1.MiRSNP in MGMT 3′ untranslated region regulates low-dose radiation-induced senescence in lung cells
Lingyu ZHANG ; Yashi CAI ; Huixian LI ; Min ZHANG ; Changyong WEN ; Weixu HUANG ; Huifeng CHEN ; Jianming ZOU
China Occupational Medicine 2025;52(1):25-32
Objective To investigate the role of the O-6-methylguanine-DNA methyltransferase (MGMT) gene-3′ untranslated region (UTR) microRNA-associated single nucleotide polymorphism (miRSNP) (rs7896488 G>A) in affecting miR-4297-targeted modulation of MGMT in senescence of lung cells with polymorphic genotypes induced by fractionated low dose ionizing radiation (LDIR). Methods i) MiRSNPs were predicted and screened using bioinformatics, and DNA from two types of lung cells, A549 cells and human bronchial epithelioid cells (HBE cells), was extracted for target gene sequencing. After co-transfection of pGL3c-MGMT-3′UTR-rs7896488 G>A reporter gene recombinant plasmid, pRL-TK Vector with micrON mimic NC #22 or micrON hsa-miR-4297 mimic (set up as the mimic NC group and the miR-4297 mimic group) in these two types of lung cells, dual luciferase reporter gene assay was performed. The relative expression of MGMT mRNA was detected by real-time fluorescence quantitative polymerase chain reaction, and the relative expression of MGMT protein was detected by Western blotting. ii) These two types of lung cells were randomly divided into the control group and irradiation group, which received either 0 or 100 mGy X-rays irradiation seven times. After irradiation, the cells were transfected with either micrON mimic NC #22 or micrON hsa-miR-4297 mimic, resulting in mimic NC + control group, miR-4297 mimic + control group, mimic NC + irradiation group, and miR-4297 mimic + irradiation group. Cells were collected for senescence-associated-β-galactosidase (SA-β-Gal) staining, and the relative expression of matrix metalloproteinase-9 (MMP-9) and chemokine (C-X-C motif) ligand-1 (CXCL-1) proteins was detected via Western blotting. Results i) The rs7896488 G>A was the miRSNP located in the conserved binding region targeted by miR-4297 in the MGMT gene 3′UTR. A549 cells were the rs7896488 GG wild-type homozygous genotype, while HBE cells were the rs7896488 GA heterozygous mutant genotype. In the miR-4297 mimic group, A549 and HBE cells carrying the rs7896488 G allele showed significantly lower dual-luciferase activity compared with that in the mimic NC group (both P<0.01). However, there was no significant difference in dual-luciferase activity between the two groups in both A549 and HBE cells carrying the rs7896488 A allele (both P>0.05). The relative expression levels of MGMT mRNA and MGMT protein of A549 cells in the miR-4297 mimic group were lower than those in the mimic NC group (both P<0.05). However, there was no significant difference in MGMT mRNA and MGMT protein of HBE cells between these two groups (both P>0.05). ii) The relative activity of SA-β-Gal and the relative expression of MMP-9 and CXCL-1 proteins of A549 cells in the miR-4297 mimic+irradiation group were higher than those in the mimic NC + control group, the miR-4297 mimic + control group, and the mimic NC + irradiation group (all P<0.05). The relative activity of SA-β-Gal and the relative expression of MMP-9 and CXCL-1 proteins of HBE cells in the miR-4297 mimic + irradiation group were higher than those in the mimic NC + control group and the miR-4297 mimic + control group (all P<0.05), while there was no significant difference compared with those in the mimic NC + irradiation group (all P>0.05). Conclusion MGMT-3′UTR-miRSNP rs7896488 G>A plays a role in LDIR-induced senescence of lung cells with different polymorphic genotypes by affecting miR-4297-targeted regulation of MGMT.
