Metabolic disturbances, particularly glucose imbalances, are common in sepsis and are strongly associated with increased mortality. However, the mechanisms underlying glucose dyshomeostasis remain poorly understood. Here, we revealed the role of triggering receptor expressed on myeloid cells 2 (TREM2) in regulating glucose metabolism during sepsis. Macrophage-specific TREM2 deficiency significantly increased the level of abdominal IL-1β, which is predominantly released by pyroptotic peritoneal macrophages. IL-1β then acts on IL-1R1 receptors on pancreatic islet β-cells, promoting insulin release and inducing hypoglycemia. Transfusing TREM2-overexpressing macrophages and administering glucose solutions can restore glucose homeostasis and improve sepsis outcomes in mice. In summary, our study reveals a mechanism by which TREM2 orchestrates glucose metabolism during sepsis and highlights the potential of TREM2 as a therapeutic target for sepsis.

Congenital heart disease (CHD) is a common birth defect in children, and surgical intervention is the primary treatment. The traditional standard median sternotomy (MS) has drawbacks such as significant trauma and obvious scarring. The right axillary incision (RAI) has gradually become a conventional approach due to its advantages of preserving thoracic cage integrity, small incision size, rapid recovery, and hidden scarring. However, there is currently a lack of relevant guidelines and consensus for its application. This consensus adopts the international Delphi process, systematically searching domestic and foreign literature on CHD from 1982 to 2024. It uses the GRADE system for evidence grading and, through multidisciplinary expert discussions, clarifies the applicable CHD types, surgical techniques, establishment of extracorporeal circulation, organ protection strategies, management of special disease types, and approaches to common complications of RAI. Results show that RAI is strongly recommended for most simple congenital heart diseases (CHDs) (e.g., simple ventricular septal defect, atrial septal defect), weakly recommended for some complex CHDs (e.g., mild tetralogy of Fallot), and not recommended for complex CHDs such as transposition of the great arteries or in children with severe right thoracic deformity. Additionally, it standardizes key operational parameters: weight (5-30 kg as optimal), age (6 months-6 years as preferred), incision location, extracorporeal circulation cannulation, and organ protection measures. This consensus provides an evidence-based basis for standardizing the clinical application of RAI in open-heart surgery for CHD, ensuring surgical safety and efficacy.

Pediatric sepsis is a leading cause of childhood mortality, and early diagnosis plays a pivotal role in improving patient prognosis. However, current detection strategies represented by the pSOFA score and classic inflammatory biomarkers are lagging indicators dependent on overt organ dysfunction or systemic inflammation, which fails to achieve pre-symptomatic early detection and timely intervention. Herein, we report a novel fluorescence sensing platform for rapid early diagnosis of pediatric sepsis based on detecting viscosity alterations of lipid droplets (LDs) in peripheral blood mononuclear cells (PBMCs) using the viscosity-responsive probe DCVP-NO₂. Early sepsis-induced immune metabolic reprogramming triggers LDs accumulation and elevated microviscosity in PBMCs, which is transduced into a significant fluorescence turn-on signal by DCVP-NO₂. This strategy was validated in a cecal ligation and puncture (CLP) rat sepsis model and a retrospective pediatric clinical cohort, achieving high-contrast differentiation between septic and healthy PBMCs in both preclinical and clinical samples. With only 10-minute probe incubation, this platform offers simple, rapid, and quantitative detection, establishing LDs metabolic status as a promising early diagnostic target and providing a translatable sensing tool for pediatric sepsis management.

Current neonatal congenital heart disease (CHD) screening strategies face significant challenges in low-income or underdeveloped regions due to a shortage of experienced physicians. Therefore, we aim to develop a cost-effective method to identify high-risk populations, supplementing neonatal screening. A multicenter case-control study was conducted in three hospitals in Zhejiang, China, from September 2022 to July 2024. Pregnant women were surveyed using a self-designed questionnaire, and newborns were diagnosed using echocardiography. We utilized three steps to establish a prediction model for neonatal CHD. Initially, LASSO regression was used to screen variables. Subsequently, five representative machine learning (ML) algorithms, including SVM, XGBoost, Random Forest (RF), Logistic Regression (LR) and LightGBM, were applied to establish the CHD risk prediction models. Finally, the Shapley Additive exPlanation (SHAP) method and logistic regression were adopted to identify key risk factors for CHD. A total of 1,633 mother-infant pairs were included, with 437 infants diagnosed with CHD. Among the five machine learning models, XGBoost showed the best performance, with an AUC of 0.724 on the internal test set and 0.706 on the external validation cohort. The internal AUCs for RF, SVM, LightGBM, and LR were 0.673, 0.647, 0.672, and 0.649, respectively. The key risk factors for CHD were identified as COVID-19 infection within the three months prior to the last menstrual period, gestational medication use and viral infections during pregnancy. The odds ratios (ORs) with 95

