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.

IntroductionHeterozygous mutations in the ACAN gene are a key genetic cause of non-syndromic familial short stature. The associated disease spectrum includes short stature, advanced bone age, early-onset osteoarthritis, and osteochondritis dissecans (SSOAOD). The clinical phenotype is highly heterogeneous, ranging from isolated short stature to severe skeletal developmental abnormalities, reflecting a continuous pathological process from growth plate dysfunction to premature joint degeneration.MethodsThis summary synthesizes current clinical evidence and management approaches for ACAN-related short stature. Recombinant human growth hormone (rhGH) is the primary treatment used to improve height in affected children. Clinical management also integrates growth promotion, joint protection, genetic counseling, and screening of at-risk family members.ResultsrhGH therapy provides moderate improvement in height, but its efficacy decreases with increasing age. Long-term safety of rhGH on joint health remains unclear. The disease spectrum illustrates progressive severity from short stature alone to significant skeletal and joint pathology.DiscussionClinical care should adopt a multidisciplinary approach combining growth promotion, joint protection, and genetic counseling, including screening for at-risk family members. Future multicenter, long-term follow-up studies are needed to further clarify the molecular mechanisms of ACAN haploinsufficiency, assess the long-term articular effects of rhGH therapy, and establish early identification criteria, thereby providing a basis for developing targeted therapies.

This article reports on two unrelated young female patients (gender assigned female at birth) who initially presented with hypertension. Patient 1 was admitted to the hospital with an acute cerebral infarction due to poorly controlled hypertension, while Patient 2 was a first-time visitor presenting with hypertension as the initial complaint. Physical examination on admission revealed absent breast development, feminized and immature external genitalia, and no history of menarche. Laboratory investigations showed markedly elevated adrenocorticotropic hormone (ACTH) levels, significantly decreased cortisol levels and a disrupted circadian rhythm. For sex hormones, progesterone was markedly elevated, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were mildly increased, while estrogen and testosterone levels were low. Combined with karyotype analysis and gene sequencing, Patient 1 was confirmed to have a karyotype of 46,XX, and Patient 2 had a karyotype of 46,XY. In addition, pathogenic allelic variants in the CYP17A1 gene (c.985_987delinsAA) differed between the two patients: Patient 1 harbored a heterozygous mutation, whereas Patient 2 had a homozygous mutation. Both patients were ultimately diagnosed with 17α-hydroxylase deficiency (17-OHD). During the 6-month follow-up after initiation of dexamethasone replacement therapy, the patients’ blood pressure and serum potassium levels were well controlled. This case suggests that although 17-OHD is a rare disorder, clinicians should be alert to the possibility of 17-OHD in patients presenting with disorders of sex development or primary hypertension. Early and definitive diagnosis followed by appropriate glucocorticoid replacement therapy can significantly improve the patient’s quality of life.

Although gonadotropin-releasing hormone analogs (GnRHa) are the standard treatment for central precocious puberty (CPP), the efficacy of GnRHa monotherapy in older children (around 8 years) and that of combination therapy with recombinant human growth hormone (rhGH) both remain unclear. This study aims to evaluate the real-world efficacy of each regimen. This retrospective cohort study enrolled Chinese girls with CPP. Two groups were formed: GnRHa monotherapy and GnRHa + rhGH combination therapy. Outcomes included adult height gain [AHG, final adult height (FAH) standard deviation score (SDS)– predicted adult height (PAH) SDS]，genetic height gain [GHG, FAH SDS–target height (Tht) SDS], and change in height (FAH SDS – baseline height SDS). In the GnRHa group, the mean age at treatment initiation was 8.87 ± 0.87 years. After 17.87 months of treatment, the AHG was 1.33 SDS (0.82, 2.00). In the GnRHa + rhGH group, the mean age at treatment initiation was 9.01 ± 0.80 years. After 23.02 months of GnRHa treatment and 14.02 months of rhGH treatment, the group showed significantly greater AHG [1.72 SDS (1.24, 2.59)]. GnRHa monotherapy initiated after age 8 may still provide meaningful height gains, and adding rhGH is associated with improved FAH in patients with severe baseline height impairment.

