The new synergistic education model integrating the “five arts” medical talent cultivation philosophy and the red doctor spirit could form a virtuous cycle of “spiritual guidance-technological breakthrough-spiritual reshaping” in the field of military medical education. Addressing the existing challenges in the process of military medical cadets’ training， such as mission awareness， humanistic care， battlefield rescue， and emergency response， this study proposed integrating the red doctor spirit， characterized by political steadfastness， healing the wounded and rescuing the dying， selfless devotion， relentless pursuit of excellence， and seeking truth and innovation， into the training system under the guidance of the “five arts” philosophy， including establishing a foundation through Daoist arts， forging the soul with benevolence， empowering through academia， tempering through technology， and nurturing the mind through artistry. A cultivation model was constructed featuring “moral education as the priority and cultivating through soul-forging； military spirit as the root and medical professionalism as the foundation and training for warfare； mastery in medicine for battlefield success and cultivating talent through rigorous scholarship.” Furthermore， through pathways including the optimization and implementation of the curriculum system， the enhancement and innovation of practical teaching， the development and training of the faculty team， and the improvement and innovation of the evaluation system， this model assisted in achieve the goal of cultivating compound talents with “the red medicine essence plus the five arts foundation.” These talents also built their foundation on the “five arts” philosophy， forge their spirit with the red doctor spirit， and was tempered with battlefield adaptability.

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.

As a third major discipline on par with internal medicine and surgery,interventional radiology is one of the key branches of modern medicine.The unique practicality and innovation of interventional radiology make it play an irreplaceable role in the diagnosis and treatment of diseases.In recent years,with the rapid development of technology and the updating of educational concepts,the teaching mode of interventional radiology is facing new challenges and opportunities.This article combines the clinical training methods adopted by interventional physicians in Europe and Germany,integrates imaging,anatomy and pathology teaching,strengthens the foundation,uses virtual reality(VR),augmented reality(AR)technology,and simulation training to enhance the practical ability of medical students.At the same time,with the help of online education platforms,the innovative methods and optimization strategies such as personalized learning program are implemented,which can greatly improve the teaching effectiveness of interventional radiology and provide useful references for teaching reform in this field.

BACKGROUND:Sema3A is a power secretory osteoprotective factor.However,studies about Sema3A-modified dental pulp stem cells(Sema3A-DPSCs)are rare. OBJECTIVE:To explore the osteogenic differentiation ability of Sema3A-DPSCs and their regulatory effect on the osteogenic differentiation of the pre-osteoblast cell line MC3T3-E1. METHODS:First,Sema3A-DPSCs were constructed using a lentivirus infection system carrying the Sema3A gene.Control lentivirus-treated DPSCs(Vector-DPSCs)were used as controls.Sema3A-DPSCs or Vector-DPSCs were co-cultured with proosteoblast line MC3T3-E1 at the ratio of 1∶1 and 1∶3 for 24 hours.Finally,the Sema3A-DPSCs,Vector-DPSCs and their co-cultured cells with MC3T3-E1 were cultured for osteogenic induction and differentiation.Osteogenic gene expression was detected by alkaline phosphatase staining,alizarin red staining and real-time quantitative RT-PCR to evaluate osteogenic differentiation ability. RESULTS AND CONCLUSION:(1)Sema3A mRNA and protein expression levels in Sema3A-DPSCs were significantly up-regulated.The level of secreted Sema3A in cell supernatant was up-regulated.(2)Compared with the Vector-DPSCs,mRNA expressions of osteogenic genes alkaline phosphatase,Runt-related transcription factor 2,osteocalcin and Sp7 transcription factors in Sema3A-DPSCs were up-regulated;the activity of alkaline phosphatase was enhanced,and the formation of mineralized nodules increased.(3)There were no obvious differences in proliferation between Sema3A-DPSCs and Vector-DPSCs.(4)Compared with MC3T3-E1/Vector-DPSCs co-culture system,the expression of MC3T3-E1 osteogenic genes was up-regulated,and the total alkaline phosphatase activity was enhanced and more mineralized nodules were formed in the MC3T3-E1/Sema3A-DPSCs co-culture system.(5)The results suggest that overexpression of Sema3A can enhance the osteogenic differentiation of DPSCs.Overexpression of Sema3A in DPSCs can promote osteogenic differentiation of MC3T3-E1 in the DPSCs/MC3T3-E1 co-culture system.

