MKRN3 gene loss-of-function mutations cause central precocious puberty (CPP), whereas its deletion in Prader–Willi syndrome (PWS) paradoxically leads to hypogonadism. The mechanistic basis for these opposing reproductive phenotypes remains largely unclear. We performed whole-exome sequencing in 98 Chinese CPP patients along with a systematic review of previously reported MKRN3 pathogenic and likely pathogenic variants to summarize genotype–phenotype correlations. Subsequently, genome-wide DNA methylation profiling was performed in CPP patients with the MKRN3 pathogenic variant, and the results were compared with those of patients with PWS, idiopathic CPP, and healthy controls. A pathogenic frameshift MKRN3 variant [c.476dupC (p.Ala159fs*15)], representing the first frameshift mutation reported within the inter-C3H1 hotspot region in an Asian cohort, was identified. Patients with severe MKRN3 variants exhibited significantly earlier pubertal onset (5.80 vs. 7.50 years, P = 0.029) and higher GnRH-stimulated peak LH levels (34.55 vs. 11.00 IU/L, P = 0.047) than those with missense mutations. Methylation analysis revealed no differences in MKRN3 but identified 18,609 differentially methylated positions between MKRN3-CPP and PWS. Key findings included hypermethylation of IGSF10 (Δβ = 0.37), ZC3H18 (Δβ = 0.27), SH3RF3 (Δβ = 0.36), and PTH1R (Δβ = 0.28), alongside hypomethylation of MAGEL2 (Δβ = − 0.19), and PTPA (Δβ = − 0.23), where Δβ represents the difference in DNA methylation β values between groups. We identified a first frameshift pathogenic variant localized to the inter-C3H1 region in Asia, further confirming its functional significance. Our study suggests an epigenetic framework that could potentially explain how divergent pubertal phenotypes in MKRN3 deficiency might arise from dysregulated epigenetic programming of downstream neuroendocrine pathways.

INTRODUCTION:Idiopathic short stature (ISS) is characterized by short stature without identifiable underlying disorders. Long-acting PEGylated recombinant human growth hormone (PEG-rhGH) has emerged as a promising treatment option for ISS children. The objective of this study was to evaluate the long-term efficacy and safety of weekly PEG-rhGH in ISS children. METHODS:This multicenter, open-label, uncontrolled extension study (extension phase) followed the initial 52-week trial (main phase). All subjects received once-weekly PEG-rhGH at 0.2 mg/kg/week with dose adjustment (up to 0.4 mg/kg/week) based on height velocity (HV) and insulin-like growth factor-1 (IGF-1) standard deviation score (SDS). The primary endpoint was change in height SDS (ΔHT SDS) from baseline; secondary endpoints mainly included HV, changes in bone age/chronological age ratio, IGF-1 SDS, and average annual prescribed dose. Safety was evaluated through adverse events and clinical findings. RESULTS:Of 280 children enrolled in extension study, 268 completed 52-week treatment. This analysis included results up to week 104, representing 52-week extension phase following the 52-week main phase. At week 104, the least squares means of ΔHT SDS were 1.52, 1.24, and 1.07 for PEG-rhGH 0.2/0.2 mg/kg/week, 0.1/0.2 mg/kg/week, and 0/0.2 mg/kg/week groups, respectively. The 0.2/0.2 mg/kg/week group maintained significantly greater height improvements. HV was highest in the 0/0.2 mg/kg/week group (9.16 ± 1.33 cm/year), reflecting typical first-year catch-up growth. Mean IGF-1 SDS remained within 2SDS during 2 years. CONCLUSION:Once-weekly PEG-rhGH in children with ISS showed sustained efficacy over 2 years in all assessed height-based outcomes. Treatment remained safe and well tolerated with no new safety signals.