Disordered lipid metabolism and inflammation, the hallmark features of metabolic dysfunction-associated steatohepatitis (MASH), present a significant therapeutic challenge even in the absence of obesity, making the discovery of novel pathogenic mechanisms and therapies imperative. Although Celastrol (Cel) markedly ameliorates high-fat diet (HFD)-induced obesity, whether and by what molecular basis it directly ameliorates hepatic inflammation and disordered lipid metabolism remains unclear. Here, using a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced MASH model, we demonstrate that Cel ameliorates steatohepatitis and identify CD36 in liver sinusoidal endothelial cells (LSECs)-the key gatekeepers of hepatic immunometabolic homeostasis-as the central mediator coordinating hepatic lipid transport and inflammatory responses. Elucidating the regulatory mechanism, we found that USP12 removes K48-linked ubiquitination from CD36 and stabilizes it in LSECs. Cel downregulates USP12, thereby promoting CD36 ubiquitination and subsequent degradation, which in turn attenuates chemokine-driven macrophage recruitment and suppresses pathological lipid transport. The clinical relevance of this axis is supported by the concurrent upregulation of both USP12 and CD36 in human livers with steatohepatitis. These findings reveal that LSEC heterogeneity orchestrates hepatic metabolism and inflammation via the USP12/CD36 axis, designating it a therapeutic target for interventions with agents such as Cel.

OBJECTIVE:To investigate deep phenotypes and evaluate the efficacy of recombinant human growth hormone (rhGH) therapy in children with growth retardation carrying heterozygous ACAN variants. METHODS:We retrospectively analyzed 37 children with heterozygous ACAN variants identified among 1,528 individuals with growth retardation at a tertiary pediatric medical center in China between January 2017 and April 2024. Deep phenotyping and follow-up were conducted. RESULTS:Among the 37 children, 78.4% had short stature, and 75.7% exhibited advanced bone age (BA). 33 distinct heterozygous ACAN variants were identified, including 19 novel variants. In the treatment group (n = 17), rhGH therapy lasted 4-61 months. Growth velocity (GV) at 3, 6, 9, 12, and 18 months was significantly higher than baseline (all P < 0.05). Changes in height standard deviation score (Ht SDS) at 18 and 24 months were significantly greater than those at 3 and 6 months (all P < 0.05). In the untreated group (n = 13), follow-up lasted 3-58 months, with final GV of 0-6.98 cm/year. CONCLUSION:Short stature and advanced BA are common features of individuals with ACAN variants and represent strong indications for ACAN genetic screening. rhGH therapy demonstrates a growth-promoting effect in these children.

SOX11 variants have been associated with Coffin–Siris syndrome and a broader neurodevelopmental spectrum (IDDMOH), but their role in isolated or syndromic hypogonadotropic hypogonadism (HH) remains under-recognized. We report a 13-year-old Chinese girl who presented with delayed puberty (Tanner B1, PH1), infantile uterus and low basal gonadotropins. Trio whole-exome sequencing identified a de-novo heterozygous SOX11 c.346_348del (p.Tyr116del) variant. Olfactory and pituitary MRI revealed bilateral olfactory-bulb/nerve hypoplasia and a pituitary height of 3.4 mm, fulfilling Kallmann-syndrome criteria. GnRH-pump therapy restored gonadotropin output within 72 h. A systematic literature review of 32 additional SOX11-related HH cases (total n = 33) showed that 25/26 phenotyped individuals exhibited Coffin–Siris-compatible features, whereas 13/33 met Kallmann-syndrome criteria. Thirty unique variants were identified, 17/30 clustering within the HMG domain and 15/18 proven de-novo. SOX11 should be included in Kallmann syndrome gene panels. We propose “SOX11-related disorder” as an overarching diagnostic framework for all individuals with SOX11 likely pathogenic/pathogenic variants, mandating comprehensive baseline evaluation—including endocrine assessment, neurodevelopmental screening, and MRI of olfactory tracts and pituitary—regardless of initial presentation.

Perfluorononanoic acid (PFNA) is a ubiquitous persistent organic pollutant, yet its impact on gut health and associated mechanisms remains poorly understood. Here, we used multi-omics approaches to explore PFNA-induced alterations in intestinal homeostasis. Adult male zebrafish were exposed for 28 days to a series of concentrations (0, 0.1, 10 μg/L) of PFNA. Comprehensive analyses revealed that PFNA caused physical barrier damage, characterized by intestinal villus vacuolation and decreased mucin secretion. Furthermore, PFNA altered gut microbial composition by reducing beneficial bacteria and promoting opportunistic pathogens. Transcriptome analysis implicated intestinal barrier dysfunction and abnormalities in lipid and inflammatory pathways. Correspondingly, metabolomic analysis revealed significant perturbations in glycerolipid, phospholipid, and amino acid metabolism. Integrated multi-omics established strong correlations among the observed dysbiosis, altered gene expression, and metabolic disruption. Our findings demonstrate that PFNA exposure compromises intestinal barrier integrity and induces gut dysbiosis, providing crucial mechanistic insights into the PFNA toxicity and informing human health risk assessment.

