PURPOSE:Pathogenic UNC13A variants are increasingly recognized in pediatric neurodevelopmental disorders, but epilepsy phenotypes and antiseizure medication (ASM) responses remain poorly characterized. This study aimed to define the epileptic spectrum of UNC13A-related disorders in children and identify effective ASM strategies. METHODS:We retrospectively analyzed 10 children with pathogenic/likely pathogenic UNC13A variants. Clinical data, seizure phenotypes, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), and ASM outcomes were systematically evaluated. RESULTS:We identified 10 patients, including eight with de novo heterozygous variants and two with biallelic variants. Most missense variants were localized within the critical hinge regions of Munc13-1, with p.Pro814Leu identified as a recurrent variant in three individuals. Six patients (60%) presented with developmental and epileptic encephalopathy, with a median seizure onset of 19 months (range: 5 months-7 years). Focal seizures were the predominant seizure type, and all affected patients experienced status epilepticus. Febrile seizures occurred in half of these patients. While seizures were largely refractory, levetiracetam (LEV) was observed effective in three out of four treated patients. Genotype-phenotype analysis revealed distinct clinical trajectories: biallelic variants resulted in catastrophic early-onset symptoms and early mortality, whereas heterozygous variants were characterized by drug-resistant epilepsy, tremor and ataxia. CONCLUSIONS:UNC13A variants represent an underrecognized cause of developmental and epileptic encephalopathy in children, characterized by refractory seizures, a high incidence of status epilepticus, and increased susceptibility to febrile seizures. Preliminary observations noted favorable clinical outcomes in a small subset of patients treated with LEV.

Purpose The ketogenic diet (KD) is a well-established therapy for drug-resistant epilepsy, reducing seizure burden in children and improving cognition in epileptic encephalopathy patients, but its underlying mechanisms remain incompletely understood. This study aimed to establish a translational zebrafish model to investigate KD’s anti-epileptic potential and mechanisms, focusing on neurotransmitter homeostasis. Method Acute epilepsy was induced in 7-day post-fertilization (dpf) zebrafish larvae (n = 24/group, randomly assigned) using pentylenetetrazol (PTZ), a selective GABA-A receptor antagonist. KD was administered to the treatment group, with behavioral assays (locomotor activity, thigmotaxis), electroencephalographic (EEG) recordings, and high-performance liquid chromatography (HPLC) for neurotransmitter quantification. Statistics were analyzed via two-way ANOVA/Tukey’s test or Student’s t-test. Results Results showed KD significantly ameliorated PTZ-induced epileptiform behaviors (prolonged seizure latency, reduced stage-specific duration), attenuated EEG multi-peak discharges, increased inhibitory neurotransmitters (GABA, glycine, taurine), and reversed PTZ-induced excitatory-inhibitory neurotransmitter imbalance (e.g., Glu/GABA, Gln/Tau ratios). Conclusion We established a PTZ-induced amphibian epilepsy model with KD intervention. KD exerts anti-epileptic effects, likely mediated partially by rebalancing central nervous system neurotransmitter homeostasis, providing a valuable translational platform for further mechanism research.

BACKGROUND/OBJECTIVES:Acute hypobaric hypoxia at high altitude may impair hearing, but the earliest cochlear lesion site and associated biological responses remain unclear. We aimed to characterize the early cochlear phenotype after 7 days of hypobaric hypoxia in adult C57BL/6J mice. METHODS:Mice were exposed to simulated hypobaric hypoxia equivalent to 5500 m altitude for 7 days. Auditory brainstem response (ABR), electrocochleography (ECochG), cochlear immunofluorescence, presynaptic ribbon quantification, oxidative-stress marker analysis, and bulk RNA sequencing were used to assess early functional, structural, and molecular changes. RESULTS:Hypoxia induced predominantly high-frequency auditory dysfunction, including elevated ABR thresholds at 16 kHz, reduced suprathreshold ABR wave I amplitude, and an increased SP/AP area ratio on ECochG. Gross hair-cell and spiral-ganglion-cell counts were preserved, whereas CtBP2-positive presynaptic ribbons were reduced, with the most prominent change in the basal turn. Oxidative-stress-associated immunolabeling was increased, as shown by elevated 4-HNE and 8-OHdG-related signals in hair cells and increased 4-HNE in spiral-ganglion tissue. Transcriptomic analysis identified 676 differentially expressed genes enriched in synaptic transmission, neurotransmitter transport, postsynaptic membrane organization, ion-channel activity, and calcium signaling. CONCLUSIONS:Seven-day hypobaric hypoxia induces an early cochlear injury state characterized by basal-turn-predominant presynaptic ribbon injury, oxidative stress, and reduced suprathreshold auditory-nerve output before overt cellular loss. Transcriptomic findings support glutamatergic and calcium-signaling remodeling as mechanistic directions but do not establish individual hub genes as validated causal drivers.

