Pediatric discovery最新文献

The study of cells aids in comprehending the pathophysiology of diseases. However, obtaining a large number of primary cells in a short period is challenging, and they senesce and die after repeated passages. Therefore, establishing immortalized cell lines is necessary for conducting cellular experiments. Researchers commonly use antibiotics to screen immortalized cell models upon construction. However, due to the low transfection rate of the immortalized genes, a significant number of nonimmortalized cells are killed. The connections between the cells act as a web that floats when many cells die. As a result, successfully transfected immortalized cells are lifted and carried away, leading to only a small number of immortalized cells surviving. The surviving cells survive in the absence of other cell-secreted factors. However, their proliferative ability is limited, which makes obtaining immortalized cell lines a time-consuming process. This study aimed to shorten the time required to obtain immortalized cell lines by constructing immortalized Schwann cells and improving the traditional screening method. The immortalized gene transfectants were first cultured, passaged, and then screened. A comparison with the traditional screening method demonstrated the feasibility and advantages of the improved method.

Monteggia fractures represent relatively infrequent injuries in the pediatric population, accounting for approximately 2% of all forearm fractures. However, the rate of missed diagnoses ranges from 30% to 50%, leading to the development of chronic Monteggia fractures in children. Chronic Monteggia fractures frequently result in elbow deformities and functional limitations, significantly impacting the patients' quality of life. The classification systems and treatment approaches for this condition are complex, and therapeutic strategies remain a subject of considerable debate. This review comprehensively examines the definition, incidence, etiology, classification, pathophysiological characteristics, diagnosis, treatment strategies, and prognosis of chronic Monteggia fractures in children. The aim of this study is to provide a reference for further research into the management of this challenging pediatric orthopedic condition.

Small for gestational age (SGA) and twin infants are at increased risk of growth deviations, but postnatal catch-up growth (CUG) patterns across singleton, twin, appropriate for gestational age (AGA), and SGA groups remain unclear. This prospective cohort study (n = 340) investigated the postnatal growth trajectories and physical growth deviations in singleton and twin AGA and SGA infants during the first year of life. The primary findings indicated that SGA infants exhibited rapid CUG in weight and head circumference within the first 6 months, whereas length catch-up required a longer period. Twin SGA infants displayed distinct patterns: faster weight CUG but slower length CUG compared with singleton SGA infants, with gender differences-male SGA twins had lower length z-scores than SGA singletons. The rate of deviation in physical growth of SGA infants improved significantly within the first year of life, with wasting being infrequent. In conclusion, the mechanism underlying SGA is more complex among twins than singletons. Twin SGA infants require prolonged growth monitoring, and regular follow-up is essential to optimize growth outcomes and mitigate long-term risks. This preliminary study offers a foundation for further investigation into the biological and environmental factors driving these differences.

Autism spectrum disorder (ASD) involves neuroimmune dysregulation and synaptic pruning defects. This study aimed to investigate the role of triggering receptor expressed on myeloid cells 2 (TREM2) in ASD pathogenesis and its link to retinoic acid (RA)/retinoic acid receptor α (RARα) signaling. Prefrontal cortex-specific knockdown of TREM2 in rats induced core ASD-like behaviors (e.g., social deficits), microglial hyperactivation, aberrant synaptic pruning, reduced serum soluble TREM2 (sTREM2) levels, and disrupted RA/RARα signaling. Oral RA supplementation (6 mg/[kg·day]) reversed these neuroimmune abnormalities and behavioral impairments. In vitro studies demonstrated that TREM2 knockdown and RA supplementation induced RARα-level alterations consistent with in vivo observations. These findings indicated that TREM2 deficiency was a key factor in the pathophysiology of ASD, mediated by the RA/RARα signaling pathway. Furthermore, serum sTREM2 might serve as a potential diagnostic biomarker for ASD. Collectively, these findings underscore the pivotal role of TREM2 in ASD pathogenesis and provide novel perspectives for diagnostic and therapeutic strategies.

This is a retrospective study. In order to investigate the effect of specific immunotherapy on the improvement of lung function and symptoms in children with bronchial asthma, 256 children with bronchial asthma were selected and divided into an experimental group and a control group according to whether they chose to use sublingual specific immunotherapy or not. The control group was given basic drug therapy, and the experimental group was given specific immunotherapy on the basis of basic drug therapy. Differences between the two groups were compared in terms of lung function, efficacy, and asthma medication dose. The results showed that peak expiratory flow (PEF), maximum expiratory flow at 25% of forced vital capacity (MEF₂₅), maximal mid-expiratory flow curve (MMEF), maximum expiratory flow at 75% of forced vital capacity (MEF₇₅), maximum expiratory flow at 50% of forced vital capacity (MEF₅₀), and airway hyperresponsiveness improved in both groups after 1 year of treatment (P < 0.05), and the result of experimental group was better than that of the control group (P < 0.05). This study shows that sublingual specific immunotherapy combined with inhaled corticosteroid therapy has positive therapeutic effects on asthma patients, which can reduce the dose of medication used in asthma patients and improve symptoms.

