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.

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.

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 6431 medical radiologists who ordered occupational health checkups from January 2022 to December 2023, and basic information such as demographic characteristics, occupational characteristics, lifestyles, and dietary habits was collected through questionnaires. Physical examinations were conducted using a standardized protocol. Individual dose equivalents of occupational external exposure were monitored by dosimeters worn by medical radiologists. Logistic regression model was used for identifying influencing factors of MetS and sensitivity analysis, and restricted cubic spline model was used to explore the dose-response relationship between cumulative effective dose and MetS. Two-stage linear regression was used to evaluate threshold effect of association between cumulative effective dose and MetS. Results The positive rate of MetS was 13.6% (877/6431) among the enrolled 6431 study participants. The logistic regression showed that gender, age, monthly income, body mass index (BMI), cumulative effective dose, and smoking were influencing factors for MetS. The risk of MetS was higher in males (OR=1.511, 95%CI: 1.209, 1.888); using the < 30 years old group as reference, the risk of MetS was higher in the 30-39 years old (OR=1.509, 95%CI: 1.095, 2.079), 40-49 years old (OR=2.214, 95%CI: 1.551, 3.161), and ≥50 years old (OR=3.480, 95%CI: 2.338, 5.181) groups; using the <10000 yuan group as reference, the risk of MetS was lower in the group with a monthly income of 10000-14999 yuan (OR=0.715, 95%CI: 0.582, 0.878); the risk of MetS was higher in the BMI ≥ 24 kg·m⁻² group (OR=7.548, 95%CI: 6.223, 9.156); using the < 0.76 mSv group as reference, the risk of MetS was higher in the cumulative effective dose of 0.76-2.73 mSv group (OR=1.270, 95%CI: 1.017, 1.586); the risk of MetS was higher in the smoking group (OR=1.734, 95%CI: 1.428, 2.107). The results of restricted cubic spline showed that the cumulative effective dose was nonlinearly correlated with MetS (P _{non-linearity}=0.028), with an inflection point of 1.25 mSv. The risk of developing MetS increased by 34.1% for each unit increase in cumulative effective dose up to 1.25 mSv, whereas above 1.25 mSv, the statistical association was not significant. The sensitivity analysis results showed that after excluding the self-reported hypertensive and diabetic patients, the cumulative effective dose 0.76-2.73 mSv group still had an increased risk of developing MetS compared with the < 0.76 mSv group (P < 0.05), and the results were robust. Conclusion Among medical radiologists, male, age, BMI, and smoking are positively correlated with MetS, and monthly income is negatively correlated with MetS; cumulative effective dose is non-linearly correlated with MetS among medical radiologists.

Objective To explore the differentially expressed mRNAs and related biological processes and pathways in fractional low-dose ionizing radiation (LDIR)-induced senescence of normal human bronchial epithelial (HBE) cells by high-throughput mRNA sequencing and bioinformatics techniques. Methods Senescence-associated β-galactosidase staining and senescence-associated secretion phenotype gene mRNA and protein expression levels were measured at 24 and 48 h after irradiating HBE cells 7 times at doses of 0, 50, 100, and 200 mGy, respectively. The differentially expressed genes were screened by high-throughput sequencing for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results The senescence-positive area of fractional low-dose irradiated HBE cells increased in a dose-dependent manner (P < 0.05). The mRNA levels and protein expression of transforming growth factor-β1(TGF-β1) and matrix metalloproteinase-9(MMP-9) genes were increased in the 100 mGy × 7 and 200 mGy × 7 groups at 24 and 48 h after the end of irradiation compared with the control group. High-throughput sequencing showed that there were 882, 475, and 1205 differentially expressed mRNAs in each dose group compared with the control group. GO analysis showed that the differentially expressed mRNAs in each dose group were mainly enriched in biological processes such as cell cycle regulation, regulation of nitrogen compound metabolic process, regulation of cell division and response to stimulus. KEGG analysis showed that the differentially expressed mRNAs were mainly enriched in the pathways of cell cycle, cell senescence, and ferroptosis. Conclusion Fractional LDIR induced senescence in HBE cells, and differentially expressed mRNA-associated biological processes and pathways in senescent cells are related to cell cycle and cell senescence.