BACKGROUND:Significant differences exist in the patterns and timing of organ involvement in Tuberous sclerosis complex (TSC). We sought to analyze potential differences in multiorgan involvement between TSC1 and TSC2 genotypes based on imaging findings, thereby elucidating the disease expression profile of TSC. METHODS:This retrospective investigation encompassed 112 individuals diagnosed with tuberous sclerosis at a tertiary hospital in China between March 2020 and March 2025. Clinical presentations, imaging findings, and genetic data were analyzed to evaluate the involvement of the brain, heart, and kidneys in patients with TSC1 and TSC2 mutations. RESULTS:Among 112 patients (median age 7.17 years; 60.7% male). No significant differences were observed in cerebral and cardiac involvement between TSC1 and TSC2 mutations (p > 0.05). However, patients with TSC2 mutations faced an elevated cumulative risk of renal angiomyolipoma (TSC2: 48.5% vs. TSC1: 11.4%, p < 0.001) and renal cysts (TSC2: 33.8% vs. TSC1: 9.1%, p = 0.003). The most frequent combined involvement patterns include brain-heart and brain-heart-kidney involvement, while isolated brain involvement was the predominant single-organ phenotype. CONCLUSION:Multisystem imaging heterogeneity and co-occurrence analysis in pediatric tuberous sclerosis complex may facilitate the prediction of disease evolution and inform long-term clinical management.

The ATP-binding cassette subfamily A member 2 (ABCA2) gene encodes an ABC transporter protein. Bi-allelic loss-of-function variants in ABCA2 have been associated with an intellectual disability disorder. We aimed to delineate the phenotypic spectrum of individuals with monoallelic (MV) or bi-allelic (BV) variants in the ABCA2 gene. We collected clinical data via questionnaires and literature review. The ABCA2 protein was constructed using homology modeling. Untargeted plasma metabolomics was performed at Metabolon. A docetaxel toxicity cell culture model system was used to study the effects of plasmid-encoded ABCA2 and four ABCA2 variants (p.Asp615Glu [c.1845C>A], p.Phe754Ser [c.2261T>C], p.Ile786del [c.2356_2358del], and p.Arg926Trp [c.2776C>T]) on cell viability. Seventeen individuals with seventeen candidate ABCA2 variants were identified (seven MVs and ten BVs). Protein modeling predicted a likely significant impact for eight of 13 assessed variants. In cell viability assays, enforced expression of wild-type ABCA2 reduced viability in docetaxel-exposed cells. In contrast, none of the four variants affected viability, suggesting a loss or a marked reduction in transporter function. Untargeted metabolomics of three samples from two individuals showed a trend toward lower levels of polyunsaturated acylcarnitines. This study describes 17 individuals with candidate variants in the ABCA2 gene. The cell viability assays revealed that four variants (p.Asp615Glu, p.Phe754Ser, p.Ile786del, and p.Arg926Trp) had an altered ability to function as a transporter compared to wild-type ABCA2. Further studies are needed to clarify the pathomechanism of ABCA2 and the clinical significance of the variants.

