This study aimed to evaluate the diagnostic potential of hemocyte parameters and procalcitonin (PCT) in detecting bloodstream infections (BSI) in neonates and explore the contribution of hemocyte activation-related genes to pediatric sepsis through bioinformatics analysis. A cohort of 419 neonates, categorized as BSI (positive blood culture) and control, underwent comparative analysis of PCT and hemocyte parameters. A predictive model for neonatal BSI was established, demonstrating an impressive area under the receiver ROC curve of 0.968 with remarkable sensitivity (92%) and specificity (87.3%). Hemocyte parameters, including lymphocyte and neutrophil percentages, platelet distribution width (PDW), platelet to lymphocyte ratio (PLR), and PCT, emerged as independent predictors of neonatal BSI. Furthermore, bioinformatics analysis utilizing Gene Expression Omnibus (GEO) datasets yielded significant insights. Differential gene expression (DEGs), gene ontology (GO), pathway enrichment, gene set enrichment analysis (GSEA), and protein– protein interaction (PPI) networks were explored. The differentially expressed genes and hub genes were notably enriched in the activation of neutrophils, lymphocytes, and platelets. Notably, elevated expression levels of SPI1, TYROBP, and FCER1G were observed in pediatric sepsis or septic shock, with positive correlations between SPI1, FCER1G, and TYROBP. In summary, the combination of lymphocyte, PDW, PLR, and PCT effectively diagnosed neonatal BSI. Bioinformatics analysis underscored the pivotal role of activated hemocytes in diagnosing pediatric sepsis, with SPI1, TYROBP, and FCER1G co-expression influencing the disease’s pathophysiology by modulating neutrophil and platelet activity.

Preterm infants may need supplemental oxygen due to immature lungs. Regardless of the type of oxygen therapy used, bedside clinicians frequently adjust the FiO₂ level. Automatic oxygen management is progressively developing as a viable alternative to these corrections. The purpose of this study is to compare the efficacy and safety of automated versus manual oxygen control in preterm infants receiving respiratory support. All the studies were searched from PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wan Fang, VIP, and CBM on 7 May 2022. PICOS criteria were as follows: (P) participants were preterm infants receiving respiratory support; (I) intervention was automatic oxygen control; (C) comparator mode was manual oxygen control; (O) the primary outcome was the percentage of time within the target pulse oxygen saturation range; (S) randomized clinical trials. Sixteen studies were included in this meta-analysis. The results showed that automated oxygen control can increase the percentage of time spent within the target SpO₂ range while reducing the percentage of time spent above the target SpO₂ range, the percentage time of hypoxemia, and manual FiO₂ adjustments/hour. No significant difference was observed in the percentage of time spent below the target SpO₂ range, incidence of bradycardia, and the mean SpO₂ or mean FiO₂ level. Automatic oxygen control can improve preterm infants’ oxygen saturation, reduce periods of hypoxemia and the percentage of time spent above the target SpO₂ range, and ease the workload of medical staff without affecting the mean FiO₂ and mean SpO₂ levels.

Mutations in the ERCC5 gene can lead to different clinical phenotypes, few articles have reported the clinical phenotypes in detail and explained the relationship between genotype and phenotype. The clinical data of cases with ERCC5 gene mutations diagnosed in our center and reported in previous studies were collected. The cases were divided into three groups based on phenotype; the differences of clinical manifestation and genotype among groups were analyzed. Genetic tests showed a complex heterozygous mutation of the ERCC5 gene with paternal C.402_C.403 (exon 4) insA (p.T135Nfs*28) and maternal C.1096 (exon 8) C > T (p.R366X.821) in our case. The gene mutation has not been reported and was predicted to seriously affect the protein structure. According to a review of 59 cases of ERCC5 mutations, cerebrooculofacioskeletal syndrome (COFS) occurred in 16 cases, XP in 19 cases, and XP/CS in 24 cases. The incidence of physical retardation, mental retardation, peripheral neuropathy, magnetic resonance abnormalities and fundus/vision abnormalities in XP/CS patients was significantly higher than that in XP patients. In addition, patients with the XP/CS phenotype were more prone to appearance abnormalities, deafness, and epilepsy, and cheilitis and tumors were more common in patients with the XP phenotype, but the differences were not significant. XP/CS can cause abnormal liver function and even fatality, which should be given attention. ERCC5 mutation-related diseases were characterized by mild to severe clinical phenotypes. In addition to tumors, liver function should be considered in ERCC5-related diseases, and patients should be cautious with medication to avoid drug-induced liver injury.