IntroductionAdolescents and young adults with rare diseases face a “medical cliff” when they age out of paediatric services, losing established care relationships and disease-specific expertise. Most rare diseases begin in childhood, since 69.9% of catalogued rare diseases are of exclusively paediatric onset. The problem is acute in China, where an estimated 20 million people live with a rare disease and systematic transitional care pathways remain largely absent.MethodsWe describe the development and implementation of an integrated paediatric–adult continuity of care model for rare diseases, the adult population it serves, and early operational indicators of its feasibility. This retrospective, descriptive analysis used clinical service data from the Children's Hospital of Fudan University, Shanghai, over a 38-month window (3 January 2023–25 February 2026); the model was implemented from September 2023. Its four components were expanded treatment authority with proactive management; a multidisciplinary paediatric–adult joint clinic; proactive follow-up with dynamic evaluation; and medical social work with psychosocial support. The programme admits patients aged 18–35 years.ResultsIn total, 2,341 patients aged ≥18 years generated 4,847 outpatient, emergency, and inpatient encounters (mean age at first encounter 22.7 ± 5.9 years; 51.7% female). Annual encounter volumes rose from 240 in 2023 to 1,412 in 2024 and 2,628 in 2025, with a further 567 in January and February 2026. Return attendances accounted for 4,373 encounters (90.2%), and 843 patients (36.0%) attended more than once. The leading specialities were neurology (29.1%), hepatology (12.2%), and endocrinology (8.1%); most encounters were by Shanghai residents (54.8%).DiscussionRepeat attendance measures utilisation rather than adherence, and rising volumes likely reflect progressive implementation and growing awareness rather than model effectiveness. With enabling policies, paediatric hospitals can deliver continuous care for adult rare disease patients, although these indicators describe service activity rather than clinical or patient-reported outcomes. The model is best characterised as continuity of care delivered within paediatric services rather than as a conventional transition programme, and offers a replicable blueprint for health systems lacking established adult subspeciality services; cross-provincial health insurance portability remains the single most critical barrier to nationwide scale-up.

BACKGROUND:Susceptibility to adult metabolic diseases varies significantly across ethnicities. Asian adults exhibit elevated risks associated with obesity at lower body mass index (BMI) levels; whether similar patterns occur in pediatric populations remains unclear. This study aimed to evaluate how metabolic indicators associated with childhood obesity vary across diverse racial/ethnic groups. METHODS:Age-matched adolescents (12-18 years) from diverse regions across China-along with adolescents from Hispanic, Mexican American (MA), Non-Hispanic Black (NHB), Non-Hispanic White (NHW), and Other ethnic groups from the National Health and Nutrition Examination Survey (NHANES)-were enrolled. Comprehensive demographic, anthropometric and metabolic data-including glycemic parameters, lipid profiles, and insulin resistance indices-were analyzed. Cross-sectional mediation analysis was conducted to explore the potential biological pathways underlying the relationship between obesity (BMI standard deviation score [SDS] as the exposure) and metabolic dysfunction (metabolic indicators as the outcomes), testing cortisol and adrenocorticotropic hormone (ACTH) as potential mediators. Average direct and causal mediation effects were evaluated, with results interpreted as statistical associations consistent with the mediation framework. RESULTS:The study included 632 adolescents (55.22% male, mean age 14.51 ± 1.87 years, median BMI 31.55 kg/m2). Compared to Chinese adolescents, NHB had higher HbA1c, NHW had lower HbA1c; both showed lower HOMA-β. All groups had higher HDL-C, lower total cholesterol and LDL-C levels than Chinese adolescents. HbA1c correlated positively with BMI SDS in Chinese and MA adolescents. Fasting insulin and HOMA-IR correlated positively with BMI SDS in all groups except Hispanic adolescents, while HOMA-β correlated positively in all groups except Hispanic and NHW adolescents. In Chinese adolescents, ACTH mediated the associations of BMI SDS with fasting insulin and HOMA-IR (P = 0.014 and 0.020 for mediation effects, respectively). CONCLUSIONS:This first multiethnic pediatric metabolic comparison reveals distinct racial/ethnic patterns, with ACTH emerging as a novel mediator in Chinese adolescents. Findings underscore the need for ethnicity-tailored prevention strategies.

