The mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential mechanism of hypertension in children. Serum samples from 29 control children, 38 children with normal body mass index and simple hypertension (NBp), 8 children overweight with simple hypertension (OBp), 37 children with normal body mass index and H-type hypertension (NH) and 19 children overweight with H-type hypertension (OH) were analyzed by non-targeted metabolomics. A total of 1235 differential metabolites were identified between children with hypertension and normal controls, of which 193 metabolites including various lipids were significantly expressed. Compared with the control group, 3-dehydroepiandrosterone sulfate, oleic acid and linoleic acid were up-regulated, and gamma-muricholic acid was down-regulated in the NBp group; 3-dehydroepiandrosterone sulfate, 4-acetamidobutanoate and 1-hexadecanoyl-2-octadecadienoyl-sn-glyero-3-phosphocholine were up-regulated in the OBp group, whereas adenosine and 1-myristoyl-sn-glyero-3-phosphocholine were down-regulated; in the NH group, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, phenol and 3-methoxytyramine were up-regulated, while pentadecanoic acid was down-regulated; in the OH group, NG,NG-dimethyl-L-arginine, 1-palmitoyl-sn-glycero-3-phosphocholine and monoethyl phthalate were up-regulated, while phloretin and glycine were down-regulated. The results showed that the children with hypertension had obvious disorders of lipid metabolism (especially in the overweight hypertension group), which led to the occurrence of hypertension. Additionally, the concentration of NO production-related NG, NG-dimethyl-L-arginine, was significantly increased, which may play an important role in H-type hypertension in children.

This study aims to explore the pathogenic mechanism of H-type hypertension. A rat model of H-type hypertension was established through high-methionine dietary intervention, with subsequent folic acid administration. Untargeted serum metabolomic profiling identified a significant reduction in arachidonic acid (AA) levels in the methionine-enriched group, which were effectively normalized following folic acid supplementation. Transcriptomic analysis revealed methionine-induced upregulation of AA pathway-associated genes Cyp1a1 and Gpr75. In contrast, after the intervention with folic acid, a downregulation of these genes was observed. These findings were corroborated through Western blotting and RT-qPCR validation. In vitro studies using EA.hy926 endothelial cells demonstrated that methionine exposure significantly elevated CYP1A1 expression. Furthermore, methionine stimulation induced marked upregulation of GPR75 and its downstream signaling components (NRAS, MEK1, and ERK1). Population-level evidence from the U.S. NHANES database substantiated significant correlations between essential fatty acids (AA, LA, and GLA) and H-type hypertension prevalence. Our research findings suggest that the CYP1A1/20-HETE/GPR75 axis-mediated dysregulation of AA metabolism may be one of the key pathological mechanisms of H-type hypertension. The research results provide clues for the discovery of new therapeutic targets for H-type hypertension.

Objectives: Hypospadias is one of the most common congenital malformations of the male genitourinary system, and postoperative complications remain a major concern affecting surgical outcomes and patients‘ quality of life. Whether machine learning models can effectively predict complication risk using routinely available clinical variables remains unclear. Methods: A retrospective analysis was performed on 671 hypospadias patients who underwent urethroplasty at the Department of Urology, Capital Children’s Medical Center, between December 2015 and September 2024. The final dataset included 671 patients (training set: 536; validation set: 135). The median follow-up duration was 48 months (range: 19 to 72 months). Least absolute shrinkage and selection operator (LASSO) regression with nested cross-validation within the training set was used for feature selection, followed by the development of five machine learning models (Random Forest, XGBoost, LightGBM, Logistic Regression, and Support Vector Machine). Model performance was evaluated using AUC, calibration curves, Brier score, and decision curve analysis. Feature importance was assessed using SHapley Additive exPlanations (SHAP). Results: LASSO retained four features for model development: hypospadias type, surgical technique, surgeon experience, and patient age. The overall complication rate was 22.9% (154/671). Among the models evaluated, the Support Vector Machine (SVM) showed the most balanced performance in the validation set, achieving an AUC of 0.810 and a Brier score of 0.157. LightGBM demonstrated comparable performance (AUC: 0.802). SHAP analysis identified surgical technique as the most influential predictor, followed by surgeon volume and hypospadias type, though these findings should be interpreted with caution given the confounding between surgical complexity and disease severity. Conclusions: An interpretable SVM-based prediction model was developed and internally validated to stratify risk for postoperative complications after hypospadias repair using routinely available clinical variables. SHAP provided clinicians with visual insights into key risk-associated factors. However, given the single-center retrospective design and lack of external validation, further multicenter prospective studies are warranted to confirm the generalizability of these findings before clinical implementation.