Hematopoietic stem cell transplant (HSCT) is associated with some complications requiring advanced support in the pediatric intensive care unit (PICU). However, the outcome of children requiring admission to a PICU following HSCT in middle-income countries (MICs) are limited. One hundred and four children undergoing hematopoietic stem cell transplantation at a bone marrow transplant service in Colombia from January 2012 to June 2019 were enrolled. Baseline characteristics and clinical courses were described. In addition, we compared some characteristics of patients who survived or died in the PICU through a bivariate analysis. Twenty five PICU admissions were reported. Sixty-four percent survived to be discharged from any PICU admission. Immunodeficiency was the most common underlying disease among patients admitted to the PICU (33%). Respiratory problems (12/25, 48%), and cardiovascular instability (10/25, 40%) were the most common reasons for admission. Cardiovascular support was the most common PICU treatment (21/25, 84%), followed by respiratory support (18/25, 72%). We found that children who require admission to PICU after an allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) present a high mortality rate. Invasive respiratory support, higher vasoactive-inotropic score, renal replacement therapy, and the presence of multi-organ failure were associated with mortality.

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disorder that frequently affects premature infants, and its pathogenesis is closely related to macrophage polarization. This study investigated the effects of succinate, a metabolite of the intestinal flora, on macrophage polarization in NEC. Succinate aggravated intestinal injury caused by NEC and inhibited the proliferation of damaged mouse monocyte‒macrophage leukemia cells (RAW264.7 cells). It was confirmed by multiple methods that succinate intervention promotes the polarization of intestinal macrophages toward the M1 phenotype in neonatal NEC. This polarization was characterized by a significant upregulation of inducible nitric oxide synthase (iNOS) protein levels and iNOS mRNA expression, along with a marked suppression of arginase 1 (ARG1) protein levels and Arg1 mRNA expression. Moreover, immunofluorescence analysis revealed that in the NEC intestine, the coexpression of the M1 macrophage marker F4/80⁺/CD86⁺ was significantly increased, whereas the coexpression of the M2 macrophage marker F4/80⁺/CD206⁺ was significantly decreased. Mechanistic studies revealed that succinate upregulated the expression levels of phosphorylated protein kinase B (p-AKT) and hypoxia-inducible factor 1 alpha (HIF1a) by activating the PI3K/AKT signaling pathway through its specific receptor succinate receptor 1 (SUCNR1). Further experiments revealed that the expression of polarization-related markers in M1-type macrophages was significantly suppressed after treatment with the SUCNR1-neutralizing antibody or the PI3K inhibitor LY294002. These findings suggest that succinate may activate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway via SUCNR1 to promote the polarization of NEC macrophages toward the M1 phenotype, thereby accelerating NEC progression.

Pediatric high-grade gliomas (pHGG) were first defined as a distinct entity in the 2021 fifth edition of the WHO classification of tumors of the central nervous system. These tumors, designated primarily as Grade 4, include the following subtypes: (1) diffuse midline glioma with H3-K27 alterations (DMG, H3-K27M), (2) diffuse hemispheric glioma with H3-G34 mutations (DHG, H3G34M), and (3) diffuse pediatric-type high-grade glioma with wild-type H3 and isocitrate dehydrogenase (pHGG, H3-WT/IDH WT). Clinically, pHGGs are known for their poor outcomes and marked tumor heterogeneity. Despite this, the characteristics of the tumor microenvironment (TME) and the processes governing tumor cell lineage transitions remain incompletely understood. In this study, we used single-cell RNA sequencing (scRNA-seq) to analyze pHGG tumor cells (excluding infant-type hemispheric gliomas). Through comprehensive bioinformatic approaches-including cell proportion analysis, Gene Ontology (GO) enrichment, metabolic activity inference via scMetabolism, proliferation gene scoring, stemness assessment by CytoTRACE2, SCENT, and pseudotime trajectory analysis with Monocle2-we thoroughly investigated the TME features and heterogeneity of these aggressive brain tumors. Our findings highlight the presence of oligodendrocyte precursor cell (OPC)-like subpopulations, with epidermal growth factor receptor (EGFR)-expressing OPC-like cells emerging as a potential tumorigenic origin in diffuse midline gliomas due to their distinct stemness properties. Notably, platelet-derived growth factor receptor alpha (PDGFRA)-positive cells exhibit high specificity in DMG, suggesting greater diagnostic and therapeutic potential than EGFR. Next-generation sequencing (NGS) and multiplex immunofluorescence analyses confirmed their distinct expression pattern, supporting PDGFRA as a key molecular marker. Moreover, OPC-like cells at different differentiation states may drive lineage transitions in DMG. Together, these findings enhance our understanding of pHGG-especially DMG-and point to new avenues for targeted therapy.