Pituitary adenomas are rare in pediatric populations, with prolactinomas representing 20–39

Introduction:Objective: the aim of this study was to investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and echocardiographic indices in children and adolescents with obesity combined with metabolic syndrome (MetS). Methods: we performed a retrospective study of patients hospitalized between January 2018 and December 2022. A total of 180 patients with obesity combined with MetS were enrolled and underwent anthropometric measurements and serum 25(OH)D level detection. Spearman correlation, multiple linear regression, and binary logistic regression analyses were employed to assess the association between serum 25(OH)D levels and echocardiographic indices of cardiac structure and function in this population. Results: Serum 25(OH)D concentrations showed significant inverse correlations with end-diastolic interventricular septal thickness (IVSd; r = -0.285, p < 0.001), left ventricular posterior wall thickness in diastole (LVPWd; r = -0.168, p = 0.024), left ventricular mass (LVM; r = -0.217, p=0.004), and relative wall thickness (RWT; r = -0.247, p = 0.001). No significant correlations were found with left-ventricular end-diastolic diameter (LVEDd), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), or left ventricular mass index (LVMI). After multivariate adjustment (age, sex, BMI, season, blood pressure, lipids, uric acid, glucose), 25(OH)D remained independently and inversely associated with IVSd (β = -0.242, 95% CI: -0.382, -0.101; p = 0.001) and RWT (β = -0.241, 95% CI: -0.392, -0.091; p = 0.002), but not with LVPWd or LVM. Logistic regression identified vitamin D deficiency as an independent predictor of concentric hypertrophy, even after full adjustment. Conclusions: our findings underscore the importance of maintaining sufficient vitamin D levels in pediatric populations with obesity and MetS as a potential strategy to mitigate adverse cardiac remodeling. Vitamin D deficiency may represent a modifiable risk factor for cardiac complications in this high-risk population.

Recombinant human growth hormone (rhGH) treatment for idiopathic short stature (ISS) in China faces challenges including delayed initiation, poor persistence, limited adoption of advanced therapies, and conservative dosing. This study characterized real-world temporal and geographical patterns of rhGH therapy and identified associated socioeconomic factors. Data from two nationwide registries comprising 24,384 children with ISS initiating rhGH were analyzed. Predictors of treatment effectiveness were identified via linear regression. Provincial variations and temporal trends were assessed via descriptive analysis and seasonal-trend decomposition. Spearman correlation was used to examine associations between treatment patterns and socioeconomic indicators. The median rhGH initiation age was 8.45 years. Most patients (81.3

Substitute for perfluorooctanoic acid (PFOA), like hexafluoropropylene oxide trimer acid (HFPO-TA), are sparking growing environmental and health worries because of their persistence and capacity for bioaccumulation. Here, we employed an integrated multi-omics approach to systematically investigate HFPO-TA-induced hepatic lipid metabolic dysregulation in zebrafish. Exposed to a series of concentrations (0, 5, 50, 500 μg/L) of HFPO-TA induced hepatic lipid accumulation and significantly elevated serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C). Integrated transcriptomic and epigenome analyses revealed that HFPO-TA reprogrammed the hepatic epigenome by selectively activating lipid synthesis-associated enhancers while suppressing lipid oxidation pathways, predisposing to metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, HFPO-TA preferentially remodeled chromatin accessibility and distal enhancers, driving lipogenic gene activation through nuclear receptors, such as peroxisome proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR). Finally, functions of PPARα and FXR in HFPO‑TA‑induced lipid imbalance were validated by pharmacological modulators. Overall, our study delivers comprehensive evidence connecting PFOA alternatives to epigenetically driven hepatic steatosis, providing mechanistic understanding to support environmental risk evaluations of emerging perfluoroalkyl and polyfluoroalkyl substances (PFAS) compounds.

