INTRODUCTION:Lonapegsomatropin, a prodrug of somatropin, is approved for once-weekly treatment of paediatric growth hormone deficiency (GHD) in the USA and Europe. Here, we report the first trial to assess the efficacy and safety of weekly lonapegsomatropin compared to daily somatropin in treatment-naive Chinese children with GHD. METHODS:The briGHt trial was a randomized, open-label, active-controlled, 52-week, phase 3 trial (NCT04326374; CTR20200399) conducted at 17 sites across China. Treatment-naive, prepubertal children with GHD were enrolled and randomized 2:1 to either lonapegsomatropin 0.24 mg hGH/kg/week or equivalent weekly dose of daily somatropin 0.034 mg/kg/day. The primary endpoint was annualized height velocity (AHV) at week 52. Secondary endpoints included change in height standard deviation score (ΔHT SDS) from baseline, insulin-like growth factor 1, and safety. RESULTS:A total of 153 participants received treatment. Least squares (LS) mean ± standard error (±SE) of AHV at week 52 was 10.66 ± 0.22 cm/year for weekly lonapegsomatropin and 9.75 ± 0.26 cm/year for daily somatropin; weekly lonapegsomatropin demonstrated non-inferiority and superiority over daily somatropin, with a difference of 0.91 ± 0.28 cm/year (95% confidence interval: 0.37-1.45; p = 0.0010). LS mean (±SE) of ΔHT SDS was 1.01 ± 0.04 for weekly lonapegsomatropin and 0.83 ± 0.05 for daily somatropin at week 52, favouring lonapegsomatropin from week 13 (p < 0.05) onward. The safety profile was similar between treatment groups. CONCLUSIONS:Weekly lonapegsomatropin demonstrated non-inferiority and superiority in efficacy compared to daily somatropin among treatment-naive Chinese children with GHD. The treatment groups showed comparable safety and tolerability profiles.

Burosumab has shown benefits in treating X-linked hypophosphatemia (XLH), a rare genetic bone disorder that causes rickets among pediatric patients. However, data in Chinese children with XLH are lacking. Therefore, we evaluated the effectiveness, safety, and pharmacokinetics of burosumab among Chinese children (aged 1-12 yr) with XLH in this open-label, multi-center, single-arm, phase 4 study. Of the 28 patients enrolled (12 male, 16 female), 27 completed the study. All patients received s.c. injections of burosumab at a starting dose of 0.8 mg/kg every 2 wk for 64 wk. The mean ± SD patient age was 5.68 ± 3.07 yr. Burosumab treatment increased the serum phosphorus level by 0.96 ± 0.27 mg/dL from baseline during the burosumab dose cycles (average of week 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64). The improvement from baseline (2.33 ± 0.24 mg/dL) to week 64 (3.29 ± 0.30 mg/dL) was significant (p < .05). The Radiograph Global Impression of Change was significantly improved at week 64 (1.90 ± 0.48; p < .0001 vs baseline), and the percentage predicted 6-min walking test among patients aged ≥5 yr with post-baseline values (n = 16) was significantly increased from 67.32% ± 8.27% at baseline to 71.91% ± 8.25% at week 64 (p < .05). All patients experienced treatment-emergent adverse events; most were mild to moderate. In conclusion, burosumab treatment in Chinese children with XLH corrected serum phosphorus levels and improved clinical parameters with tolerable safety profiles.

Short stature may be caused by a multitude of conditions, including genetic and non-genetic causes. Over the last decade, advances in genetic sequencing technologies have revolutionized our understanding of the underlying physiology of growth and greatly increased our ability to identify genetic etiologies of short stature. The current guideline provides a general overview of the approach to the evaluation of a child with short stature, followed by recommendations identifying factors in the medical and family history, physical examination, radiographic, and laboratory work up which increase the likelihood of identifying a genetic etiology. An algorithm is proposed for the genetic workup of individuals with short stature based on their clinical presentation. The benefits and risks of genetic testing are discussed as well.

