Progressive aging is known to negatively affect cardiopulmonary function, which increases the risk of developing cardiac/respiratory diseases. However, the relationship between the decline in pulmonary function and aortic arch stiffness in aging is not well understood. This study investigated the correlation between lung function impairment and aortic arch stiffness in male and female C57BL/6 mice from 2 to 52 weeks of age. Lung function was assessed using forced oscillation ventilation and aortic arch stiffness was measured through echocardiography. Our results show a progressive decline in lung function markers such as respiratory system resistance (Rrs) and tissue elastance (H) with age, alongside an increase in inspiratory capacity (IC) and compliance of the respiratory system (Crs). Aortic arch stiffness significantly increased with age, particularly during early adulthood, and was found to be a strong predictor of lung function impairment in both sexes. While linear regression models indicated that body weight was a more accurate predictor of lung function variability, aortic arch stiffness emerged as a reliable marker for the decline in pulmonary function. These findings suggest that aortic arch stiffness can serve as an early indicator of declining lung function and therefore provide a noninvasive method to assess cardiopulmonary health in aging populations. Future studies should explore the molecular mechanisms underlying these changes and extend the investigation to older mice to fully understand the long-term impacts of aging on cardiopulmonary function.

Asthma, chronic pulmonary obstructive disease (COPD), cystic fibrosis, and acute respiratory infections are severe respiratory conditions that significantly contribute to global morbidity and mortality. Airway mucus hypersecretion is an important common pathophysiological and clinical manifestation of these diseases and is closely associated with adverse clinical outcomes. At present, the management of airway mucus hypersecretion lacks a viable clinical intervention. However, the revelation that the EGFR signaling pathway acts as a convergent intracellular pathway for many inflammatory mediators indicates that it exhibits the greatest potential for inhibiting excessive mucus production. This review provides a comprehensive overview of the role of EGFR in airway mucus hypersecretion and the therapeutic progress of targeting it, intending to improve clinicians' understanding of the mechanism and offer insights and recommendations for developing novel pharmaceutical interventions to regulate mucus secretion.

Currently, there are no reliable pediatric biomarkers for assessing the severity of asthma. Therefore, the study aimed to assess the potential of glucocorticoid-induced TNFR-related ligand (GITRL) in assessing asthma severity. Bone marrow-derived dendritic cells (BMDCs) were isolated and treated with phosphate-buffered saline (PBS) or house dust mites (HDM). Flow cytometry, immunofluorescence, and RT-qPCR results revealed that GITRL expression was increased in HDM-treated BMDCs (p < 0.05). An asthma mouse model was established using HDM. Asthmatic mice exhibited significantly increased lung inflammation scores, serum IgE, total cell counts, and eosinophil counts in bronchoalveolar lavage fluid (BALF) (p < 0.05). Tissue immunofluorescence and immunohistochemistry indicated elevated GITRL expression levels (p = 0.03). Flow cytometry analysis of peripheral blood mononuclear cells (PBMCs) isolated from children showed that the proportion of GITRL + dendritic cells (DCs) and the mean fluorescence intensity (MFI) of GITRL were significantly increased in asthmatic children compared with healthy individuals (p < 0.01). RT-qPCR analysis showed that GITRL mRNA expression levels were significantly elevated in children with moderate-to-severe asthma compared to those with mild asthma (p = 0.006), and GITRL mRNA levels were higher in both groups of asthmatic children than in healthy controls (p < 0.05). Correlation analysis indicated that GITRL expression was negatively correlated with lung function and the Children's Asthma Control Test (C-ACT) score (p < 0.001). ROC analysis assessed its diagnostic value, with AUC values of 0.89 (asthma vs. healthy diagnosis) and 0.70 (distinguishing moderate-to-severe from mild asthma). These findings suggest that GITRL is an important biomarker for assessing asthma severity.

Sleep disturbances significantly impact children with autism spectrum disorder (ASD), yet their heterogeneous manifestations remain poorly understood. This multicenter prospective cohort study employed latent profile analysis to identify distinct sleep phenotypes among 631 children with ASD (aged 3–6 years) and 768 typically developing (TD) controls across three Chinese cities representing Northern, Central, and Western regions. Analysis of Children's Sleep Habits Questionnaire data revealed three distinct sleep phenotypes based on optimal model fit determined by Bayesian information criterion. Compared to TD children who showed generally better sleep patterns with lower sleep onset delay and fewer disturbances overall, the ASD groups exhibited distinctive profiles: Cluster 1 (9.2%) exhibited severe disturbances across multiple domains (sleep anxiety, parasomnias, night wakings and sleep-disordered breathing) and demonstrated the most severe autism symptoms; Cluster 2 (36.0%) presented a mixed profile with comparable bedtime resistance, sleep duration, and daytime sleepiness to TD children but elevated sleep-disordered breathing; and Cluster 3 (54.8%) showed reduced sleep-disordered breathing but elevated night waking and bedtime resistance. One-year follow-up data indicated that Cluster 3, characterized by mild sleep-disordered breathing, showed significant improvements in core symptoms particularly in social cognition, communication, and motivation domains, whereas Clusters 1 and 2 demonstrated modest changes. These findings suggest that early identification of sleep phenotypes may predict treatment response and inform personalized intervention strategies. Our results underscore the importance of incorporating comprehensive sleep assessment and management into ASD care protocols.