IntroductionAdolescents and young adults with rare diseases face a “medical cliff” when they age out of paediatric services, losing established care relationships and disease-specific expertise. Most rare diseases begin in childhood, since 69.9% of catalogued rare diseases are of exclusively paediatric onset. The problem is acute in China, where an estimated 20 million people live with a rare disease and systematic transitional care pathways remain largely absent.MethodsWe describe the development and implementation of an integrated paediatric–adult continuity of care model for rare diseases, the adult population it serves, and early operational indicators of its feasibility. This retrospective, descriptive analysis used clinical service data from the Children's Hospital of Fudan University, Shanghai, over a 38-month window (3 January 2023–25 February 2026); the model was implemented from September 2023. Its four components were expanded treatment authority with proactive management; a multidisciplinary paediatric–adult joint clinic; proactive follow-up with dynamic evaluation; and medical social work with psychosocial support. The programme admits patients aged 18–35 years.ResultsIn total, 2,341 patients aged ≥18 years generated 4,847 outpatient, emergency, and inpatient encounters (mean age at first encounter 22.7 ± 5.9 years; 51.7% female). Annual encounter volumes rose from 240 in 2023 to 1,412 in 2024 and 2,628 in 2025, with a further 567 in January and February 2026. Return attendances accounted for 4,373 encounters (90.2%), and 843 patients (36.0%) attended more than once. The leading specialities were neurology (29.1%), hepatology (12.2%), and endocrinology (8.1%); most encounters were by Shanghai residents (54.8%).DiscussionRepeat attendance measures utilisation rather than adherence, and rising volumes likely reflect progressive implementation and growing awareness rather than model effectiveness. With enabling policies, paediatric hospitals can deliver continuous care for adult rare disease patients, although these indicators describe service activity rather than clinical or patient-reported outcomes. The model is best characterised as continuity of care delivered within paediatric services rather than as a conventional transition programme, and offers a replicable blueprint for health systems lacking established adult subspeciality services; cross-provincial health insurance portability remains the single most critical barrier to nationwide scale-up.

Autism spectrum disorder is a common and heterogeneous neurodevelopmental condition. Although its etiologies are diverse, converging evidence suggests that genetic susceptibility and environmental exposures intersect across a limited set of biological pathways. We interpret recent advances through a microenvironment dysregulation perspective that connects immune imbalance, epigenetic regulation, synaptic plasticity, and gut-brain interactions. We distinguish mechanistic evidence from experimental models from predominantly correlative findings in human studies and emphasize that these processes may involve multiple entry points across biological subgroups. We propose that early-life immune challenges can, in some individuals, interact with genetic risk to shape epigenetic programs and neural-immune signaling, with downstream consequences for microglial states and synaptic development, potentially reinforced by gut-brain feedback loops. This integrative view highlights testable hypotheses, convergent mechanistic hubs, and a conceptual basis for subgroup-aware biomarker discovery and mechanism-informed interventions.

OBJECTIVE:Drug-resistant epilepsy (DRE) affects approximately one-third of patients with epilepsy. The molecular heterogeneity underlying DRE remains poorly defined, largely due to limited access to resected brain tissue and substantial genetic diversity. Current classifications rely primarily on clinical symptoms and histopathological features rather than molecular mechanisms, constraining mechanistic insight and the development of targeted therapies. This study aimed to develop a transcriptome-based, machine learning-guided framework for molecular classification of DRE. METHODS:We performed comprehensive RNA sequencing on 153 surgically resected samples from 95 patients with DRE. Two transcriptomic subtypes were identified through unsupervised clustering. We also leveraged a weighted correlation network-based framework and systematic transcriptional signature comparison and developed a classification model using machine learning algorithms. RESULTS:Unsupervised clustering revealed two molecular subtypes that diverged from traditional pathological classifications, indicating an alternative transcriptomic basis for epilepsy pathogenesis. A classification model was constructed based on four key differentially regulated pathways: (1) neuroactive ligand-receptor interaction, (2) cAMP signaling, (3) γ-aminobutyric acid (GABA)ergic synapse, and (4) calcium signaling. Among the tested algorithms, the random forest model demonstrated superior performance, achieving 96% classification accuracy with an area under the curve (AUC) of .95. SIGNIFICANCE:These molecular subtypes and their pathways could serve as key molecular hallmarks of epilepsy, offering valuable insights for developing targeted therapies. Moreover, our findings introduce a novel framework for classifying epilepsy based on its molecular nature, potentially connecting the clinical symptoms with the underlying causes more effectively.