The mode of electron transport in mitochondrial respiratory chain determines whether it generates energy or more reactive oxygen species (ROS), a key for cellular adaptation to diverse oxygen environments. However, the understanding of the mechanisms remains incomplete. Here, we find that NIMA-related kinase 7 (NEK7), targeted to mitochondria by its signal peptides, binds to succinate dehydrogenase complex iron sulfur subunit B (SDHB), stabilizing the spatial conformation of complex II and promoting forward electron transport. Deficiency of NEK7 in hepatocytes induces reverse electron transport (RET) and inhibits mitochondrial respiration, thereby promoting ROS generation, triggering spontaneous liver fibrosis and aggravating CCl4-induced liver fibrosis, which can be attenuated by RET inhibitors. More importantly, NEK7 overexpression effectively alleviates CCl4- and choline-deficient, high-fat diet-induced liver fibrosis. Overall, these findings highlight the pivotal role of NEK7 in orchestrating complex II and electron transport, providing new insights into the regulation of mitochondrial homeostasis and potential fibrosis treatments.

Objective:This study aims to evaluate the epidemiological features of multiple pediatric fractures and identify specific injury patterns. Methods:This cross-sectional study retrospectively analyzed medical records for children with multiple fractures who presented to Children's Hospital of Nanjing Medical University between 2016 and 2024. Fractures were categorized into six anatomical regions: Craniofacial, Trunk/Pelvis, Upper Limb, Lower Limb, Hand, and Foot. Patients were divided into single-region and multi-region groups based on the number of affected regions. Hierarchical clustering on principal components (HCPC) was applied to explore potential injury patterns. Results:Among the 1950 children with multiple fractures, 65.0% were boys, with a median age of 8.7 years (4.8-12.3 years). The primary mechanisms of injury included ground-level falls (36.3%), traffic accidents (13.8%), and play/sports activities (10.8%). Single-region fractures accounted for 77.2%, while multi-region fractures accounted for 22.8%. There were statistically significant differences in age and injury mechanism distributions between the two groups (p < 0.001). In the single-region group, children aged 6-11 years predominated, with ground-level falls being the most common cause (44.4%) primarily resulting in upper limb fractures (74.4%). The multi-region group had a higher representation of adolescents aged 12-17 years, with traffic accidents as the primary cause and injuries mainly involving the lower limbs (63.5%), trunk (56.8%), and upper limbs (50.5%). HCPC identified five distinct injury patterns: Lower Limb-Foot, Trunk/Pelvis-High Fall, Upper Limb-Hand, Craniofacial-Traffic Accident, and Upper Limb-Trunk/Pelvis patterns. Conclusion:Most pediatric multiple fractures involve a single anatomical region; however, the burden of cross-regional fractures should not be overlooked. Identifying potential injury patterns is crucial for developing targeted preventive strategies.

The prevalence of childhood obesity has been increasing worldwide, garnering increasing public attention due to various complications and long-term effects. Many researchers have indicated that obese children experienced higher fracture risk compared with nonobese children. However, the findings from different researchers reported a controversial result and few of them paid attention to the differences in BMI Z-score and obesity between different fracture sites, which would be quite useful since these can guide obese children in protecting specific regions. This study comprised 17,942 hospitalized children diagnosed with fractures and 3219 healthy children who came for physical examination and had not been diagnosed with any illness. Data on age, gender, fracture seasons, fracture sites, height, weight, total cholesterol, triacylglycerol, and high-density lipoprotein were collected. One-way ANOVA, t-test, Chi-square test, propensity score matching, and logistic regression models were used in statistical analysis. Children with lower limb fractures exhibited the highest BMI Z-score (0.58 ± 1.74), followed by those with upper limb fractures (0.50 ± 1.52), axial fractures (0.31 ± 1.56), and head fractures (-0.02 ± 1.52). In terms of obesity, children with lower limb fractures exhibited the highest obesity rate (20.20%), whereas those with upper limb fractures (15.61%) and axial fractures (14.96%) displayed comparable obesity rates. Children with head fractures had the lowest obesity rate (8.42%). Moreover, BMI Z-score (2.43 ± 1.22vs0.15 ± 1.43, P < 0.001), obesity (62.97%vs8.61%, P < 0.001) and dyslipidemia (31.22%vs24.67%, P < 0.001) were statistically significant difference between the fracture and healthy groups. The logistic regression models showed that BMI Z-score was associated with an increased risk of fracture (P < 0.001, OR = 4.89, 95%CI: 4.53-5.27). This study suggests that children with lower limb fractures exhibited the highest BMI Z-score and obesity rate, while those with head fractures had the lowest BMI Z-score and obesity rate. When compared with the healthy group, fracture children had higher BMI Z-score, obesity, and dyslipidemia rates. In addition, BMI Z-score was associated with an increased risk of fractures.