Abstract Introduction Regulatory T cells (Tregs) maintain immune homeostasis through FOXP3-centered transcriptional complexes that tightly control lineage stability and suppressive function. However, how specific FOXP3 mutations disturb this complex and drive pathogenic Treg reprogramming in IPEX syndrome remains unclear. We identified a distinctive mechanism by which the FOXP3 V408M mutation promotes Th1-skewed inflammation and also explored a pharmacological strategy to restore Treg stability. Methods We generated FOXP3 V408M knock-in mice and performed immunophenotyping, transcriptomic, and chromatin conformation analyses to determine how the mutation affects FOXP3—T-bet interaction and Ifng transcription. An AI-driven virtual screening strategy integrating sequence- and structure-based modeling was applied to identify compounds that stabilize FOXP3—T-bet interaction. Functional validation was performed in vitro and in multiple in vivo mouse models. Results FOXP3 V408M mutation disrupted the FOXP3—T-bet interaction, thereby releasing T-bet from FOXP3-mediated repression and enhancing Ifng transcription. This defect reprogrammed Tregs toward an IFN-γ—producing phenotype that promoted Th1 inflammation. Among the AI-driven screening hits, 430C10 emerged as a first-in-class FOXP3-targeting stabilizer binding an allosteric pocket within the FKH domain. 430C10 reinforced the FOXP3—T-bet interaction and suppressed T-bet—driven IFN-γ production by Tregs. Oral 430C10 treatment markedly alleviated IFN-γ+ Treg—driven inflammation in FOXP3 V408M mice and improved disease outcomes in an acute colitis model under FOXP3 WT settings. Conclusion Our findings define the FOXP3—T-bet interaction as a tunable checkpoint controlling Treg stability and IFN-γ—driven autoimmunity. Pharmacological stabilization of this interaction with 430C10 provides a proof-of-concept therapeutic strategy for restoring immune homeostasis in IPEX syndrome and related autoimmune diseases. Funding Source Our research is supported by National Natural Science Foundation of China (82271829, 32130041, 82441047, 82241222); The Innovation Program of Shanghai Municipal Education Commission (21140902900); Noncommunicable Chronic Diseases-National Science and Tech Topic Categories Therapeutic Approaches to Autoimmunity (THER)

Regulatory T-cell (Treg) stability is maintained by dynamic remodeling of the FOXP3 transcriptional complex, and disruption of this complex leads to Treg dysfunction and immune dysregulation. However, how specific FOXP3 mutations alter the dynamic remodeling of the FOXP3 complex and thereby contribute to pathogenic Treg reprogramming in IPEX syndrome remains unclear. Here, we demonstrate that predominant Th1 inflammation manifests in both FOXP3V408M IPEX patients and FOXP3V408M knock-in mice and reveal that the mutation intrinsically impairs Treg-mediated control of Th1 inflammation, revealing a distinct pathogenesis of this mutation in IPEX syndrome. Mechanistically, the V408M mutation disrupts the FOXP3-T-bet interaction, impairing the FOXP3-mediated restraint of T-bet-driven IFN-γ production and thereby contributing to increased Th1 inflammation. Using an AI-driven virtual screening approach, we identified a first-in-class small molecule, FM029, that directly binds to FOXP3 and reinforces its interaction with T-bet. FM029 strongly suppressed Treg-derived IFN-γ production and alleviated IFN-γ-driven tissue inflammation in both FOXP3V408M mice and an acute colitis model. Collectively, these findings establish the FOXP3-T-bet interaction as a central checkpoint that governs Treg stability and IFN-γ-driven Th1 pathology, providing a proof-of-concept that pharmacologic stabilization of the FOXP3-T-bet interaction can mitigate IFN-γ-driven immune disorders.

BACKGROUND:Patients with sitosterolemia (ST) are often misdiagnosed as familial hypercholesterolemia (FH) because of overlapping lipid phenotypes. Sitosterol is considered a disease-specific biomarker; however, its diagnostic utility in highly heterogeneous populations-particularly among children-remains unclear. OBJECTIVE:To evaluate the diagnostic value of phytosterol biomarkers and develop a multivariate model to improve the diagnostic accuracy of ST. METHODS:We conducted a cross-sectional study of 379 children with suspected lipid disorders: ST (n = 38), ABCG5/8 heterozygous carriers (n = 12), genetically confirmed FH (n = 54), individuals with FH-like (n = 50), and healthy controls (n = 225). Clinical characteristics, lipid profiles, phytosterols, liver enzymes, and genetic data were collected. The diagnostic performance of single biomarkers and a multivariate model was evaluated. A clinical gray zone based on sitosterol levels was defined to assess the models' ability. RESULTS:Sitosterol demonstrated near-perfect discrimination for ST in the overall population area under the curve ([AUC] 0.994; 95% CI, 0.988-1.000), outperforming conventional lipid markers. However, substantial overlap in phytosterol distributions was observed among ST, heterozygotes, and FH-related phenotypes. Within the gray zone (sitosterol: 17.7-50 μg/mL), the diagnostic performance of sitosterol declined markedly (AUC 0.653). The multivariable model demonstrated comparable overall performance (AUC 0.983) but significantly improved discrimination in the gray zone (AUC 0.806), with good calibration and greater net clinical benefit. CONCLUSION:Although sitosterol is highly effective for identifying ST, its diagnostic performance declines significantly in clinically significant gray zone cases. A combined sterol-based model improves diagnostic discrimination in these challenging scenarios and supports a stepwise diagnostic strategy for children with suspected ST.