Objective:This study aims to examine the relationship between habitual nighttime sleep duration and anxiety symptoms in preschoolers, and to identify a potential sleep-health threshold for mental health promotion. Methods:This cross-sectional study included 1589 participants from two public kindergartens. Parents reported habitual nighttime sleep duration using the Children's Sleep Habits Questionnaire (CSHQ) and anxiety symptoms using the Preschool Anxiety Scale (PAS). Initial non-parametric tests were supplemented with linear mixed-effects models (LMM) incorporating for fixed effects for sleep duration and covariates, with family cluster as random intercepts. Results:Among the participants, the mean age was 4.58 ± 0.86 years, and 52.2% were male. Initial nonparametric analysis revealed significant overall differences in anxiety symptoms (PAS: H=8.503, P=0.014) and generalized anxiety (GAD: H=7.427, P=0.024) across nighttime sleep duration groups. Adjusted LMM showed preschoolers with ≤9 hours of nighttime sleep had significantly higher PAS total scores (β=3.13, 95% CI: 1.01~5.25, P=0.004) and elevated scores across multiple anxiety subdomains (physical injury fears, social phobia, and obsessive-compulsive symptoms; all P<0.05) compared to >10h sleepers. Although the overall GAD model was nonsignificant (P=0.056), these children showed elevated GAD subscale scores (β=0.60, 95% CI: 0.14~1.07, P=0.011) aligns with prior evidence. Sensitivity analyses using alternative nighttime sleep duration thresholds (8.5h, 9.5h) and weekday-specific data confirmed the robustness of these findings. Conclusion:Our data suggests that nighttime sleep duration of 9 hours is an approximate sleep-health indicator for preschool aged children. These findings reinforce the importance of prioritizing healthy sleep habits as part of early childhood wellness initiatives, including age-appropriate nighttime sleep duration.

Objective To investigate the predictive value of dynamic changes in blood glucose, blood ketones and glucose-ketone index (GKI) for the efficacy of the classic ketogenic diet (CKD)in children with refractory epilepsy. Methods Data from 189 children with refractory epilepsy who received classic ketogenic diet(CKD) between January 2018 and December 2024 were retrospectively analyzed. Blood glucose, blood ketones and the glucose-ketone index (GKI) which defined as the ratio of blood glucose to blood ketone were monitored at multiple time points, from the 2-day period of halving carbohydrate intake to 90 days after CKD initiation. Patients were divided into a responder group (≥50% seizure reduction) and a non-responder group based on Engel’s classification after three months of treatment. Group differences in metabolic indices were assessed, and receiver operating characteristic(ROC) analysis identified optimal GKI thresholds for predicting response. Results On the first day of CKD therapy, GKI (AUC = 0.638) was the best single predictor of efficacy among all time points, with a cut-off value of 9.63 (sensitivity and specificity both 0.63). Combining blood glucose (<4.95 mmol/L) and blood ketone (>0.75 mmol/L) levels improved predictive performance (AUC = 0.661). Conclusion A GKI > 9.63 on the first day of CKD therapy may serve as an early-warning indicator of poor treatment response. The early treatment phase—from the second day of halving carbohydrate intake to the first day of CKD—represents a critical window for metabolic transition. Monitoring dynamic changes in GKI and blood ketone may facilitate timely adjustment of intervention strategies.

