Cleft lip (CL) and cleft palate (CP), collectively referred to as orofacial clefts (OFCs), are among the most common birth defects and can have significant effects on speech, nutrition, and physical and psychosocial development. Manifestation, classification, and treatment plans of OFCs are diverse and not standardized. Recent technological advancements and genetic testing have enabled researchers to propose relationships between certain genes and the development of OFCs. Potential genetic precursors for OFCs have been found to be numerous and diverse. Treatment strategies are also numerous and vary greatly between individuals. In this review article, we summarize the most commonly discussed genetic factors in the literature, variation in classification, and advances in management.

The specific mechanisms and screening methods for congenital heart disease (CHD) remain elusive. Evidence indicates that aberrant maternal metabolomic profiles are associated with CHD, but it is uncertain whether such an association exists in umbilical cord blood. This study aimed to measure the metabolome shifts in monozygotic (MZ) twins discordant for CHD and, if present, identify the altered metabolites and metabolic pathways. Umbilical cord blood from three pairs of MZ twins discordant for CHD, identified through the prospective, population-based longitudinal twin study (LoTiS), was subjected to ultrahigh-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) based metabolomic analysis. Orthogonal partial least square-discriminate analysis (OPLS-DA) and random forest (RF) analysis were used to determine differences in metabolic profiles and individual metabolites. In univariate analysis, two specific metabolites were identified in the umbilical cord blood of CHD cases compared to their MZ twins without complications. After the paired-sample t-test, four differentially expressed metabolites (DEMs) were identified, three of which were closely related to fatty acids and their metabolism. Enrichment pathway analysis revealed dysregulation of various metabolic pathways, including glucose metabolism, lipid metabolism, and amino acid metabolism pathways, in MZ twins with CHD compared to their healthy counterparts. The results demonstrated that the metabolomic signature of umbilical cord blood in CHD differs from that of their healthy MZ co-twins, and the revelation of associated metabolites and pathways provide preliminary clues for generating hypotheses about the metabolic correlates of CHD predisposition. Findings are limited by small sample size and require validation in larger, independent cohorts.

Jervell and Lange-Nielsen syndrome (JLNS) is defined by electrocardiographic QT prolongation and sensorineural hearing loss, caused by homozygous or compound heterozygous variants in KCNQ1 and/or KCNE1. KCNQ1 encodes the alpha subunit Kv7.1 of the ion channels accountable for slow delayed rectifier potassium currents (IKs), whereas KCNE1 encodes the beta subunit mink, which modulates the function of IKs. This review comprehensively summarizes the clinical features and genetic traits of JLNS. The pathogenicity of the amino acid substitutions in Kv7.1 and mink was assessed using AlphaFold. Furthermore, we systematically evaluated recent progress in experimental models of JLNS as well as phenotypic characterization and mechanistic studies across these experimental platforms, encompassing nonexcitable cell systems, genetically engineered murine models, and patient-specific induced pluripotent cell-derived cardiomyocytes and inner ear hair cells.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may impact immune-related micro ribonucleic acids (miRNAs). The role of salivary miRNAs as predictors of severe infection in children is unknown. This study sought to examine the relationship between SARS-CoV-2 severity and salivary miRNA levels in children. A convenience sample of 400 children with SARS-CoV-2 infection was prospectively evaluated between March 2021 and February 2022 at two U.S. children's hospitals. Saliva swabs were obtained. Levels of 3 miRNAs previously implicated in SARS-CoV-2 pathophysiology were measured with quantitative polymerase chain reaction (miR-1273c, miR-296-5p, and miR-4495). The primary outcome measure was the occurrence of severe illness, including respiratory failure, shock, or death from a related cause within 1 month of evaluation. Disease resolution was determined through chart review and caretaker phone calls 4 weeks after the initial visit. Saliva samples from 395 (severe = 105) participants (mean age: 7.4 ± 5.9 years, 51.7% female, 54.7% African American) were analyzed. Children with severe outcomes had lower levels of miR-296-5p (fold difference: 0.361, d = 0.111, p = 0.046). Multivariable adjusted logistic regression analysis demonstrated an inverse association between severe outcomes and levels of miR-296-5p (adjusted odds ratio = 0.89; 95% confidence interval [0.81, 0.98], p = 0.021) while controlling for age, sex, race, weight, insurance, diabetes, asthma, fever, and symptom duration. The model had an area under curve of 0.744 (sensitivity = 0.71, specificity = 0.66). Measurement of saliva miRNA in conjunction with demographic and clinical characteristics may aid in the prediction of severe illness. Larger, longitudinal studies to assess the utility of salivary miRNAs in SARS-CoV-2 and other viral infections are needed.

