Abstract Background The increasing incidence of precocious puberty is a major health challenge for Chinese children, while related risk factors remain less well explored. Exposure to ambient fine particulate matter (PM 2.5 ) is a leading environmental hazard in China. Although certain components of PM 2.5 have been reported to be endocrine disruptors for sex hormones, population-based evidence is still lacking on the association between PM 2.5 exposure and precocious puberty in China. Objective Based on a cross-sectional survey covering 30 cities in 2017 to 2019, this study was designed to explore the association between long-term exposure to PM 2.5 and its 5 major components with precocious puberty in China and to check the potential modifying effects of family-related and personal factors. Methods We included 34,105 children aged 6 to 9 years. We collected the 5-year average concentrations of PM 2.5 and its 5 major components (sulfate , nitrate , ammonium , organic matter, and black carbon) in the area (at a spatial resolution of 0.1° × 0.1°) where each school was located. We used mixed effect logistic regression to estimate the effect sizes of the total mass of PM 2.5 and each of its components on precocious puberty, and we examined the modifying effects of family-related and personal factors using an additional interactive term. A weighted quantile sum (WQS) regression model was applied to identify the weights of each component in explaining the effect size of the total mass of PM 2.5 . Results We found that the odds ratio (OR) for precocious puberty per IQR increase in the concentration of total PM 2.5 mass was 1.27 (95% CI 0.92-1.75) for the whole population, 2.12 (95% CI 1.27-3.55) for girls, and 0.90 (95% CI 0.62-1.30) for boys. Similarly, the effect sizes of the 5 major components were all substantial for girls but minimal for boys. Results of the WQS analysis showed that organic matter could explain the highest proportion of the effect of PM 2.5 , with the weight of its contribution being 0.71. Modification effects of family income and dietary habits were only observed in certain population subgroups. Conclusions Long-term exposure to total PM 2.5 mass was significantly associated with precocious puberty in girls, with organic matter identified as the major effect contributor. The results add evidence on the detrimental effects of PM 2.5 on children’s development and growth.
To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of Y-shape branched PEGylated recombinant human growth hormone (YPEG-rhGH) and evaluate its short-term efficacy and safety in children with growth hormone deficiency (GHD).A total of 43 children with GHD from 12 sites in China were enrolled in this randomized, multicenter, active-controlled, double-blind (YPEG-rhGH doses) trial. Patients were randomized 1:1:1:1 to 100, 120, and 140 μg/kg/week of YPEG-rhGH groups and daily rhGH 35 μg/kg/day groups. The treatment lasted 12 weeks. The primary outcome was the area under the curve of the change of insulin-like growth factor-1 (IGF-1). The secondary outcome was the height velocity (HV) increment at week 12.A dose-dependent response of maximum plasma concentration (Cmax) and area under the concentration-time curves from 0 to 168 hours (AUC0-168h) were observed for YPEG-rhGH. The ratio of Cmax and the ratio of AUC0-168h from the first to the last dosing were 1.09~1.11 and 1.22~1.26 respectively. A YPEG-rhGH dose-dependent increase in area under effect curve (AUEC) of IGF-1 fold change was observed. Model-derived mean IGF-1 SDS was in the normal range for all three YPEG-rhGH doses. At week 12, HV was 7.07, 10.39, 12.27 cm/year, and 11.58 cm/year for YPEG-rhGH 100, 120, and 140 μg/kg/week and daily rhGH respectively. Adherence and safety were consistent with the profile of daily rhGH. No related serious adverse events were reported.The PK/PD suggests that YPEG-rhGH is suitable for the once-weekly treatment of pediatric GHD. YPEG-rhGH 120 ~ 140 μg/kg/week provides the closest HV increment with similar safety and tolerability compared to daily rhGH 35 μg/kg/day in children with GHD.ClinicalTrials.gov, identifier [NCT04513171].
Abstract Context Pegpesen is a novel Y-shape pegylated recombinant human growth hormone (rhGH) for once-weekly treatment of children with growth hormone deficiency (GHD). Objective This work aimed to evaluate the efficacy and safety of Pegpesen in children with GHD vs daily rhGH. Methods A multicenter, randomized, controlled phase 3 clinical trial was conducted at 23 centers in China with a duration of 52 weeks’ treatment. There were 391 pediatric participants diagnosed with GHD. Participants were randomly assigned 2:1 to a weekly Pegpesen group (140 μg/kg/week) or a daily rhGH group (245 μg/kg/week) for 52 weeks. The primary end point was the growth velocity (GV) at 52 weeks, and the secondary end points mainly involved changes from baseline in height SD scores for chronological age and bone age (ΔHt SDS CA and ΔHt SDS BA). Results At 52 weeks, the least squares mean (LS means) of GV was 9.910 cm/year in the Pegpesen group and 10.037 cm/year in the daily rhGH group. The LS means difference between groups was −0.127 (95% CI, −0.4868 to 0.2332), confirming that weekly Pegpesen is noninferior to daily rhGH. The LS means of ΔHt SDS CA, ΔHt SDS BA, were similar across both groups (all P > .05). Safety profiles and adherence were comparable. Conclusion Pegpesen was noninferior to daily rhGH, with similar safety, lower dosage requirements, thus presenting a new therapeutic option for children with GHD.
