Translational pediatrics最新文献

Background: Metabolic cardiomyopathy is characterized by structural and functional changes to the heart and interstitial fibrosis without coronary artery disease or hypertension. Inborn metabolic defects are a common cause of cardiomyopathy in children. There are more than 40 kinds of inborn metabolic defects that cause cardiomyopathy. The heart is one of the most metabolically active organs in the human body. Metabolic disorders may lead to insufficient myocardial energy production, and unwanted metabolites may be produced, which may cause spontaneous chemical damage in the body. Specific metabolic repair enzymes are required to remove accumulated metabolites. The metabolite repair enzyme NAD(P)HX dehydratase (NAXD) is a key enzyme that combats the accumulation of damaged metabolites. It specifically acts on the S exome of NAD(P)HX, restoring NADHX and NADPHX to the functional cofactors NADH and NADPH, respectively. NAD(P)H plays a central role in many biochemical processes, including key oxidation-reduction reactions related to energy production. Patients with NAXD mutations develop severe systemic multisystem impairment after febrile illness that is mainly characterized by severe psychomotor regression with recurrent skin lesions and death. However, cardiomyopathy caused by this gene mutation has rarely been reported.

Case description: This paper reported a patient with a novel NAXD gene compound mutation whose condition deteriorated sharply after febrile illness, causing heart failure, cardiogenic, and ultimately death.

Conclusions: This is one of the few cases of metabolic cardiomyopathy caused by a compound heterozygous NAXD mutation in China.

Background: Necrotizing enterocolitis (NEC) is a devastating gastrointestinal condition mainly affecting premature infants, and gasdermin D (GSDMD) has emerged as a molecule of interest due to its pivotal role in the inflammatory process called pyroptosis in NEC pathogenesis. The aim of this study is to examine the potential of GSDMD and interleukin-1β (IL-1β) as early diagnostic biomarkers for NEC.

Methods: We examined 207 infants with clinical symptoms of NEC admitted to our neonatal intensive care unit (NICU) between December 2023 and June 2024. After excluding those with congenital gastrointestinal diseases and other factors, 180 infants were included in the study. Among these, 59 were confirmed to have NEC according to Bell Stage II criteria, and 56 matched controls were selected through propensity score matching (PSM). Blood samples were analyzed for GSDMD expression using quantitative polymerase chain reaction (qPCR) and for IL-1β levels using enzyme-linked immunosorbent assay (ELISA).

Results: Patients with NEC exhibited significantly elevated levels of GSDMD (18.46±8.58) and IL-1β (9.05±3.42) compared to controls. Receiver operating characteristic (ROC) curve analysis indicated that GSDMD had a higher predictive value for NEC with an area under the curve (AUC) of 0.83 than IL-1β (AUC 0.77). Clinical symptoms such as fatigue, abdominal distention, and reduced bowel sounds were significantly more common in patients with NEC. Laboratory results showed lower neutrophil and red blood cell counts, higher platelet counts, and increased levels of C-reactive protein (CRP) and procalcitonin (PCT) in patients with NEC.

Conclusions: GSDMD and IL-1β can serve as valuable biomarkers for the early diagnosis of NEC, providing insights into the disease's pathogenesis and facilitating improved strategies for early detection and intervention.

Background: Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease in which the Epstein-Barr virus (EBV) persists and replicates, causing chronic symptoms and fatal complications. The treatment of CAEBV is still evolving. Our case report showed a new therapy for CAEBV.

Case description: A 14-year-old boy presented with a 10-month history of recurrent diarrhea, intermittent fever, abdominal pain, distension, dizziness, and fatigue. Physical examination findings included severe malnutrition and hepatosplenomegaly. The local hospital's test results showed that the load of EBV DNA in peripheral blood was 5.99×10⁶ copies/mL. Despite treatment with acyclovir, chemotherapy, and supportive care, the symptoms persisted. We determined the lymphocyte subtypes of EBV infection by fluorescence quantitative polymerase chain reaction and the expression of EBV envelope glycoprotein 350 (gp350) in peripheral blood lymphocytes. EBV not only infects B cells but also T and NK cells. According to the clinical manifestations, elevated EBV DNA levels, and positive EBV-encoded small RNA (EBER) status, the patient was diagnosed with CAEBV infection. The patient received a conditioning regimen of fludarabine and cyclophosphamide and an intravenous infusion of gp350-targeted chimeric antigen receptor T (CAR T) cells. After infusion, the patient developed grade I cytokine release syndrome (CRS) and was discharged 10 days later. During the follow-up, the EBV-DNA count remained undetectable.

Conclusions: Our case report showed that CAR T-cell therapy is relatively safe and effective for treating CAEBV in children, with milder CRS compared to that in malignant tumors. However, a greater number of cases are needed to further evaluate the efficacy and safety.

Background: Alagille syndrome (ALGS) is a rare disease. The variable clinical manifestations make the diagnosis of ALGS difficult. This study aimed to provide a basis for the early diagnosis of ALGS patients whose clinical identification is difficult and to enrich the spectrum of genetic variants implicated in Chinese children with ALGS.

