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.

Checkpoint blockade immunotherapy has emerged as a transformative approach in cancer treatment by activating tumor-infiltrating T cells. However, the efficacy of PD-L1 blockade is restricted in "cold" tumors, which are characterized by low immunogenicity, presenting a challenge to immunotherapy. This study introduces an innovative strategy, utilizing cathepsin-cleavable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-assisted combined photodynamic therapy (PDT) and PD-L1 degradation for the first time, effectively treating T cell-deficient tumors. The degradable main-chain polymer, conjugated with photosensitizer porphyrin, facilitates the accumulation of reactive oxygen species (ROS), triggering immunogenic cell death (ICD) and promoting cytotoxic T lymphocytes (CTLs) infiltration into tumors. Multivalent peptide antagonists of PD-L1 promote PD-L1 degradation in lysosomes through receptor crosslinking, overcoming the adaptive cycling of PD-L1 to the tumor cell surface. These findings demonstrate that polymer-assisted PDT and PD-L1 crosslinking degradation represent a potential novel strategy for anti-tumor immunotherapy, providing valuable tools for expanding immunotherapy applications in immunosuppressive cancers.

Objective:To investigate the mechanism of long non-coding RNA taurine up-regulated gene 1(lncRNA TUG1)in acute pancreatitis(AP).Methods:The mouse pancreatic acinar cell line(MPC-83)was cultured in vitro,and treated with lipopoly-saccharide(LPS,10 μg/ml)and cerulein(Caerulein,100 nmol/L)for 3 h to establish the AP model.The experiment was divided into control group,AP group,AP+sh-NC group,AP+sh-TUG1 group,AP+sh-TUG1+inhibitor-NC group,and AP+sh-TUG1+miR-31-5p inhibitor group.Quantitative real-time PCR(qRT-PCR)was performed to measure the expression levels of lncRNA TUG1 and miR-31-5p in cells;CCK-8 method was performed to measure cell viability;flow cytometry was performed to measure apoptosis;ELISA was performed to measure the levels of IL-1β and tumor necrosis factor α(TNF-α)in the cell supernatant;and dual-luciferase reporter gene experiments was performed to verify the targeting relationship between lncRNA TUG1 and miR-31-5p.The AP mouse model was constructed,and after corresponding intervention,qRT-PCR was performed to determine the lncRNA TUG1 and miR-31-5p expres-sion levels in pancreatic tissue;the serum inflammatory factors IL-1β,TNF-α contents and amylase(AMY)and lipase(Lipase)activities were determined by kits;HE staining was performed to observe histopathological changes of pancreas;TUNEL was per-formed to detect apoptosis in pancreatic tissue.Results:In MPC-83 cells co-treated with Caerulein and LPS,the lncRNA TUG1 level,apoptosis rate,IL-1β and TNF-α levels were increased,while miR-31-5p level and cell viability were decreased(all P<0.05);knock-down of lncRNA TUG1 up-regulated miR-31-5p,increased cell viability,decreased IL-1β and TNF-α levels,and inhibited cell apop-tosis(all P<0.05);down-regulation of miR-31-5p expression attenuated the inhibitory effect of lncRNA TUG1 knockdown on cellular inflammatory responses.miR-31-5p was a direct target of lncRNA TUG1.Knockdown of lncRNA TUG1 expression in vivo was able to up-regulate the expression of miR-31-5p in pancreatic tissue of AP mice,reduce the levels of IL-1β and TNF-α,reduce cell apoptosis,and improve pancreatic tissue damage.Conclusion:Knockdown of lncRNA TUG1 may improve AP by up-regulating the expression level of miR-31-5p and inhibiting the inflammatory response.

