Objective To explore whether there is a causal relationship between intestinal flora and esophageal cancer. Methods Summary statistics of intestinal flora and esophageal cancer were obtained from the Genome-wide Association Studies (GWAS) database. Five methods, including inverse variance weighted (IVW), weighted median estimation, Mendelian randomization (MR)-Egger regression, single mode, and weighted mode, were used for analysis, with IVW as the main analysis method. Sensitivity analysis was used to evaluate the reliability of MR results. Results In the IVW method, Oxalobacteraceae [OR=1.001, 95%CI (1.000, 1.002), P=0.023], Faecalibacterium [OR=1.001, 95%CI (1.000, 1.002), P=0.028], Senegalimassilia [OR=1.002, 95%CI (1.000, 1.003), P=0.006] and Veillonella [OR=1.001, 95%CI (1.000, 1.002), P=0.018] were positively correlated with esophageal cancer, while Burkholderiales [OR=0.999, 95%CI (0.998, 1.000), P=0.002], Eubacterium oxidoreducens [OR=0.998, 95%CI (0.997, 0.999), P=0.038], Romboutsia [OR=0.999, 95%CI (0.998, 1.000), P=0.048] and Turicibacter [OR=0.998, 95%CI (0.997, 0.999), P=0.013] were negatively correlated with esophageal cancer. Sensitivity analysis showed no evidence of heterogeneity, horizontal pleiotropy and reverse causality. Conclusion Oxalobacteraceae, Faecalibacterium, Senegalimassilia and Veillonella increase the risk of esophageal cancer, while Burkholderiales, Eubacterium oxidoreducens, Romboutsia and Turicibacter decrease the risk of esophageal cancer. Further studies are needed to explore how these bacteria affect the progression of esophageal cancer.

Objective To develop and validate a machine learning model based on preoperative clinical characteristics, laboratory indices, and radiological features for the non-invasive prediction of spread through air spaces (STAS) in patients with early-stage lung adenocarcinoma. Methods Preoperative data from patients with early-stage lung adenocarcinoma who underwent surgical resection at Northern Jiangsu People's Hospital between January 2020 and August 2025 were retrospectively collected. The data included clinical characteristics, laboratory indices, and radiological features. Patients were divided into a STAS-positive and a STAS-negative group based on postoperative pathological findings. The dataset was randomly split into a training set and a testing set at a 7 : 3 ratio. Feature variables were selected using the maximum relevance and minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator (LASSO) regression. Five machine learning models were constructed: logistic regression (LR), random forest (RF), support vector machine (SVM), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The shapley additive explanations (SHAP) method was employed to interpret the optimal prediction model. Results A total of 377 patients were included, comprising 177 (46.9%) males and 200 (53.1%) females, with a mean age of (63.31±9.73) years. There were 261 patients in the training set and 116 patients in the testing set. In the training set, statistically significant differences were observed between the STAS-positive group (n=130) and STAS-negative group (n=131) across multiple features, including age, sex, neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), clinical T stage, and maximum solid component diameter (P<0.05). A final set of 10 feature variables was selected by combining mRMR and LASSO regression, and five machine learning models (LR, RF, SVM, LightGBM, XGBoost) were developed. The XGBoost model demonstrated optimal performance in both the training and testing sets, achieving AUCs of 0.947 [95%CI (0.920, 0.975)] and 0.943 [95%CI (0.894, 0.993)], respectively. DCA indicated that the XGBoost model provided a high net clinical benefit across a wide range of threshold probabilities. SHAP analysis revealed that the vessel convergence sign, clinical T stage, age, consolidation-to-tumor ratio (CTR), and MLR were the features with the highest contributions to STAS prediction. Conclusion The XGBoost model effectively predicts preoperative STAS status in early-stage lung adenocarcinoma, exhibiting excellent discriminative performance and good clinical interpretability. Key predictors such as the vessel convergence sign, clinical T stage, age and CTR provide a crucial reference for preoperative risk assessment and the individualized selection of surgical strategies, ultimately benefiting patients.

