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 analyze the institutional and regional differences in influenza vaccination for teachers and students, so as to provide a basis for influenza prevention and control in campus. Methods: Influenza vaccination data for teachers and students in Shandong Province from 2015 to 2024 were collected from Immunization Information Systems. Joinpoint regression models were used to calculate the annual percent change (APC) and average annual percent change (AAPC) in first-dose vaccination rates. Results: The vaccination coverages for the first dose of influenza vaccine among teachers in Shandong Province from 2015 to 2024 were 0.01%, 0.02%, 0.15%, 0.29%, 0.60%, 2.06%, 1.64%, 2.27%, 3.00%, and 2.43%, with a turning point in 2020. For preschools, primary/secondary schools, and higher education institutions, APCs during 2015-2020 were 163.36%, 162.09%, and 174.94%, respectively( P <0.01), declining to 9.53%, 9.92%, and 8.14% during 2020-2024( P >0.05). Corresponding AAPCs were 78.32%, 78.13%, and 81.61%( P <0.01). High, middle, and low GDP regions exhibited APCs of 173.84%, 162.75%, and 136.67% during 2015-2020( P <0.01) and 5.77%, 13.92%, and 11.86% during 2020-2024( P >0.05), with AAPCs of 79.42%, 81.23% , and 69.63%( P <0.01), respectively. Among students, vaccination coverage ranged from 1.59% to 7.20%. Preschool students showed no turning points, with an AAPC of 18.73%( P <0.01). Primary/secondary students had turning points in 2018 and 2022, APCs were -32.59% during 2015-2018( P <0.01), 48.45% during 2018-2022( P <0.01), and -26.25% during 2022-2024( P =0.04), yielding an AAPC of -2.32%( P =0.45). Higher education students had a turning point in 2020, with APCs of 63.27% during 2015-2020( P <0.01) and 4.31% during 2020-2024 ( P =0.77), and the AAPC was 33.79% during 2015-2024 ( P <0.01). High, middle, and low GDP regions for students showed no turning points, with AAPCs of 10.46%( P =0.18), 13.67%( P =0.01), and 10.42%( P = 0.05 ), respectively. Conclusions The influenza vaccination rate among teachers and students in Shandong Province has shown an upward trend from 2015 to 2024, but the overall level is still relatively low. However, continued efforts are needed to enhance health education on influenza and vaccination, to further improve the vaccination rate of teachers and students.

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 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.

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.

Objective To investigate the relationship between serum interleukin-1β(IL-1β),C-reactive pro-tein to albumin ratio(CAR)and heparin-binding protein(HBP)levels and secondary pulmonary Candida albi-cans infection during chemotherapy in patients with lung cancer.Methods A total of 175 patients with lung cancer admitted to this hospital from January 2018 to April 2022 were selected,and all patients were treated with chemotherapy.According to whether they had secondary pulmonary Candida albicans infection,they were divided into infection group(37 cases)and non-infection group(138 cases).The clinical data,serum levels of IL-1β,HBP and CAR were compared between the two groups.Multivariate Logistic regression analysis was used to analyze the influencing factors of secondary pulmonary Candida albicans infection in patients with lung cancer during chemotherapy.The receiver operating characteristic(ROC)curve was used to analyze the pre-dictive value of serum IL-1β,CAR and HBP for secondary pulmonary Candida albicans infection during chemo-therapy,and the prognosis of lung cancer patients with different serum IL-1β,HBP levels and CAR were com-pared.Results There were significant differences in smoking,pathological stage,diabetes mellitus,chemo-therapy cycle,chronic obstructive pulmonary disease and anatomical location between the infection group and the non-infection group(P＜0.05).The serum levels of IL-1β,HBP and CAR in the infection group were higher than those in the non-infection group(P＜0.05).Multivariate Logistic regression analysis showed that smoking,diabetes,anatomical site,chronic obstructive pulmonary disease,pathological stage,chemotherapy cycle and serum IL-1β,HBP,CAR were the influencing factors of secondary pulmonary Candida albicans infec-tion in patients with lung cancer during chemotherapy(P＜0.05).The area under the curve(AUC)of serumIL-1β,CAR and HBP in predicting pulmonary Candida albicans infection was 0.779,0.732 and 0.796,respec-tively.The AUC of the combination of the three was 0.931,and the sensitivity and specificity were 86.49％and 90.58％,respectively.The survival rate of lung cancer patients with high levels of IL-1β,CAR and HBP was sig-nificantly lower than that of patients with low levels of Il-1β,CAR and HBP(P＜0.05).Conclusion The in-crease of serum IL-1β,CAR and HBP levels in patients with lung cancer is related to secondary pulmonary Candida albicans infection during chemotherapy.Detection of these serum Il-1β,CAR and HBP levels is helpful to predict the risk of pulmonary Candida albicans infection and death.

