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 investigate the causal relationship between gut microbiota and viral pneumonia,as well as the underlying mechanisms,using two-sample and two-step Mendelian randomization(MR)approaches,thereby providing novel insights for the prevention and treatment of viral pneumonia.Methods All data were obtained from publicly available genome-wide association studies(GWAS)pooled datasets,including gut microbiota data from the MiBioGen Consortium and the Netherlands Microbiome Project,viral pneumonia data from the FinnGen R10 database,and plasma metabolome data from the publicly available GWAS Catalog.Instrumental variables(IVs)were extracted according to the predefined threshold values.MR analyses were conducted using inverse variance weighting(IVW),MR-Egger,weighted median(WME),weighted mode(WM),and Bayesian-weighted Mendelian randomization(BWMR)methods.Reverse MR analysis was performed to determine whether there was a reverse association.Two-step MR analysis was used to explore the potential mediating role of plasma metabolites,and a series of sensitivity analyses were performed to test the stability of the results.Results Among 196 gut microbiota taxa from the MiBioGen consortium GWAS,11 taxa were associated with viral pneumonia.An increase in the abundance of 4 taxa increased the risk of viral pneumonia,while an increase in the abundance of 7 taxa had a protective effect against viral pneumonia.Among the 207 gut microbiota taxa from the Dutch Microbiome Project GWAS data,10 taxa were associated with viral pneumonia,with 6 risk-increasing and 4 protective taxa identified.Mediation analysis results showed that the causal effect of Defluviitaleaceae on viral pneumonia(OR=0.708,95%CI 0.540-0.929,P=0.013)was mediated to some extent by the N6-acetyllysine levels,with a mediation ratio of 18.4%.Sensitivity analyses did not reveal significant heterogeneity or horizontal pleiotropy.Conclusions Specific gut microbiota are causally associated with viral pneumonia and show potential differences across different populations;the protective effect of Defluviitaleaceae against viral pneumonia may be mediated by the N6-acetyllysine levels.Targeting metabolites may become a potential therapeutic approach for viral pneumonia.

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.

Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.

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.

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.

Objective:To investigate the influencing factors for safe abdominal wall recons-truction in giant ventral hernia based on imaging and clinical features.Methods:The retrospective case-control study was conducted. The imaging and clinical data of 369 patients with giant ventral hernia who were admitted to Beijing Chaoyang Hospital of Capital Medical University from January 2017 to December 2023 were collected. There were 182 males and 187 females, aged (63±14)years. Among 369 patients, 311 cases underwent safe abdominal wall reconstruction and 58 underwent high-risk abdominal wall reconstruction. Observation indicators: (1) clinical and imaging characteris-tics; (2) analysis of influencing factors for safe abdominal wall reconstruction in giant ventral hernia. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametic rank sum test. Logistic regression, Lasso regression, and random forest analyses were used for influencing factors analysis. Results:(1) Clinical and imaging characteristics. There were significant differences between patients with safe and high-risk abdominal wall reconstruction in presence of a definite secondary abdominal cavity, maximum axial diameter of the defect, maximum transverse diameter of the defect, abdominal wall defect area, component separation index (CSI), abdominal wall opening angle, ratio of CSI, muscle grayscale at the defect, hernia sac volume, hernia sac-abdominal cavity volume ratio, and defect long-axis-to-abdominal cavity ratio ( P<0.05). (2) Analysis of influencing factors for safe abdominal wall reconstruction in giant ventral hernia. Results of Logistic regression analysis showed that presence of a definite secondary abdominal cavity, maximum axial diameter of the defect, maximum transverse diameter of the defect, abdominal wall defect area, CSI, abdominal wall opening angle, ratio of CSI, muscle grayscale at the defect (inner-superior or right), hernia sac volume, hernia sac-abdominal cavity volume ratio, and defect long-axis-to-abdominal cavity ratio were factors associated with safe abdominal wall reconstruction in giant ventral hernia [ odds ratio ( OR)=3.955, 1.189, 1.395, 1.127, 2.006, 1.042, 1.095, 0.881, 1.102, 1.109, 1.601, 95% confidence interval ( CI) as 2.179-7.178, 1.113-1.271, 1.267-1.537, 1.090-1.166, 1.651-2.437, 1.014-1.071, 1.066-1.125, 0.798-0.972, 1.057-1.148, 1.067-1.153, 1.343-1.909]. The top 3 factors for discriminative performance were abdominal wall CSI, ratio of CSI, maximum transverse diameter of the defect and the abdominal wall defect area, with area under the curve of 0.794, 0.777, 0.772, and 0.772, respectively. Results of Lasso regression analysis showed that body mass index, smoking, chronic obstructive pulmonary disease, American Society of Anesthesiologists classification, presence of a definite secondary abdominal cavity, abdominal wall defect area, abdominal wall opening angle, abdominal wall CSI, muscle grayscale at the defect (inner-superior or right), and hernia sac-to-abdominal cavity volume ratio were associated factors with safe abdominal wall reconstruction in giant ventral hernia (coefficients as -0.002, 0.003, 0.007, 0.014, 0.021, 0.077, 0.023, 0.059, -0.010, 0.037). Results of random forest analysis showed the abdominal wall CSI, maximum transverse diameter of the defect, abdominal wall defect area, ratio of defectr opening angle, maximum axial long diameter of the defect, hernia sac-to-abdominal cavity volume ratio, abdominal wall opening angle, defect long-axis-to-abdominal cavity ratio, muscle grayscale at the defect (inner-superior or right), and body mass index as associated factors with safe abdominal wall reconstruction in giant ventral hernia (importance score=0.092, 0.089, 0.079, 0.056, 0.051, 0.047, 0.045, 0.039, 0.038, 0.035). Conclusion:Abdominal wall CSI, abdominal wall defect area, abdominal wall opening angle, muscle grayscale at the defect (inner-superior or right), and hernia sac-to-abdominal cavity volume ratio are factors associated with safe abdominal wall reconstruction in giant ventral hernia.

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 aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*