ObjectiveTo investigate the effects of Toll-like receptor 4 （TLR4） inhibition on autophagy and oxidative stress， as well as its regulatory role and mechanism in the inflammatory response in a mouse model of gastric ulcer. MethodsSixty adult male Kunming mice were equally divided into five groups： control group， model group， model+TLR4-IN-C34 group， model+TLR4-IN-C34+3-MA group， and model+TLR4-IN-C34+H₂O₂ group. Except for the control group， all groups were administered 40 mg/kg indomethacin via gavage. Treatment groups received injections every three days， and all groups were treated for 30 days. Mice were euthanized by cervical dislocation， and gastric tissues were collected. Gastric ulcer scores were assessed， and pathological changes were evaluated via HE staining and scoring. Serum levels of interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）， advanced oxidation protein products （AOPP）， and prostaglandin E2 （PGE2）， as well as gastric tissue levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and reduced glutathione （GSH）， were measured using ELISA. Western blot analysis was performed to detect the expression of TLR4， microtubule-associated protein 1 light chain 3-Ⅰ （LC3-Ⅰ），LC3-Ⅱ， autophagy-related protein 5 （Atg5）， Beclin-1， nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， and NAD（P）H quinone dehydrogenase 1 （NQO1） in gastric tissues. Immunofluorescence staining was used to assess LC3-Ⅱ fluorescence intensity in gastric tissues. ResultsCompared with the control group， the model group exhibited upregulation of ulcer scores， HE staining scores， TLR4， IL-1β， IL-6， TNF-α， and AOPP levels， and downregulation of LC3-Ⅱ fluorescence intensity， PGE2 levels， Atg5， Beclin-1， nuclear Nrf2， HO-1， NQO1 levels， and the LC3-Ⅱ/Ⅰ ratio （all P < 0.05）. Compared with the model group， the model+TLR4-IN-C34 group showed downregulation of ulcer scores， HE staining scores， TLR4， IL-1β， IL-6， TNF-α， and AOPP levels， and upregulation of LC3-Ⅱ fluorescence intensity， PGE2 levels， Atg5， Beclin-1， nuclear Nrf2， HO-1， NQO1 levels， and the LC3-Ⅱ/Ⅰ ratio （all P < 0.05）. Compared with the model+TLR4-IN-C34 group， the model+TLR4-IN-C34+3-MA group exhibited upregulation of ulcer scores， HE staining scores， IL-1β， IL-6， TNF-α， and AOPP levels， and downregulation of LC3-Ⅱ fluorescence intensity， PGE2 levels， Atg5， Beclin-1， and the LC3-Ⅱ/Ⅰ ratio （all P < 0.05）. Compared with the model+TLR4-IN-C34 group， the model+TLR4-IN-C34+H₂O₂ group showed upregulation of ulcer scores， HE staining scores， IL-1β， IL-6， TNF-α， and AOPP levels， and downregulation of PGE2 levels and nuclear Nrf2， HO-1， and NQO1 levels （all P < 0.05）. ConclusionInhibition of TLR4 ameliorates gastric ulcer symptoms and suppresses the inflammatory response in mice by upregulating autophagy and reducing oxidative stress.

Objective To observe the origin and course of the obturator artery(OA),so as to provide anatomical reference for reducing hemorrhage during pelvic surgery and pubic fracture fixation.Methods A total of 65 human hemi-pelvises specimens with intact structure were dissected to observe the origin,course and other variations of OA.Measure the length of the inner section of OA basin and the outer diameter at the origin,etc.Results OA originated from the internal iliac artery in 57 cases(87.7%),including 3 cases(4.6%)of the superior gluteal artery,5 cases(7.7%)of the inferior gluteal artery,3 cases(4.6%)of the external iliac artery and 5 cases(7.7%)of the inferior epigastric artery.OA participated in the formation of the arterial trunk in 3 cases(4.6%).The length of the pelvic segment of the OA in male and female was(50.87±15.41)mm and(51.71±14.19)mm,respectively,with no statistically significant difference between them(P>0.05).The outer diameters at the origin of the OA in male and female were(2.79±1.05)mm and(2.35±0.86)mm,and there was no statistically significant difference between them(P>0.05).Conclusion OA mainly originated from the anterior trunk of the internal iliac artery,with a few OA originated from the branches of the posterior trunk or the inferior epigastric artery,or participated in the formation of the arterial trunk.In pelvic surgery involving OA area,attention should be paid to the length of its pelvic segment and the outer diameter at the origin of OA,so as to better locate and protect blood vessels during surgery.