In addition to the well-characterized programmable nucleic acid cleavage activity, prokaryotic Argonaute proteins (pAgos) possess a guide-independent nuclease activity capable of degrading nucleic acids into small fragments in the absence of exogenous guide strands, a function commonly referred to as “chopping”, which remains poorly understood. Here, we report the robust chopping activity of Thermus brockianus Argonaute (TbAgo) and leverage this activity to develop chop-NAD (chopping-based Nucleic Acid Detection), a minimal guide-free platform for sequence-specific nucleic acid sensing. When integrated with loop-mediated isothermal amplification (LAMP), chop-NAD enables sensitive, specific, and multiplexed detection of Bordetella pertussis, Bordetella parapertussis, and Mycoplasma pneumoniae in a single tube, with detection limits of 2.38 genome equivalents (gEq)/μL, 2.04 gEq/μL, and 59.7 copies/μL, respectively. Furthermore, a paraffin-encapsulated, lyophilized one-pot format facilitates contamination-resistant, sample-to-answer testing, showing 100 % concordance with clinical PCR results. This one-pot chop-NAD platform offers reduced reagent costs, simplified assay adaptation, improved biosafety, and a streamlined workflow, collectively establishing it as a versatile and scalable diagnostic platform with broad potential for point-of-care testing.

Background:Fulminant myocarditis (FM) in children can progress rapidly to cardiogenic shock, with high risk of mortality. Early recognition of prognostic markers is critical to guide timely escalation of circulatory support. This multicenter study sought to characterize clinical features and identify early predictors of in-hospital mortality in pediatric FM. Methods:We conducted a retrospective cohort study of patients <18 years with FM admitted to eight ECMO-capable pediatric intensive care units between January 2018 and August 2023. Clinical, biochemical, electrocardiographic, and echocardiographic variables were analyzed. Logistic regression was used to identify predictors of mortality, and receiver operating characteristic (ROC) curves were generated to assess discriminatory performance. Results:A total of 187 children were included; 157 (84.0%) required ECMO. In-hospital mortality was 16.6% (31/187). Univariate analysis identified elevated CK-MB, higher peak lactate, and ventricular tachycardia as associated with mortality. In multivariate analysis, peak lactate (AUC 0.791) and CK-MB (AUC 0.774) remained independent predictors. A combined model of peak lactate and ventricular tachycardia demonstrated moderate discrimination (AUC 0.772), whereas a composite model incorporating CK-MB, peak lactate, and ventricular tachycardia achieved the best predictive performance (AUC 0.815). Elevated lactate measured 12 h after initiation of extracorporeal membrane oxygenation or intensive conventional therapy further increased mortality risk (OR 1.219, 95% CI 1.004-1.481). Conclusion:Peak lactate, CK-MB, and ventricular tachycardia are early independent predictors of in-hospital mortality in pediatric FM. Persistent hyperlactatemia within 12 h of advanced support provides additional prognostic value and may assist clinicians in early risk stratification.

Pediatric heart transplantation is limited by donor avail-ability with those needing transplantation often requiring prolonged mechanical circulatory support.

Acute viral diarrhea is a common childhood illness and a major cause of morbidity and mortality worldwide, particularly in low-income countries. Nucleic acid testing is critical for clinical management because it enables accurate identification of the causative virus and supports targeted treatment. However, conventional nucleic acid detection methods rely on sophisticated instruments and trained personnel, limiting their use in home testing and primary care settings. Therefore, a user-friendly, miniaturized, and portable platform integrating extraction-free nucleic acid release, amplification, and result readout is urgently needed. In this study, a Finger-Actuated STEerable microfluidic CHip (FASTECH) integrating recombinase polymerase amplification and lateral-flow analysis was developed. This platform enabled simultaneous detection of three major diarrhea-associated viruses in children, including rotavirus A, norovirus, and adenovirus, with sensitivities of 1 copy/μL, 1 copy/μL, and 5 copies/μL, respectively. Combined with a self-developed disposable lysis tube, FASTECH completed sample processing and nucleic acid release at room temperature within 5 min and achieved sample-in-result-out detection in under 25 min. Validation using 90 clinical samples demonstrated high concordance with gold-standard qPCR. In summary, FASTECH is expected to provide a reliable platform for point-of-care diagnosis of pediatric infectious diseases in resource-limited settings and offer strong support for public health efforts.