Objective·To systematically review the effectiveness of actigraphy on the evaluation of circadian rhythm characteristics in patients with depression.Methods·A systematic literature search was conducted in PubMed,Embase,Web of Science,Cochrane Library,PsycINFO,CNKI,WanFang Data,and Chinese biomedical literature database(CBM),from the inception of each database to May 5th,2023.Case control studies that used actigraphy to evaluate circadian rhythms in patients with depression and compared them with healthy controls were collected.Literature was screened according to the inclusion and exclusion criteria,and the quality of the included literature was evaluated by using the Newcastle-Ottawa Scale.The meta-analysis was performed by using RevMan 5.4 software.Results·A total of 9 articles were included,including 390 patients with depression and 288 healthy controls.The meta-analysis showed that the MESOR(midline statistic of rhythm)(SMD=-0.29,95%CI-0.51 ?-0.07,P=0.009)of the circadian cosine function in patients with depression was lower than that in healthy controls;sleep onset(MD=33.06,95%CI 14.90 ? 51.23,P=0.000)and sleep offset(MD=53.80,95%CI 22.38 ? 85.23,P=0.000)were later in patients with depression than those in healthy controls;no statistical difference was found in the activity level of the most active 10 hours(SMD=-0.26,95%CI-0.52 ? 0.01,P=0.060)between patients with depression and healthy controls,although there was a trend for lower activity in patients with depression;no statistical difference was found in the acrophase(MD=25.33,95%CI-12.41 ? 63.06,P=0.190)of the circadian cosine function between patients with depression and healthy controls;no clear statistical significance of the difference was found in the amplitude(SMD=-0.14,95%CI-0.42 ? 0.14,P=0.340)and the activity level of the least active 5 hours(SMD=0.31,95%CI-0.10 ? 0.71,P=0.140)between patients with depression and healthy controls.Conclusion·Actigraphy can reflect circadian rhythm disruption in patients with depression to some extent,but the limited number of included studies and inconsistencies in the study populations and methodologies have affected the quality and results of the analyses.More high-quality clinical trials are needed to provide evidence.