Inflammatory response,immunosuppression,and drug sensitivity have been reported to have a significant correlation with the disulfidptosis levels in cancer patients.However,the value of disulfidpto-sis in colorectal cancer therapy remains unclear.Therefore,we classified the CRC cells into different cell types using single-cell sequencing data and cell-specific markers and analyzed their relationship with the cell disulfidptosis level.We found that the high disulfidptosis regions were concentrated in epithelial-like CRC cells.Further exploration using the disulfidptosis and programmed cell death 1 inhibitor therapy treated differential expression genes indicated that CRC patients with high disulfidptosis levels exhibited a lower risk profile and increased sensitivity to immunotherapy.By using the spatial transcriptomic analy-sis,we found that ubiquinol-cytochrome c reductase core protein 1(UQCRC1),a disulfidptosis-related gene,is highly expressed in epithelial-like CRC cells and co-localized with immune-infiltrated tumor re-gions.Additional bioinformatic analyses and experimental validation further confirmed that UQCRC1 was downregulated in CRC tissues.Overexpression of UQCRC1 suppressed CRC cell proliferation and migra-tion.These findings indicate that UQCRC1 is a potential target for CRC diagnosis and treatment.

Objective This study investigated feasible cases and their significance in promoting the"generalized"development of inspection through digital-intelligent equipment.Methods A qualitative research approach was used,involving interviews conducted between February 2025 and March 2025 with experts in traditional Chinese medicine diagnostics,clinical research methodology,medical engineering integration,and related disciplines,using both online and offline methods.In accordance with the Consolidated Criteria for Reporting Qualitative Research,feasible cases involving the specific application of digital equipment in various parts of observation were collected through item enrichment.The significance of extending observation capabilities via these cases was analyzed,along with the overall implications of integrating digital technologies with traditional inspection method.Results Interviews were completed with 11 experts from domestic universities and research institutes in the fields of traditional Chinese medicine diagnosis,medical engineering integration,and related disciplines.A total of 78 feasible cases of digital-intelligent inspection were identified,along with 69 insights regarding the significance of enhancing the inspection capabilities.These insights were synthesized into two dimensions and 23 holistic meanings.The first dimension is to expand the scope of inspection,including obtaining internal environmental characteristics,observing external environmental characteristics,expanding thermodynamic characteristic data,and crossing time and space.The second dimension is to improve the quality of observation and diagnosis information collection and analysis,including 19 specific meanings,such as standardized collection environment,objective quantification,and refined observation.Conclusion Digital-intelligent equipment plays a significant role in expanding the scope of inspection content and achieving high-quality acquisition and analysis of extensive inspection information.These advancements extend and enrich the capabilities of traditional inspection method in traditional Chinese medicine.

Objective:To investigate the expression of miRNAs in thymus of patients with myasthenia gravis(MG)and the re-lated mechanism of action,so as to provide theoretical and experimental basis for clinical diagnosis and treatment.Methods:miRNA microarray technology was used to analyze the differential miRNA expression in MG patients thymus.Fluorescence quantitative PCR and in situ hybridization were used to verify the expression of miR-19a-3p in thymus tissue.The TALL-104 cell line was transfected with miR-19a-3p mimics to observe the effects of miR-19a-3p on cell proliferation,apoptosis and expressions of related molecules(BCL2 and SOCS3).Results:Compared to normal thymus tissue,a total of 282 differentially expressed miRNAs were detected in the thymus of MG patients,among which 103 were up-regulated and 179 were down-regulated.The target genes of differentially expressed miRNAs were mainly related to nuclear molecules,cytoplasmic membrane-like structures and organelle related molecules.Quantita-tive fluorescence PCR and in situ fluorescence hybridization confirmed that the expression of miR-19a-3p in MG patients thymus was significantly lower than that in normal control group.Compared with the control group,miR-19a-3p mimics transfection could signifi-cantly inhibit the apoptosis of TALL-104 cells,increase the expression of BCL2 and decrease the expression of SOCS3(P<0.05).Conclusion:The expression of miRNA in the thymus of MG patients is significantly different from that of non-MG patients,and miR-19a-3p inhibits T cell apoptosis through up-regulation of BCL2 and down-regulation of SOCS3.