Methods: From August 2016 to August 2022, 14 children with ALGS were enrolled in this retrospective study. Clinical and related data were obtained from medical records.

Results: Among the 14 patients, 11 were males and 3 were females. The age of first manifestation of liver disease mean (Q1, Q3) was 0.4 (0.1, 37.0) months, and the age of diagnosis mean (Q1, Q3) was 5.6 (2.4, 48.5) months. Cholestasis was seen in 14 patients, cardiac defects in eight, characteristic facial features in 11, skeletal abnormalities in six, and renal abnormality in one. Among eight patients who underwent ophthalmological examination, posterior embryotoxon was seen in two. We identified 12 different JAG1 gene mutations and two different NOTCH2 gene variations. Among the mutations detected, six were novel, including c.2849_2850del (p.S950*), c.35_45delGCCCCCTAAGC (p.R12Pfs*57), c.1860delC (p.F621Sfs*122), and c.1293_1294insTAGTAGACA (p.A432*) in JAG1, and c.6040_6041 del (p.L2014Vfs*10) and c.1915+1G>T (splicing) in NOTCH2. The follow-up time mean (Q1, Q3) was 48.5 (11.5, 69.0) months; four patients had delayed growth, eight had pruritus, two had xanthomas, seven had elevated bilirubin, and 13 had elevated transaminase. All patients were stable after medical treatment.

Conclusions: ALGS presents a variety of clinical manifestations. Some patients may be misdiagnosed with biliary atresia due to bile duct proliferation in liver biopsies along with biochemical abnormalities. Genetic testing is helpful for early diagnosis. JAG1 and NOTCH2 gene mutant spectra are abundant and there are many novel mutations in Chinese children with ALGS.

Background and objective: Pectus excavatum is a common congenital chest wall abnormality characterized by a concave appearance of the chest, and minimally invasive repair of pectus excavatum (MIRPE) is the surgical treatment of choice. A rapidly growing field of research is pain management in children undergoing MIRPE, with many shifts in practice occurring over the last decade. The primary objectives of this narrative review are to describe current methods of perioperative pain management and the development of enhanced recovery after surgery (ERAS) to improve the experience of patients undergoing MIRPE.

Methods: Recent literature was found using the PubMed database using combinations of keywords: pectus excavatum, pediatric, pain management, minimally invasive repair of pectus excavatum (MIRPE), and enhanced recovery after surgery (ERAS). Literature search was conducted by the authorship team and an independent, certified librarian. Articles published in English from 2010-2024 were the focus of our review; however, older literature was included when appropriate.

Key content and findings: Perioperative pain management for patients undergoing MIRPE continues to evolve and improve patient outcomes. While evidence supports the use of more traditional analgesia, such as opioid-based or epidural analgesia, it also supports the trend toward contemporary multimodal pain control via pre-, intra-, and post-operative strategies including opioid-sparing analgesics, intercostal nerve cryoablation (INC), intercostal nerve blocks (INBs), and single or continuous infusion regional anesthesia techniques.

Conclusions: Patients undergoing surgical repair of pectus excavatum benefit from the use of contemporary pain control techniques discussed in this review, with a growing body of literature supporting the use of INC, regional pain blocks and multimodal analgesia. Additionally, ERAS pathways and institutional protocols are discussed that are currently transforming postoperative MIRPE pain management and are being implemented widely.

Background: Micro RNA-490-3p (miR-490-3p) is associated with a variety of malignancies. However, the role of miR-490-3p in osteosarcoma and its underlying mechanism are not yet fully understood. This study aimed to explore the role and the mechanism of miR-490-3p in osteosarcoma.

Methods: MiR-490-3p and nucleolar and spindle-associated protein 1 (NUSAP1) expression in osteosarcoma was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), wound-healing, and transwell assays were used to detect cell proliferation, migration and invasion. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot were used to evaluate the cell apoptosis. Flow cytometry was used to assess the cell cycle. In addition, luciferase reporter assay was used to confirm the binding of miR-490-3p and NUSAP1. Western blot and RT-qPCR was used to examine cell division cycle associated 8 (CDCA8) and activating transcription factor 3 (ATF3) expression.

Results: MiR-490-3p expression was significantly decreased in the osteosarcoma cells. Following the transfection with miR-490-3p mimic, it was found that 143B cell proliferation, migration, and invasion were inhibited, while the cell apoptotic levels and cell-cycle arrest were promoted, accompanied with decreased B cell lymphoma protein-2 (Bcl-2) protein expression, and increased protein expressions of Bcl-2-associated X (Bax), cleaved caspase-3, and cleaved caspase-9. In addition, miR-490-3p was found to bind to NUSAP1, and negatively regulate NUSAP1 expression. NUSAP1 upregulation reversed the inhibitory effects of miR-490-3p overexpression on cell proliferation, migration, and invasion, and the promoting effects on cell apoptosis and cell-cycle arrest in osteosarcoma. Moreover, miR-490-3p was identified to mediate CDCA8/ATF3 by targeting NUSAP1.