Pediatric stroke, although relatively rare, poses considerable health risks with substantial morbidity and mortality. Despite its clinical impact, comprehensive global assessments of its long-term trends and disparities remain limited. Using estimates from the Global Burden of Disease (GBD) 2021 study, we evaluated the burden of pediatric stroke—including both hemorrhagic stroke (HS) and ischemic stroke (IS)—across 204 countries and territories from 1990 to 2021. Our original analyses included the calculation of the estimated annual percentage change (EAPC) of age-standardized rates, stratified by age, sex, and sociodemographic index (SDI). In 2021, there were approximately 2.7 million prevalent pediatric stroke cases worldwide, with HS contributing 41.4% and IS 58.6%. Globally, stroke-related disability-adjusted life years (DALYs) declined from about 5.9 million in 1990 to 2.4 million in 2021. However, the incidence among adolescents aged 10–19 years increased during this period. Marked geographic disparities were observed, with low-SDI regions experiencing disproportionately higher burdens, particularly from HS. India recorded the highest number of DALYs and incident cases in 2021. These findings provide a comprehensive global analysis focused specifically on pediatric stroke, underscoring that although the overall burden has declined, persistent and widening disparities highlight the need for targeted strategies, improved early recognition and strengthened healthcare systems in resource-limited regions.

The minimum alveolar concentration of sevoflurane varies with age in children, and the median effective concentration (EC₅₀) of sevoflurane for I-gel insertion in children of different ages has not been reported. The aim of this study was to determine the EC₅₀ of end-tidal sevoflurane maintained for 2.5 min for I-gel insertion in children aged 1–10 years and also to estimate the 95% effective concentration (EC₉₅)_. This study aimed to recruit children who were scheduled to undergo laparoscopic high ligation of the inguinal hernia sac or laparoscopic high ligature of the sheath process. Children were stratified into three age groups. We employed Dixon's up-and-down method in this study. The target end-tidal sevoflurane concentration was then maintained at 2% for 2.5 min for the first child. The concentration for the subsequent patient was determined based on the response of the previous patient, with adjustments of 0.2%. This study was terminated when seven crossover points were reached. In the 1–3-year-old group including 3-year-old, EC₅₀ was 1.75% (95% confidence interval [CI], 1.72%–2.03%), and EC₉₅ was 2.17% (95% CI, 1.96%–2.18%). In the 3–6-year-old group including 6-year-old, EC₅₀ was 1.60% (95% CI, 1.35%–1.83%), and EC₉₅ was 1.96% (95% CI, 1.77%–1.98%). In the 6–10-year-old group, EC₅₀ was 0.96% (95% CI, 0.93%–2.20%) and EC₉₅ was 2.36% (95% CI, 2.15%–2.38%). Our study determined the EC₅₀ of end-tidal sevoflurane required for I-gel insertion in unpremedicated children aged 1–10 years and the results demonstrate to be both safe and effective for pediatric patients.

Refractory lung diseases (RLDs) encompass a spectrum of progressive pulmonary disorders, including acute respiratory distress syndrome (ARDS), bronchopulmonary dysplasia (BPD), and idiopathic pulmonary fibrosis (IPF). These conditions are defined by poor responsiveness to current therapeutic interventions and pose substantial clinical challenges, primarily due to their high morbidity and mortality rates. This review synthesizes the current understanding of the molecular mechanisms underlying RLDs and explores promising therapeutic strategies. A core feature of RLD pathogenesis is the disruption of alveolar microenvironmental homeostasis, which triggers a bidirectional vicious cycle between structural damage and disease progression. This homeostatic collapse is driven by interconnected pathological networks—including oxidative stress coupled with mitochondrial dysfunction, inflammatory immune dysregulation, and mechanical stress-induced extracellular matrix (ECM) remodeling—all of which are elaborated in this review. Collectively, these pathological processes contribute to therapeutic resistance. Based on these mechanistic insights, potential therapeutic approaches are discussed, such as antioxidant therapies (e.g., the mitochondria-targeted antioxidant Mitoquinone mesylate [MitoQ]) and antifibrotic agents (e.g., pirfenidone, nintedanib, as well as emerging strategies targeting Wnt pathway modulation). Additionally, the critical significance of early diagnosis and personalized precision medicine is emphasized. Future research should focus on a deeper characterization of the dynamic alterations within the alveolar microenvironment under pathological conditions, with the aim of developing more precise diagnostic tools and targeted therapeutic strategies. Ultimately, the therapeutic goal for RLDs should shift from mere symptom management to achieving pathological reversal.