Objective To explore the role of DNAJC5B in immunotherapy for esophageal squamous cell carcinoma (ESCC). Methods Using the ESCC dataset from The Cancer Genome Atlas (TCGA) database, genes correlated with DNAJC5B expression were identified through Pearson correlation analysis. Subsequently, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Additionally, single-cell RNA sequencing (scRNA-seq) data were utilized to analyze the expression of DNAJC5B in different T-cell subsets. The prognostic value of DNAJC5B was evaluated using Kaplan-Meier survival curves, receiver operating characteristic curves, and Cox proportional hazards models. Results DNAJC5B was highly expressed in patients with advanced-stage ESCC, particularly in males. GO and KEGG analyses revealed a significant correlation between DNAJC5B expression and immune-related processes, such as the adaptive immune response and cell surface receptor signaling pathways. Single-cell analysis results indicated that DNAJC5B expression was positively correlated with immune function, with DNAJC5B predominantly accumulating in CD8+ T cells. Kaplan-Meier survival curves showed that the median survival time for patients with high DNAJC5B expression was 681 days, significantly shorter than the 1 361 days for patients with low expression (P<0.05). Furthermore, univariate and multivariate independent prognostic analyses demonstrated that DNAJC5B was an independent risk factor, with hazard ratios (HRs) of 3.577 and 4.114, respectively (both P<0.05). Conclusion DNAJC5B may play a crucial immunomodulatory role in ESCC, particularly in regulating CD8+ T-cell function and tumor immune escape. These findings support the potential of DNAJC5B as a biomarker for the treatment and prognostic assessment of ESCC.

As an extension of the central nervous system, the retina is the only tissue in the body that allows direct in vivo observation of both neural and vascular structures, offering a unique non-invasive window for the assessment of cerebral neurovascular diseases. Recent studies have shown that multimodal imaging techniques—such as fundus photography, optical coherence tomography(OCT), and OCT angiography(OCTA)—enable quantitative analysis of retinal indicators including vascular caliber, fractal dimension, retinal nerve fiber layer thickness, and microvascular density. These metrics can, to some extent, reflect the severity and progression risk of cerebrovascular and neurodegenerative diseases such as stroke, Alzheimer's disease, and Parkinson's disease. Consequently, retinal imaging holds promise as a powerful tool for early screening, risk stratification, and treatment monitoring. This article systematically reviews the application of retinal imaging technologies in the diagnosis and management of cerebral neurovascular disorders, with a particular focus on the important role of artificial intelligence(AI)-driven image analysis in enhancing screening efficiency, improving risk assessment accuracy, and promoting multidisciplinary collaborative care, thereby providing insights for clinical translation.

In recent years, the global prevalence of myopia has continued to rise. In China, myopia shows a trend toward widespread prevalence, earlier onset, and greater severity, and high myopia poses a serious threat to adolescent ocular health. Orthokeratology is currently one of the most effective clinical interventions for slowing myopia progression, yet its exact mechanisms of action have not been fully elucidated. Focusing on the various hypotheses proposed in the literature, this review summarizes the role of peripheral retinal defocus, choroidal thickness and blood flow, higher-order aberrations, accommodation, and biomechanics in myopia control with orthokeratology lenses. Specifically, the induction of peripheral myopic defocus through the reverse-geometry design of orthokeratology lenses constitutes the core mechanism by which axial elongation is slowed. After lens wear, choroidal thickening and increased blood perfusion improve the nutritional supply to the outer retina and inhibit scleral remodeling. Increases in higher-order aberrations, such as spherical aberration and coma, expand the depth of focus and reduce accommodative lag. Improvements in accommodative function and alterations in corneal biomechanics also act synergistically. These mechanisms are interrelated and act in a cascading manner to jointly inhibit axial elongation. This review aims to provide a theoretical basis for a deeper understanding of the mechanisms of orthokeratology lenses and to offer clinical references for individualized lens fitting, optimized lens design, and future research on myopia prevention and control.