Objective To observe the origin and course of the obturator artery(OA),so as to provide anatomical reference for reducing hemorrhage during pelvic surgery and pubic fracture fixation.Methods A total of 65 human hemi-pelvises specimens with intact structure were dissected to observe the origin,course and other variations of OA.Measure the length of the inner section of OA basin and the outer diameter at the origin,etc.Results OA originated from the internal iliac artery in 57 cases(87.7%),including 3 cases(4.6%)of the superior gluteal artery,5 cases(7.7%)of the inferior gluteal artery,3 cases(4.6%)of the external iliac artery and 5 cases(7.7%)of the inferior epigastric artery.OA participated in the formation of the arterial trunk in 3 cases(4.6%).The length of the pelvic segment of the OA in male and female was(50.87±15.41)mm and(51.71±14.19)mm,respectively,with no statistically significant difference between them(P>0.05).The outer diameters at the origin of the OA in male and female were(2.79±1.05)mm and(2.35±0.86)mm,and there was no statistically significant difference between them(P>0.05).Conclusion OA mainly originated from the anterior trunk of the internal iliac artery,with a few OA originated from the branches of the posterior trunk or the inferior epigastric artery,or participated in the formation of the arterial trunk.In pelvic surgery involving OA area,attention should be paid to the length of its pelvic segment and the outer diameter at the origin of OA,so as to better locate and protect blood vessels during surgery.

Objective:To evaluate the clinical efficacy, safety and treatment persistence of upadacitinib in Crohn's disease (CD) patients.Methods:The single-center retrospective cohort study was conducted. The patients with moderate-to-severe active CD initiating upadacitinib therapy from November 2023 to November 2024 in Nanjing Drum Tower Hospital were collected through searching the electronic medical records and paper-based patient databases. The primary outcome was the clinical remission rate at week 12. Secondary outcomes included the clinical response rate at week 12; clinical response and remission rates at weeks 4, 24 and 48; biomarker (fecal calprotectin or C-reactive protein) remission rates at all time points; as well as endoscopic remission and response rates, treatment persistence and safety evaluation.Results:A total of 44 CD patients were included, comprising 24 males (54.5%) and 20 females (45.5%). The median age was 33 (25, 40) years. The baseline Crohn's disease activity index (CDAI) score was 260.5 (225.9, 550.0) points. Patients had previously received a median of 2 (1, 2) biologic treatments. All 44 patients completed the 12-week induction therapy. With a median follow-up of 30.00 (16.25, 46.25) weeks, the clinical remission rate was 50.0% (22/44) at week 12. The clinical remission rate, clinical response rate, and biomarker remission rate were 52.3% (23/44), 88.6% (39/44) and 72.7% (32/44) respectively at week 4, and the clinical response rate and biomarker remission rate were 88.6% (39/44) and 77.2% (34/44) respectively at week 12. The clinical remission rates, clinical response rates and biomarker remission rates evolved to 43.3% (13/30), 86.7% (26/30) and 80.0% (24/30) at week 24, and further to 44.4% (4/9), 77.8% (7/9) and 77.8% (7/9) at week 48. During the follow-up period, 13 CD patients completing endoscopic evaluation, endoscopic remission and response rates were 30.8% and 23.1% respectively. CD-related surgery rate was 4.5% (2/44). Safety analysis demonstrated that the overall adverse events rate was 56.8% (25/44) including 7 patients with serious adverse events. A total of 8 patients discontinued treatment, among which 3 were due to primary loss of response, 1 due to secondary loss of response, 2 due to drug-related adverse events alone, and 2 due to concurrent primary loss of response and adverse events. The Kaplan-Meier curve for treatment persistence showed that among 39 CD patients who achieved clinical response at week 12, the continued treatment rates were 90.3% at week 12 and 85.3% at week 24 of follow-up. Two patients (5.6%) received dose escalation of upadacitinib, both of whom achieved clinical remission.Conclusion:Real-world research data demonstrate that upadacitinib exhibits significant clinical efficacy and a favorable safety profile in the treatment of moderate-to-severe active CD patients with prior biologic exposure, and no new unexpected adverse events are identified.

