Junkai Duan

Myocardial injury caused by Doxorubicin has limited its clinical application. Our research has demonstrated that doxorubicin induces various forms of cell death, oxidative stress, and metabolic abnormalities. We have confirmed, through both in vitro and in vivo studies, that apoptosis, iron overload, inflammatory responses, and arachidonic acid metabolism contribute to doxorubicin's cardiotoxic effects. Treatment with quercetin effectively reduces iron accumulation and preserves mitochondrial structural integrity by inhibiting oxidative stress and inflammatory responses. Using molecular docking and surface plasmon resonance (SPR) techniques, our study suggests that quercetin activates the HO-1/PGC-1α pathway, which may involve downregulation of ALOX5 expression, thereby alleviating oxidative stress, inhibiting iron-dependent lipid peroxidation and ferroptosis-like changes, mitigating inflammatory responses, and modulating arachidonic acid metabolism. Additionally, quercetin enhances energy availability and supports mitochondrial function. We propose quercetin, a promising active compound derived from traditional Chinese medicine, as a potential mitigator of doxorubicin-induced cardiotoxicity.

Background: We analyzed the perioperative metabolomic alterations in children undergoing ventricular septal defect (VSD) repair under cardiopulmonary bypass (CPB), identified evidence of postoperative injury, and explored strategies to mitigate such injuries. Methods: We conducted an untargeted metabolomic analysis of serum at three distinct time points (preoperative (Tp), immediate postoperative (T0), and 24 h postoperative (T24)) in eight children undergoing VSD repair under CPB. Subsequently, we identified the key enzymes associated with perioperative injury for molecular docking prediction studies. Results: We identified 623 metabolites in serum samples with VIP scores exceeding 1 in all three groups; 37 of these metabolites exhibited significant differences throughout the study phases. Three metabolic pathways—glycerophospholipid metabolism, arginine and proline metabolism, and retrograde endogenous cannabinoid signaling recurred in various comparisons between the two groups. Molecular docking predictions confirmed that arginine-glycine amidinotransferase may possess binding sites for bosentan and AdipoRon. Conclusion: The perioperative metabolic profiles in children undergoing VSD repair under CPB were significantly altered, presumably because of the inflammatory response and endothelial cell dysfunction induced by CPB. Molecular docking predictions suggested that bosentan and AdipoRon may be potent compounds that influence perioperative damage.

Coronavirus disease 2019 (COVID-19) has become a significant global public health problem. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes the disease, utilizes angiotensin-converting enzyme II (ACE2) as a major functional receptor to enter host cells. No study has systematically assessed ACE2 expression in multiple tissues in children. This study investigated ACE2 expression and ACE2 protein’s histological distribution in various organs in paediatric patients (the small intestine, thymus, heart and lungs). Our study revealed that ACE2 was highly expressed in enterocytes of the small intestine and widely expressed in the myocardium of heart tissues. The most notable finding was the positive staining of ACE2 in the Hassall’s corpuscles epithelial cells. Negligible ACE2 expression in the lung tissues may contribute to a lower risk of infection and fewer symptoms of pneumonia in children than in adults with COVID-19 infection. These findings provide initial evidence for understanding SARS-CoV-2 pathogenesis and prevention strategies in paediatric clinical practice, which should be applicable for all children worldwide.

Introduction: To investigate the clinical characteristics and disease outcomes of a pedigree with compound heterozygous mutations in the SLC22A5 gene.Methods: Serum acylcarnitine profiles of patients were analyzed using tandem mass spectrometry. DNA samples isolated from patients and their first-degree relatives were subjected to high-throughput sequencing, and mutations were validated using Sanger sequencing.Results: The proband, a 4-month-old girl, presented with seizure episodes and mild cardiac hypertrophy and was diagnosed with primary carnitine deficiency (PCD), with carnitine levels of 5.165 mol/L. Her brother, a 6-year-and 4-month-old boy, was also diagnosed with PCD with serum-free carnitine levels of 1.014 mol/L (reference values 10–60 mol/L). Compound heterozygous mutations (c.760C > T [p.R254X] and c.825G > A [p.W275X]) were detected in the SLC22A5 gene in both patients and were inherited from the mother and father, respectively. Oral L-carnitine significantly improved or resolved the clinical symptoms.Conclusion: Children with compound mutations in SLC22A5 may present different clinical manifestations, particularly at different ages. Early clinical manifestations have a greater impact on the organs and may cause irreversible damage. PCD can cause epilepsy and dilated cardiomyopathy. Tandem mass spectrometry and high-throughput sequencing are recommended to confirm the diagnosis. Early L-carnitine supplementation can improve symptoms and reverse organ damage in some children. Tandem mass spectrometry should be used to screen for newborns with a family history of PCD.