ECG-age, derived from ECG signals using deep neural networks (DNNs), correlates with health status but has been predominantly studied in adults, neglecting the unique development trajectories of pediatric hearts. This study evaluates and proposes a pediatric-specific ECG-age model for clinical application. Validated on 58,672 ECGs from healthy children, three approaches were assessed: a pre-trained adult model, the same model retrained on pediatric data, and feature-enhanced models which was used to enhance the interpretability of the model. Results demonstrate limited applicability of adult-derived models, while dedicated pediatric models achieved accurate age assessment (MAE: 7.878 ± 6.658 months, R²=0.821), further confirmed on external data. Analysis of 209,644 ECGs across 21 pediatric diseases and 102,441 ECGs with 20 abnormalities revealed that an large ECG-age gap between chronological age indicates stronger associations with diseases or abnormalities. In a specific scenario study, ECG-age significantly correlated with postoperative complications in tetralogy of Fallot (TOF) surgery children. These findings indicate that pediatric-specific ECG-age models can effectively measure children's cardiac development and signal pathological conditions, supporting their potential as a widely applicable clinical digital biomarker in pediatrics.

Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality among preterm neonates. However, the timely diagnosis of NEC is hindered by the lack of reliable biomarkers. A key pathogenic feature of NEC is the overproduction of hypochlorous acid (HClO) by activated neutrophils and macrophages via the MPO-H2O2-Cl-system. Therefore, the development of robust HClO detection tools is crucial for the early diagnosis of NEC. In this study, a novel near-infrared (NIR) fluorescent probe (Cy-1) was developed to monitor HClO, with the aim of enabling early NEC diagnosis. Cy-1 displayed high sensitivity and selectivity toward HClO with a rapid response (40 s), and was capable of detecting both exogenous and endogenous HClO in living cells. Using this probe, we successfully tracked dynamic changes in HClO levels during the cisplatin-induced apoptosis. Furthermore, in vivo fluorescence imaging showed significantly increased fluorescence signals in NEC model mice after Cy-1 administration. This work demonstrated the great potential of Cy-1 as a powerful tool for investigating HClO-associated apoptotic processes, as well as a promising candidate for the early clinical diagnosis of NEC.

AIMS:To determine whether the SARS-CoV-2 nucleocapsid (N) protein promotes lung injury by augmenting GRP75-dependent endoplasmic reticulum (ER)-mitochondria tethering and reprogramming alveolar macrophages (AMϕs). MATERIALS AND METHODS:MAMs, ER, and mitochondria were isolated from mouse lungs. Bone marrow-derived and RAW264.7 macrophages were stimulated with recombinant N protein ± lentiviral GRP75 knockdown. ER-mitochondria interactions, tethering complex formation, mitochondrial Ca2+ dynamics, and function were assessed by confocal imaging, transmission electron microscopy, proximity ligation assay, co-immunoprecipitation, and biochemical approaches. In vivo, GRP75 was knocked down in C57BL/6 mouse lungs prior to intratracheal N protein challenge. Lung injury, AMϕ polarization, mitochondrial function, and single-cell transcriptomic changes were assessed. KEY FINDINGS:N protein promoted redistribution of GRP75 to MAMs without altering total lung GRP75 levels. It enhanced ER-mitochondria contacts and IP3R1-GRP75-VDAC1 complex assembly, resulting in excessive mitochondrial Ca2+ accumulation, membrane depolarization, increased mitochondrial reactive oxygen species, ATP depletion, and proinflammatory cytokine production. GRP75 knockdown reversed these defects, restoring mitochondrial function and suppressing inflammation. In vivo, pulmonary GRP75 knockdown alleviated N protein-induced lung injury, inflammatory cell infiltration, cytokine release, M1 polarization, and mitochondrial dysfunction in AMϕs. Single-cell RNA sequencing further demonstrated that GRP75 knockdown reversed N protein-induced AMϕ transcriptional reprogramming by reducing the proinflammatory Car4+ subset while expanding an anti-inflammatory CD74+ subset. SIGNIFICANCE:These findings establish GRP75-dependent ER-mitochondria tethering as a critical mechanism by which N protein disrupts AMϕ homeostasis and promotes COVID-19-associated lung injury, identifying GRP75-mediated MAM signaling as a potential therapeutic target.