Objective To investigate the mechanism of fractionated low-dose ionizing radiation (LDIR) in the induction of EA.hy926 cell senescence. Methods EA.hy926 cells were irradiated with X-ray at 0, 50, 100, and 200 mGy × 4, respectively, and cultured for 24, 48, and 72 h. Several indicators were measured, including the levels of cellular senescence-associated β-galactosidase (SA-β-gal) staining, mRNA levels of senescence-associated cell cycle protein-dependent kinase inhibitor genes CDKN1A and CDKN2A, reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and phosphorylated H2A histone family member X (γ-H2AX). Results After 4 fractionated LDIR, compared with the control group, the treatment groups showed increased nucleus area, blurred cell edge, and increased SA-β-gal positive area (P < 0.05) at 24, 48 and 72 h. After 4 fractionated LDIR, the mRNA level of CDKN1A increased in the 100 and 200 mGy × 4 groups at 24 and 48 h (P < 0.05), and CDKN2A mRNA level increased in the 100 and 200 mGy × 4 groups at 48 and 72 h (P < 0.05). The fluorescence intensity of ROS increased in treatment groups at 24, 48, and 72 h after 4 fractionated LDIR (P < 0.05). After 4 fractionated LDIR, the T-AOC level increased in the 100 and 200 mGy × 4 groups at 24 h (P < 0.05), and T-AOC level increased in all treatment groups at 48 and 72 h (P < 0.05). After 4 fractionated LDIR, γ-H2AX fluorescence intensity increased in all treatment groups at 24 h (P < 0.05), and the fluorescence intensity increased in the 100 and 200 mGy × 4 groups at 48 and 72 h (P < 0.05). Conclusion Fractionated LDIR can induce cellular senescence in EA.hy926 cells by impacting the cellular oxidation-antioxidation and oxidative damage levels, and the effects were relatively evident at 100 and 200 mGy.

OBJECTIVES: Digital subtraction angiography (DSA) is the current gold standard for diagnosing spinal dural arteriovenous fistulas (SDAVF). However, DSA is invasive and associated with risks such as ionizing radiation and iodine contrast allergy. Contrast-enhanced magnetic resonance angiography (CE-MRA) with high temporal/high spatial resolution allows dynamic multiphase contrast-enhanced imaging with excellent detail. This study aims to evaluate the diagnostic value of spinal CE-MRA with high temporal/high spatial resolution for SDAVF. METHODS: Clinical data were retrospectively collected from patients who underwent both conventional spinal MRI and high temporal/high spatial resolution CE-MRA at Xiangya Hospital between January 1, 2021, and January 1, 2024, and who subsequently underwent DSA or surgery within 90 days. Two experienced radiologists independently reviewed all conventional MRI and CE-MRA images. The sensitivity and specificity of conventional MRI and CE-MRA for diagnosing SDAVF were calculated against the gold standard DSA findings. Kappa statistics were used to evaluate the consistency of MRI and CE-MRA compared to DSA. The diagnostic value was further assessed by calculating the area under curve (AUC) of the receiver operating characteristic (ROC). RESULTS: A total of 60 patients were included, of whom 47 were diagnosed with SDAVF and 13 were not. Conventional MRI had 3 false negatives and 1 false positive; CE-MRA had 2 false positives and 0 false negative. The sensitivity and specificity of conventional MRI were 93.62% and 92.31%, respectively. CE-MRA demonstrated 100% sensitivity and 84.62% specificity. The main cause of false positives was the misidentification of posterior spinal arteries as feeding arteries. CE-MRA clearly displayed most feeding arteries, and the accuracy of fistula localization was 74.47% (35/47). Kappa values for conventional MRI and CE-MRA were 0.814 and 0.896, respectively (both P<0.001), indicating good agreement, with CE-MRA outperforming conventional MRI. The AUCs for diagnosing SDAVF were 0.930 for conventional MRI and 0.923 for CE-MRA (both P<0.05). CONCLUSIONS Spinal CE-MRA with high temporal/high spatial resolution is a reliable, non-invasive imaging technique with high sensitivity for diagnosing SDAVF. It can clearly visualize feeding arteries and provides valuable preoperative diagnostic and localization information to support DSA or surgical planning.
Humans ; Central Nervous System Vascular Malformations/diagnosis* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Magnetic Resonance Angiography/methods* ; Angiography, Digital Subtraction/methods* ; Aged ; Adult ; Sensitivity and Specificity ; Contrast Media ; Magnetic Resonance Imaging/methods*

Objective:To investigate the method and effect of retroauricular three flaps for repair of congenital earlobe defect.Methods:From March 2019 to December 2021, the data of patients with congenital earlobe defect treated with retroauricular three-flap method in Beijing Anzhen Hospital, Capital Medical University and Plastic Surgery Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. The specific method was to design three flaps in the posterior auricular region, A, B, C respectively. The area of flap A was larger 10%-20% than the defect area, and the flap A was rotated in the direction of the anterior and inferior earlobe. The flap B was designed as a rotation flap to repair the secondary defect after flap transplantation. The flap C was designed as a sliding flap to reduce the tension of the wound in the retroauricular region. Postoperative observation included flap blood flow, complications of infection, hematoma, and so on, and scar after wound healing. A questionnaire was used to investigate the satisfaction of patients or guardians, with scores from 1 to 4 indicating dissatisfaction, general satisfaction, satisfaction, and very satisfaction respectively.Results:A total of 10 patients were included, including 3 males and 7 females. Aged from 7-18 years old, with an average of 11 years old. All cases were unilateral lobe defects. Postoperative infection occurred in 1 case and small local hematoma in 1 case. All cases were cured after dressing change without flap necrosis and other complications. After 3 to 6 months of follow-up, there was no flap necrosis, the color, shape and plumpness of the repaired earlobe were good, and the scar behind the ear was concealed. The satisfaction survey showed that 8 cases had great satisfaction and 2 cases had satisfaction.Conclusion:Partial or total defects of earlobe can be repaired by retroauricular three flaps. The reconstructed earlobe has natural shape, hidden scar and satisfactory clinical effect.