ObjectiveTo investigate the effect of trophoblast-derived mesenchymal stem cell （T-MSC） on concanavalin A （Con A）-induced immune-mediated liver injury in mice， as well as its association with the changes in inflammatory response. MethodsMorphological assessment， flow cytometry， and tri-lineage differentiation assay were used to observe the biological characteristics of T-MSC. In the pilot experiment， mice were divided into PBS group， T-MSC monotherapy group， and Con A groups at a concentration of 10， 15， or 20 mg/kg to evaluate the safety of T-MSC monotherapy on liver function and determine the appropriate dose for modeling. In the formal experiment， mice were divided into healthy control group （HC group）， Con A group， and Con A+T-MSC group， with 5 mice in each group. The mice were given injection of Con A （15 mg/kg） via the caudal vein to establish a mouse model of immune-mediated liver injury， while the mice in the T-MSC monotherapy group were given transfusion of 1×10⁶ T-MSCs via the caudal vein at 3 hours after modeling， and samples were collected 12 hours later. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and lactate dehydrogenase （LDH） were measured； liver histopathological changes were observed， and Ishak inflammatory activity score and inflammatory necrosis area were assessed； the serum levels of inflammatory cytokines were measured； transcriptome sequencing， immunofluorescence assay， and Western blot were used to measure the changes in inflammation-related molecules in liver tissue. The Shapiro-Wilk test was used to assess the normality of continuous data， and the homogeneity of variance test was also performed； a one-way analysis of variance was used for comparison of normally distributed data with homogeneity of variance between multiple groups， and the Tukey’s post-hoc test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed data with heterogeneity of variance between multiple groups， and the Wilcoxon test was used for further comparison between two groups. ResultsT-MSC had a long spindle shape， showed the characteristics of fibroblast-like morphology and adherent growth， and possessed the osteogenic， chondrogenic， and adipogenic differentiation abilities. Flow cytometry showed high expression levels of CD90， CD105， and CD73 in T-MSC， with a positive rate of 96.8%， 99.0%， and 99.9%， respectively， while there was low or no expression of CD31， human leukocyte antigen DR， CD45， and CD34， with a positive rate of 0.120%， 0， 0.061%， and 0， respectively. Administration of T-MSC alone did not cause obvious abnormalities in ALT， AST， or LDH. Con A at the concentrations of 10， 15， and 20 mg/kg all increased the serum levels of biochemical parameters for liver injury in a dose-dependent manner， with mortality observed in the 20 mg/kg group. In the formal experiment， compared with the HC group， the Con A group had significant increases in the serum levels of ALT， AST， and LDH （P<0.01）， and after T-MSC treatment， there were significant reductions in these markers compared with the Con A group （P<0.01）. HE staining showed that the Con A group had disordered structure of the liver， accompanied by marked inflammatory cell infiltration and focal/patchy necrosis， and these pathological changes were alleviated after T-MSC treatment. Compared with the HC group， the Con A group had significant increases in Ishak score and the percentage of inflammatory necrosis area （P<0.001）， while there were significant reductions in these indicators after T-MSC treatment compared with the Con A group （P<0.01）. ELISA showed that compared with the HC group， the Con A group had significant increases in the serum levels of interleukin-21 （IL-21）， interleukin-1β （IL-1β）， interleukin-2 （IL-2）， interleukin-17A （IL-17A）， and tumor necrosis factor-α （TNF-α） （P<0.05）， and there were significant reductions in these markers after T-MSC treatment compared with the Con A group （P<0.05）， with no significant differences in IL-21， IL-1β， IL-17A， and TNF-α compared with the HC group （P>0.05）； although there was a significant reduction in the level of IL-2， the Con A+T-MSC group still had a significantly higher level of IL-2 than the HC group （P=0.001）. In contrast， compared with the HC group， the Con A group had a significant increase in IL-10 （P<0.05）， with a further increase after T-MSC treatment （P<0.05）. The transcriptome analysis showed that T-MSC treatment downregulated the expression of the inflammation- and chemokine-related genes including Ccl2， Cxcl10， Il-21， and Il-6 and inhibited the inflammation-related pathways such as TNF， IL-17， nuclear factor-κB， and JAK-STAT. Immunofluorescence assay showed that compared with the HC group， the Con A group had a significant increase in the expression of IL-21 in the liver （P<0.001）， and there was a significant reduction in IL-21 after T-MSC treatment compared with the Con A group （P<0.001）； the results of Western blot showed the same trend. ConclusionT-MSC can alleviate Con A-induced immune-mediated liver injury in mice， as evidenced by the improvement in liver biochemical parameters， the alleviation of histopathological damage， and the overall downregulation of inflammation-related molecules. T-MSC exerts marked anti-inflammatory and immunomodulatory effects in this model， and IL-21 shows a significant change in inflammatory response and can be used as a candidate molecule for further investigation.

