OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Objective To analyze the main active components and potential molecular mechanism of Sophora flavescens against breast cancer based on network pharmacology and molecular docking. Methods The chemical constituents were collected and screened by TCMSP, ETCM database and literature review. The targets of active ingredients were predicted by Swiss Target Prediction database. Breast cancer-related targets were collected by GeneCards, TTD, Drugbank and OMIM. The anti-breast cancer targets of Sophora flavescens were screened by Venny 2.1.0 software. Cytoscape software was used to construct the network diagram of Sophora flavescens-key active ingredients-targets. STRING database was used to analyze the common targets, and PPI network diagram was constructed. GO function enrichment analysis and KEGG pathway enrichment analysis of key target proteins were performed by DAVID database and Hiplot online platform. Schrodinger software was used to calculate the molecular docking between the active ingredients and targets. Molecular biological methods were used to verify the key targets. Results A total of 36 active components with clear structures were screened from Sophora flavescens. 70 anti-breast cancer targets of Sophora flavescens were screened out. 12 core targets including EGFR, AKT1, ESR1, SRC, CYP19A1, AR and ABCB1 participate in endocrine resistance, EGFR tyrosine kinase inhibitors and estrogen signaling pathways in breast cancer. Moreover, the docking score between the core component and the key target AR is the highest. In vitro experiments showed that the extract of Sophora flavescens can inhibit the proliferation of breast cancer cells, induce cell apoptosis and up-regulate AR protein expression. Conclusion It was revealed that Sophora flavescens plays an anti-breast cancer role by regulating complex biological processes through multiple components acting on multiple targets and signaling pathways. The upregulation of AR protein by Sophora flavescens may become a new therapeutic strategy for the treatment of breast cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in China. The results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. The aim of tihs study is to establish the China National lung cancer screening guidelines for clinical practice. METHODS: The China lung cancer early detection and treatment expert group (CLCEDTEG) established the China National Lung Cancer Screening Guideline with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 2 medical oncologists, 2 pulmonologists, 2 pathologist, and 2 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with at risk for lung cancer. The expert group reviewed the literature, including screening trials in the United States and Europe and China, and discussed local best clinical practices in the China. A consensus-based guidelines, China National Lung Cancer Screening Guideline (CNLCSG), was recommended by CLCEDTEG appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China. RESULTS: Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation. CONCLUSIONS A lung cancer screening guideline is recommended for the high-risk population in China. Additional research , including LDCT combined with biomarkers, is needed to optimize the approach to low-dose CT screening in the future.
Aged ; China ; epidemiology ; Early Detection of Cancer ; Female ; Humans ; Lung Neoplasms ; diagnostic imaging ; epidemiology ; Male ; Mass Screening ; Middle Aged ; Patient Selection ; Practice Guidelines as Topic ; Radiation Dosage ; Risk ; Rural Population ; statistics & numerical data ; Tomography, Spiral Computed

Objective To explore the activity signs and clinical value of CT in evaluation of anti -tuberculosis chemotherapy in elderly patients with active tuberculosis.Methods Clinical and imaging data of 78 cases with elderly active tuberculosis were retrospectively analyzed.The changes of CT sign between bacterium negative and posi-tive,before and after chemotherapy were compared.Results The detection rates of ground glass opacity,thick -walled cavity in bacterium positive were 72.1% and 55.8%,which were significantly higher than those in bacterium negative 45.7% and 28.6%(P <0.05).Compared with before chemotherapy,the detection rates of ground glass opacity,tree -in -bud,thick -walled cavity,pulmonary consolidation,centrilobular nodule,lobular consolidation after chemotherapy were significantly reduced(P <0.05).The active CT signs of ground glass opacity,tree -in -bud were completely absorbed,and other signs were lapsed to non -active signs including cord -like shadow,thin -walled cav-ity,calcification,bronchia aggregation and circuity.Conclusion There is conversion rule of CT signs in elderly active pulmonary tuberculosis before and after anti -tuberculosis chemotherapy,and CT is helpful in the evaluation of anti -tuberculosis chemotherapy results of active tuberculosis.

Effects of salviae miltiorrhizae (SM) and SOD on serum and tissue (liver, intestine) lipid peroxidation were studied on rabbits in reperfusion after hemor rhage shock.The results showed that both SM and SOD could effectively reduce the serum MDA,while the inhibitory effect of SM on tissue (intestine) lipid Peroxidation was more significant than that of SOD.90 min after shock,18 rabbits were equally divided into 3 groups,one third of shed blood was re-infused and simultaneously teperfused with balanced salt solution (BSS) (group A), SOD in BSS (group B) and SM in BSS (group C). After reperfusion, serum MDA increased significantly in group A, while serum in MDA in group B and C decreased gradually and was significantly lower than that of group A after reperfusion of 3 hr (I3). Intestine MDA in group C was evidently lower than that in group A (P