The 15q26 deletion and duplication syndromes are rare chromosome diseases with growth deviation and structural anomalies such as facial abnormality, cardiac malformation and hand/foot/skeleton malformations. Insulin-like growth factor 1 receptor (IGF1R), located on chromosome 15q26, is key for pre- and postnatal growth. The present study aimed to determine whether IGF1R serves as a key factor in growth regulation in 15q26 deletion and duplication syndromes. Patients with 15q26 deletions and duplications enrolled in the China Neonatal Genomes Project (CNGP) were recruited. A systematic review of 15q26 deletion and duplication cases was performed, followed by meta-analysis to evaluate the roles of IGF1R and three other genes [myocyte enhancer factor 2A (MEF2A), leucine-rich repeat kinase 1 (LRRK1) and nuclear receptor subfamily 2 group F member 2] involved in growth regulation. A total of 10 eligible patients from the CNGP, including seven with deletions and three with duplications, were identified. The literature search and screening yielded 78 patients with 15q26 deletions and 10 with 15q26 duplications. Clinical features observed in >70% of the patients in the deletion group were facial abnormalities, developmental delay, short stature and hand/foot/skeleton malformations, whereas the duplication group exhibited facial abnormality, hand/foot/skeleton malformation and speech development delay. In 15q26 deletion, three candidate genes were associated with an increased risk of short stature: IGF1R [odds ratio (OR): 8.43; 95% confidence interval (CI): 2.22-32.00], LRRK1 (OR: 100.00; 95% CI: 11.86-843.23) and MEF2A (OR: 32.21; 95% CI: 3.81-272.47). In 15q26 duplication, none of the candidate genes significantly affected tall stature. Using meta-analysis, the present study revealed that IGF1R is not the only key gene responsible for growth abnormalities in 15q26 deletion and duplication syndromes.