Glycogen storage disease type IIIa (GSDIIIa) causes progressive cardiomyopathy, and current high-fat dietary strategies lack consensus regarding long-term cardiovascular safety. We evaluated the efficacy and safety of high-protein versus high-fat diets in a novel cardiac-specific AGL knockout (CKO; AGLflox/flox/MHC-Cre) mouse model to specifically assess isolated cardiac responses. CKO mice were randomized at weaning to High-Protein (HPD), High-Protein High-Fat (HPHFD), or Low-Protein (LPD) diets, with approximate protein/fat/carbohydrate distributions of 40%/4%/50%, 40%/50%/10%, and 10%/4%/80%, respectively; CKO mice on normal diet (ND) and AGLflox/flox mice served as controls. Cardiac phenotypes and hepatic gluconeogenic enzymes were evaluated longitudinally up to 24 weeks. CKO-ND mice developed progressive cardiomyopathy with elevated myocardial glycogen at 24 weeks (32.01 ± 3.22 vs. 5.90 ± 2.21 mg/g in controls, p < 0.001), reduced left ventricular ejection fraction, and elevated serum creatine kinase. Both HPD and HPHFD significantly reduced myocardial glycogen burden (12.82 ± 3.58 and 15.07 ± 4.40 mg/g, p < 0.001), restored systolic function, and normalized hypertrophy. However, HPHFD induced distinct hyperlipidemia, whereas HPD maintained a stable lipid profile. Furthermore, therapeutic benefits in high-protein groups were associated with upregulated hepatic rate-limiting gluconeogenic enzymes (FBP2, PCK1). In this cardiac-specific AGL knockout model, a high-protein, non-high-fat diet attenuated cardiac glycogen accumulation and systolic dysfunction without the hyperlipidemia observed with the high-fat regimen. These preclinical findings support further evaluation of high-protein dietary strategies for GSDIIIa cardiomyopathy and suggest a possible liver-heart metabolic axis involving hepatic gluconeogenesis.

Microglial pro-inflammatory activation contributes to neuroinflammatory processes in many neurological disorders. Saturated fatty acids such as palmitic acid (PA) are increasingly recognized as inflammatory cues, yet the molecular mechanisms linking PA to microglial inflammatory responses remain incompletely defined. In this study, using BV-2 microglia as an exploratory in vitro model, we investigated whether C5aR1-sensitive signaling and JMJD3/H3K27me3-related epigenetic changes are involved in PA-associated inflammatory responses. PA exposure increased Iba1 expression, altered CD86/CD206 expression, and enhanced the secretion of IL-1β, IL-6 and TNF-α. Exogenous C5a produced broadly similar inflammatory changes. Under heat-inactivated serum conditions, PA increased cell-associated C5a immunoreactivity and extracellular C5a levels, and these C5a-related readouts were reduced by PMX53. PMX53 also attenuated PA-associated increases in inflammatory markers and in the expression of TLR4, total NF-κB p65, c-Fos, and c-Jun. In parallel, PA and C5a increased JMJD3 expression and JMJD3 enrichment at selected IL-1β and IL-6 promoter regions, accompanied by reduced H3K27me3 enrichment at these loci. Pharmacological KDM6 inhibition with GSK-J4 attenuated PA-associated increases in IL-1β and IL-6 expression. Together, these findings support the involvement of C5aR1-sensitive inflammatory signaling and JMJD3/H3K27me3-related epigenetic regulation in PA-associated microglial inflammatory responses.