The subject of the study is an 11-month old IVF baby girl with the typical clinical manifestation of malonyl coenzyme A decarboxylase deficiency, including developmental delay, limb weakness, cardiomyopathy, and excessive excretion of malonic acid and methylmalonic acid. Whole genome sequencing (WGS) revealed a novel heterozygous nonsense mutation (c.672delG, p.Trp224Ter) in the MLYCD gene of the proband and her father and a novel heterozygous deletion in 5'-UTR-exon1-intron1 of the MLYCD gene of the proband and her mother. The patient's cardiac function and limb weakness improved considerably after 3 months of a low-fat diet supplemented with L-carnitine. Furthermore, mapping of gene mutations and clinical manifestations was done by case collection.

Objectives. Interleukin‐10 (IL‐10) has been suggested as a biomarker of disease activity in patients with adult‐onset Still’s disease (AOSD). In this study, we evaluated the serum IL‐10 levels and investigated its clinical relevance in systemic‐onset juvenile idiopathic arthritis (SoJIA). Methods. IL‐10 levels were determined in 21 patients diagnosed with SoJIA and 35 patients with fever diseases which were suspected as SoJIA, and IL‐10 levels were compared between SoJIA patients with regard to disease activity, disease courses, and other biomarkers. Results. Patients with SoJIA had significantly higher levels of IL‐10 compared to patients with other febrile diseases. The serum levels of IL‐10 were significantly higher in active SoJIA compared to inactive and positively correlated with known disease activity markers such as erythrocyte sedimentation rate (ESR), C‐reactive protein level (CRP), ferritin (FER), and IL‐6 levels. Moreover, the levels of IL‐10 at diagnosis were significantly higher in SoJIA patients with a nonmonocyclic pattern than in patients with a monocyclic pattern. Compared to CRP, ESR, FER, and IL‐6, IL‐10 levels were superior in predicting monocyclic patients from nonmonocyclic patients. Conclusion. Compared to other febrile diseases, SoJIA patients have markedly higher levels of IL‐10 which may assist with diagnosis. And a clear association of serum IL‐10 levels with disease activity and disease courses in SoJIA was found. These results suggest that serum IL‐10 might be a reliable clinical marker in SoJIA.

This study aimed to examine and summarize clinical characteristics of Kawasaki disease (KD) at different ages to further strengthen clinicians understanding of children with KD, improving the level of diagnosis, and reducing coronary artery complications of KD. A total of 398 patients with KD who were diagnosed between January 2016 and December 2017 were reviewed retrospectively. These participants were allocated into three groups according to age: group A (<1 year, n=62), group B (≥1 and <5 years, n=286), and group C (≥5 years, n=50). Clinical manifestations, laboratory results, and echocardiographic findings were compared among the groups. Most (71.86%) patients with KD were aged 1-5 years. The prevalence of cervical lymphadenopathy was lowest in group A. The duration of fever before admission was longest in group A. The rate of cervical lymphadenopathy and laboratory data were different among the groups. Group A had higher frequencies of gastrointestinal involvement, neurological symptoms, and redness at the Bacillus Calmette-Guerin inoculation site than the other groups. Infants aged <1 year with KD often have a longer duration of fever before admission, a lower prevalence of cervical lymphadenopathy, and a higher prevalence of gastrointestinal and neurological symptoms.