Disclosure: J. Chen: None. Y. Lv: None. H. Du: None. Y. Ma: None. L. Han: None. F. Luo: None. G. Li: None. L. Chen: None. B. Cao: None. M. Qin: None. C. Su: None. L. Wei: None. Q. Wang: None. P. Li: None. Z. Xu: None. R. Xie: None. X. Chen: None. H. Wu: None. J. Xia: Jing Xia is employee of Changchun GeneScience Pharmaceutical Co., Ltd. D. Pang: Dongqing Pang is employee of Changchun GeneScience Pharmaceutical Co., Ltd.. C. Gong: None. Objective: To evaluate the efficacy and safety of weekly PEGylated recombinant human growth hormone (PEG-rhGH, Jintrolong) over 3-year in prepubertal children with Turner Syndrome (TS). Methods: This multicenter, randomized, negative-controlled phase 2 study (NCT03189160) included a 52-week main phase followed by an ongoing open-label extension. Prepubertal patients with genetically confirmed TS, bone age <12 years, height≤-2.5 SD for age, and no prior GH therapy were randomized 1:1:1 across 8 centers to receive weekly subcutaneous Jintrolong at 0.1 mg/kg, 0.2 mg/kg, or no treatment with monitoring only. Patients completing the main phase entered the open-label extension, during which all received Jintrolong (0.1-0.4 mg/kg/week). Doses were adjusted every 13 weeks based on annualized height velocity (AHV), IGF-1 SDS, and clinical guidelines. Treatment continued until near-adult height, with follow-up every 26 weeks thereafter until final height was attained. The primary endpoint was change in height SDS (HT-SDS) calculated using the LMS method from baseline at Week 52 and every 52 weeks during extension. Other growth-related parameters and safety were also evaluated. Results: A total of 177 patients were included in the main phase analysis, and 170 in the extension phase. The mean (SD) age at baseline was 7.87 (3.01) years, and mean HT-SDS was -3.33 (0.63). At Week 52, mean (SD) changes in HT-SDS from baseline were -0.07 (0.29) in the control group, 0.28 (0.35) in the 0.1 mg/kg/week group, and 0.60 (0.41) in the 0.2 mg/kg/week group. Both treatment groups showed significantly improvement compared with control (p<0.0001 for each), and the 0.2 mg/kg/week group improved significantly than the 0.1 mg/kg/week group (p<0.0001). After two years of extension (Year 3 overall), mean (SD) increases in HT-SDS from baseline were 0.81 (0.68) and 1.15 (0.63) in the 0.1 and 0.2 mg/kg/week groups, respectively, indicating sustained benefit, particularly in patients initially received the higher dose. AHV in both Jintrolong groups peaked at Week 52 and gradually declined over time but remained above baseline at Week 104 and Week 156. During the extension, 84.1% of patients (143/170) underwent dose escalation. The incidence of adverse events (AEs) and treatment adherence were comparable across groups during the main phase. Most AEs during long-term treatment were mild to moderate and consistent with the known GH safety profile. Conclusion: Weekly Jintrolong at 0.1 to 0.4 mg/kg/week provided sustained and clinically meaningful growth improvements over 3 years in girls with TS. Most patients required dose escalation after the first year to achieve optimal growth velocity. This dosing range was appropriate for most patients and associated with a favorable long-term safety profile. Jintrolong offers a convenient long-acting formulation for managing short stature associated with TS. Presentation: Saturday, July 12, 2025

Disclosure: A. Leong: None. S. Chen: None. M. Alimussina: None. J. Bryce: None. M. Chen: None. A. Fu: None. E.F. Gevers: None. C. Hoybye: None. M. Hughes: None. V. Iotova: None. M.Y. Jalaludin: None. G.F. Kerkhof: None. F. Luo: None. J. Miller: None. O. Nyunt: None. E.F. Roche: None. M.G. Shaikh: None. T. Strong: None. M. Tauber: None. L.S. Tyszler: None. S.F. Ahmed: None. Introduction: Recombinant Human Growth Hormone (GH) was approved in the US (2000) and Europe (2001) for children with Prader-Willi Syndrome (PWS) to improve growth and body composition, with reported benefits in cognition, motor skills and behaviour. However, longer term safety and efficacy data of GH in PWS are still lacking and may be difficult to interpret due to lack of consistency in data collection among studies. This study aimed to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, to minimise burden on clinician data entry and improve quality of data collection to facilitate future studies on long term outcomes. Methods: The study was undertaken by the PWS Expert Working Group in GloBE-Reg, an international registry platform which supports studies on long-term safety and effectiveness of drugs. Twelve clinical experts on PWS from 10 countries and two patient representatives collaborated to develop this recommendation, based on previously published methodology (Chen et al. Horm Res Pediatr 2023). Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided <50% deemed the item difficult to collect. Several anomalies to the MDS rule were discussed to formulate the final MDS recommendation. Results: In total, 294 items were compiled from routine clinical practice with 33 redundant items removed and 261 items subjected to the grading system. 151/261 items achieved consensus as important data to collect when monitoring children with PWS on GH treatment, while 218/261 items were deemed easy to collect. Combining both the criteria for importance and ease of collection, 126 items fulfilled the MDS requirement. Four items were designated as core data, two were computed fields, five reassigned as non-MDS, 13 removed as unrelated to safety and effectiveness and 65 were merged into 18 fields. Several anomalies which did not fulfill MDS criteria were also extensively discussed to determine its validity within the MDS, in particular family history of Type 2 diabetes, change of GH therapy (if applicable) and adherence, to produce the final MDS recommendations of 58 items; of which 24 are only to be completed once. Conclusion: This exercise has identified by consensus the minimum dataset considered necessary, which can be collected through real-world data, to provide consistency and comparability in global studies for monitoring the safety and effectiveness of GH in children with PWS, applicable to the current daily preparations and potential newer long-acting GH. Presentation: Saturday, July 12, 2025