Objective:To investigate the clinical effect of filling orbital septum with autologous fat granules for correction of severe upper eyelid depression.Methods:From January 2019 to January 2021, the data of patients with severe upper eyelid depression admitted to Beijing Anzhen Hospital, Capital Medical University were retrospectively analyzed. Fat granules were obtained from the abdomen or inner thigh. The middle part of the upper eyelid depression near the lower edge of eyebrow were selected as the injection point. The needle for filling was successively passed through the skin, subcutaneous fat layer, orbicularis oculi muscle, retro-orbicularis oculi fat, and the superior orbital margin. The needle was inserted into the orbital septum closedly to the superior orbital wall. Fat granules were injected into the orbital septum until the upper eyelid depression was corrected with slight fullness. Postoperative follow-up was conducted on the improvement of upper eyelid depression and the occurrence of complications in the patients. For the patients with poor correction of upper eyelid depression, autologous fat granule injection was performed again half a year later.Results:A total of 42 female patients with severe upper eyelid depression were included, aged 18-57 years with an average age of 36.8 years. Fat injection volume was 1.8-3.0 ml in each side. After 6-12 months of follow-up, 39 patients (92.9%) were significantly improved after one operation, and the other 3 patients (7.1%) were effectively improved after two fat filling. 2-3 days after operation, 4 cases of fat nodules appeared on upper eyelid, which subsided after local repeated massage by doctors. No complications such as hematoma, ptosis and embolism occurred.Conclusion:Filling the orbital septum with autologous fat granules can effectively improve the severe upper eyelid depression to attain eyelid rejuvenation.

Objective:To investigate the method and effect of retroauricular three flaps for repair of congenital earlobe defect.Methods:From March 2019 to December 2021, the data of patients with congenital earlobe defect treated with retroauricular three-flap method in Beijing Anzhen Hospital, Capital Medical University and Plastic Surgery Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. The specific method was to design three flaps in the posterior auricular region, A, B, C respectively. The area of flap A was larger 10%-20% than the defect area, and the flap A was rotated in the direction of the anterior and inferior earlobe. The flap B was designed as a rotation flap to repair the secondary defect after flap transplantation. The flap C was designed as a sliding flap to reduce the tension of the wound in the retroauricular region. Postoperative observation included flap blood flow, complications of infection, hematoma, and so on, and scar after wound healing. A questionnaire was used to investigate the satisfaction of patients or guardians, with scores from 1 to 4 indicating dissatisfaction, general satisfaction, satisfaction, and very satisfaction respectively.Results:A total of 10 patients were included, including 3 males and 7 females. Aged from 7-18 years old, with an average of 11 years old. All cases were unilateral lobe defects. Postoperative infection occurred in 1 case and small local hematoma in 1 case. All cases were cured after dressing change without flap necrosis and other complications. After 3 to 6 months of follow-up, there was no flap necrosis, the color, shape and plumpness of the repaired earlobe were good, and the scar behind the ear was concealed. The satisfaction survey showed that 8 cases had great satisfaction and 2 cases had satisfaction.Conclusion:Partial or total defects of earlobe can be repaired by retroauricular three flaps. The reconstructed earlobe has natural shape, hidden scar and satisfactory clinical effect.

Objective:To investigate the clinical effect of filling orbital septum with autologous fat granules for correction of severe upper eyelid depression.Methods:From January 2019 to January 2021, the data of patients with severe upper eyelid depression admitted to Beijing Anzhen Hospital, Capital Medical University were retrospectively analyzed. Fat granules were obtained from the abdomen or inner thigh. The middle part of the upper eyelid depression near the lower edge of eyebrow were selected as the injection point. The needle for filling was successively passed through the skin, subcutaneous fat layer, orbicularis oculi muscle, retro-orbicularis oculi fat, and the superior orbital margin. The needle was inserted into the orbital septum closedly to the superior orbital wall. Fat granules were injected into the orbital septum until the upper eyelid depression was corrected with slight fullness. Postoperative follow-up was conducted on the improvement of upper eyelid depression and the occurrence of complications in the patients. For the patients with poor correction of upper eyelid depression, autologous fat granule injection was performed again half a year later.Results:A total of 42 female patients with severe upper eyelid depression were included, aged 18-57 years with an average age of 36.8 years. Fat injection volume was 1.8-3.0 ml in each side. After 6-12 months of follow-up, 39 patients (92.9%) were significantly improved after one operation, and the other 3 patients (7.1%) were effectively improved after two fat filling. 2-3 days after operation, 4 cases of fat nodules appeared on upper eyelid, which subsided after local repeated massage by doctors. No complications such as hematoma, ptosis and embolism occurred.Conclusion:Filling the orbital septum with autologous fat granules can effectively improve the severe upper eyelid depression to attain eyelid rejuvenation.