BackgroundTreating pediatric acute myeloid leukemia (AML) with NUP98 rearrangement (NUP98-R) is challenging. Standard chemotherapy results in low remission rates. This study aimed to evaluate different induction regimens and explore alternative therapies to improve outcomes.MethodsThis retrospective study included 111 pediatric patients with AML treated at our institution from March 2012 to March 2023. Patients were classified into two groups: NUP98-R-positive (n = 10) and NUP98-R-negative (n = 101). We compared their clinical characteristics, treatment responses, and prognoses. Additionally, we presented three cases of NUP98-R-positive patients to elaborate on the role of targeted therapies during induction in treatment outcomes and prognosis.ResultsPatients with NUP98-R fusion genes had a complete remission (CR) rate of 20% after the first induction, which was significantly lower than the 64.3% reported in those without NUP98-R fusion genes (P < 0.05). The 3-year event-free survival (EFS) rate was also lower, with only 30% for NUP98-R patients and 55.3% for non-NUP98-R patients (P < 0.05). The prognosis of NUP98-R patients improved with targeted therapies during induction. For example, Patient 1 achieved CR with FLT3 and BCL-2 inhibitors plus conventional chemotherapy. Patient 2, who was treated with a CDK6 inhibitor, a BCL-2 inhibitor, azacitidine, and an FLT3 inhibitor, also achieved CR and underwent successful stem cell transplantation. Conversely, Patient 3, who received only standard chemotherapy, did not achieve remission and died from a severe infection.ConclusionsThis study demonstrated that using targeted drugs for the induction in NUP98-R pediatric AML improved treatment outcomes. BCL-2, FLT3, and CDK6 inhibitors available at our institution are promising options for this phase of treatment.Graphical abstract

BackgroundSpinal cord injury is a catastrophic medical condition and a growing global public health priority, with divergent etiologies, risk factors, and epidemiology. Comprehensive analyses of trends in pediatric spinal cord injury burden both in China and globally are lacking.MethodsWe investigated temporal trends in pediatric spinal cord injury burden [incidence, prevalence, and years lived with disability (YLDs)] from 1990 to 2021 and projected future burden to 2045 using Global Burden of Disease (GBD) 2021 data. The year with the most significant changes in trends was identified via joinpoint regression analysis. Age-standardized rates, average annual percentage changes (AAPC), and subgroup analyses by injury location, sex, age, and sociodemographic index were calculated. To project burden data to 2045, we employed a Bayesian age‒period‒cohort model.ResultsOur analyses revealed that global pediatric spinal cord injury incidence [AAPC: − 1.13; 95% confidence interval (CI): − 1.49 to − 0.76], prevalence (AAPC: − 1.13; 95% CI: − 1.16 to − 1.11), and YLDs rates (AAPC: − 1.37; 95% CI: − 1.41 to − 1.35) decreased significantly from 1990 to 2021. The highest burden was observed in males, adolescents (15–19 years), and high-sociodemographic index regions; falls were the leading cause. China exhibited similar declining trends (e.g., incidence AAPC: − 1.33; 95% CI: − 1.71 to − 0.83). It is predicted that by 2045, the global trend of pediatric spinal cord injury will decline; China will exhibit an upward trend.ConclusionsPersistent disparities in pediatric spinal cord injury disease burden and causes necessitate targeted prevention strategies, optimized rehabilitation services, and equitable resource allocation. This is particularly important in high-risk groups and regions with rising burdens.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s12519-025-00991-7.

BackgroundChildren and adolescents with chronic physical conditions have an increased probability of mental health problems, which may be partly attributed to the variations in play behavior. This study explores the associations between having a chronic physical condition, play behavior, and having mental health problems.MethodsData from the Generation R Study were analyzed, a population-based, prospective cohort in the Netherlands. Chronic physical conditions were typically identified before six years of age. Play behavior was assessed at ages 6 and 10. Mental health problems were measured with the Child Behavior Checklist at 14 years of age. Logistic, ranked-order, and linear regression analyses were used to examine direct associations, and mediation analyses were used to investigate indirect paths. P values were false discovery rate adjusted.ResultsOf the 4043 included participants, 691 (17%) had a chronic physical condition. Having a chronic physical condition was associated with more mental health problems and limited activity at the age of six years. Playing sports and engaging in social interactions at age 10 were related to fewer mental health problems at age 14. Limited activity mediated the relationship between having a chronic physical condition and mental health problems (social: mediatedproportion = 8.33%, 95% CI = 2.02%; 15.7%, Padj < 0.001; physical: mediatedproportion = 7.72%, 95% CI = 1.73%; 19.1%, Padj = 0.040).ConclusionsHealth-related limitations in social and physical activities mediate the relationship between having a chronic physical condition and mental health problems in children. Participation in social and physical activities early in life may be crucial for the mental well-being of children with a chronic physical condition.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1007/s12519-025-00945-z.