2.Coagulation abnormalities in acute decompensated cirrhosis comorbid with infection: A prospective observational study based on thromboelastography
Ruiqing ZHANG ; Shumin CAI ; Xiuhua JIANG ; Jianming HUANG ; Beiling LI ; Jinjun CHEN
Journal of Clinical Hepatology 2025;41(5):907-913
ObjectiveTo investigate the changes in coagulation system in acute decompensated cirrhosis (ADC) patients with or without sepsis and the association of these changes with short-term prognosis. MethodsA prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023, among whom there were 86 patients with sepsis and 30 patients without sepsis, and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography (TEG) and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected, and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. ResultsFor the ADC patients with sepsis, the lungs and bloodstream were the main infection sites, and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone, the patients with ADC and sepsis had a significant reduction in median maximum amplitude (MA), a significant increase in coagulation time (K time), and a significant reduction in α angle (all P<0.05); the patients with ADC and sepsis had a significantly longer reaction time (R time) than those with ADC alone (P=0.02), and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis (P=0.04). There was no correlation between MA and platelet count in the patients with ADC and sepsis (r=-0.133, P=0.057), while there was a significant correlation between MA and platelet count in the patients with sepsis alone (r=0.595, P=0.001). SOFA score was negatively correlated with MA in sepsis patients with or without ADC (r=-0.503 and -0.561, both P<0.001), and for the patients with ADC and sepsis, R time, K time, and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT (all P<0.05). The patients with ADC alone all survived within 90 days, and compared with the death group, the patients with sepsis alone who survived had significantly higher values of MA and α angle (all P<0.05); there was a significant difference in α angle on day 90 between the survival group and the death group, no matter whether the patients were comorbid with ADC or not (both P<0.01), while for the patients with ADC and sepsis, there was no significant difference in MA value on day 90 between the survival group and the death group (P>0.05). ConclusionFor ADC patients comorbid with sepsis, coagulation function assessment and monitoring should be taken seriously in clinical practice, and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.
3.Effects of fractionated low-dose ionizing radiation on differentially expressed genes in ferroptosis of human bronchial epithelial cells
Min ZHANG ; Lingyu ZHANG ; Yashi CAI ; Huixian LI ; Yanting CHEN ; Guanyou CHEN ; Xin LAN ; Changyong WEN ; Weixu HUANG ; Jianming ZOU ; Huifeng CHEN
Chinese Journal of Radiological Health 2025;34(3):310-317
Objective To investigate the effects of fractionated low-dose ionizing radiation (LDIR) on the ferroptosis in human bronchial epithelial (HBE) cells as well as the associated differentially expressed genes (DEGs), biological processes, and signaling pathways. Methods HBE cells were exposed to different single doses of X-ray irradiation (0, 25, 50, 75, and 100 mGy) for 24, 48, and 72 h, respectively. The change in cell viability was detected by MTT assay. Cells were irradiated with 0, 25, 50, and 100 mGy X-rays 5 times, with 48 h between each irradiation and a dose rate of 50 mGy/min. Cells were harvested 24 h after irradiation for the measurement of the expression of ferroptosis-related genes SLC7A11 and GPX4 at the mRNA and protein levels, cellular iron content, and the expression of FTH1 and FTL mRNAs. High-throughput sequencing was used to screen for the DEGs in each dose group, followed by Gene Ontology-Biological Process (GO-BP) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA). Results Compared with the control group, single-dose LDIR significantly increased cell proliferation at 75 mGy after 24 h (P < 0.05), at 50, 75, and 100 mGy after 48 h (P < 0.05), and at 75 and 100 mGy after 72 h (P < 0.05). Compared with the control group, at the end of the fifth fractionated LDIR, SLC7A11 and GPX4 mRNAs decreased at all doses (P < 0.05), SLC7A11 protein decreased at all doses, GPX4 protein decreased at 25 and 100 mGy, iron content increased at all doses, and FTH1 and FTL mRNAs decreased at all doses (P< 0.05). Sequencing analysis identified 248, 30, and 291 DEGs and 10, 2, and 9 ferroptosis-associated genes at the three doses compared to the control. Gene Ontology-Biological Process analysis showed that DEGs were mainly enriched in biological processes such as response to lipids, cell death, and response to unfolded proteins. Kyoto Encyclopedia of Genes and Genomes analysis showed that DEGs were mainly enriched in the JAK-STAT signaling pathway, lipids and atherosclerosis, ferroptosis, protein processing in the endoplasmic reticulum, and FoxO signaling pathway. Gene set enrichment analysis showed that DEGs were mainly enriched in ferroptosis, fatty acid degradation, and glutathione metabolism. Conclusion Fractionated low-dose radiation induced ferroptosis in HBE cells, and DEGs were predominantly enriched in biological processes and signaling pathways related to inflammation, ferroptosis, and endoplasmic reticulum stress.
