Objective:To investigate the expression changes at the transcriptional level in normal lung tissues of mice after exposure to heavy ion radiation for different durations at different doses, aiming to provide evidence for exploring sensitive genes of heavy ion radiation, heavy ion radiation effect and the damage mechanism.Methods:Experiments on the temporal kinetics: the whole thorax of mice was irradiated with 14.5Gy carbon-ions and the total RNA of lung tissue was extracted at 3days, 7days, 3 weeks and 24 weeks. In dose-dependent experiment, the total RNA of lung tissue was extracted at 1 week after irradiated with a growing thoracic dose of 0, 7.5, 10.5, 12.5, 14.5, 17.5 and 20Gy. Protein-to-protein interaction (PPI) analysis and gene-ontology biological process enrichment analysis were performed on significant differentially expressed genes (DEGs).Results:A clearly differential expression patterns were observed at 3-day (acute stage), 1-week (subacute stage), 3-week (inflammatory stage) and 24-week (fibrosis stage) following 14.5Gy carbon-ions irradiation. Among those, the 3-day time point was found to be the mostly different from the other time points, whereas the 7-day time point had the highest uniformity with the other time points. Cellular apoptosis was the main type of cell death in normal lung tissues following carbon-ions exposure. The interactive genes of Phlda3, GDF15, Mgmt and Bax were identified as the radiosensitive genes, and Phlda3 was the center ( R=0.76, P<0.001). Conclusion:The findings in this study provide transcriptional insights into the biological mechanism underlying normal lung tissue toxicity induced by carbon-ions.

OBJECTIVE: To explore the clinical and genetic characteristics of eight children with Primary hypertrophic cardiomyopathy (HCM). METHODS: Eight children with HCM admitted to the Department of Cardiology of Henan Children's Hospital from January 2018 to December 2021 were selected as the study subjects. Clinical data of the children were collected. Whole exome sequencing was carried out on two children, and trio whole exome sequencing was carried out on the remainder 6 children. Sanger sequencing was used to verify the candidate variants in the children and their parents, and the pathogenicity of the variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The patients had included 5 males and 3 females, with their ages ranging from 5 to 13 years old. The average age of diagnosis was (7.87 ± 4.8) years old, and the cardiac phenotype showed non-obstructive HCM in all of the patients. WES has identified variants of the MYH7 gene in 4 children, including c.2155C>T (p.Arg719Trp), c.1208G>A (p.Arg403Gln), c.1358G>A (p.Arg453His), and c.1498G>A (p.Glu500Lys). Based on the guidelines from the ACMG, the first 3 variants were classified as pathogenic, while c.1498G>A (p.Glu500Lys) was classified as likely pathogenic (PM1+PM2_Supporting+PM6+PP3), which was also unreported previously. The remaining four children had all harbored maternal variants, including MYL2: c.173G>A (p.Arg58Gln; classified as pathogenic), TPM1: c.574G>A (p.Glu192Lys) and ACTC1: c.301G>A (p.Glu101Lys)(both were classified as likely pathogenic), and MYBPC3: c.146T>G (p.Ile49Ser; classified as variant of uncertain significance). Seven children were treated with 0.5 ~ 3 mg/(kg·d) propranolol, and their symptoms had improved significantly. They were followed up until September 30, 2022 without further cardiac event. CONCLUSION Genetic testing can clarify the molecular basis for unexplained cardiomyopathy and provide a basis for clinical diagnosis and genetic counseling. Discovery of the c.1498G>A (p.Glu500Lys) variant has also expanded the spectrum of MYH7 gene mutations underlying HCM.
Female ; Male ; Humans ; Child ; Child, Preschool ; Adolescent ; Cytoskeletal Proteins ; Family ; Genetic Counseling ; Genetic Testing ; Cardiomyopathy, Hypertrophic/genetics*