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.

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.

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.

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.

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.

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.

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.

Ropivacaine is a commonly used local anesthetic for brachial plexus blocks in children, but the minimum effective dose of ropivacaine for interscalene brachial plexus blocks has not been reported. The aim of this study was to determine the 90% minimum effective concentration (MEC90) of ropivacaine for an ultrasound-guided interscalene brachial plexus block (ISB). A total of 155 patients, aged from 1 to 10 years, underwent unilateral surgical procedures on areas of the upper extremity not innervated by the ulnar nerve. The biased coin design up-and-down sequential method (BCD-UMD) was used to determine the MEC90 of ropivacaine for ultrasound-guided ISB. In our study, the initial concentration of ropivacaine was 0.07% in the toddler group and 0.09% in the preschool and school-age groups. During the trial, the concentration of ropivacaine for each subsequent patient was determined by the blocking effect of the previous patient. In case of failure, the concentration for the next patient was increased by 0.01%. Otherwise, the concentration was either decreased by 0.01%, with a probability of 0.11, or kept the same, with a probability of 0.89. Overall, the MEC90 of ropivacaine was 0.104% (95% confidence interval (CI), 0.070%–0.106%) in the toddler group, 0.114% (95% CI, 0.090%–0.117%) in the preschool group, and 0.133% (95% CI, 0.099%–0.136%) in the school-age group. No adverse events occurred. Our study showed that lower concentrations of ropivacaine could provide effective nerve blocks and reduce the risk of local anesthetics.

The crucial role of ribonucleotide reductase M2 (RRM2) enzyme in cancer occurrence and progression has been well-established, but its specific function and significance in medulloblastoma (MB) remains largely unknown. First, we conducted a bioinformatics analysis of public genomic databases and observed highly expressed RRM2 in MB and an association of high RRM2 expression with adverse outcomes. In addition, by collecting clinical MB specimens for polymerase chain reaction (PCR), western blotting (WB), and immunohistochemistry (IHC), RRM2 was confirmed to be highly expressed in tumor tissues. Furthermore, immunohistochemical analysis linked adverse prognosis to high RRM2 expression. Moreover, knocking down RRM2 significantly inhibited MB cell proliferation, migration, and invasion in vitro. This report is the first to demonstrate the oncogenic role of RRM2 in MB, associated with adverse patient outcomes. Knocking down RRM2 contributes to weakened proliferating, migrating, and invading potentials of MB cells. RRM2 is expected to be a novel prognostic biomarker and therapeutic target for MB.

Infectious intracranial aneurysm (IIA) and embolic cerebral infarction are well-known devastating complications of children suffering infective endocarditis. In this report, we describe a successfully embolized IIA concurrent with bilateral middle cerebral artery (MCA) occlusion. Unfortunately, a newly formed IIA located in the contralateral MCA bifurcation ruptured at the seventh day following embolization. A 6-month-old female child was admitted to hospital 3 days following acute right limb mobility disorder. An interventional surgery history of congenital heart disease was confirmed. She was immediately started on antibiotic therapy and the computed tomography agiography (CTA) scan showed occlusion of the upper branch of the left MCA. Unfortunately an IIA was located in the distal artery region (DAR) of the ipsilateral anterior cerebral artery. Angiography (digital subtraction angiography) was performed and the DAR IIA was embolized by OnyX-18 with Magic 1.2 Fr. microcatheter. On the sixth day, magnetic resonance imaging during the hospital stay showed reduced infarction area with no other special sign. Desperately, a major seizure with opisthotonos attacked the baby on the seventh day after embolization. An immediate CTA scan showed massive hematoma in the right basal ganglia and a ruptured bifurcate aneurysm of the right MCA. The parents refused positive treatment and discharged in considering the critical situation. It should be noted that IIA can be fast formed anywhere in cerebral artery and dynamic angio-image should be performed as supervision.

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.

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.

Neuroblastoma (NB), as a representative of tumors of embryonic origin in children, has specific clinical features. On the one hand, a very small number of NBs may appear to regress on their own. On the other hand, highly malignant NBs can invade the surrounding blood vessels and organs and metastasize to distant bone, bone marrow, and lymph nodes in the early stages of the disease. Based on differential affinities to insulin growth factors (IGFs), insulin growth factor binding proteins (IGFBPs) are classified into two groups: IGF binding proteins (IGFBP1-6) with high-affinity and IGF low-affinity binding proteins, such as IGFBP-related proteins (IGFBP rP1-10). IGFBP are crucial regulators of the bioavailability and function of IGF in metabolic signaling and as modulators of IGF signaling, and their role in NB is gaining increasing attention. In this study, we investigate the involvement of IGFBP family members in the growth and differentiation of NB cells, as well as the potential of IGFBPs as prognostic biomarkers and therapeutic targets for human NB.

Primary immunodeficiency diseases (PIDs) present a heterogeneous group of diseases with aberrant immune response caused by monogenic mutations. Due to the immune dysfunction and dysregulation, PIDs have a wide clinical spectrum such as infections, autoimmunity, autoinflammation, allergy, and malignancies. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized with multiple autoantibodies and multiple organ damage, which could be the predominant phenotype in patients with PIDs. In recent years, the increasing identification of monogenic causes of SLE and PIDs discloses the partially shared genetic background and common pathogenic process. The study of PIDs with SLE-like phenotype paves the way for the exploration of lupus pathogenesis and new perspectives in targeted therapies concurrently.

Recently, single-cell RNA sequencing (scRNA-seq) has emerged as a novel and high-resolution technique for identifying cell types, states, and subpopulations. This technique enables researchers to uncover cellular heterogeneity and detect rare cell populations that might be indistinguishable in bulk RNA-seq data. The primary aim of scRNA-seq analysis is to investigate cellular heterogeneity and distinguish distinct cell types or states. scRNA-seq provides a detailed understanding of intercellular differences and diversity by obtaining gene expression data for each individual cell. Moreover, clustering methods in scRNA-seq can be used to group cells bring into subpopulations based on their gene expression patterns, thereby uncovering similarities and differences that assist in identifying and defining cell types. Newly discovered cell types can be validated and named by labeling known cell marker genes. Additionally, scRNA-seq helps in identifying genes specifically expressed at different developmental stages, in various tissue types, or under various disease states. Recently, there has been a growing trend in using single-cell transcriptome sequencing technology for neuroblastoma (NB) research. Through conducting a comprehensive review of relevant articles published thus far, our understanding of NB has been significantly enriched from three critical perspectives: differentiation trajectory, tumor heterogeneity, and immune microenvironment. Firstly, in exploring the differentiation trajectory of NB, we have summarized the tumor’s origin and subsequent directions of differentiation. By elucidating a complete tumor differentiation pathway, we can enhance our understanding of the mechanisms underlying spontaneous tumor regression. Secondly, we have summarized the heterogeneity of tumors, which encompasses different states, cell morphologies, and characteristic genes of NB identified through single-cell sequencing technology. This consolidation of knowledge enhances our understanding of the heterogeneity of NB. Lastly, we have employed single-cell sequencing technology to analyze the immune microenvironment, focusing on the cellular components within the tumor’s surrounding environment and the diverse states of immune cells. This valuable information contributes to the advancement of NB diagnosis, treatment, and prognosis. In conclusion, the application of single-cell sequencing technology in NB research has significantly advanced our understanding of the disease and carries great significance.