4.Association between long-term exposure to low-dose ionizing radiation and metabolic syndrome among medical radiologists
Changyong WEN ; Xiaoman ZHOU ; Xiaolian LIU ; Yiqing LIAN ; Weizhen GUO ; Yanting CHEN ; Xin LAN ; Mingfang LI ; Sufen ZHANG ; Weixu HUANG ; Jianming ZOU ; Huifeng CHEN
Journal of Environmental and Occupational Medicine 2025;42(10):1209-1215
Background In recent years, the increasingly widespread application of nuclear and medical radiation technologies has resulted in a large number of occupational populations exposed to low-dose ionizing radiation (LDIR). At present, there is no consistent conclusion on the effects of long-term exposure to LDIR on the metabolic health of the occupational population. Objective To explore the association between long-term exposure to LDIR and metabolic syndrome (MetS) among medical radiologists. Methods A cross-sectional study was conducted to enroll
5.Effects of low-dose fractionated X-ray radiation on the senescence of L02 hepatocytes
Xin LAN ; Lina CAI ; Lingyu ZHANG ; Yashi CAI ; Linqian ZHOU ; Weiyi KE ; Weixu HUANG ; Jianming ZOU ; Huifeng CHEN
Chinese Journal of Radiological Health 2025;34(5):672-678
Objective To investigate the induction of senescence in L02 hepatocytes by low-dose fractionated X-ray radiation and its effects on oxidative stress, oxidative damage, and nuclear factor-κB (NF-κB) pathway protein levels. Methods L02 cells were subjected to fractionated X-ray irradiation at doses of 0.1, 0.2, and 0.5 Gy per fraction for a total of six fractions. Assays were performed 24 hours after the final irradiation. Measurements included SA-β-gal staining, the mRNAs of senescence-related genes p53 and p21 and their encoded proteins, mRNAs of genes encoding senescence-associated secretory phenotype factors (IL-6, IL-8, GM-CSF, MMP-15), reactive oxygen species, oxidative and anti-oxidative markers (malondialdehyde, glutathione, superoxide dismutase), DNA oxidative damage markers (8-OHdG and γ-H2AX), and NF-κB pathway protein levels. Results Compared with the control group, at 24 hours after the end of six irradiations, the number of cells positive in SA-β-gal staining was significantly increased in all dose groups. The mRNA and protein levels of p21 and p53 were significantly elevated in the 0.2 Gy × 6 and 0.5 Gy × 6 groups (P < 0.05). The mRNA levels of genes encoding IL-6, GM-CSF, and MMP-15 were significantly increased in all dose groups (P < 0.05). The mRNA levels of the gene encoding IL-8 were significantly increased in the 0.2 Gy × 6 and 0.5 Gy × 6 groups (P < 0.05). The levels of reactive oxygen species, malondialdehyde, and glutathione were significantly increased in all dose groups (P < 0.01). The level of superoxide dismutase was significantly increased in the 0.5 Gy × 6 group (P < 0.01). The levels of 8-OHdG were significantly increased in all dose groups (P < 0.05). In both the 0.2 Gy × 6 and 0.5 Gy × 6 groups, the expression levels of γ-H2AX and p-NF-κB p65 were significantly increased (P < 0.05), and the levels of IκBα were significantly decreased (P < 0.05). Conclusion Low-dose fractionated X-ray radiation can induce senescence and cause alterations in oxidative stress, oxidative damage, and the levels of NF-κB pathway proteins in L02 hepatocytes.