Patient-reported outcome measures (PROMs) are standardized and validated self-administered questionnaires for assessing patients’ overall well-being, disease burden, and health-related quality of life. For children, their cognitive development, reading ability and language skills need to be considered when selecting the optimal PROM. High-quality systematic reviews (SRs) can provide a comprehensive overview of the available PROMs and provide evidencebased recommendations for pediatricians. Therefore, this study aims to provide an overview of pediatric SRs of PROMs. PubMed, Embase and Cochrane Library were searched to identify SRs of PROMs published in English focusing on the health of children and adolescents. Four researchers performed literature screening and data extraction, and evaluated the methodological quality of SRs using the A MeaSurement Tool to Assess systematic Reviews tool. Forty-four SRs of PROMs published between 2006 and 2022 were included, recommending 123 PROMs, of which the most recommended were the pediatric quality of life inventory and its subscales and the EuroQol five dimension questionnaire. Thirty-six conditions were addressed; the most frequent ICD-11 category was “Mental, behavioral or neurodevelopmental disorders” (n = 9, 20.5%). The PROMs covered nine categories of contents to measure, the most frequent being the quality of life (n = 37, 30.1%). Content validity (n = 67, 54.5%) and internal consistency (n = 65, 52.9%) were the most commonly reported and measurement error (n = 10, 8.1%) was the least. The methodological and reporting of psychometric properties for SRs need further improvement. In addition, reporting of details such as the age when children should self-report the measures needs also improvement.

DNA methylation is widely involved in the modification of intestinal function, but the methylation mechanism in the enteric nervous system has not been studied in vitamin A deficiency (VAD). Herein, we firstly found that in the VAD group, gastrointestinal transit time was delayed compared with the vitamin A normal (VAN) group. RNA sequencing between VAD and VAN rats identified enriched pathways associated with enteric nerves and methylation transferase complexes. Then expression levels of DNA methyltransferases (DNMT1, DNMT3a and DNMT3b) were validated to significant increase in the VAD group. Representative reduced bisulfate sequencing showed that the VAD rats had high levels of DNA methylation in promoters and exons compared with the VAN rats. A combined methylomic and transcriptomic analysis identified that methylation levels of Sgk1, a key gene associated with enteric neural development, were elevated in the VAD group, and the activity of the SGK1/FOXO signaling axis was reduced. Furthermore, the colonic neuronal morphology and synaptic architecture were impaired in the VAD offspring. Interestingly, the above alterations in the VAD group were alleviated by vitamin A (VA) supplementation in the early postnatal period. These data suggest that VAD triggers colonic hypermethylation, which probably downregulates the SGK1/FOXO signaling pathway to cause colonic transfer dysfunction.

Research from the past has indicated a link between the risk of chronic kidney disease (CKD) and metabolic syndrome (MetS). It is yet unknown. Nevertheless, exactly how the dynamic process of declining renal function and metabolic syndrome are related. The study’s purpose is to evaluate the causal relationship between MetS and the deterioration in kidney function using a Mendelian randomization (MR). Univariable and multivariable MR were applied to evaluate the causal relationships between MetS and its components with Rapid3, CKDi25, and CKD. The main source of MetS data was the GTC database, whose constituents came from extensive genome-wide association research. The CKDGen Consortium provided data on dynamic changes in kidney function. Preliminary analysis was conducted using five different statistical techniques, including Inverse Variance Weighting and Weighted Median. Rucker’s Q, MR-Egger, and Cochran’s Q test were used in sensitivity studies. In order to address reverse causality, the Steiger test was used. The IVW results showed Rapid3, CKDi25, and CKD all exhibited positive correlations with MetS. Rapid3, CKDi25, and CKD were found to have a positive causal relationship with SBP and WC, while DBP was also linked to an increased risk of Rapid3 and CKDi25. Even after accounting for other variables, MVMR analysis showed a correlation between WC and the drop in kidney function indices. MetS, together with its constituents WC, SBP, and DBP, are separate risk factors for the deterioration of renal function. However, the causal relationship between FBG, HDL, TG, and the decline in kidney function indicators remains uncertain.