Objective:To establish a predictive model for myocardial contusion (MC) in patients with rib fractures and evaluate its clinical application value.Methods:A retrospective case-control study was conducted to analyze the clinical data of 370 patients with rib fractures admitted to the Affiliated Jiangsu Shengze Hospital of Nanjing Medical University from January 2017 to December 2019, including 257 males and 113 females, aged 18-95 years [(56.5±14.0)years]. All the patients underwent electrocardiogram examination and myocardial biomarker test within 24 hours on admission, of whom 159 were diagnosed with MC, and 211 with non-MC (NMC). The 370 patients were divided into a training set of 264 patients (106 with MC, 158 with NMC) and a validation set of 106 patients (53 with MC, 53 with NMC) at a ratio of 7∶3 through the completely randomized method. In the training set, the MC group and NMC group were compared in terms of their demographic characteristics, vital signs on admission, types of rib fractures, number of rib fractures, locations of rib fractures, associated thoracic injuries, trauma scores, and laboratory indices. Variables of positive correlation with MC in patients with rib fractures were screened by Spearman correlation analysis, followed by univariate binary Logistic regression analysis for these variables to determine the risk factors for MC in patients with rib fractures. LASSO regression analysis and multivariate Logistic regression analysis were applied to identify the independent risk factors for MC in patients with rib fractures, and the regression equation was constructed. A nomogram prediction model was plotted based on the regression equation with R software. The receiver operating characteristic (ROC) curve was plotted to evaluate the model′s discriminability. Hosmer-Lemeshow (H-L) goodness-of-fit test and calibration curves of 1000 repeated samplings by the Bootstrap method were used to evaluate the calibration of the model. The decision curve analysis (DCA) and clinical impact curve analysis (CIC) were plotted to evaluate its clinical efficacy. A risk scoring was performed according to the assigned β coefficient of independent risk factors. Accordingly, the 370 selected patients with rib fractures were divided into low-risk subgroup of 202 patients, moderate-risk subgroup of 108 patients, high-risk subgroup of 50 patients, and extremely high-risk subgroup of 10 patients. The incidence of MC and in-hospital mortality were compared among different subgroups so as to further verify the clinical application value of the predictive model.Results:In the training set, there were significant differences between the MC group and NMC group in bilateral rib fractures, flail chest, number of rib fractures, upper chest proximal sternum segment, upper chest anterolateral segment, upper chest proximal spinal segment, middle chest anterolateral segment, middle chest proximal spinal segment, lower chest anterolateral segment, pneumothorax, mediastinal emphysema, hemothorax, sternal fractures, chest abbreviated injury scale (c-AIS), injury severity score (ISS), new injury severity score (NISS), white blood cell counts, hemoglobin, hematocrit, total cholesterol, low density lipoprotein, albumin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen ( P<0.05 or 0.01). Spearman correlation analysis showed that the bilateral rib fractures, flail chest, number of rib fractures, upper chest proximal sternum segment, upper chest anterolateral segment, upper chest proximal spinal segment, middle chest anterolateral segment, middle chest proximal spinal segment, lower chest anterolateral segment, pneumothorax, hemothorax, sternal fractures, c-AIS, ISS, NISS, white blood cell count, aspartate aminotransferase and blood urea nitrogen were positively correlated with MC ( P<0.05 or 0.01). Univariate binary Logistic regression analysis verified that the above variables with positive correlation were significantly correlated with MC in patients with rib fractures ( P<0.05 or 0.01). The 4 predictor variables screened by LASSO regression analysis were the upper chest anterolateral segment, middle chest proximal spinal segment, pneumothorax, and sternal fractures. Multivariate Logistic regression analysis confirmed that the aforementioned 4 predictor variables were independent risk factors for MC in patients with rib fractures ( P<0.05 or 0.01). The regression equation of the training set was established based on the above independent risk factors: P=e x/(1+e x), with the x=1.57×"upper chest anterolateral segment"+0.73×"middle chest proximal spinal segment"+1.36×"pneumothorax"+2.16×"sternal fractures"-1.10. In the predictive model for MC in patients with rib fractures established based on the equation, the area under the ROC curve (AUC) was 0.77 (95% CI 0.72, 0.83) and 0.77 (95% CI 0.71, 0.82) in the training set and validation set. The H-L goodness-of-fit test showed χ2=2.77, P=0.429 in the training set, and χ2=1.33, P=0.515 in the validation set, indicating that there was no significant difference between the predicted probability and the actual probability of the model ( P>0.05). The calibration curves showed that the bias-corrected curves of the training set and validation set were in good consistency with the actual curves and were both close to the ideal curves. The DCA of the training set and the validation set showed that within the threshold probability range of 0.2-0.8, the predictive model could obtain good net clinical benefits. The CIC of the training set and the validation set indicated that when the threshold probability was >0.4, the population identified as high-risk MC patients by the predictive model highly matched the actual MC patients. Risk scoring of subgroups found that the incidence of MC and in-hospital mortality among the patients with rib fractures were 80.0% and 6.0% in the high-risk subgroup and 90.0% and 20.0% in the extremely high-risk subgroup, significantly higher than those in the low-risk subgroup (24.8%, 1.0%) and the moderate-risk subgroup (55.6%, 1.9%) ( P<0.05). Conclusions:The predictive model for MC in patients with rib fractures constructed based on the upper chest anterolateral segment, middle chest proximal spinal segment, pneumothorax, and sternal fractures has good predictive efficacy and clinical application value.

Objective To study the differences in features of event-related potentials(ERPs)and target detection accuracy between five brain regions(frontal,temporal,central,parietal,and occipital)in target detection tasks based on rapid serial visual presentation(RSVP)brain computer interface(BCI)under six target concealment conditions.Methods Twelve participants were selected for the study,whose scalp electroencephalogram(EEG)signals were collected under the six concealment conditions using a NeuroScan SynAmps2 EEG acquisition system.The ERP waveforms,P300 amplitudes and latencies,among other things,were compared across the five brain regions.The hierarchical discriminant component analysis(HDCA)algorithm was used to classify the EEG signals while the differences in classification accuracy were probed across the five brain regions.Results(1)Under the six concealment conditions,target images elicited distinct ERP waveforms in all the five brain regions;(2)For P300 amplitudes,the temporal region exhibited the smallest values;(3)Regarding P300 latencies,the parietal and central regions showed longer durations than other brain regions(except for small camouflage and small occlusion conditions);(4)In terms of classification accuracy,the parietal and central regions outperformed other brain regions(except for the large camouflage condition).Conclusion The selection of parietal and central channels can offer a new perspective for enhancing the performance in concealed target detection based on RSVP-BCI,and is expected to spark new ideas for the design of miniaturized,simple and wearable BCI devices.