X-linked hypophosphatemia (XLH) is a rare hereditary disorder characterized by PHEX gene mutations, elevated FGF23 levels, and impaired bone mineralization. Burosumab, a monoclonal antibody targeting FGF23, has demonstrated clinical efficacy; however, the immunological dynamics during treatment remain unexplored. This study employed longitudinal single-cell RNA sequencing (scRNA-seq) to characterize peripheral blood immune cell alterations across multiple treatment stages in pediatric XLH. We performed scRNA-seq on peripheral blood mononuclear cells from pediatric patients with XLH at five time points spanning pretreatment and burosumab therapy phases, along with healthy pediatric controls. A total of 93,112 cells were analyzed using comprehensive bioinformatic pipelines, including unsupervised clustering, pseudotime trajectory analysis, temporal gene expression profiling, and cell–cell communication inference. Eleven major immune cell populations were identified, with notable dynamic alterations in T cells and natural killer (NK) cell subtypes across treatment stages. The cellular proportion of T helper 2 (Th2) cells and regulatory T (Treg) cells were elevated before treatment and normalized during therapy, whereas T helper 17 (Th17) cells exhibited reciprocal patterns. Genes upregulated in Treg cells during early treatment were enriched in osteoclast differentiation pathway. Natural killer subtype 2 cells showed enrichment in osteoclast differentiation and interleukin-12 response pathways. Cell–cell communication analysis identified dynamic interactions among Th2 cells, Th17 cells, Treg cells, and NK cell subtypes mediated by KLRB1–CLEC2D and SELL–SELPLG ligand-receptor pairs. This longitudinal transcriptomic study provides the first comprehensive characterization of peripheral immune dynamics during burosumab therapy in XLH, offering new insights into the immunological mechanisms underlying treatment response.

Childhood asthma remains a global public health challenge with suboptimal control, despite the availability of inhaled corticosteroids (ICS) as first-line therapy. Glucocorticoids suppress inflammation and protect the airway epithelial barrier (AEB) via genomic and nongenomic pathways. However, a significant subset of patients, particularly those with severe asthma, exhibits glucocorticoid resistance. Emerging evidence reveals a dual role of glucocorticoids on the AEB: beyond protection, they may inadvertently compromise barrier integrity by inducing epithelial apoptosis and dysfunction. This review synthesizes current knowledge on glucocorticoid mechanisms in asthma, focusing on the AEB as a critical interface between therapeutic efficacy and treatment failure. We show that AEB impairment serves as one of the key mechanisms underpinning glucocorticoid resistance and the progression to severe asthma, with heightened relevance in children due to the unique vulnerability of their developing airways. Furthermore, we examine how infections, nutritional factors (e.g., vitamins A and D), and immune maturation intersect with AEB integrity and glucocorticoid responsiveness. By reframing the AEB as both a target and a determinant of glucocorticoid efficacy, this review highlights the urgent need for barrier-focused strategies to overcome resistance and improve outcomes in childhood asthma.

Mild malnutrition in infants and young children is an early stage of nutritional deficiency characterized by a slight reduction in nutritional reserves and mild impairment of physiological functions but no obvious clinical symptoms or severe growth retardation. Parents often overlook this condition because typical signs are absent. This cross-sectional study aimed to investigate the current status of mild malnutrition in infants and young children aged 6–24 months attending a pediatric health clinic, analyze its influencing factors, and provide a basis for nutritional health guidance. The study included 879 infants and young children aged 6–24 months who underwent physical examinations at the Outpatient Clinic of Pediatric Health Care, The Third Affiliated Hospital of Zhengzhou University, China, from December 2024 to August 2025. The survey results showed a detection rate of mild malnutrition of 13.88% (122/879). After including statistically significant factors from univariable analysis in a multivariable logistic regression, the following risk factors were identified: food allergies (odds ratio (OR) = 3.117, 95% confidence interval (CI): 1.902–5.108), low maternal education level (OR = 1.969, 95% CI: 1.166–3.325), low birth weight (OR = 1.759, 95% CI: 1.041–2.973), maternal prepregnancy BMI < 18.5 (OR = 2.197, 95% CI: 1.252–3.855), frequent nighttime awakenings (OR = 2.427, 95% CI: 1.481–3.975), and insufficient complementary feeding frequency (OR = 1.550, 95% CI: 1.030–2.332). The detection rate of mild malnutrition in infants and young children aged 6–24 months at pediatric clinics is relatively high, and clinical work should give sufficient attention to this issue. Proactive guidance should be provided to these children to promote healthy growth.

The global prevalence of heart failure in children continues to increase, accompanied by a growing disease burden. To advance early prevention and intervention by shifting the focus upstream in the disease process, the Cardiovascular Group of the Pediatrics Society of the Chinese Medical Association has introduced the concept of pediatric cardiac function staging applicable to all children. This framework categorizes pediatric cardiac function into three distinct stages: the stage of cardiac function sufficiency (Stage A), the stage of cardiac dysfunction (Stage B), and the stage of cardiac function failure (Stage C). Based on this staging system, the diagnostic criteria and management strategies for each stage are delineated, with the aim of establishing a comprehensive management pathway rooted in cardiac function staging. This approach seeks to further reduce the incidence and burden of pediatric heart failure, providing a theoretical foundation and practical guidance for achieving the goal of making pediatric heart failure preventable, manageable, and treatable.