Sepsis-associated encephalopathy (SAE) is characterised by long-term cognitive impairment and psychiatric illness in sepsis survivors, associated with increased morbidity and mortality. There is a lack of effective therapeutics for SAE. Molecular hydrogen (H2) plays multiple roles in septic diseases by regulating neuroinflammation, reducing oxidative stress parameters, regulating signalling pathways, improving mitochondrial dysfunction, and regulating astrocyte and microglia activation. Here we report the protective effect of hydrogen-rich saline in the juvenile SAE rat model and its possible underlying mechanisms. Rats were injected intraperitoneally with lipopolysaccharide at a dose of 5 mg/kg to induce sepsis; Hydrogen-rich saline (HRS) was administered 1 h after LPS induction at a dose of 5 ml/kg and nigericin at 1 mg/kg 1 h before LPS injection. H&E staining for neuronal damage, TUNEL assay for detection of apoptotic cells, immunofluorescence, ELISA protocol for inflammatory cytokines and 8-OHdG determination and western blot analysis to determine the effect of HRS in LPS-induced septic rats. Rats treated with HRS showed decreased TNF-α and IL-1β expression levels. HRS treatment enhanced the activities of antioxidant enzymes (SOD, CAT and GPX) and decreased MDA and MPO activities. The number of MMP-9 and NLRP3 positive immunoreactivity cells decreased in the HRS-treated group. Subsequently, GFAP, IBA-1 and CD86 immunoreactivity were reduced, and CD206 increased after HRS treatment. 8-OHdG expression was decreased in the HRS-treated rats. Western blot analysis showed decreased NLRP3, ASC, caspase-1, MMP-2/9, TLR4 and Bax protein levels after HRS treatment, while Bcl-2 expression increased after HRS treatment. These data demonstrated that HRS attenuated neuroinflammation, NLRP3 inflammasome activation, neuronal injury, and mitochondrial damage via NLRP3/Caspase-1/TLR4 signalling in the juvenile rat model, making it a potential therapeutic agent in the treatment of paediatric SAE.

Background: Language developmental delay is one of the most common neurodevelopmental concerns in early childhood. Early intervention is considered critical for improving communication outcomes, yet the comparative effectiveness of different intervention approaches remains incompletely understood. Objective: To examine the association between three early intervention strategies, clinic-based structured language rehabilitation, parent-led family intervention, and specialist-mediated play therapy, and language developmental outcomes in toddlers with mild language developmental delay in a non-randomized observational design. Methods: This single-center case-control observational pilot study included 180 children aged 18–36 months diagnosed with mild language developmental delay using the Gesell Developmental Diagnosis Scale. No randomization was performed. Participants were categorized into three intervention groups according to the clinical management strategy selected following standardized physician consultation and parental preference: clinic-based structured language rehabilitation ( n = 60), parent-led family intervention ( n = 60), and specialist-mediated play therapy ( n = 60). Language developmental quotient (DQ) scores were assessed at baseline, 6 months, and 12 months. Changes in DQ scores over time were analyzed using repeated-measures analysis of variance. Results: Language DQ improved significantly over time in all three groups ( p < 0.001). However, children receiving specialist-mediated play therapy demonstrated greater improvement than those receiving clinic-based structured rehabilitation or parent-led intervention. At 6 months, 43.3% of children in the play therapy group improved to the borderline language category compared with 21.7% in the clinic-based group and 23.3% in the family intervention group. At 12 months, 50.0% of children in the play therapy group achieved language scores within the normal range, compared with 18.3% and 25.0% in the clinic-based and family intervention groups, respectively. A significant group-by-time interaction was observed ( p < 0.001), suggesting different developmental trajectories across intervention approaches. Conclusion: Early intervention was associated with improvements in language development among toddlers with mild language delay. Specialist-mediated play therapy demonstrated a stronger association with language gains compared with clinic-based structured rehabilitation and parent-led interventions. These findings demonstrate association rather than causation owing to the non-randomized observational design. Further large-scale, multicenter randomized controlled trials are required to confirm these findings, establish causal efficacy, and determine optimal early intervention strategies.

Background Sepsis-associated encephalopathy (SAE) is one of the most common types of sepsis-related organ dysfunction without overt central nervous system (CNS) infection. It is associated with higher mortality, low quality of life, and long-term neurological sequelae in suspected patients. At present there is no specific treatment for SAE rather than supportive therapy and judicious use of antibiotics, which are sometimes associated with adverse effects. Molecular hydrogen (H2) has been reported to play crucial role in regulating inflammatory responses, neuronal injury, apoptosis and mitochondrial dysfunction in adult models of SAE. Here we report the protective effect of hydrogen-rich saline in juvenile SAE rat model and its possible underling mechanism(s). Materials and methods Rats were challenged with lipopolysaccharide (LPS) at a dose of 8ml/kg injected intraperitoneally to induce sepsis and hydrogen-rich saline (HRS) administered 1h following LPS induction at a dose of 5ml/kg. Rats were divided into: sham, sham+HRS, LPS and LPS+HRS. At 48h, rats were sacrificed and Nissl staining for neuronal injury, TUNEL assay for apoptotic cells detection, immunohistochemistry, and ELISA protocol for inflammatory cytokines determination, mitochondrial dysfunction parameters, electron microscopy and western blot analysis were studied to examine the effect of HRS in LPS-induced septic rats. Results Rats treated with HRS improved neuronal injury, improvement in rats’ survival rate. ELISA analysis showed decreased TNF-α and IL-1β and increased IL-10 expression levels in the HRS-treated group. Apoptotic cells were decreased after HRS administration in septic rats. The numbers of GFAP and IBA-1positive cells were attenuated in the HRS-treated group when compared to the LPS group. Subsequently, GFAP and IBA-1 immunoreactivity were decreased after HRS treatment. Mitochondrial membrane potential detected by JC-1 dye and ATP content were decreased in septic rats, which were improved after HRS treatment, while release of ROS was increased in the LPS group reverted by HRS treatment, ameliorating mitochondrial dysfunction. Further analysis by transmission electron microscopy showed decreased number of mitochondria and synapses, and disrupted mitochondrial membrane ultrastructure in the LPS group, while HRS administration increased mitochondria and synapses number. Conclusion These data demonstrated that HRS can improve survival rate, attenuate neuroinflammation, astrocyte and microglial activation, neuronal injury and mitochondrial dysfunction in juvenile SAE rat model, making it a potential therapeutic candidate in treating paediatric SAE.