The transcription factor SOX9 is crucial in the development and differentiation of various tissues and cells. However, the roles of SOX9-dependent genes and pathways in normal urethral development and the mechanism of hypospadias are unclear. This study collected 15 foreskin tissue specimens from patients who underwent hypospadias repair surgery and compared them to normal foreskin tissue specimens obtained during circumcision. The expression levels of SOX9, WNT signaling pathway markers, and epithelial-mesenchymal transition (EMT) markers were analyzed in both groups. It was found that mRNA and protein levels of SOX9, WNT signaling pathway, and EMT mesenchymal markers were significantly reduced in the hypospadias group compared to the normal foreskin group. In contrast, mRNA and protein levels of epithelial markers were significantly increased in the hypospadias group. Immunofluorescence confirmed the decrease in SOX9 expression. Experiments using siRNA to inhibit SOX9 expression in foreskin fibroblasts yielded similar results to the hypospadias group. The findings suggest that downregulation of SOX9 expression may contribute to the development of hypospadias by down-regulating the WNT pathway and inhibiting EMT. These findings provide new insights into the embryonic development of the urethra.

Liver fibrosis is a hepatic scar repair response associated with a wide range of liver injuries, which is mediated by an imbalance between extracellular matrix (ECM) synthesis and degradation, leading to massive ECM deposition and disruption of normal liver architecture. Hepatic stellate cells (HSCs) are the main source of ECM during liver fibrosis and are the first identified cell subpopulation associated with liver fibrosis formation. Various current studies on the mechanism and treatment of liver fibrosis require resting-state HSCs as study subjects. However, spontaneous activation of primary HSCs occurs after 2–3 days of culture after isolation, and it is common that HSCs cell lines gradually differentiate into fibroblasts with culture time. This study provides an induction medium for quiescent HSCs-containing all-trans retinoic acid, sodium oleate, and S-nitroso-N-acetyl penicillamine (SNAP)-and an induction method. The induction method not only maintains the HSCs cell line in a quiescent state but also restores the activated HSCs to a quiescent state. The method has a good induction effect, short induction time, and convenient operation, which is worth being popularized and used in a wide range of laboratories.

Therapeutic drug monitoring (TDM) plays an important role in guiding treatment plan adjustments and clinical outcomes in Crohn’s disease. To evaluate the role of TDM-guided optimization of infliximab dosage in patients with pediatric Crohn’s disease. Medical records of patients with pediatric Crohn’s disease who were treated with infliximab and had proactive TDM from June 2020 to June 2022 at the Children’s Hospital of Chongqing Medical University were included. Baseline influencing factors for infliximab trough concentration (TC) and clinical outcomes before and after the treatment change were analyzed to assess the value of adjusting treatment in the patients. Forty-six patients (male-to-female ratio = 1.55:1, age <18 years) were included. Univariate and multivariate analyses showed that hormone exposure (odds ratio: 0.042, 95% confidence interval: 0.002–0.924, p = 0.044), perianal lesions (5.813, 0.984–34.349, p = 0.052), simplified endoscopic score for Crohn’s disease (1.656, 1.065–2.577, p = 0.025), and total protein (TP) (0.851, 0.749–0.967, p = 0.014) were correlated with infliximab TC. Shortening the treatment interval increased the infliximab TC (pre vs. post = 1.69 ± 0.8 vs. 12.03 ± 6.64, p = 0.001, n = 12) after 93.9 ± 37.47 days, decreased the pediatric Crohn’s disease activity index and simplified endoscopic score for Crohn’s disease, and increased the biochemical remission, clinical remission, endoscopic remission, and endoscopic response rates; however, there was no statistical significance. Hormone exposure, perianal lesions, simplified endoscopic score for Crohn’s disease, and TP levels before the first infliximab use affected the infliximab TC. Shortening the treatment interval can improve infliximab TC levels and clinical outcomes.