This study aims to characterize and analyze the expression of representative biomarkers like lymphocytes and immune subsets in children with thyroid disorders. It also intends to develop and evaluate a machine learning model to predict if patients have thyroid disorders based on their clinical characteristics, ultimately providing insights to enhance the clinical guidelines for the pathogenesis of childhood thyroid disorders. This cross-sectional study conducted in China examined diagnosed cases to describe the characteristics and expression of lymphocyte and immune subsets as predicted by the model. The study included two groups of children: 139 who were hospitalized in the Department of Endocrinology and a control group consisting of 283 children who underwent routine health checks at the Department of Children Healthcare. Cases were classified into three groups based on diagnoses: Graves’ disease (GD), Hashimoto’s thyroiditis (HT), and hypothyroidism. By employing 11 readily obtainable serum biochemical indicators within three days of admission, the median concentrations and percentages of subset measurements were analyzed. Additionally, nine machine learning (ML) algorithms were utilized to construct prediction models. Various evaluation metrics, including the area under the receiver operating characteristic curve (AUC), were employed to compare predictive performance. GD cases had increased levels of CD3-CD19 + and CD3 + CD4 + T lymphocytes, and a higher CD4+/CD8 + ratio. In both GD and HT, the levels of complement C3c, IgA, and IgG were higher than those in the control group. HT cases also had an increasing percentage of CD3-CD16 + 56 + T lymphocytes. Most immune markers increased in hypothyroidism, except for some T lymphocyte percentages and the CD4+/CD8 + ratio. To reduce age-related bias, propensity score matching was used, yielding consistent results. Among the nine machine learning models evaluated, logistic regression showed the best performance, being useful in clinical practice. Specific lymphocytes with different biomarkers are positively correlated with autoimmune thyroid disease (AITD) in children. Complement proteins C3c and C4, along with IgG, IgA, IgM, and T/B cells, are significant in childhood thyroid diseases. Our best model can effectively distinguish these conditions, but to enhance accuracy, more detailed information such as clinical images might be needed.

Increasing evidence suggests that vitamin D is one of the causes of accelerated development of Insulin Resistance (IR) and islet cell secret dysfunction. Numerous studies have shown that vitamin D can reduce inflammation, activate the transcription of the insulin receptors and related genes, and increase insulin-mediated glucose transport, thereby reducing IR. This article reviews the molecular mechanisms related to vitamin D deficiency and pancreatic β-cell dysfunction in patients with Type 2 Diabetes (T2D).

BACKGROUND:Emerging evidence suggests the presence of distinct endotypes of Type 1 diabetes mellitus (T1DM): T1DE1 in individuals diagnosed at age < 7 years in contrast to T1DE2 in those diagnosed at ≥ 13 years of age. We aimed to comprehensively explore the phenotypic heterogeneity of T1DM with respect to the age-related endotypes. METHODS:This cross-sectional study was conducted in China and involved 1204 children newly diagnosed with T1DM who were admitted to the pediatric department of a tertiary hospital from January 1, 2010 to December 31, 2023. The patients were divided into three age groups: < 7 years (T1DE1), 7-12 years, and ≥ 13 years (T1DE2). A comparison was made among the age groups regarding demographic characteristics, glucose metabolism, β-cell autoimmunity, and metabolic decompensation. RESULTS:Patients under 7 years exhibited a shorter symptom duration before diagnosis, along with the lowest fasting and postprandial C-peptide and C-peptide to glucose ratio levels and the highest postprandial glucose levels. They also showed the highest insulin autoantibody positivity rate and creatine kinase-MB levels. In contrast, patients aged 13 and older had the highest HbA1c levels and glutamate decarboxylase antibody positivity rate. In addition, this group showed the highest prevalence of TPOAb and TgAb positivity, as well as the largest proportion of abnormal liver function cases. CONCLUSIONS:The study illustrates age-specific phenotypic heterogeneity in pediatric T1DM, indicating the presence of distinct endotypes. Further investigation of these endotypes may offer more evidence for the precise treatment of T1DM.