Obesity is a risk factor for glucose metabolism disorder. This study explored the association between the tri-ponderal mass index (TMI) and indicators of glucose metabolism disorder in children with obesity in China. This retrospective case–control study included children aged 3 to 18 years old diagnosed with obesity at Jiangxi Provincial Children’s Hospital (China) between January 2020 and April 2022. Demographic and clinical characteristics were obtained from the medical records. Factors associated with glucose metabolism disorder were explored by logistic regression analysis. Pearson correlations were calculated to evaluate the relationships between TMI and indicators of glucose metabolism disorder. The analysis included 781 children. The prevalence of glucose metabolism disorder was 22.0% (172/781). The glucose metabolism disorder group had an older age (11.13 ± 2.19 vs 10.45 ± 2.33 years old, P = .001), comprised more females (76.8% vs 66.9%, P = .008), had a higher Tanner index ( P = .001), and had a larger waist circumference (89.00 [82.00–95.00] vs 86.00 [79.00–93.75] cm, P = .025) than the non-glucose metabolism disorder group. There were no significant differences between the glucose metabolism disorder and non-glucose metabolism disorder groups in other clinical parameters, including body mass index (26.99 [24.71–30.58] vs 26.57 [24.55–29.41] kg/m 2 ) and TMI (18.38 [17.11–19.88] vs 18.37 [17.11–19.88] kg/m 3 ). Multivariable logistic regression did not identify any factors associated with glucose metabolism disorder. Furthermore, TMI was only very weakly or negligibly correlated with indicators related to glucose metabolism disorder. TMI may not be a useful indicator to screen for glucose metabolism disorder in children with obesity in China.
Abstract Prader-Willi syndrome (PWS) is a complex and multisystem neurobehavioral disease, which is caused by the lack of expression of paternally inherited imprinted genes on chromosome15q11.2-q13.1. The clinical manifestations of PWS vary with age. It is characterized by severe hypotonia with poor suck and feeding difficulties in the early infancy, followed by overeating in late infancy or early childhood and progressive development of morbid obesity unless the diet is externally controlled. Compared to Western PWS patients, Chinese patients have a higher ratio of deletion type. Although some rare disease networks, including PWS Cooperation Group of Rare Diseases Branch of Chinese Pediatric Society, Zhejiang Expert Group for PWS, were established recently, misdiagnosis, missed diagnosis and inappropriate intervention were usually noted in China. Therefore, there is an urgent need for an integrated multidisciplinary approach to facilitate early diagnosis and optimize management to improve quality of life, prevent complications, and prolong life expectancy. Our purpose is to evaluate the current literature and evidences on diagnosis and management of PWS in order to provide evidence-based guidelines for this disease, specially from China.
The primary objective of this investigation was to elucidate the manner in which ginsenoside Rg5 (Rg5) ameliorates nonalcoholic fatty liver disease (NAFLD) via the modulation of the gut microbiota milieu. We administered either a standard diet (ND) or a high-fat diet (HFD), coupled with 12-week treatment employing two distinct doses of Rg5 (50 and 100 mg/kg/d), to male C57BL/6J mice. In comparison to the HFD cohort, the Rg5-treated group demonstrated significant enhancements in biochemical parameters, exemplified by a substantial decrease in lipid concentrations, as well as the reduced expression of markers indicative of oxidative stress and liver injury. This signifies a mitigation of hepatic dysfunction induced by an HFD. Simultaneously, Rg5 demonstrates the capacity to activate the LKB1/AMPK/mTOR signaling pathway, instigating energy metabolism and consequently hindering the progression of NAFLD. Furthermore, we underscored the role of Rg5 in the treatment of NAFLD within the gut-microbiota-liver axis. Analysis via 16S rRNA sequencing unveiled that Rg5 intervention induced alterations in gut microbiota composition, fostering an increase in beneficial bacteria, such as Bacteroides and Akkermansia, while concurrently reducing the relative abundance of detrimental bacteria, exemplified by Olsenella. Furthermore, employing fecal microbiota transplantation (FMT) experiments, we observed analogous outcomes in mice subjected to fecal bacterial transplants, providing additional verification of the capacity of Rg5 to mitigate NAFLD in mice by actively participating in the restoration of gut microbiota via FMT. Drawing from these data, the regulation of the gut microbiota is recognized as an innovative strategy for treating or preventing NAFLD and metabolic syndrome. Consequently, these research findings suggest that Rg5 holds promise as a potential therapeutic agent for NAFLD management.
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