Purpose:High-risk infants often show atypical postnatal growth and may be vulnerable to visual impairment, yet evidence linking early-life systemic growth with ocular development remains limited. This study investigated the associations between growth trajectories during early childhood (birth to 3 years) and ocular development in high-risk infants. Methods:In this population-based prospective study, 10,030 high-risk infants underwent repeated measurements of weight, length, body mass index (BMI), and head circumference from birth to 36 months. Growth velocities were calculated as changes in World Health Organization (WHO)-standardized z scores across developmental intervals. Uncorrected visual acuity (UCVA; logMAR) and cycloplegic spherical equivalent refraction (SER; diopters [D]) were assessed at 3 to 4 years. Associations between growth increments and ocular outcomes were examined using multivariable linear regression adjusting for demographic and perinatal factors. Results:Of the total, 36.6% were preterm, 6.9% were term low-birth-weight, and 31.7% were macrosomic. UCVA exhibited a graded pattern (P < 0.001): poorest in preterm infants (0.229 [0.224-0.234]), followed by term low-birth-weight (0.225 [0.215-0.235]) and term normal-birth-weight infants (0.219 [0.213-0.225]), whereas macrosomic infants showed comparable or slightly better UCVA (0.213 [0.207-0.219]). SER was most hyperopic among preterm infants (0.433 [0.410-0.456]) and least hyperopic among macrosomic infants (0.389 [0.360-0.419]). Accelerated growth during 0 to 6 and 6 to 12 months was consistently associated with poorer visual acuity and a more hyperopic refractive profile, with no significant associations observed beyond 12 months. Conclusions:Accelerated early-life growth was linked to less favorable visual acuity and refractive outcomes, highlighting the first postnatal year as a critical period for coordinated systemic and ocular development.

BACKGROUND:There is a gap in the pharmacokinetic data on tacrolimus in children with juvenile dermatomyositis (JDM). This study aimed to develop a population pharmacokinetics (PopPK) model for tacrolimus in patients with JDM and formulate model-based recommended dosing regimens. METHODS:The PopPK model for tacrolimus was retrospectively developed in 31 children with JDM using nonlinear mixed-effects modeling. The trough concentrations of tacrolimus at different doses were simulated using the Monte Carlo method in children with different body weights. RESULTS:The one-compartment model with first-order absorption and elimination best described the pharmacokinetic data of tacrolimus. In the final model, body weight and concomitant use of voriconazole (VRC) significantly affected the apparent clearance (CL/F) of tacrolimus. The calculation of interindividual clearance was performed as follows: 12.635 × (WT/33.5)0.296 × (1-0.426 × VRC). The tacrolimus CL/F ratio in children with JDM was 1:0.574 between those without VRC coadministration and those with VRC coadministration at equivalent body weights. For patients with JDM and body weights of 10-20, 20-30, 30-40, and 40-60 kg, the recommended initial doses of tacrolimus without the combined use of VRC were 0.12, 0.08, 0.06, and 0.05 mg·kg-1·d-1 (q12h), respectively; the recommended initial doses of tacrolimus with the combined use of VRC were 0.07, 0.05, 0.04, and 0.03 mg·kg-1·d-1 (q12h), respectively. CONCLUSIONS:This is the first study to establish a PopPK model for tacrolimus. Drug dosage regimens devised on the basis of this model provide evidence-based recommendations for patients with JDM.

Background Optically pumped magnetometers magnetoencephalography (OPM-MEG) have demonstrated their value in the diagnosis and mapping of epilepsy, as well as their advantages in pediatric applications. Case presentation We present a case of 8-year-old boy with drug-resistant epilepsy, whose epileptogenic lesion is in left Broca's region. The boy underwent language function evaluation and localization by on-scalp OPM-MEG before surgery. Dipole clusters and Dipole Density of epileptogenic signals by OPM-MEG were located in the left inferior frontal gyrus, though language verbal generation mapping of OPM-MEG signals were mainly located in left frontal orbital gyrus, indicating a localization of the language function area. Seizure freedom and no loss of language function were achieved after MRI-guided laser interstitial thermal therapy. Conclusions This article underscores the feasibility of using OPM-MEG to record abnormal discharges of seizure and assess language function area in children, especially in drug-resistant epilepsy surgery involving brain functional areas.

This study aimed to investigate the quality of dying and death in an end-stage intensive care unit (ICU). We surveyed the quality of death of 99 end-stage ICU patients at a tertiary hospital in Suzhou using the Chinese nurse version of the ICU Quality of Death Questionnaire and a self-developed family version of the Patient Quality of Death Questionnaire. The patients' mean total quality of dying and death score was 44.72 ± 8.20. Moreover, 43.8% of the surveyed family members believed that the patients were peaceful at the end of their life, whereas 34.4% did not, and 21.9% were unsure. Health insurance status showed a significant negative correlation with both the total patient quality of death score (r = -0.205) and the end-of-life care score (r = -0.352). Based on the observational data and limited family interview sample from this study, the overall quality of death for end-stage ICU patients was relatively low. Scores on the quality of dying and death were correlated with patient age and health insurance status; however, these findings require further validation through multi-center, large-sample studies.