Conclusions: MiR-490-3p upregulation inhibited cell proliferation and metastasis but promoted the cell apoptosis and cell-cycle arrest in osteosarcoma via the regulation of CDCA8/ATF3 by targeting NUSAP1. Thus, miR-490-3p might be a potential therapeutic target for the treatment of osteosarcoma.

Background: Migraine is a neurological disorder that is chronic and presents with episodes of paroxysmal features consisting of multiphase attacks of head pain, along with other symptoms related to neurological dysfunction such as sensitivity to movement, photophobia, phonophobia, nausea, and vomiting. Antiseizure medications are frequently used for the treatment of migraine. Of the antiseizure medications, sodium valproate and topiramate have received approval from the Food and Drug Administration (FDA) to prevent adult migraine. More recently, topiramate gained approval for pediatric migraine, whereas sodium valproate did not. Nevertheless, the off-label utilization of these drugs for pediatric migraine is widespread. The objective of this review is to assess the prophylactic efficacy of sodium valproate in the management of pediatric migraines.

Methods: The protocol of this study was registered with PROSPERO (CRD42023454491). Therefore, this systematic review aims to assess the efficacy of sodium valproate as a prophylaxis treatment for pediatric migraine. A comprehensive unrestricted search of indexed databases, including PubMed, Embase, Web of Science, and Cochrane, was conducted without any restrictions until May 2024.

Results: The review included five randomized controlled trials (RCTs). Among these, two exhibited a generally low risk of bias (RoB), while the remaining RCTs demonstrated a high risk for bias.

Conclusions: The findings from the current evidence suggest no significant differences in the effectiveness of sodium valproate compared to other frequently used medications in preventing pediatric migraine. Subsequent studies should maintain uniformity in their protocol design and introduce blinding methodologies across outcome assessment, participants, and researchers. These strategies hold significant importance in mitigating potential sources of bias.

Background: It has been reported that the emergence of coronavirus disease 2019 (COVID-19) has changed the epidemiological characteristics of many pathogens, but the epidemiological characteristics of Mycoplasma (MP) infection in hospitalized children with community-acquired pneumonia (CAP) are not clear. The aim of this study was to answer this question.

Methods: Children with CAP in three tertiary hospitals (hospitals A, B and C) from 2018 to 2023 were selected. Data on gender, age, number and date of MP infection were obtained from the medical record. The intensity of the epidemic was measured as a percentage of the number of CAP.

Results: In hospitals A and B, before the pandemic (in 2018 and 2019), the number of hospitalized children with MP pneumonia and the proportion of total pneumonia had shown a significant upward trend, but the control measures led to a slight decline. In hospital C, the number and percentage of hospitalized children with MP pneumonia were low before and during the COVID-19 period. After the epidemic control was lifted, the number and percentage of children with MP pneumonia in the three hospitals increased sharply, and the proportion of children aged more than 7 years old increased significantly in 2022 and 2023.

Conclusions: From 2018 to 2019, there was already an epidemic trend of MP in the study hospital. From 2020 to 2022, after the outbreak of COVID-19, the incidence of MP pneumonia stabilized, but after the epidemic control was lifted, it broke out. This may be due to the severe restrictive measures taken early during the COVID-19 pandemic that effectively controlled the spread of MP, pausing its pandemic.

Background: Aggressive behavior in adolescent patients is a common phenomenon in clinical treatment and nursing care. The objective of this study was to conduct an assessment of the prevailing patterns and determinants of aggressive behavior among adolescents with mental disorders, with the intent to offer valuable insights for enhancing clinical intervention and nursing practices.

Methods: Adolescent patients with mental disorders admitted to the psychiatric department of Suzhou Guangji Hospital from January 1, 2022, to June 30, 2024 were included. The characteristics of patients with or without aggressive behavior were compared and evaluated. Multivariate logistic regression analysis was conducted to evaluate the factors influencing aggressive behavior in adolescents with mental disorders.

Results: There were 395 adolescent patients with mental disorders included in the study, with 42 patients having aggressive behavior, and the incidence of aggressive behavior in adolescent patients with mental disorders was 10.63%. Pearson correlation analysis revealed that age (r=0.459), only child (r=0.583), education level (r=0.497), pre-morbid personality (r=0.520), and history of past aggressive behavior (r=0.516) were related with the aggressive behavior in adolescent patients with mental disorders. Age [odds ratio (OR) =1.766; 95% confidence interval (CI): 1.213-1.980], only child (OR =2.642; 95% CI: 2.009-2.858), education level (OR =1.823; 95% CI: 1.104-2.518), pre-morbid personality (OR =2.336; 95% CI: 1.991-2.694) and history of past aggressive behavior (OR =2.708; 95% CI: 2.357-3.102) were the influencing factors for aggressive behavior.

Conclusions: The incidence of aggressive behavior in adolescent patients with mental disorders is relatively high and influenced by a multitude of factors. The healthcare team should conduct a thorough nursing assessment to identify potential triggers and implement targeted nursing strategies to mitigate the aggressive behavior.