Background Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of childhood cancer deaths. The nucleosome remodeling and deacetylase (NuRD) complex is a major chromatin remodeling complex that regulates chromatin accessibility and gene transcription. However, its role in the pathogenesis of neuroblastoma remains poorly understood.Methods The genetic dependency and clinical significance of MBD3 in neuroblastoma were evaluated by analysis of public datasets. The function of MBD3 in neuroblastoma cell growth was evaluated by shRNA knockdown experiment. Cleavage under targets and tagmentation sequencing (CUT&Tag-seq), coupled with RNA-sequencing, was employed to explore the mechanisms involved in the epigenetic regulation executed by NuRD decommissioning following MBD3 deficiency.Results Here we find that MBD3 is the most lineage-selective dependency among the nonenzymatic subunits of the NuRD complex in neuroblastoma. Knockdown of MBD3 induces cell cycle arrest and apoptosis, and inhibits neuroblastoma growth in vivo. Mechanistically, MBD3 deficiency leads to decommissioning of the NuRD complex and dissociation of the EZH2-PRC2 complex from chromatin, thereby orchestrating the epigenetic regulation of gene expression by modulating the balance between histone acetylation and methylation. NuRD decommissioning upon MBD3 deficiency selectively downregulates the expression of core regulatory transcription factors and upregulates a tumor suppressor, SRCIN1, collectively suppressing neuroblastoma progression.Conclusions Our data identify MBD3 and the NuRD complex as potential therapeutic targets in neuroblastoma, highlighting the critical role of epigenetic regulation in tumor maintenance. Targeting this pathway may offer a novel strategy to selectively impair neuroblastoma cell survival and improve outcomes.

MYOM1, a major component of the vertebrate myofibrillar M band, binds myosin, titin, and light meromyosin, has been linked to cardiomyopathy and unexpected sudden death, yet the pathogenic mechanisms remain unclear. Leveraging the UK Biobank, we identified a significant association between dilated cardiomyopathy (DCM) and loss-of-function (LoF) MYOM1 variants. Functional studies showed that MYOM1 deficiency precipitates DCM with overt heart failure, accompanied by sarcomeric disorganization, pathological structural remodeling, and mitochondrial abnormalities. Optical mapping of cardiac electrophysiology revealed slowed ventricular conduction with increased heterogeneity, alongside marked prolongation of action potential duration and depolarization. At the molecular level, transcriptomic and immunoblot analyses demonstrated downregulation of key sarcoplasmic reticulum regulators, including RYR2 and SERCA2. Consistent with these findings, calcium imaging documented impaired calcium conduction velocity and blunted intracellular calcium transients, indicating sarcoplasmic reticulum dysfunction. Our study provided significant insights into the role of MYOM1 variants in DCM. LoF of MYOM1 contributes to DCM and heart failure by disrupting sarcomere integrity and destabilizing sarcoplasmic reticulum calcium homeostasis, with secondary mitochondrial abnormalities. These data establish MYOM1 as a disease-relevant determinant of myocardial remodeling and excitation-contraction coupling, and support MYOM1 as a potential target for risk stratification and therapy in DCM.

BACKGROUND:This study aims to investigate the severity and risk factors of acute lower respiratory tract infections (LRTIs) caused by human bocavirus (HBoV) in children. METHODS:We conducted a prospective cohort study of children hospitalized with LRTIs and confirmed HBoV monoinfection via polymerase chain reaction from March 2022 to February 2024. Viral load and genome analysis were performed, with clinical data collected. Patients were followed for 1 year post-discharge. RESULTS:Among 412 hospitalized patients with HBoV-positive LRTIs, 268 (65.0%) had HBoV monoinfection. Severe infection occurred in 45.5%, with 10.8% critical, 6.3% requiring ICU admission, and 2 (0.7%) deaths. Higher HBoV-DNA loads (>10⁶ copies/mL) significantly increased critical disease risk (OR1 = 9.33, 95% CI 2.90-30.09). IFN-γ levels weakly correlated positively with DNA loads (r = 0.20, P = .024) and neutrophil counts (r = 0.26, P = .003). Furthermore, elevated neutrophil counts (>60%) were associated with hypoxemia (P < .001), pulmonary consolidation (P = .034), critical LRTI (P < .001), and ICU admission (P < .001). Despite high HBoV conservation, the VP1_40 (L→S) amino acid variation significantly increased critical LRTI risk (P = .03). CONCLUSIONS:HBoV monoinfection can cause critical LRTI in children. High DNA load, associated with elevated IFN-γ levels and neutrophilia, along with the viral VP1_L40S variant, may be key factors contributing to severe disease outcomes.