Diffuse glioma-related epilepsy (dGRE) frequently presents with epilepsy as the initial symptom and is closely associated with tumor progression or recurrence, imposing significant social and psychological burdens on patients. The pathogenesis of dGRE is highly complex, involving both peritumoral microenvironmental mechanisms and tumor-intrinsic factors. Diagnosis requires a comprehensive approach integrating neuroimaging, EEG, molecular biomarkers, and spatial correlation between the tumor and the epileptogenic zone. Management aims to control seizures and improve prognosis. Non-enzyme-inducing anti-seizure medications (ASMs), such as levetiracetam and lacosamide, are recommended as first-line therapy, while valproic acid serves mainly as a second-line agent. Surgical resection, particularly maximal safe and supratotal removal guided by electrophysiological monitoring, significantly improves seizure outcomes. Radiotherapy, chemotherapy, and targeted agents further contribute to seizure control. The updated 2025 Chinese clinical practice guidelines incorporate recent advances in ASM use, postoperative withdrawal strategies, and multidisciplinary treatment algorithms. These updates provide an evidence-based reference for standardized diagnosis and management of dGRE.

ObjectiveTo reveal the pattern of effects of exposure to high-altitude hypobaric hypoxia environment on the auditory function of C57BL/6J mice, so as to provide a theoretical basis for the targeted prevention and treatment of hearing loss, tinnitus, and otogenic vertigo in high-altitude areas.MethodsForty male C57BL/6J mice were randomly divided into a control group and an experimental group. The experimental group was further subdivided into 9 subgroups according to the exposure duration (3, 5, 7, 10, 15, 20, 25, 30, and 35 days), with 4 mice in each subgroup. Mice in the experimental group were housed in a hypobaric hypoxic chamber simulating an altitude of 6000 meters. Auditory function-related indicators of mice in both groups were detected using auditory brainstem response (ABR), electrocochleography (ECochG), and distortion product otoacoustic emissions (DPOAE). Statistical methods were used to compare the intergroup differences.ResultsResults of ABR testing: Under click stimulation, the latencies of Waves I, II, III, IV, and V, as well as the I-III interwave interval, were significantly prolonged in all subgroups of the experimental group. Abnormal changes (elevation or reduction) in the amplitudes of Waves II and III were observed, and hearing thresholds were significantly elevated (P < 0.05). Under stimulation with low-frequency 4000 Hz and 8000 Hz pure tones, all subgroups of the experimental group also exhibited similar changes as mentioned above (P < 0.05). Horizontal comparison of different stimulation conditions (click, 4000 Hz, 8000 Hz) within the experimental group revealed that the degree of hearing loss was more significant in the click group and 4000 Hz pure tone stimulation group than in the 8000 Hz group (P < 0.05). Results of ECochG testing: The latencies of the summating potential (-SP) and compound action potential (AP) were generally prolonged in all subgroups of the experimental group. Among them, the -SP/AP amplitude ratio was > 0.4 in the subgroups exposed for 3, 5, 15, 20, 25, and 30 days (P < 0.05), and the -SP/AP area ratio was > 2.0 in the 7-day exposure subgroup. Results of DPOAE testing: Among all 40 mice, only 3 passed the test, with a pass rate of 7.5%, and all of these 3 mice were from the control group.ConclusionExposure to a high-altitude hypobaric hypoxia environment can induce low-frequency hearing loss in C57BL/6J mice, and the process of auditory response regulation and adaptation of mice to this environmental stimulus exhibits time dependence. Further analysis revealed that this low-frequency hearing loss is closely associated with the slowing of postsynaptic electrical signal transmission speed in the cochlea-inferior colliculus auditory conduction pathway; the mechanism underlying this slowing of electrical signal transmission may be related to changes in voltage or resistance at various sites of the auditory pathway during sound signal conduction. Based on auditory physiological mechanisms, it is hypothesized that the aforementioned abnormal changes in voltage or resistance may be associated with endolymphatic hydrops, suggesting that endolymphatic hydrops may be one of the potential key links through which the high-altitude hypobaric hypoxia environment affects auditory conduction function.

