCWLD group. And the incidence of hyperlipidemia was markedly increased in NASH group compared with SNAFL group. NAFLD group had higher free insulin and more severe IR compared with that of OCWLD group. When OCWLD developed to SNAFL and NASH, free insulin and IR deteriorated calculated by HOMA-IR and WBISI. However there was no significant difference between NAFLD and MS children concerning free insulin and IR.The prevalence of NAFLD and MS hits high in obese children. The prevalence of NAFLD was very high among children with MS and NAFLD and MS shared the common mechanism of IR. The higher prevalence of MS and higher frequencies of MS components were tightly associated with the development of NAFLD and severity of IR.

To establish a rabbit model of juvenile nonalcoholic steatohepatitis (NASH) for further study.Twenty-eight New Zealand rabbit pups were fed with a high-fat diet (standard diet+10 % lard+2 % cholesterol) for 8 or 12 weeks as the two model groups, and 10 rabbits were fed with standard diet as the controls. Liver tissue samples were collected for Heamatoxylin-Eosin staining and pathological examination.Typical histological hepatic lesions of NASH were observed in both model groups. Compared with control group, model groups showed a significant increase in serum ALT, AST, TG, TC levels (P0.01), and decrease in serum adiponectin, IL-10 levels (P0.05), meanwhile there was no significant difference between two model groups. TC and the degree of liver fatty infiltration were independent determinants of serum adiponectin level by stepwise multiple regression, beta=-1.33, P=0.006 and beta=-0.97, P=0.038, respectively, R square equal to 0.294.The juvenile steatohepatitis rabbit model has been established and the level of adiponectin can partly reflect the severity of liver steatosis.

To determine the clinical value of hepatic fibrosis parameters and serum ferritin (SF) in obese children with nonalcoholic fatty liver disease.One hundred and one obese children aged 6-15 years and 30 healthy children aged 9-14 years were enrolled in the study. Body mass index (BMI), waist circumference (WC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic fibrosis parameters including hyaluronic acid (HA), laminin (LN), serum type III procollagen (PCIII) and type IV collagen (CIV), serum ferritin and hepatic B-ultrasonography were assessed. All subjects were divided into 4 subgroups: simple obese children (SOC), simple nonalcoholic fatty liver (SNAFL), nonalcoholic steatohepatitis (NASH) and control group. ALT, AST, hepatic fibrosis parameters and serum ferritin were compared in these four groups.Compared with control group, the serum levels of HA and PCIII increased significantly in SOC group (P0.05); Serum levels of HA, PCIII, SF, ALT and AST also elevated markedly in SNAFL group and NASH group compared with those in control group. PCIII, SF, ALT, AST increased stepwise as the disease developed from SOC to SNAFL and NASH (P0.05). SF was correlated with PCIII, ALT and AST (r=0.33,0.63,0.69,P0.05) and PCIII was well related to ALT and AST (r=0.55,0.56,P0.05). There were only 6 cases with SF301 microg/L among all obese children, they were all NASH. The average levels of HA, CIV, PCIII, ALT, AST of these 6 cases were significantly higher than those of other NASH children.Among all hepatic fibrosis parameters, serum PCIII level is an early and sensitive indicator of NAFLD and is correlated with the disease progress. SF may be also involved in early injury of fatty liver and the process of NAFLD.

To evaluate the role of fasting plasma ghrelin levels [ln(ghrelin)] and polymorphisms of ghrelin gene in Chinese obese children.Genotyping for ghrelin polymorphism was performed in 230 obese and 100 normal weight children. Among them, plasma ghrelin levels were measured in 91 obese and 23 health subjects.(1) Bivariate correlation analysis showed the ln(ghrelin) was inversely correlated with abnormality of glucose metabolism (r = -0.240, P = 0.023). Stepwise multiple regression analysis showed that abnormality of glucose metabolism was an independent determinant of plasma ghrelin levels (P = 0.023). (2) There was no difference in frequency of Leu72Met polymorphisms between obese and control groups (36.09 vs. 41.00%).Ghrelin is associated with obesity in childhood, especially associated with the glucose homeostasis. Lower ghrelin levels might be a result of obesity, but not a cause of obesity. The Leu72Met polymorphism of ghrelin gene is not associated with obesity and metabolic syndrome in Chinese children.