Background X-linked hypophosphataemia (XLH) is a rare inherited disorder often misdiagnosed and lacking sufficient aetiological treatment. Previous studies have shown that XLH is associated with worse health-related quality of life (HRQoL) and greater economic burden for children and their families compared with the general population, but evidence from China is scarce. This study aimed to comprehensively explore the burden and HRQoL of XLH children in China.Methods An online retrospective survey of paediatric patients with XLH and their caregivers was conducted nationwide during March to June 2021. A self-administered questionnaire was used to collect socio-demographic, clinical and economic data. The EQ-5D-Y-3L instrument was employed to assess HRQoL, and the health utility score was calculated. Direct medical, non-medical and indirect costs were determined. Multivariate regression analysis was performed to explore potential associations between HRQoL and identified influencing factors.Results The study included 221 subjects with a mean age of 7.25 years, of whom 119 (53.8%) were girls. Most XLH children (63.8%) lived in rural areas, and 39.4% reported a family history. Over 70% experienced misdiagnosis. The average total annual cost per patient was found to be 34 657.85 CNY. Of direct medical costs, patients’ out-of-pocket expenses were substantial. The incidence of catastrophic health expenditure was 19.9%. The means (SD) of EQ-5D-Y-3L health utility and EQ-5D VAS scores were 0.83 (0.14) and 56.07 (10.95). Both univariate and multivariate analyses found older age and lower economic affordability were associated with poorer HRQoL.Conclusions The study underscores the significant burden of XLH on paediatric patients and their families in China, both in terms of HRQoL and economic costs. The findings emphasise the importance of early detection, accurate diagnosis, cost-effective targeted interventions and long-term multidisciplinary management strategies to improve the lives of XLH children and their families.

Long-term fine particulate matter (PM2.5) exposure was associated with childhood obesity. However, the key PM2.5 components and whether PM2.5 effect may vary by obesity type, growth stage, sex, and individual/family characteristics have yet been examined. In this study, we investigated 213,907 Chinese children and adolescents aged 3-18 years in 2017-2019. Three-year average concentrations of PM2.5 and five major components were assigned to each participant's address. Multivariable mixed-effects model and weighted quantile sum regression were used to estimate the effect sizes of each component. Stratified analyses were performed by age and sex groups, with the interactive effects of a series of individual/family features evaluated. The odds ratio of childhood obesity was 1.28 (95 %CI: 1.15-1.43) for per interquartile range increase in PM2.5, with organic matter identified as the key contributor. General central obesity and mixed obesity were more sensitive to PM2.5 exposure than peripheral obesity. As children aged, the effect size of PM2.5 attenuated for general central obesity, remained unchanged for mixed obesity and increased for peripheral obesity. Females, children with obese parents, and those with lower levels of physical activity were more vulnerable than others. Other adverse effect modifiers for certain children included family with one child, low family income, and less sleep duration. Our findings emphasize that the influence of exposure to PM2.5 and its components on risk of obesity in children and adolescents should be considered comprehensively in developing adequate obesity prevention strategies.

Objective:To investigate whether human leukocyte antigens (HLAs) influence gut microbiota composition and contributes to delayed type 1 diabetes mellitus (T1DM) onset in children. Methods:This multicenter cross-sectional study included 106 newly diagnosed pediatric T1DM patients (age <18 years) and 69 healthy controls from nine Chinese cities. Gut microbiota was profiled via whole-metagenome shotgun sequencing, and HLA alleles were genotyped by PCR sequence-based typing. Participants were stratified by HLA-risk scores. Statistical analyses included α/β-diversity metrics, linear discriminant analysis effect size analysis (LEfSe), and Spearman correlation adjusted for confounders. Results:Principal coordinates analysis (PCoA) exposed discernible disparities in gut microbiota structures within the high-HLA-risk T1DM cohort relative to both high- and low-HLA-risk control groups (R 2 = 0.0562, p=0.003 and R 2 = 0.0343, p=0.003). HLA-C ∗ 0304 carriers exhibited delayed T1DM onset compared to noncarriers (adjusted R 2 = 0.225, p=0.017). High-HLA-risk T1DM patients showed distinct microbiota divergence from controls (R 2 = 0.0562, p=0.003), driven by reduced Lachnospiraceae and Blautia (butyrate producers) in noncarriers. Conversely, HLA-C ∗ 0304-positive T1DM patients had enriched Blautia (p=0.005) and Lachnospiraceae (p=0.039), alongside lower opportunistic pathogens (Citrobacter; p < 0.05). High-HLA-risk patients also displayed lower fasting C-peptide levels than low-risk counterparts (0.19 ± 0.14 vs. 0.26 ± 0.19 µg/mL, p=0.029). Conclusions:Our study demonstrates that specific HLA class I subtypes (e.g., C ∗ 0304) may modulate T1DM onset through selective enrichment of beneficial gut microbiota. Elucidating the mechanisms by which HLA variants regulate mucosal immunity and coordinate HLA-microbiota-immune interactions holds significant potential for developing targeted interventions against T1DM pathogenesis.