6.Antimicrobial susceptibility of 72 strains of Corynebacterium striatum and the clinical characteristics of the patients infected or colonized with these strains
Xiaoli YAN ; Qingqing CHEN ; Yuling LIN ; Ruiya SONG ; Jianming ZHANG ; Tingjin ZHENG ; Zhishan ZHANG
Chinese Journal of Infection and Chemotherapy 2024;24(4):395-401
Objective To investigate the antimicrobial susceptibility of clinical isolates of Corynebacterium striatum and the clinical characteristics of the patients infected or colonized with these strains.Methods The C.striatum strains isolated from clinical specimens were collected in Quanzhou First Hospital Affiliated to Fujian Medical University from July 2020 to September 2022.The clinical data were analyzed to examine the clinical characteristics of patients with C.striatum colonization or infection.The susceptibility of these strains to 18 antimicrobial agents were tested by broth microdilution method.The gyrA gene related to quinolone resistance determining region was amplified and sequenced to analyze the position of amino acid mutations.The ribosomal methylase gene ermX and aminoglycoside enzyme gene aphA1 were amplified by PCR and sequenced.Results Antimicrobial susceptibility testing indicated that all of the 72 strains were susceptible to vancomycin,linezolid and daptomycin.All stains were resistant to ceftriaxone,ciprofloxacin and moxifloxacin.The C.striatum strains showed high resistance rate to penicillin(87.5%),cefepime(95.8%),meropenem(95.8%),trimethoprim-sulfamethoxazole(90.3%),erythromycin(98.6%)and clindamycin(98.6%),but relatively lower resistance rate to gentamycin(25.0%),tetracycline(30.6%)and rifampicin(23.6%).Sequencing analysis indicated that 3 strains of C.striatum had single mutation of gyrA gene(Ser87Val),67 strains had double mutations(Ser87Phe,Asp91Ala or Ser87Tyr,Asp91Ala)and 2 strains had three point mutations(Ser87Phe,Ala88Pro and Asp91 Ala),which was newly identified in this study.The ermXgene was detected in all of the isolates and the prevalence of aphA1 gene was 43.1%.The 72 strains of C.striatum were mainly isolated from ICU(65.2%)and lower respiratory tract specimen(91.6%).The average age of patients was 68.0±15.3 years old.About 72.2%(52/72)of the C.striatum strains were isolated from the patients with infection and 27.8%(20/72)were colonizers.Compared to the patients colonized with C.striatum,the patients with C.striatum infection had statistically significant higher percentages of hospital stay ≥ 28 days,cerebral hemorrhage,disturbance of consciousness and disease deterioration(P<0.05).Conclusions All of the 72 C.striatum isolates were multidrug resistant,and the outcome of patients with C.striatum infection was relatively poor.
7.Metabolically unhealthy status and its influencing factors of male residents around a uranium mine in Guangdong Province
Huixian LI ; Huifeng CHEN ; Kengkeng CHEN ; Weixu HUANG ; Jianming ZOU
China Occupational Medicine 2024;51(6):638-644
Objective To investigate the status of metabolically unhealthy status (MUS) and its influencing factors in male residents living around a uranium mine in Guangdong Province. Methods A total of 867 local male residents born and living around a uranium mine in Guangdong Province were selected as the study subjects using two-stage random sampling method. The residents were divided into 10 km- and 20 km- radius groups, according to their living distance <10 km or 10-20 km from the uranium mine. Blood pressure, fasting blood glucose, and blood lipid levels were tested among the study subjects. The influencing factors of MUS and its components were analyzed by multiple logistic regression. Results The detection rate of MUS was 42.2%. The detection rates of MUS component such as elevated diastolic blood pressure, elevated systolic blood pressure, elevated fasting blood glucose, elevated triglyceride and low high-density lipoprotein cholesterol (HDL-C) were 48.8%, 60.9%, 11.9%, 40.7% and 19.3%, respectively. The MUS detection rate in the 10 km group was lower than that in the 20 km group (38.5% vs 45.9%, P<0.05). The result of multivariate logistic regression analysis showed that subjects aged >50 years had a higher risk of MUS and elevated systolic blood pressure than those aged ≤ 50 years (all P<0.05). Drinkers had a higher risk of MUS, elevated systolic blood pressure, elevated diastolic blood pressure, elevated triglyceride, and low HDL-C than non-drinkers (all P<0.05). Those who ate fruit occasionally had a higher risk of MUS than those who ate fruit regularly (P<0.05). Overweight and obese individuals had a higher risk of MUS, elevated systolic blood pressure, elevated diastolic blood pressure, elevated triglyceride, and low HDL-C than those with normal body mass (all P<0.05). Individuals in the 20 km group had a higher risk of MUS and low HDL-C than the 10 km group (all P<0.05). Conclusion The risk factors of MUS detection among male residents living around the uranium mines are age > 50 years, drinking, occasional fruit intake, and being overweight or obese. Age > 50 years, drinking alcohol, overweight and obesity can affect the detection of MUS components in different degrees. Environmental radiation levels have not been identified as a risk factor for MUS in these study subjects.