With the continuous refinement of China's rare disease prevention and treatment policies, the diagnosis and treatment capacity for rare diseases in China has been steadily improved; however, delayed diagnosis, inadequate transition of care, and poor continuity of long-term management remain common, particularly in pediatric rare diseases. Pediatric rare diseases often arise during critical developmental stages and exhibit age-dependent phenotypic evolution, such that diagnostic delays may lead to the missing of critical intervention windows. As the leading institution of the Hubei Provincial Rare Disease Medical Center and the Rare Disease Quality Control Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (hereinafter referred to as "Tongji Hospital") has established and implemented a rare disease discipline cluster model centered on platform convergence and specialty clustering. This model centers on the whole-life-cycle management needs of pediatric rare diseases, and constructs a systematic operational framework covering technical and data support, platform governance, specialized cluster operation, as well as regional and policy coordination. By summarizing the organizational pathway and practical effects of the rare disease discipline cluster construction at Tongji Hospital, this paper aims to provide a reference for general hospitals in promoting the development of rare disease diagnosis and treatment systems.

INTRODUCTION:The ACHieve study assessed growth velocity, body proportionality, and clinical events in children with achondroplasia not receiving growth-promoting therapy. METHODS:ACHieve was a global, longitudinal, prospective, observational study. Children ≤8 years old with achondroplasia were enrolled and evaluated every 6 months for anthropometric parameters and clinical events. RESULTS:ACHieve enrolled 259 children in 15 countries, including 83 from China. Median follow-up was 21 months; median age of diagnosis was approximately 52 weeks in China and 2 weeks elsewhere. Growth parameters were similar regardless of region. Mean annualized growth velocity was 9.3 cm/year for males and 10.4 cm/year for females at age 1 and decreased to 4.1 cm/year and 4.6 cm/year, respectively, at age 4. Upper-to-lower-body segment ratio was generally consistent across regions. Overall, 77.2% of participants experienced clinical events, 34.0% of which were considered related to achondroplasia. Two deaths occurred (one accident and one cardiac arrest of unknown origin). CONCLUSION:ACHieve was one of the largest longitudinal natural history studies of achondroplasia to date and included the largest prospective Chinese achondroplasia cohort. The results demonstrated common trajectories in growth parameters regardless of region, indicating the generalizability of findings.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder characterized by hyperphosphatemia and ectopic calcifications. Mutations in GALNT3, which encodes a key enzyme responsible for O-glycosylation of FGF23, represent a major genetic cause of HFTC. This modification is essential for the stability and secretion of FGF23. We investigated a 4-year and 6-month-old Chinese girl with HFTC to characterize the clinical features, identify the causative variants, and explore the underlying pathogenic mechanism. Whole-exome sequencing followed by Sanger validation identified novel compound heterozygous variants in GALNT3 (c.659T>A, p.Ile220Asn and c.1850C>A, p.Ser617*). The patient exhibited hyperphosphatemia with a biochemical profile consistent with FGF23 deficiency, including extremely low intact FGF23 and elevated C-terminal fragments. Functional studies using Western blotting and wheat germ agglutinin affinity chromatography demonstrated that the mutant GALNT3 caused a severe defect in FGF23 O-glycosylation, leading to impaired secretion of intact FGF23. Glycosylated FGF23 was detected only in the medium of cells expressing wild-type GALNT3. These findings indicate that defective O-glycosylation results in failure of FGF23 secretion and functional inactivation. This study expands the mutational spectrum of GALNT3 and provides mechanistic insight into the role of GALNT3 in phosphate homeostasis.

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.