Objective:To explore the clinical effects of free anterolateral thigh perforator flaps in repairing diabetic foot ulcers (DFUs) under a multi-disciplinary team (MDT) cooperation model.Methods:The study was a retrospective observational study. From June 2018 to December 2022, 49 DFU patients who met the inclusion criteria were admitted to the Department of Hand and Foot Microscopy and Wound Repair Surgery of Henan Provincial People's Hospital (People's Hospital of Zhengzhou University), including 28 males and 21 females, aged from 47 to 68 years, with type 2 diabetes history period ranging from 6 months to 21 years. Under a MDT cooperation model, the physicians from department of endocrinology comprehensively assessed the patients, stabilized the patients' general condition, and controlled their complications, the surgeons from department of vascular surgery assessed and improved the patients' lower limb blood supply, the physicians from department of infectious diseases provided anti-infection treatment plans, the physicians from department of anesthesiology and perioperative medicine assessed the patients' perioperative risk and ensured their perioperative safety, and according to the patients' condition, the physicians from departments such as cardiology, neurology, nutrition, and rehabilitation actively and timely participated in the treatment. The surgeons from department of hand and foot microscopy and wound repair surgery prepared the wound base and used free anterolateral thigh perforator flaps to repair the wounds. After once or multiple debridement in the first stage, the wound area ranged from 5.0 cm×4.5 cm to 17.0 cm×10.0 cm. After once or twice vacuum sealing drainage treatment, the free anterolateral thigh perforator flaps were used to repair the wounds with incision area of 6 cm×5 cm to 18 cm×11 cm in the second stage. The descending branches of lateral circumflex femoral artery and the accompanying veins of flaps were anastomosed to the arteries and veins in the recipient sites, respectively. The wounds in the flap donor sites were sutured directly. After surgery, whether the patient's perioperative period was stable, the survival of flaps, the healing of wounds in the flap donor and recipient sites were observed. During the follow-up, the texture and appearance of flaps, whether there was a new ulcer, and the patient's walking ability were observed.Results:All the patients had stable perioperative period. Among them, the flaps in 46 patients survived successfully; the flaps in 2 patients developed complete necrosis, including 1 case whose ulcer was healed after repair of pedicled flap from the lower leg, and 1 case who underwent amputation of the lower leg; the flap in 1 patient developed partial necrosis, which was healed after dressing change and skin grafting. The wounds in the flap donor and recipient sites healed well. During the postoperative follow-up of 6-24 months, the flaps had good texture and appearance with no new ulcers, and the patients had no obvious impairment in daily walk.Conclusions:The MDT cooperation model can sufficiently ensure the perioperative safety of DFU patients. The free anterolateral thigh perforator flaps can repair the DFU wounds achieving good clinical effects with high flap survival rate and decreased amputation rate.

Objective:To explore the immunological characteristics of peripheral blood and genetic variations of 11 immunodeficiency virus(HIV)-negative children with Talaromyces marneffei(TM) infection, thus enhancing the diagnostic and therapeutic levels of TM infection in children. Methods:Clinical data of 11 HIV-negative children with TM infection who presented to Guangzhou Women and Children′s Medical Center, Guangzhou Medical University from January 2010 to December 2022 were retrospectively analyzed, including clinical characteristics, peripheral immune profile and genetic test results.Results:A total of 11 HIV-negative children with TM infections were recruited, involving 9 males and 2 females with a median age of 19 months.The main clinical manifestations were fever (10/11, 90.91%), cough (10/11, 90.91%) and hepatomegaly (7/11, 63.64%). Common severe complications included acute respiratory distress syndrome (7/11, 63.64%) and septic shock (5/11, 45.45%). Finally, 2 children died.Transient neutropenia occurred in 6 cases (6/11, 54.55%), and lymphocytopenia combined with serum immunoglobulin (Ig) G decrease was observed in 4 cases (4/11, 36.36%). IgA decrease, IgM decrease, IgE decrease, IgM increase and IgE increase were observed in 6 cases, 3 cases, 5 cases, 3 cases, and 2 cases, respectively.Both T-lymphocyte and B-lymphocyte counts decreases was observed in 1 case.Genetic testing was performed in all recruited children, and genetic variations were detected in all of them.Inborn errors of immunity (IEIs) were diagnosed in 8 cases, including 4 diagnosed as CD 40 ligand deficiency with CD40LG variation, 1 of severe combined immunodeficiency with IL2RG variation, 1 of Signal transduction and activator of transcription 3(STAT3)-hyper-IgE syndrome with STAT3 variation and 1 of familial candidiasis type 2 with CARD9 compound heterozygous mutations.In the other 3 cases, 2 carried genetic variations that were likely pathogenic, and 1 case was considered uncertain. Conclusions:The clinical manifestations of HIV-negative children with TM infection are atypical, which is characterized as serious complications and high mortality.Early identification and gene testing to detect potential IEIs can improve the prognosis of TM infection.