Respiratory syncytial virus (RSV) is an essential cause of lower respiratory tract infection in children under 2 years of age, especially under 6 months. In decades, studies have shown that the respiratory tract microflorae with RSV infection were related to disease severity and played a role in the development of recurrent wheezing, but the effect of respiratory microflorae on RSV infection are still underestimated. This study aims to conclude the effect of respiratory microflorae colonization on RSV infectious disease severity and recurrent wheezing and provide suggestions for future research directions from the perspective of respiratory tract florae. We conducted a scoping review. Studies were eligible if they reported on the effect of microflorae on RSV infectious diseases among children. We exacted the following information: title, publication time, first author’s country, and article type. We finally included 33 articles in this scoping review. The number of studies rapidly increased since 2013 and the highest number of hospitalizations were reported in children <2 years. More than half (69.70%) were conducted in America and most studies are original studies (57.58%). The Review highlighted that the respiratory microflorae played an important role in RSV infectious disease severity and recurrent wheezing. We found that Streptococcus pneumoniae (S. pn), Haemophilus influenza (HI), Moraxella catarrhalis (M.ca), and Staphylococcus aureus (SA) were the dominant profiles in children with RSV infection. Understanding the respective role of respiratory microflorae on RSV infection and its mechanisms would improve prevention and treatment strategies from the perspective of microflorae.

Multidisciplinary clinics bring together multiple specialists to care for patients with complex diseases, such as swallowing disorders. Little information exists regarding dysphagia in pediatric patients and its multidisciplinary management in Colombia. This study aimed to characterize patients under the age of 18 with swallowing disorders treated in a multidisciplinary dysphagia clinic at San Vicente Fundacion Hospital in Medellin, Colombia, between 2014 and 2021. A longitudinal, descriptive, observational study with retrospective data collection was conducted. Sociodemographic and clinical data were obtained at three points. A total of 293 patients were included. The most frequent underlying diseases were neurological (mainly cerebral palsy), followed by genetic disorders, with Down syndrome being the most representative. More than 50% of the patients had been hospitalized at least twice for dysphagia. The diagnosis was primarily clinical, supported by a videofluoroscopic swallowing study. The primary prescribed intervention was speech therapy, followed by an alternate feeding route. This study described pediatric patients with swallowing disorders seen in a multidisciplinary clinic. This overview provides healthcare personnel with an understanding of the complexity of swallowing disorders and their relationships to various medical conditions in children.

With recent changes in hematopoietic stem cell transplantation (HSCT) practices, such as the increasing use of alternative donors and ex vivo T-cell depletion, how various risk factors interplay and affect the timeline of infections have not been well elucidated. We retrospectively reviewed the first 100 consecutive HSCT from April 2019 to October 2021 in the only pediatric HSCT center in Hong Kong. We found that the vast majority of the allogeneic transplant recipients (69/74, 93.2%) had infections after HSCT, amongst which bacterial, viral, and fungal infection rates were 35.1%, 90.5%, and 9.5%, respectively. In contrast, only 30.8% (8/26) of autologous transplant recipients had infections (rate of bacterial, viral, and fungal infection were 19.2%, 15.4%, and 3.8%, respectively). Human herpesvirus 6 (HHV-6) and BK virus (BKV) typically occurred early after HSCT, adenovirus (ADV) and varicella zoster virus (VZV) thereafter, and cytomegalovirus (CMV) and Epstein–Barr virus (EBV) throughout the entire 2.5-year observation period. Ex vivo T-cell depletion was a general risk factor for viral infection with HHV-6 (hazard ratio [HR] = 3.03), BKV (HR = 3.36), CMV (HR = 4.45), and EBV (HR = 7.15); all p < 0.02. Cancer in second-complete remission compared with firstcomplete remission was a risk factor for bacterial infection (OR = 6.0, 95% CI = 1.12–32.2, and p = 0.037). Patients with gut graft-versus-host disease were at risk for fungal infections (OR = 12.3, 95% CI = 1.33–114.4, and p = 0.027). The infection-related mortality rate was 10.0%, which occurred only in allogeneic HSCT patients with hematological malignancies receiving cord blood (n = 4) or haploidentical HSCT (n = 6). Collectively, our findings in pediatric patients after contemporary HSCT support both time-dependent and risk-adapted measures against infective complications to improve transplant outcome.