Familial partial lipodystrophy type 3 (FPLD3) is a rare autosomal dominant disorder caused by mutations in peroxisome proliferator-activated receptor gamma(PPARG), which encodes the key adipogenic transcription factor peroxisome proliferator-activated receptor gamma(PPARγ). Clinical diagnosis is challenging due to phenotypic overlap with common metabolic syndromes. We identified a novel PPARG variant in a Chinese family and performed comprehensive functional characterization to elucidate its pathogenic mechanism. The proband, a 15-year-old boy presenting with atypical fat distribution, severe insulin resistance, hypertriglyceridemia, and pancreatitis, underwent clinical evaluation and whole-exome sequencing. The identified variant was confirmed by Sanger sequencing. Its functional impact was assessed through in silico modeling, luciferase reporter assays, protein stability analysis (cycloheximide chase), and evaluation of mitochondrial function (JC-1 staining) and adipocyte gene expression in cellular models. A heterozygous PPARG c.634C>T (p.Arg212Trp, R212W) variant was identified and segregated with the phenotype. Functional studies revealed that the R212W mutant exhibits a partial loss of transcriptional activity (~40% of wild-type) while retaining ligand sensitivity. Crucially, we demonstrated that the mutant protein has significantly reduced stability due to accelerated degradation. In adipocyte models, R212W expression led to impaired mitochondrial membrane potential, depleted cellular ATP levels, and downregulated expression of key metabolic genes (glucose transporter 4[GLUT4], adiponectin[ADIPOQ], fatty acid binding protein 4[FABP4], lipoprotein lipase[LPL], perilipin 1[PLIN1]). These functional deficits were partially rescued by treatment with the PPARγ agonist rosiglitazone. We report a novel pathogenic PPARG R212W variant associated with FPLD3. Our data extend beyond a simple loss-of-function model by establishing a multi-faceted pathogenic mechanism involving protein destabilization, mitochondrial dysfunction, and cellular bioenergetic failure. The partial rescue by rosiglitazone suggests a potential therapeutic avenue. This study underscores the importance of integrating clinical phenotyping with deep functional analysis to diagnose and understand rare monogenic lipodystrophies.

Autism spectrum disorder (ASD) involves heterogeneous neurodevelopmental alterations, yet the genetic mechanisms linking ASD to variation in brain structure remain unclear. Imaging-derived phenotypes (IDPs) from large population cohorts offer the opportunity to explore structural features contributing to ASD risk, but the convergence of genetic evidence with structural imaging alterations observed in ASD cohorts has not been systematically investigated. We integrated ASD genome-wide association study (GWAS) summary statistics with 3,935 UK Biobank imaging-derived phenotypes to identify brain structural features with potential causal roles in ASD. Causal inference was performed using inverse-variance weighted Mendelian randomisation (MR) with extensive sensitivity analyses. Genetic sharing was evaluated using Linkage disequilibrium (LD) score regression and local genetic correlation modelling with Local Analysis of Variant Association (LAVA). Independent phenotypic convergence was evaluated in the ABIDE cohort by mapping genetically implicated IDPs onto case–control differences in cortical–subcortical connectivity. Multi-trait co-localisation (HyPrColoc) was conducted across ASD, IDPs, and brain expression quantitative trait loci (eQTL) datasets. Cell-type specificity and transcriptional alterations were examined using single-cell RNA-seq from ASD post-mortem cortex. MR identified 59 IDPs in the combined-sex analysis indicating robust causal associations with ASD after heterogeneity correction. LD score regression revealed 20 of 59 IDPs with significant global genetic correlation with ASD, while LAVA identified 91 loci with significant local genetic correlation. In the Autism Brain Imaging Data Exchange I (ABIDE I) cohort, IDPs identified as genetically causal mapped onto reduced cortical–subcortical connectivity in ASD. Multi-trait co-localisation detected 22 ASD–IDP shared variants, among which rs2668622 showed joint association with ASD, the right anterior thalamic radiation intracellular volume fraction (ICVF), and brain-region–specific gene expression, with LRRC37A emerging as the most consistently supported gene. Single-cell RNA-seq further showed that LRRC37A is enriched in L2/3 and L5/6 corticocortical projection neurons and significantly downregulated in ASD. Together, these multi-omics findings support a model in which genetically mediated alterations in white matter microstructure contribute to ASD and converge with structural connectivity differences. The identification of LRRC37A as a co-localised gene with consistent evidence of genetic, imaging, and cell-type expression highlights a potential molecular effector linking genetic risk to circuit-level alterations. Network perturbation analyses further revealed that LRRC37A dysregulation induces layer-specific disruption of gene regulatory networks, characterised by widespread destabilisation in L2/3 neurons and hub-targeted perturbation in L5/6 corticocortical neurons. This study delineated cross-scale biological pathways underlying ASD and provides a framework for future mechanistic investigation.