Growth hormone deficiency (GHD) is an endocrine disorder characterized by insufficient production of growth hormone (GH). PEGylated recombinant human growth hormone (PEG-rhGH; Jintrolong®, GeneScience Pharmaceuticals Co., Ltd.) is the only long-acting GH approved in China for treating paediatric GHD (PGHD). Long-term Efficacy and Safety Evaluation of Growth Hormone in Children in China (CGLS) is a large, surveillance registry database of participants with short stature treated with PEG-rhGH or rhGH in a real-world setting. In this study, we evaluated the safety profile and five-year growth response of PEG-rhGH based on the data from the CGLS database in participants with PGHD in China. In this real-world registry-based observational study, a total of 1,207 participants were included in the safety analysis set. Of these, 339 participants who had received PEG-rhGH continuously for five years were also included in the efficacy analysis. Key outcomes assessed comprised adverse events (AEs), serious AEs (SAEs), and height gain. The safety assessment indicated that 563 participants exhibited 1328 AEs with an incidence rate of 46.6

Poria cocos polysaccharides (PCP) are recognized as potential prebiotics with documented metabolic benefits in adults. However, their impact on the gut microbiota of children remains unclear. This study aimed to evaluate the effects of PCP versus inulin (INL) on the gut microbiota and bacterial metabolites in normal-weight children (CON) and obese children (OB). In vitro fermentation was conducted using fecal samples pooled from five normal-weight children and five obese children, respectively. The samples were incubated with PCP, INL, or a blank control under anaerobic conditions at 37 °C for 24 h. After fermentation, the effects of PCP and INL on gut microbiota were evaluated using 16S rRNA sequencing. Bacteria-derived metabolites were measured using targeted metabolic profiling. Single-strain validation was performed to confirm effects on key bacterial taxa. PCP supplementation promoted the growth of Bifidobacterium and Limosilactobacillus in both normal-weight and obese children, accompanied by a rise in acetic acid production, particularly in normal-weight children. Compared to INL, PCP showed similar but slightly weaker effects on Bifidobacterium growth and short-chain fatty acids (SCFAs) production, but more strongly stimulated Limosilactobacillus growth. Notably, PCP also stimulated the production of indolelactic acid in both obese and normal-weight children. Correlation analysis indicated that Bifidobacterium and Limosilactobacillus were positively associated with acetic acid, lactic acid, and indolelactic acid, and negatively associated with tryptophan. Single-strain fermentation supported the community-level findings. PCP and INL both modulate gut microbiota and metabolic profiles in children, with PCP demonstrating a distinct prebiotic profile. Notably, PCP increased health-associated metabolites such as acetic acid and indolelactic acid, which are implicated in gut barrier support, immune modulation, and metabolic regulation. These findings suggest PCP may be considered a functional food component for supporting gut health in children, warranting further research.

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 (PM2.5) is a leading environmental hazard in China. Although certain components of PM2.5 have been reported to be endocrine disruptors for sex hormones, population-based evidence is still lacking on the association between PM2.5 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 PM2.5 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 PM2.5 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 PM2.5 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 PM2.5. Results We found that the odds ratio (OR) for precocious puberty per IQR increase in the concentration of total PM2.5 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 PM2.5, 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 PM2.5 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 PM2.5 on children’s development and growth.