Postural orthostatic tachycardia syndrome (POTS) represents chronic orthostatic intolerance. Patients usually suffer from presyncopal symptoms, such as lightheadedness, headache, blurred vision, and fatigue. Central hypovolemia, peripheral vascular dysfunction, and a hyperadrenergic state may contribute to the pathogenesis of POTS. It is necessary to comprehensively assess the clinical characteristics, physiological changes, and biochemical markers to select an appropriate therapy. Since the introduction of the concept of individualized treatment for POTS, great progress has been made in the field.

Metronomic chemotherapy (MC) is an innovative therapeutic approach that involves the chronic administration of low doses of chemotherapy agents. This strategy aims to sustain prolonged and active plasma levels of drugs, which can result in favorable tolerability. MC has shown promise in the treatment of hematologic and solid tumors, including high-risk neuroblastoma and relapsed/refractory (R/R) neuroblastoma. In the contemporary management of neuroblastoma, MC stands as a viable maintenance therapy for newly diagnosed patients lacking access to autologous stem cell transplantation or immunotherapy, particularly in resource-constrained regions. Furthermore, it serves as a pragmatic alternative for individuals intolerant to intensified regimens or undergoing palliative care for R/R neuroblastoma. Nevertheless, the quest for the optimal MC regimen persists, necessitating comprehensive investigations to delineate standardized protocols. Moreover, the identification of potential biomarkers or prognostic indicators assumes paramount significance in refining MC strategies for future breakthroughs in this domain. This review embarks on a comprehensive exploration of MC in neuroblastoma, offering insights into its historical underpinnings, diverse applications, adverse effect and future prospects, endeavoring to enrich our understanding of MC role in neuroblastoma management.

The first Better evidence and RecommendatIons for the next Generation HealTh—BRIGHT symposium was held in Chongqing, China between June 21 and 23, 2024. The symposium did not only showcase the recent progress made by multidisciplinary teams in generating and translating evidence for children’s healthcare, guideline development and evaluation, and the utilization of AI applications in pediatrics but also fostered transnational and transregional cooperation to promote the advancement of high-quality evidence and guidelines in this field. The symposium contributed significantly to the future development and transformation of research endeavors in pediatrics.

Bronchopulmonary dysplasia (BPD) is one of the most prevalent and severe chronic lung diseases in premature infants. The objective of the current study was to screen for key BPD-associated genes and pathways by transcriptomic analysis from clinical patients and animal models. In our study, the differentially expressed genes were screened from 58 children with 14-day BPD and 40 normal children in the GSE32472 dataset of the Gene Expression Omnibus database. Then, we identified four hub genes (Cd3e, Cd3g, Cd247, and Itk) and a signaling pathway (T cell receptor signaling pathway) by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and protein-protein interaction analysis. The differential expression of the relevant pathways and gene sets among the groups was verified via GSEA analysis. Subsequently, a rat model of BPD with hyperoxiainduced lung injury was established, and the transcriptome sequencing of the whole lung tissue was performed. A similar analysis was done on the sequencing data of the hub genes and associated pathway screening to verify the accuracy. Ultimately, quantitative polymerase chain reaction was performed to validate the transcriptomics data of core gene expression in the rat model. Our study revealed that the downregulation of the expression of the above four key genes in the course of BPD leads to a decrease in the function of T cell receptor signaling pathways, it causes immune dysfunction and increases the severity of lung inflammation as well as susceptibility to other respiratory infectious diseases.