ABSTRACT Respiratory syncytial virus (RSV) is a leading cause of acute respiratory tract infections (ARTI) in infants and young children. Co-infection with other respiratory pathogens is common in RSV infection. However, the associations of co-infection with disease severity and their potential interactions remain poorly understood, especially in light of evolving epidemiological patterns of respiratory pathogens following the COVID-19 pandemic. This multicenter, retrospective study included 2,862 children under 5 years of age and hospitalized with RSV at three pediatric centers in Wuhan, China, between June 2020 and May 2023. We evaluated the associations of co-infecting pathogens, including bacteria, viruses, fungi, and atypical bacteria, with disease severity, length of hospital stay, and inpatient medical expenses. We found that nearly 44% of children with RSV were co-infected with at least one additional pathogen. Co-infection rates fluctuated in correlation with the implementation and relaxation of COVID-19 non-pharmaceutical interventions. While viral and atypical bacterial co-infections did not significantly alter outcomes, bacterial (OR = 2.00, 95% CI: 1.48, 2.70) and fungal (OR = 2.57, 95% CI: 1.23, 5.35) co-infections were strongly associated with increased disease severity. Both types were also linked to longer hospital stays (days, β = 0.63, 95% CI: 0.38, 0.88 for bacterial; β = 2.68, 95% CI: 1.94, 3.43 for fungal) and higher inpatient medical expenses (Chinese Yuan [CNY], β = 2,317.16, 95% CI: 1,534.43, 3,099.88 for bacterial; β = 6,636.55, 95% CI: 4,366, 8,907.10 for fungal). No significant additive interactions were found between bacterial and fungal co-infections. These findings highlight the importance of distinguishing co-infection types in the clinical management of RSV.IMPORTANCEThis study clarifies the clinical significance of pathogen co-infections in children hospitalized with respiratory syncytial virus (RSV). We demonstrate a critical distinction that co-infections with bacteria or fungi are associated with more severe disease, longer hospitalizations, and higher costs, whereas viral or atypical bacterial co-infections are not. In the context of evolving RSV epidemiology and pathogen co-infections in the post-pandemic era, this finding may help risk-based clinical management when co-infection exists.

Importance Kidney dimensions are critical in pediatric urology for assessing and monitoring various conditions. Objective This study aimed to establish normative renal growth curves for Chinese children aged 0-14 years using ultrasound imaging and to examine the influence of age, height, and sex on kidney dimensions. Methods In this cross-sectional study, we enrolled 6033 healthy children (aged 0-14 years) at our tertiary care center between June 2016 and July 2023. Standardized renal ultrasonography was performed by certified sonographers to obtain precise measurements of kidney length and width. We established comprehensive percentile-based reference ranges (P3-P97) stratified by height. Regression analysis was used to evaluate developmental patterns, with particular attention to height-related growth trajectories. Results The left kidney was consistently larger than the right in both length and width across all ages and sexes (P < 0.01). Although kidney lengths were slightly greater in males than in females, this difference was not statistically significant. Kidney length showed strong positive correlations with both age (P < 0.01) and height (P < 0.01). Notably, the association with height was significantly stronger than that with age (R2 = 0.884 vs. R2 = 0.353/0.709), particularly in children under 1 year of age. Interpretation This study provides comprehensive reference data for renal development in Chinese children aged 0-14 years, highlighting age-related patterns and strong positive associations with height. Ultrasound proves to be a reliable and non-invasive tool for monitoring renal growth and detecting abnormalities.