Autism Spectrum Disorder (ASD) is marked by a distinctive cognitive profile reflecting neurodiversity, yet whether this profile extends consistently across the functional spectrum remains uncertain. In this study, we examined the intellectual structure of children with low-functioning ASD (LF-ASD) and high-functioning ASD (HF-ASD), comparing their cognitive peak-valley profiles using the Chinese Wechsler Intelligence Scale for Children (C-WISC). Among 314 children aged 6–13 years—including 104 with LF-ASD, 122 with HF-ASD, and control groups with typical development (TD) or intellectual disabilities (ID)—both ASD subgroups displayed significantly greater discrepancies between verbal and performance IQ than controls, with pronounced strengths in visuospatial tasks and weaknesses in arithmetic reasoning. Notably, the Block Design and Object Assembly subtests emerged as cognitive peaks across both ASD groups, whereas the Arithmetic subtest constituted the most frequent trough. Although the mean peak-valley discrepancy was slightly reduced in LF-ASD compared to HF-ASD, both exceeded the 2 standard deviation (SD) threshold for neurodiversity, distinguishing them from the TD and ID groups. These profiles were positively associated with adaptive functioning and inversely related to ASD symptom severity. Our findings suggest that children with LF-ASD exhibit intellectual asymmetries comparable to those of HF-ASD, supporting the universality of neurodiversity within the autism spectrum and offering valuable insights for tailoring cognitive interventions.

This consensus aims to standardize the diagnosis and management of neonatal lactose intolerance (LI). A multidisciplinary working group was established under the auspices of the Preterm Birth International Collaborative (Australasia Branch). The development process included a comprehensive literature review of databases, which identified 61 publications. Recommendations were formulated using the Grading of Recommendations, Assessment, Development and Evaluation system for evidence evaluation. A modified Delphi method was used to achieve consensus. The consensus establishes that neonatal LI presents with nonspecific gastrointestinal symptoms, requiring stool assessment for diagnosis. Screening tests include fecal reducing sugar or urinary galactose tests, and the diagnosis is confirmed through elimination testing while excluding mimics. Treatment prioritizes lactase-supplemented breastfeeding; formula-fed infants receive lactase or reduced-lactose formulas. Probiotics with β-galactosidase activity can be used as an adjuvant therapy, and evidence-based lactase preparations are recommended, particularly for preterm infants. Treatment duration should be individualized, with a general minimum of 2 weeks; however, the routine use of lactose-free formula to prevent LI in preterm infants is not recommended. This consensus provides practical evidence-based guidance to standardize the diagnosis and management of neonatal LI, aiming to reduce variation in practice and improve patient outcomes. It emphasizes the importance of maintaining breastfeeding while incorporating lactase supplementation and highlights the need for further high-quality research, particularly randomized controlled trials, to refine diagnostic criteria and therapeutic strategies for preterm and very preterm infants. The recommendations are intended to support clinicians in making informed decisions while promoting family-centered care.

The pathogenesis of heart failure involves a highly intricate process regulated by diverse epigenetic factors, transcription factors, noncoding RNAs, and cyclins. Notably, the reexpression of embryonic cardiac transcription factors, including GATA, MEF2, and Nkx2.5, is considered to exert critical influence in the initiation and advancement of heart failure. Nevertheless, the precise mechanisms through which epigenetic modifications drive this reprogramming of gene expression remain poorly defined. This investigation aims to clarify the role of histone acetylation in regulating the reexpression of embryonic cardiac transcription factors during heart failure. Our research indicates that during heart failure of mice, there are distinct histone acetylation modifications associated with the reexpression of these factors. Notably, GATA4 and MEF2C show significant increases, whereas Nkx2.5 shows a decrease compared to normal groups during heart failure progression. These findings imply that embryonic GATA4 and MEF2C may promote the development of heart failure, whereas Nkx2.5 does not appear to participate in disease progression. Furthermore, treatment with curcumin, a known inhibitor of histone acetylation, reduces acetylation levels at H3K4, H3K9, and H3K27 within the promoter regions of GATA4 and MEF2C in a murine model of heart failure, leading to downregulation of these genes and subsequent enhancement of cardiac performance. In summary, our study demonstrates that p300 exerts site-specific regulatory effects on various transcription factors via histone modifications, and low acetylation status at specific sites can inhibit reactivation of GATA4 and MEF2C during the myocardial dysfunction period thereby improving cardiac performance of mice.