IntroductionLeft ventricular assist devices (LVADs) are widely used in advanced heart failure, but require accurate hemodynamic assessment for optimal management. Current invasive methods such as right-heart catheterisation (RHC) are limited in routine use, highlighting the need for non-invasive alternatives.MethodsA non-invasive framework combining a lumped parameter model (LPM) with a hierarchical neural network (CLPM-Net) was developed to estimate patient-specific hemodynamic parameters from echocardiography and blood pressure. Model identifiability analysis was performed to select key parameters. The model was trained on synthetic data and validated with clinical cases.ResultsThe proposed method achieved accurate parameter estimation with errors below 10% (RMSE). Simulated hemodynamic indicators showed strong agreement with ground truth (nMED < 1%). Clinical validation demonstrated close consistency with invasive measurements.DiscussionThis framework enables non-invasive, patient-specific hemodynamic assessment for LVAD management. It shows potential as an alternative to invasive monitoring, though further large-scale clinical validation is required.

BACKGROUND:The diagnosis and surgical prediction of necrotizing enterocolitis (NEC) remain challenging. Our goal is to develop an interpretable multimodal artificial intelligence model to assist these key clinical decisions. METHODS:This retrospective study included 484 neonates (242 with NEC, 242 without NEC). We developed a dual Swin Transformer integrating abdominal X-rays (2D branch) and laboratory parameters (1D branch) via late fusion. The model was refined using an external data domain adaptation strategy (n = 50) and evaluated on independent internal and external test sets. The interpretability of the model was evaluated by Grad-CAM and SHAP. RESULTS:The optimized multimodal model showed high performance on the internal test set, achieving AUCs of 0.915 for NEC diagnosis and 0.920 for surgical prediction. On the independent external test set, it achieved AUCs of 0.903 (diagnosis) and 0.894 (surgical prediction), significantly outperforming baseline models. Interpretability analyses highlighted clinically relevant features, including intestinal pneumatosis and specific inflammatory markers (such as C-reactive protein) as key predictive factors. CONCLUSIONS:The dual Swin Transformer provides an accurate, interpretable, and adaptable multimodal tool that integrates radiographic and laboratory data to support NEC diagnosis and personalized surgical decision-making. IMPACT:This study developed a dual Swin Transformer, which integrates abdominal X-rays and laboratory data to provide a robust multimodal framework for the diagnosis and surgical prediction of necrotizing enterocolitis. By implementing an external data domain adaptation strategy, the study contributes to overcoming the key challenge of clinical heterogeneity and temporal variability in NEC cohorts. Using Grad-CAM and SHAP visualization to identify specific predictive characteristics improves model transparency and clinician trust. These findings provide an explainable and adaptable AI tool to support evidence-based and personalized clinical decision-making in neonatal intensive care.

INTRODUCTION Pediatric surgery is a highly specialized disci-pline dedicated to the diagnosis and surgical treatment of congenital or acquired diseases among neonates and children.1 This field encompasses multiple highly specialized subspecialties,many of which involve rare or low-prevalence conditions,and clinical experiences are frequently concentrated in a small number of institutions.2 It is with these characteristics that the accurate identification of domain experts and informed allocation of academic resources is needed.With the advancement of artificial intelligence(AI),field-specific expert databases have increas-ingly been developed to support academic evaluation,reviewer selection,and strategic planning.3 Most existing systems rely on bibli-ometric indicators,rule-based matching,and natural language processing techniques.

Dear Editor, Preclinical studies have elegantly demonstrated that dis tinct populations of cavity-resident macrophages in the peritoneal and pleural spaces are ontogenically, transcrip tionally, and functionally related (Buechler et al., 2019). Notably, these cavities are recognized as immunosuppres sive environments that commonly facilitate cancer progres sion (Donnenberg et al., 2019; Morano et al., 2016; Porcel et al., 2015). Cavity-resident macrophages mediate a phys iological checkpoint that limited anti-tumor activity at these cancer sites (Chow et al., 2021). Previous genetic lin eage tracing has shown that, post-injury, cavity macro phages tend to accumulate on the surfaces of visceral organs, including the lungs (Jin et al., 2021, 2022), rather than deeply infiltrating the parenchyma (Deniset et al., 2019; Wang and Kubes, 2016). However, it remains unclear whether, in the context of tumors, these cavity macro phages penetrate into the lung parenchyma and promote tumor growth. Utilizing dual recombinase-mediated genetic lineage tracing, we observed the infiltration of cavity mac rophages into lung tumor metastases. Furthermore, genetic ablation or sequestration of these cavity macrophages sig nificantly reduced tumor growth in the lungs. This obser vation underscores the crucial role that cavity macrophages play in supporting tumorigenic processes, suggesting that targeting these cells may represent a viable therapeutic strategy for mitigating lung tumor progression.