The approved AAV9-based gene therapy (onasemnogene abeparvovec) extends survival and motor milestones in spinal muscular atrophy (SMA) type 1 but is administered at a high dose (1.1E14 vg/kg) and carries a boxed warning for liver injury. We engineered SKG0201, a self-complementary AAV9 vector encoding codon-optimized SMN1 under central nervous system (CNS)-selective regulatory cassette (Syn-Cbin-rGBpA), driving CNS-preferential transgene expression and minimizing acute peripheral overexpression. In SMNΔ7 mice with a median survival of 15 days, a single 1E11 vg/pup (equivalent to 6.67E13 vg/kg) injection of SKG0201 extended median survival beyond 160 days, normalized rotarod and grip performance, and ameliorated neuropathology. No aminotransferase elevations were elicited up to 4E11 vg/pup. In a phase I trial (NCT06191354), 10 symptomatic infants with SMA type 1 received 3.7-5.5E13 vg/kg SKG0201. This interim analysis reports safety and preliminary efficacy data with at least 24 weeks of follow-up. At 24 weeks post treatment, 80% remained free from permanent ventilation, 6 of 8 survivors (75%) achieved a≥4-point increase in CHOP INTEND score, and 4 of 8 survivors (50%) achieved head control. Treatment-related adverse events were largely transient and manageable, with no high-grade drug-related hepatotoxicity observed. SKG0201's design reduces the viral dose requirement while optimizing CNS target engagement, suggesting an improved therapeutic index for SMA gene therapy.

The prevention and treatment of autism spectrum disorder (ASD) is a global public health challenge. This review applies a pyramid management-community-maternal and child care-medicine (PCMM) model, incorporating hierarchical and precise services along with parenting education, to examine the evolution of ASD clinical healthcare. The findings are organized into a tiered screening-identification-intervention system tailored to contexts with limited specialist resources. Key achievements include wide screening coverage through the maternal-child health network, earlier diagnostic confirmation in leading regions, and expanded access to intervention via parent-mediated and community-based delivery. However, persistent challenges remain. These include limited diagnostic capacity, regional disparities in services, workforce shortages, insufficient financial support, and stigma that impedes follow-up. We highlight priorities for improving frontline capacity, financing and reimbursement, and services beyond early childhood. The experience in mainland China provides a scalable reference for global ASD practice.

Objective:The incidence of medication errors is much higher among children because of their unique characteristics. This study aims to establish the first Pediatric Rational Medication Intelligent Decision System (PRMIDS) database in China and apply it to the preprescription review system to enhance the safety and effectiveness of medication therapy in children. Methods:The PRMIDS database was built on authoritative drug information reference books and websites. All drug information was collected, screened, and verified by at least two senior pharmacists. After ensuring consistency with actual local drug use, the information was entered into the system. Based on the severity of potential outcomes, the warning levels of drug information in the PRMIDS were classified into three categories: red (Level 7, absolutely prohibited), yellow (Level 6, relatively prohibited), and green (Levels 1-5, use with caution). Results:Between November 2018 and June 2025, over 400,000 data entries for 1,030 drugs were integrated. Drug information included conventional dosage, maximum dosage, administration routes, frequency, duplication, drug-drug/drug-food interactions, solvents and compatibility of injections, concentration and administration duration of infusion, allergies, pharmacogenomics, compatibility of Chinese Patent Medicines and Traditional Chinese Medicine, and requirements for decoction. After the PRMIDS database was embedded into the hospital information system, it could automatically obtain the real-time disease status and the latest examination results of children. The implementation of the PRMIDS led to a significant, non-linear reduction in Level 6 prescription alerts. A regression analysis showed a significant decline in Level 6 prescriptions after implementation (p < 0.001). Conclusion:The PRMIDS is the first medication information system specifically designed for Chinese children. This study proves its clinical impact and suggests potential for scalability and generalizability across China.