Objective To explore an overcorrection quantization method and related influencing factors through analyzing relationships between the achieved and preset intrusion values of mandibular anterior teeth with clear aligners.Methods Twenty pa-tients receiving Invisalign were recruited.The relative intrusion values in the ClinCheck software were recorded as the preset intrusion.The achieved intrusion values were measured through the digital model superimposition.Statistical analysis was conducted to assess the differences and linear relationships between the preset and achieved intrusion values,and investigate the effect of related factors such as intrusion amounts on the intrusion efficiency.Results For the mandibular anterior teeth,the mean intrusion efficiency was 62.2%,with the highest in the central incisors and the lowest in the canines.The intrusion amounts,incisors labial inclinations,and canine at-tachment types affected the intrusion efficiency.The differences between the preset and achieved values were significant,and the linear relationship existed.The formula of the intrusion overcorrection for the mandibular anterior teeth is"Z=(W-0.110)/0.533-W".Z re-presents the overcorrection and W represents the ideal intrusion.Conclusion The preset intrusion values in the treatment protocol could not be fully achieved.Moreover,correction should be designed in cases of mandibular canine intrusion,large amountsof intru-sion,orlingually inclined incisors.Compared to the optimized attachments,the vertical rectangular attachments on the mandibular ca-nines could improve the efficiency.

Objective To evaluate and compare the treatment efficacy between concentrated growth factor(CGF)and blood clots(BC)as scaffolds in regenerative endodontic procedures(REPs).Methods Twenty young permanent teeth from 18 healthy children with pulp necrosis or periapical periodontitis were randomly divided into CGF group and BC group.In the CGF group(n=10),after ap-ical bleeding,CGF was inserted into the root canal as a stent.In the BC group(n=10),by stimulating apical bleeding,blood entered the root canal and produced blood clots as scaffolds.Clinical examination and apical X-ray shooting were conducted for each follow-up visit.Cone beam computed tomographic(CBCT)images were acquired preoperatively and at the 24-month recall.The increase of root length,root wall thickness,and newly-formed calcified tissue were calculated.Results The root length increased by(1.68±0.90)mm in the CGF group and(2.36±1.34)mm in the BC group.Root wall thickness increased by(0.44±0.34)mm in the CGF group and(0.50±0.31)mm in the BC group.There was no statistically significant difference in root lengthening and root wall thickening between two groups(P＞0.05).The amount of newly formed calcified tissue in the CGF group((22.13±19.12)mm3)was significantly less than that in the BC group((42.97±22.69)mm3)(P＜0.05).According to the goals for success outlined by American Association of Endodontists(AAE),90%(9/10)of the CGF cases and100%(10/10)of the BC cases achieved the primary and secondary goals(P＞0.05).40%of the CGF cases(4/10)and 60%of the BC cases(6/10)achieved the tertiary goal(P＞0.05).Conclusion CGF is found to be use-ful as a scaffold for REPs,but the success rate is slightly lower than that of BC group and the difference is not statistically significant.

Objective To explore the effect of melatonin(MT)-modified PEEK implant assisted by polydopamine(PDA)coating on osteointegration in osteoporotic rats.Methods MT was adhered to PEEK implants with PDA coating as carrier.The physicochemical properties of the materials were analyzed by SEM image,water contact angle,FTIR and protein adsorption experiment.OVX-rBMSCs were inoculated on the surface of PEEK sheet and cultured.The cytoskeleton was stained and cell adhesion morphology was observed.Cell proliferation activity was evaluated by CCK-8 assay;key enzyme activities for osteogenic differentiation were analyzed by ALP stai-ning,and expression levels of osteoblast-related genes COL-1,Runx2,OPN,OCN,BMP-2 and ALP were detected by quantitative real-time PCR.In addition,implants were implanted into the femur of osteoporotic rats and bone volume on the implant surface was de-tected and quantified by Micro-CT.Results MT was successfully loaded on PEEK;the cell adhesion was better,and the proliferation activity and osteogenic differentiation ability were significantly higher than those of control group(P＜0.01).In the rat osteoporosis mod-el,there was more new bone formation around the modified PEEK implant(P＜0.01).Conclusion MT-modified PEEK implants have excellent biocompatibility and improve osteointegration in an osteoporotic environment.