BackgroundNewborn screening (NBS) for severe combined immunodeficiency (SCID), X-linked agammaglobulinemia (XLA), and spinal muscular atrophy (SMA) enables early diagnosis and intervention, significantly improving patient outcomes. Advances in real-time polymerase chain reaction (PCR) technology have been instrumental in facilitating their inclusion in NBS programs.MethodsWe employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles (TRECs), kappa-deleting recombination excision circles (KRECs), and the absence of the survival motor neuron (SMN) 1 gene in dried blood spots from 103,240 newborns in Zhejiang Province, China, between July 2021 and December 2022.ResultsOf all the samples, 122 were requested further evaluation. After flow cytometry evaluation and/or genetic diagnostics, we identified one patient with SCID, two patients with XLA, nine patients with SMA [one of whom also had Wiskott–Aldrich Syndrome (WAS)], and eight patients with other medical conditions. The positive predictive values (PPVs) of NBS for SCID, XLA, and SMA were 2.44%, 2.78%, and 100%, respectively. The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID, 1 in 51,620 for XLA, and 1 in 11,471 for SMA.ConclusionThis study represents the first large-scale screening in mainland China using a TREC/KREC/SMN1 multiplex assay, providing valuable epidemiological data. Our findings suggest that this multiplex assay is an effective screening method for SCID, XLA, and SMA, potentially supporting the universal implementation of NBS programs across China.Graphical abstract

BackgroundPediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.MethodsData from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored.ResultsRenal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924–0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010–1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation.ConclusionsRenal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.342BNb9AdCycy4MnMisg3FSupplementary file 2 (MP4 18937 KB)

BackgroundMacrophages are involved in various immune inflammatory disease conditions. This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis (NEC).MethodsCD68, nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease-1 (caspase-1), and interleukin-1β (IL-1β) in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry, immunofluorescence, and western blot. Hypertonic pet milk, hypoxia and cold stimulation were used to establish a mouse (wild type and Nlrp3−/−) model of NEC. The mouse macrophage (RAW 264.7) and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments. Macrophages, intestinal epithelial cell injuries, and IL-1β release were determined.ResultsCompared to the gut “healthy” patients, the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3, caspase-1, and IL-1β levels. Furthermore, in vivo, the survival rate of Nlrp3−/− NEC mice was dramatically improved, the proportion of intestinal macrophages was reduced, and intestinal injury was decreased compared to those of wild-type NEC mice. NLRP3, caspase-1, and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.ConclusionsMacrophage activation may be essential for NEC development. NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development, and all these may be therapeutic targets for developing treatments for NEC.

Adenosine deaminase (ADA) is a key enzyme in the purine salvage pathway. Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency. To date, few Chinese cases have been reported. We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children's Hospital and summarized the previously published ADA deficiency cases from China in the literature. Nine patients were identified with two novel mutations (W272X and Q202 =). Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients. The ADA genotype has a major effect on the clinical phenotype. Notably, a novel synonymous mutation (c.606G>A, p.Q202=) was identified in a delayed-onset patient, which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein. Furthermore, the patient showed γδT cells expansion with an increased effect or phenotype, which may be associated with the delayed onset of disease. In addition, we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency. Five patients died with a median age of four months, while two patients received stem cell transplantation and are alive. This study described the first case series of Chinese ADA-deficient patients. Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations in our patients. We identified a synonymous mutation that affected pre-mRNA splicing in the ADA gene, which had never been reported in ADA deficiency. Furthermore, we reported cerebral aneurysm in a delayed-onset patient for the first time. Further study is warranted to investigate the underlying mechanisms.

Chemotherapy and hematopoietic stem cell transplantation (HSCT) can damage the immune system, and may result in a loss of protection from infectious diseases. This study aimedto evaluate the impact of these treatments on the decrease in antibody titers of the measles, mumps, and rubella (MMR) vaccine and seroconversion post-revaccination of MMR. After completion of treatment for primary diseases, participants received an MMR revaccination. Antibody titers for MMR before revaccination were analyzed for all 110 children. After revaccination, 68 participants received afollow-upevaluation of antibody titer and adverse reaction. Multivariable analysis showed that therapeutic schedules were the only factor correlated with lack of antibody titers for measles after completing treatment (P = 0.008), while for mumps and rubella, no statistically significant difference was observed. Importantly, our study clearly demonstrated positive seroconversion rates for measles (97.5%), mumps (81.0%), and rubella (93.2%), with antibody levels rising across the board and peaking at around 6months following revaccination. However, 6months after revaccination, a downtrend of antibody titer levels was observed, which is comparatively earlier than the waning immunity observed in healthy children. Furthermore, we found MMR revaccination to be safe, with only a single adverse reaction (local pain at the injection site) reported. MMR revaccination is immunogenic for the population. We suggest periodic monitoring of antibody titers, in addition to a booster vaccination, although the optimal timing of booster vaccination remains to be investigated further.