Aim To investigate the effect of hypobaric hypoxia on macrophage necroptosis and atherosclerotic plaque instability and explore the underlying mechanisms.Methods Mouse bone marrow-derived macrophages were i-solated and cultured,and divided into control group(21％oxygen concentration)and hypoxia group(3％oxygen concen-tration).After 48 hours,cell necroptosis was detected,and the expression of cell necroptosis related proteins was deter-mined by Western blot.Healthy male ApoE-/-mice were randomly divided into control group and hypobaric hypoxia group.After the intervention for 16 weeks,the plasma lipids and inflammatory cytokines were measured,the areas of ath-erosclerotic plaque and necrotic core were evaluated by HE staining.The content of plaque collagen was detected by Mas-son staining.The number of macrophages in the plaque and the expression of necrotic apoptosis related proteins were de-tected by immunohistochemical staining and Western blot.Results Hypoxia induced increased necrotic apoptosis of macrophages(P＜0.01),while necroptotic inhibitor necrostatin-1(Nec-1)reduced hypoxia induced cell death(P＜0.05);hypoxia leads to a decrease in the expression of adenosine deaminase acting on RNA 1(ADAR1)in macrophages(P＜0.01),and an increase in the expression of Z-DNA binding protein 1(ZBP1),phosphorylated receptor-interacting serine/threonine-protein kinase(p-RIPK3),and phosphorylated mixed lineage kinase domain-like protein(p-MLKL)(all P＜0.01).Compared with the control group,the plasma lipid levels of ApoE-/-mice in the hypobaric hypoxia group did not change significantly(P＞0.05),the plasma inflammatory cytokines(TNF-α,IL-1β,IL-6 and MCP-1)increased(all P＜0.05),the area of atherosclerotic plaque increased(P＜0.05),the area of plaque necrotic core increased,the content of plaque collagen decreased,the number of macrophages increased,the expression of ADAR1 decreased,and the expres-sion of ZBP1 and p-MLKL increased(all P＜0.01).Conclusion Hypobaric hypoxia causes the imbalance of A-DAR1/ZBP1 expression in macrophages,activates RIPK3/MLKL signaling pathway,promotes macrophage necroptosis,in-creases the area of plaque necrosis core,and leads to increase instability of atherosclerotic plaque.

Inflammatory response,immunosuppression,and drug sensitivity have been reported to have a significant correlation with the disulfidptosis levels in cancer patients.However,the value of disulfidpto-sis in colorectal cancer therapy remains unclear.Therefore,we classified the CRC cells into different cell types using single-cell sequencing data and cell-specific markers and analyzed their relationship with the cell disulfidptosis level.We found that the high disulfidptosis regions were concentrated in epithelial-like CRC cells.Further exploration using the disulfidptosis and programmed cell death 1 inhibitor therapy treated differential expression genes indicated that CRC patients with high disulfidptosis levels exhibited a lower risk profile and increased sensitivity to immunotherapy.By using the spatial transcriptomic analy-sis,we found that ubiquinol-cytochrome c reductase core protein 1(UQCRC1),a disulfidptosis-related gene,is highly expressed in epithelial-like CRC cells and co-localized with immune-infiltrated tumor re-gions.Additional bioinformatic analyses and experimental validation further confirmed that UQCRC1 was downregulated in CRC tissues.Overexpression of UQCRC1 suppressed CRC cell proliferation and migra-tion.These findings indicate that UQCRC1 is a potential target for CRC diagnosis and treatment.

Objective:To compare the changes in spherical equivalent (SE) and axial length (AL) between children with axial myopia and refractive myopia.Methods:A prospective cohort study was conducted.A total of 1 738 students from grades 1 to 6 were recruited from two consistent 9-year schools in the Binhai New Area of Tianjin using cluster random sampling.Visual acuity, refractive status, and ocular biological parameters were measured from February to May in 2018 and 2021.Participants were categorized into subgroups as follows: low, moderate, and high myopia based on SE; longer AL group and shorter AL groups based on AL; and steeper cornea and flatter cornea groups based on corneal curvature radius (CCR). Myopic children were further classified into the following groups: axial myopia (longer AL and flatter cornea), refractive myopia (shorter AL and steeper cornea), mixed myopia (longer AL and steeper cornea), and non-axial non-refractive myopia (shorter AL and flatter cornea). Changes in SE (ΔSE) and AL (ΔAL) at the end of the follow-up period were compared among the different classification groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY-39). Written informed consent was obtained from the guardians of all participants.Results:The ΔSE in the longer AL group was (-1.57±1.52)D, which was significantly greater than (-1.17±1.47)D in the shorter AL group ( t=3.99, P<0.01). The ΔAL in the steeper cornea group was (0.92±0.50)mm, which was significantly greater than (0.86±0.54)mm in the flatter cornea group ( t=-2.12, P=0.04). Among children aged 10-12 years, males, and the low myopia, SE progression was faster in those with longer AL compared to shorter AL, with statistically significant differences ( t=2.66, 3.31, 3.90; all P<0.05). In children aged 10-12 years, AL growth was faster in the longer AL group than in the shorter AL group, with a statistically significant difference ( t=-1.29, P=0.04). Among females and the low myopia, AL growth was faster in those with steeper corneas than in those with flatter corneas, with statistically significant differences ( t=-3.22, -2.43; both P<0.05). Refractive myopia had a smaller ΔSE than axial myopia and the difference was statistically significant ( P<0.05). Within the low myopia, SE progression was greater in axial myopia than in refractive myopia, with a statistically significant difference ( P<0.05). Conclusions:Among myopic children, those with longer axial lengths exhibit faster SE progression, while those with steeper corneas show faster axial elongation.Among children with low myopia, axial myopia is associated with a greater risk of SE progression than refractive myopia.