Inherited metabolic disorders (IMDs) comprise more than 1,400 rare genetic conditions affecting paediatric patients worldwide. Despite advances in newborn screening and dietary management, many children experience chronic complications, gastrointestinal symptoms, and reduced health-related quality of life (HRQoL). Emerging evidence—predominantly from phenylketonuria (PKU)—suggests that gut microbiota may influence metabolic homeostasis and patient-centred outcomes in affected children. Because of substantial methodological heterogeneity and the rarity of individual disorders, we elected a narrative review format to synthesise current evidence rather than a formal quantitative synthesis. Electronic searches were performed in PubMed, Embase, and Web of Science from inception to February 2026. We synthesise current evidence regarding gut microbiota composition in major paediatric IMDs, including PKU, organic acidemias, glycogen storage diseases, lysosomal storage disorders, and mitochondrial diseases. For PKU, controlled studies report reduced microbial diversity and depletion of butyrate-producing taxa associated with long-term dietary treatment. For the remaining disorders, direct paediatric microbiome data are sparse or absent, and proposed links rely on mechanistic extrapolation from non-IMD populations. We present the gut microbiota–metabolism–quality of life axis as a conceptual framework that integrates microbial metabolites, intestinal barrier function, immune signalling, and patient-reported outcomes, while emphasising that direct causal evidence linking microbiota alterations to HRQoL in paediatric IMDs is currently lacking. Microbiota-directed interventions remain preliminary. Future multicentre longitudinal studies integrating microbiome profiling, multi-omics technologies, and validated patient-reported outcomes are needed to clarify causal mechanisms and therapeutic potential. Importantly, the available evidence is heterogeneous: direct paediatric microbiome evidence is strongest for PKU, whereas evidence for other IMDs is sparse and often observational, preclinical, or extrapolated from non-IMD populations. The proposed microbiota–metabolism–HRQoL axis is therefore presented as a hypothesis-generating framework rather than an established causal pathway.

Background To evaluate the differences in clinical characteristics, BPD risk factors and predictors in preterm twin infants. Methods A retrospective, single-centre study was conducted on preterm twins admitted to the neonatal intensive care unit (NICU) of The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, from January 2021 to December 2022. Data, including perinatal and critical postpartum data, were collected for twin pairs with gestational age (GA) ≤ 31 weeks and birth weight ≤ 2500 g from clinical medical records, including perinatal data and critical postpartum information. Chi-square or nonparametric tests and multiple logistic regression models were used to analyse significant clinical parameters and characteristics for BPD between the two groups and to compare risk factors, respectively. Results A total of 233 twin infants were included in this study. Among them, 183 pairs had BPD, consisting of 366 twin infants. Among twins with BPD, 184 (50.3%) were discordant, and 182 (49.7%) were in one of the twin pairs with BPD. Extremely low birth weight infants (< 1000 g) and extremely preterm infants (GA < 28 weeks) were typical of twin pairs with both BPD (35.9% and 52.7%), while low birth weight infants (< 2500 g) and very preterm infants (GA > 28 < 31 weeks) were more common in one of the twin pairs with BPD (35 .2% and 86.8%). Preterm infants with a length/height between 25 cm and 35 cm were typically twin pairs with BPD (79.7% vs 20.3%). Among the twin pairs with both BPDs, 94 (51.1%) had a head circumference of 22–26 cm compared with 34 (18.7%). Among the risk factors, asphyxia, PDA, RDS, pulmonary hypertension, ROP, IVH, bloodstream infections, hypothyroidism, and hypoproteinaemia were more prevalent in both pairs of twins with BPD. Among the interventions, HFV, IMV, BiPAP, oxygen therapy, and HFNC therapy had significantly different effects on the two groups. The duration of these interventions also significantly differed between the two groups. Conclusions These data demonstrated that risk factors and predictors of BPD in preterm twins vary in magnitude and severity, particularly in extremely low birth weight infants, extremely preterm infants with smaller head circumferences, and infants with short length/height. The need for mechanical ventilation, duration of ventilation, and medication use increased in pairs of twins with both BPD. Thus, this study adds to the existing knowledge on the early detection of risk factors and stratification of clinical management strategies for preterm twins at the individual level.