8.Research progresses in MR angiography of portal venous in children
Siyin ZHOU ; Jianning HOU ; Yuankai CHEN ; Jianming LI
Chinese Journal of Medical Imaging Technology 2024;40(10):1611-1614
MR angiography(MRA)is an important imaging method for non-invasive evaluation on the structure and hemodynamics of portal venous system.With the emergence of new MR sequences and iterations of contrast agents,the applications of portal MRA in children became more and more feasible.The technical research progresses and challenges of portal MRA in children were reviewed in this article.
9.Impacts of X-rays at varying doses on liver injury and oxidative stress in mice
Mingfang LI ; Lingyu ZHANG ; Lina CAI ; Sufen ZHANG ; Yashi CAI ; Yuhua YANG ; Huifeng CHEN ; Jianming ZOU ; Weixu HUANG
Chinese Journal of Radiological Medicine and Protection 2024;44(9):734-740
Objective:To investigate the changes in liver injury and oxidative-antioxidant level in mice exposed to X-rays at varying doses.Methods:Fifty-four 8-week-old male C57BL/6J mice were divided into three groups, namely the control, 2 Gy irradiation, and 4 Gy irradiation groups. Then, each of the groups was further divided by days post-irradiation (i.e., 1, 3, and 7 d), and so nine sub-groups ( n = 6). After irradiation was performed as planned, all the mice were dissected and weighed, and their liver indexes were calculated to determine any histopathological changes in the liver. The peripheral blood cell count and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were detected. Furthermore, spectrophotometry was also used to determine the superoxide dismutase (SOD) activity, the malondialdehyde (MDA) concentration, and the reduced glutathione (GSH) concentration in liver tissues. Results:Compared to the control group, mice undergoing irradiation exhibited a significant reduction in body weight ( F = 84.03, 27.11, 25.50, P < 0.001), but significantly increased liver indexes ( F = 28.40, 17.75, P <0.001) at 1, 3, and 7 d post-irradiation. Pathological observations of these mice revealed liver injury, which proved related to dose and time course. The counts of leukocytes, neutrophils, and lymphocytes in peripheral blood decreased significantly ( F = 8.42-22.91, P < 0.05), trending downward with an increase in the radiation dose. For mice in the 4 Gy irradiation group, their AST and ALT levels increased significantly at 1 d post-irradiation ( H = 7.24, 7.82, P < 0.05), and their ALP levels rose notably at 1 and 3 d post-irradiation ( F = 11.86, 9.75, P < 0.05). Furthermore, their MDA and SOD levels initially rose and then dropped but their GSH levels exhibited an opposite trend at 1, 3, and 7 d post-irradiation. There was a positive correlation between their MDA levels in the liver and the degree of damage to histopathological lesions at 1, 3, and 7 d post-irradiation ( r = 0.30, P < 0.001). Conclusions:A model for radiation-induced liver injury of mice was preliminarily established in this study. It can be concluded that X-rays at varying doses affect the severity of liver injury, pathological grade, peripheral blood cell count, liver function index, and liver oxidative and antioxidant levels of mice, presenting a certain relationship between dose and time course effects.
10.Construction and Thinking of Data Science System of Chronic Atrophic Gastritis
Jianhui SUN ; Weichao XU ; Xia ZHANG ; Runxue SUN ; Yanzhe CHEN ; Shaopo WANG ; Yuman WANG ; Zhen LIU ; Yanru DU ; Qian YANG ; Jianming JIANG
Journal of Traditional Chinese Medicine 2024;65(12):1208-1212
Taking chronic atrophic gastritis (CAG) as an example, the frontier technologies in data science have been introduced into the inheritance, innovation and development of traditional Chinese medicine (TCM), providing reference for conducting real-world clinical research on specialized diseases of TCM. This paper put forward the construction of CAG data science system by elaborating the connotation of data science and its application value in TCM, and discussed the path to build CAG data science system, namely through "data acquisition-knowledge expression-knowledge reasoning" to establish CAG database, knowledge base and develop diagnosis platform differentiating diseases and syndromes. Besides, this paper analyzed the prospects of CAG data science in improving data governance ability and knowledge discovery efficiency, deepening the level of knowledge sharing, promoting interdisciplinary integration, and strengthening the integration process of industry, academia and research.

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