BACKGROUND:The reciprocal force generated by the molar distalization with clear aligners can lead to anchorage loss.The effect of arch shapes and missing second premolars on anchorage has not been reported. OBJECTIVE:To analyze the effect of arch shapes and missing second premolars on anchorage during molar distalization with clear aligners using the finite element method. METHODS:Cone-beam CT data from an adult male were acquired from the database to establish the maxilla-upper dentition-periodontium-rectangular attachment-clear aligner model.The distal movement amount designed on the bilateral second molars was set to 0.25 mm.First,there were two groups in the study:second premolar bilateral presence and absence groups.Then,four subgroups in each group were created:tapered arch,ovoid arch,square Class Ⅱ Division 1 arch,and Class Ⅱ Division 2 arch groups.The Ansys software was used to calculate the displacement of the anchorage tooth and the stress of the periodontal ligament. RESULTS AND CONCLUSION:Mesial tipping and extrusion of first molars and premolars,labial inclination and intrusion of anterior teeth occurred during the upper second molar distalization with clear aligners.When the bilateral second premolars were missing,the mesial displacement of first molars increased significantly while that of first premolars and anterior teeth decreased in all groups.The square Class Ⅱ Division 1 arch group showed the least anterior labial inclination,while the tapered arch group showed the most.There was no significant difference between the ovoid arch group and the tapered arch group.Moreover,the magnitude of tipping in the square Class Ⅱ Division 2 arch group was slightly higher than that in the Class Ⅱ Division 1 arch group.The stress of the periodontal ligament of the anchorage teeth was concentrated on the cervical and apical regions of the teeth.And the lowest stress level was detected in the square arch group.Compared with the other groups,the stress on the labial cervical area of the periodontal ligaments was also significantly relieved in the square arch group.To conclude,the square arch is more favorable in terms of anterior anchorage control and periodontal ligament stress distribution.Anterior labial inclination efficiency can be increased in cases of Class Ⅱ Division 2 by designing the anterior labial inclination in conjunction with molar distalization.If the second premolar is missing during molar distalization,it is not conducive to opening up the space in the area of the missing tooth.

BACKGROUND:The thin alveolar bone in the lower anterior region increases the risk of labial bone resorption when intruding the teeth with clear aligners.The effect of sagittal overcorrection design on the labiolingual control of mandibular anterior teeth intrusion has not been fully investigated. OBJECTIVE:To explore the effect of overcorrection on the changes in the displacement and stress of the mandibular anterior teeth,especially the cervical and apical regions. METHODS:Through a male volunteer cone-beam CT data,the three-dimensional reconstruction of the mandible and teeth was conducted in the MIMICS and GEOMAGIC software.Moreover,the models of periodontal ligaments,attachments,and appliances were created in the SOLIDWORKS software.First,the study was divided into canine intrusion group and incisor intrusion group.Then,the overcorrection(0°,1°,2°)was designed on the bilateral mandibular central and lateral incisors.A total of six models were established.The models were assembled and imported into the ANSYS software to analyze and calculate the displacement and stress level. RESULTS AND CONCLUSION:(1)In the canine intrusion group,canines intruded and tipped lingually while incisors extruded and tipped lingually.In the incisor intrusion group,canines extruded and tipped lingually while incisors intruded and tipped lingually.(2)Without overcorrection,the incisors necks moved lingually while apexes moved labially.With overcorrection,the incisors tended to be upright,followed by labial tilt.The least cervical and apical displacements were detected under 1° overcorrection.(3)With overcorrection,the incisal cervical stress concentration area shifted from labial to lingual in the canine intrusion group,whereas the stress concentration area shifted from lingual to labial in the incisor intrusion group.(4)The incisors tended to tilt lingually when intruding the mandibular anterior teeth with clear aligners.The sagittal overcorrection design was conductive to maintain the stable position of incisors.However,the amount of overcorrection should be moderate.Excessive overcorrection might increase the labial inclination tendencies of incisors.

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.