Objectives: To investigate the potential mechanisms of maternal pregestational diabetes-induced neural tube defects (NTDs) by integrating proteomic data and histone H4 lysine 5 acetylation (H4K5ac) ChIP-seq data from the mouse model. Methods: The diabetic mouse model was established by intraperitoneal injection of streptozotocin (STZ) into female friend leukemia virus B strain (FVB) mice, with subsequent blood glucose monitoring. Diabetic females were then mated with healthy males, and embryonic tissues were collected on embryonic day 9.5. Among the embryos obtained from diabetic pregnancies, six NTDs embryos and six control embryos were selected for protein expression profiling using tandem mass tag (TMT)-labeled liquid chromatography-tandem mass spectrometry (LC-MS/MS), as well as for assessment of H4K5ac modification by ChIP-seq. Multi-omics integration was performed to identify common differentially expressed genes, followed by functional enrichment analysis. Key genes were validated using RT-qPCR. Results: Proteomic analysis revealed that differentially expressed proteins were significantly enriched in focal adhesion pathway. Protein–protein interaction (PPI) network analysis indicated that these proteins (e.g., Integrin alpha 3 (Itga3), glycogen synthase kinase 3 beta (Gsk3b), mitogen-activated protein kinase 9 (Mapk9)) were associated with focal adhesion and cytoskeletal functions. Integrated multi-omics analysis identified 923 common differentially expressed genes, which were also significantly enriched in focal adhesion pathway. Within this pathway, the protein expression levels of Itga3, Gsk3b, and Mapk9 exhibited a consistent co-variation trend with H4K5ac enrichment. RT-qPCR results confirmed that Itga3 was significantly up-regulated, while Gsk3b was down-regulated in the NTDs group (p < 0.05). Conclusions: Maternal pregestational diabetes may contribute to NTDs by disrupting cytoskeletal reorganization, cell adhesion, and migration processes. This disruption is likely mediated through H4K5ac-regulated expression of key focal adhesion pathway genes such as Itga3 and Gsk3b.

Objectives: Hypospadias is one of the most common congenital malformations of the male genitourinary system and is frequently accompanied by other congenital anomalies. Whether patients with associated malformations exhibit distinct endocrine characteristics remains unclear. Methods: A retrospective analysis was performed on 323 hypospadias patients who underwent surgery at Capital Medical University Affiliated Capital Children’s Medical Center between January 2020 and September 2024. Data on surgical age, clinical classification, associated malformations, and sex hormone levels were collected. Propensity score matching was used for between-group comparisons. Results: Associated malformations were present in 68 of 323 patients (21.05%), most commonly involving the urogenital system (75.00%). Cryptorchidism was the most common associated anomaly. The surgical age was significantly later in patients with associated malformations (median 3.34 years) compared to those with isolated hypospadias (2.42 years). Following matching, patients with urogenital-related anomalies had significantly elevated FSH and PRL levels (both p < 0.05) compared with isolated hypospadias, whereas no significant hormonal differences were found in those with non-urogenital anomalies. Conclusions: Children with hypospadias and associated urogenital anomalies exhibited subtle differences in endocrine profiles compared with isolated hypospadias. These findings suggest that hypospadias with urogenital anomalies may represent a clinically distinct subgroup and support the need for further prospective studies and long-term endocrine follow-up.