Background: Turner syndrome (TS) is a congenital sex chromosome disorder. Krabbe disease (KD) is a rare autosomal recessive neurometabolic disorder. Here, we reported the first case of a child with both conditions. Case Description: A girl presenting as short stature was diagnosed with 45,X TS at the age of 9 years, showed significant height improvement with recombinant human growth hormone (rhGH) therapy, which was well-tolerated without drug-related adverse events. At age 14 years, she was hospitalized with nausea, abdominal pain, dizziness, fatigue, and weight loss, and was diagnosed with secondary adrenal insufficiency. Comprehensive evaluation ruled out TS and prior rhGH therapy as causes for secondary adrenal insufficiency, prompting consideration of other inherited metabolic disorders. Ultimately, the multidisciplinary team conducted an evaluation confirming KD through genetic testing and detection of below-normal galactocerebrosidase enzyme activity (40.6 nmol/17h/mg protein). Since her height improvement was satisfactory, rhGH therapy was temporarily discontinued. After evaluation, she was deemed ineligible for hematopoietic stem cell transplantation. We initiated hydrocortisone replacement therapy to address her adrenal insufficiency symptoms. Conclusions: Overall, this case highlighted that secondary adrenal insufficiency could serve as an atypical clinical manifestation of KD. Furthermore, rhGH demonstrated satisfactory efficacy and safety in improving short stature in patient with 45,X TS.

Maternal hyperhomocysteinemia (HHcy) is closely linked to fetal growth restriction (FGR), yet the underlying mechanisms remain incompletely understood. In this study, we established a rat model of HHcy by administering a high-methionine diet during pregnancy and confirmed the presence of FGR through fetal weight analysis. Histological evaluation of the maternal-fetal interface revealed reduced vascular density in both the decidua and placenta, accompanied by dysregulated expression of key angiogenic factors in decidua. To elucidate the mechanistic basis of these changes, primary decidual stromal cells (DSCs) were isolated and RNA sequencing was performed. HHcy impaired the proangiogenic capacity of DSCs by suppressing vascular endothelial growth factor A (VEGFA) secretion. Transcriptomic profiling identified significant enrichment of lipid metabolism pathways in HHcy-exposed decidua. Further molecular analyses revealed that CD36 played a central role in mediating HHcy-induced lipid metabolic disturbances, which in turn activated the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Importantly, pharmacological inhibition of CD36 in DSCs alleviated lipid accumulation, suppressed PPAR pathway activation, and restored VEGFA expression and secretion, thereby rescuing DSCs-mediated angiogenesis. Collectively, our findings suggest that maternal HHcy upregulates CD36 expression in DSCs, leading to lipid metabolism dysregulation and impaired VEGFA-mediated angiogenesis possibly via the PPAR pathway, ultimately contributing to the pathogenesis of FGR. This is the first study to implicate lipid metabolism as a critical regulator of decidual angiogenesis, offering novel mechanistic insights and a potential therapeutic target for HHcy-associated pregnancy complications.

Background:Velaglucerase alfa is approved in China for treating type 1 Gaucher disease (GD1), but data on its use in Chinese pediatric and adult patients are limited. This study evaluated the safety, efficacy, and pharmacokinetics of velaglucerase alfa in Chinese patients with GD1. Methods:This was a phase IIIb, multicenter, open-label, single-arm, 53-week study (NCT05529992). Patients received intravenous velaglucerase alfa (60 U/kg) every 2 weeks. The primary endpoint was the incidence of serious treatment-emergent adverse events (TEAEs). Secondary endpoints evaluated safety (incidence of TEAEs), efficacy (changes in hemoglobin concentrations, platelet counts, liver and spleen volumes [as percent of body weight, % BW]), and quality of life (QoL). Results:Twenty patients were enrolled (treatment-naïve, n = 16; previously treated, n = 4). Four patients experienced 4 serious TEAEs requiring hospitalization; none were treatment-related. Overall, 19 of 20 patients experienced 104 TEAEs, of which 9 were treatment-related (8.7%; all mild). No TEAEs or deaths led to discontinuation of treatment. Mean (SD) improvements in hemoglobin concentrations (baseline, 10.5 g/dL [2.2]; change, +2.3 g/dL [1.3]; +25.5%), platelet counts (baseline, 59.9 × 109/L [23.4]; change, +42.1 × 109/L [27.7]; +82.3%), normalized spleen (baseline, 5.2% BW [2.6]; change, -3.1% BW [1.6]; -58.4%), and liver volume (baseline, 4.6% BW [1.3]; change, -1.1% BW [0.9]; -21.5%) were observed through Week 53. Nineteen of 20 (95.0%) patients reported improved QoL. Conclusions:Velaglucerase alfa was well-tolerated in Chinese patients with GD1, with no new safety signals, and resulted in improved hemoglobin and platelet levels, as well as liver and spleen volumes.

Importance:Recombinant human growth hormone (rhGH) improves height in children with growth hormone deficiency (GHD). However, its metabolic effects remain unclear. Objective:To synthesize evidence regarding the metabolic effects of rhGH or growth hormone (GH) derivatives in GHD, identify knowledge gaps, and highlight future research priorities. Methods:PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang databases were searched in July 2023 to identify studies on metabolic effects of GH treatment. Bubble plots were used to visualize GH treatment effects on metabolic parameters according to treatment duration by comparison with baselines, nonpharmacological interventions, and healthy controls. Random-effects meta-analyses were conducted for outcomes with inconsistent findings across original studies when randomized controlled trial data were sufficient. The study was registered with INPLASY (INPLASY202450064). Results:Sixty-three studies (6158 participants) analyzed the effects of GH treatment on metabolic outcomes in children with GHD. Overall, GH treatment slightly affected glucose levels; lipid effects were inconsistent. GH treatment did not influence bone mineral density, bone mineral content, or parathyroid hormone levels. Most studies showed no significant effects on thyroid hormone levels, body composition, or body mass index (BMI). GH treatment may increase serum asymmetric dimethylarginine and gastrin levels while reducing tumor necrosis factor and serum urea levels. Interpretation:Glucose and thyroid outcomes are consistent with clinical observations; effects on lipids, calcium, phosphorus, body composition, BMI, and waist-to-hip ratio require further validation owing to data inconsistency. New biomarkers are warranted. Further clinical studies are needed in children across age groups, GHD severities, and nutritional statuses.

AIMS:In China, information on individuals who test positive for islet autoantibodies (IAb), including single IAb-positive individuals and those with early-stage Type 1 diabetes (T1D), and their risk of progression to Stage 3 T1D is limited. The goal of this study is to assess the risk of progression to T1D in first-degree relatives (FDRs) of people with T1D in China. MATERIALS AND METHODS:This prospective, longitudinal study, being conducted at approximately 50 hospitals in China, will screen FDRs of individuals with T1D to identify those at risk for developing the disease by testing for the presence of IAb in the blood. IAb-positive individuals will undergo further testing for up to 5 years, with the primary objective of assessing their risk of Stage 3 T1D onset. During the monitoring period, participants with single IAb-positivity will be tested for glycated haemoglobin (HbA1c) and IAb every year; those with multiple IAb-positivity will have an HbA1c and oral glucose tolerance test (OGTT) every year (Stage 1 T1D), or OGTT or random blood glucose test in alternate 6-monthly intervals and HbA1c every 3 months (Stage 2 T1D). Participants who develop Stage 3 T1D during monitoring can undergo extended follow-up to assess changes in β-cell function, glycaemic outcomes and IAb status during the first 12 months after diagnosis. The study plans to enrol 5500 participants; enrolment is ongoing. CONCLUSIONS:Through early screening and monitoring of disease progression in FDRs of T1D probands, this study will provide a comprehensive understanding of T1D progression in the Chinese population. TRIAL REGISTRATION:Chinese Clinical Trial Registry identifier: ChiCTR2600119032.