AIM:To investigate the potential mechanisms by which cell division cycle protein 42(Cdc42)regulates endothelial-mesenchymal transition(EndMT)in pulmonary hypertension(PH).METHODS:The pulmonary hypertension(PH)model was established using Sugen-5416 combined with hypoxia.Twenty-four C57BL/6 mice were ran-domly divided into four groups:normoxia control(CON)group,normoxia+ML141(CON+ML141)group,Sugen-5416+hypoxia(SuHx)group,and SuHx+ML141 group,with 6 mice in each group.After 4 weeks,right ventricular systolic pressure(RVSP)and cardiac ultrasound parameters were measured,and lung tissues were collected for immunofluores-cence staining.Pulmonary microvascular endothelial cells(PMVECs)were isolated using magnetic bead sorting.Calcium imaging was performed to assess Ca2+signaling,and Western blot was used to detect EndMT-related proteins as well as stromal interaction molecule 1(STIM1)and Orai1 expression.RESULTS:In the SuHx group,mice exhibited signifi-cantly increased RVSP,Fulton index(right ventricle/left ventricle+septum),end-diastolic right ventricular free wall thick-ness(RVEDWT),and end-systolic right ventricular free wall thickness(RVESWT)(P<0.01).Conversely,pulmonary artery acceleration time/pulmonary artery ejection time(PAT/PET)and tricuspid annulus plane systolic excursion(TAPSE)were significantly reduced(P<0.01).The Cdc42 inhibitor ML141 ameliorated these changes.The SuHx group exhibited a significant decrease in CD31 fluorescence intensity in pulmonary vascular endothelial cells(P<0.01),a marked increase in α-smooth muscle actin(α-SMA)fluorescence intensity in smooth muscle cells(P<0.01),and the emergence of CD31/α-SMA co-localization.These alterations were reversed by ML141.Hypoxia induced EndMT in PM-VECs,characterized by decreased CD31 and vascular endothelial cadherin(VE-cadherin)along with increased α-SMA and vimentin(P<0.01),which was suppressed by ML141(P<0.01).Hypoxia activated store-operated calcium entry(SOCE),enhancing intracellular Ca2? release,extracellular Ca2? influx,and basal Ca2? levels(P<0.01),while upregulat-ing STIM1 and Orai1 expression(P<0.01).These changes were reversed by ML141.Furthermore,both ML141 and STIM1 knockdown inhibited the upregulation of EndMT-related transcription factors Snail and Twist(P<0.05).CON-CLUSION:Cdc42 may participate in EndMT in PH by regulating store-operated calcium channels in pulmonary microvas-cular endothelial cells.

Objective:To observe and analyze the abnormal gait characteristics and lower limb kinematic chain in patients with bilateral moderate-to-severe hallux valgus(HV)during adaptive walking.Method:From September 2022 to August 2023,33 patients with moderate-and-severe HV were selected from the department of arthrology,Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine and en-rolled in the observation group.A group of 29 healthy subjects were matched and enrolled in the control group.DC-G-150-F2 three-dimensional gait analysis system was used to collect gait characteristics and lower limb motion chain of two groups during a 10m adaptive walking test.Temporal-spatial gait parameters and ki-nematic changes in the hip,knee,and ankle joints were observed and analyzed.Result:The gait time-space parameters of left and right support phase,total double support phase,left lateral foot deviation angle,step length,stride length and pace in the observation group were significantly lower than those in the control group(P＜0.05).In contrast,the time-space parameters of left and right swing phase and stride frequency in the observation group were significantly higher than those in the control group(P＜0.05).The two groups had no significant difference in right lateral foot deviation angle and step width(P＞0.05).The range of flexion and extension of the right hip joint,rotation of the left hip joint,rotation of the left and right knee joint and flexion and extension of the left and right ankle joint in the observation group were significantly lower than those in the control group(P＜0.05).There were no significant differences be-tween the two groups in the range of motion of left hip flexion and extension,right hip rotation,left versus right hip spreading,left versus right knee flexion and extension,and left versus right ankle rotation(P＞0.05).However,the range of motion of right hip rotation and right knee flexion and extension was lower than that of the control subjects(P=0.084,P=0.093).Conclusion:Gait changes in patients with bilateral moderate-to-severe bunions are characterized by shortened sin-gle and double support phases,prolonged swing phase,increased step frequency,reduced step length and stride length,and a"broken stride and slow catching up"walking pattern.The range of motion of each lower limb joint in the sagittal plane and horizontal plane is reduced,resulting in a rigid and twisted state through-out the lower limb kinematic chain.

Background and Aims:Laparoscopic hiatal hernia repair(LHHR)is the gold-standard surgical treatment for hiatal hernia(HH),but postoperative recurrence remains a challenge due to hiatal enlargement and disruption of the phrenoesophageal ligament.This study aimed to assess the feasibility,safety,and short-term efficacy of a novel three-dimensional small intestinal submucosa(3D-SIS)patch designed for circumferential crural reinforcement and ligament-like reconstruction in a porcine LHHR model.Methods:Twelve healthy pigs(35-40 kg)were equally randomized into non-mesh group,SIS flat patch group,and 3D-SIS patch group.All animals underwent LHHR and Nissen fundoplication under general anesthesia.In the non-mesh group,the hiatal defect was closed with interrupted sutures.In the SIS flat patch group,a U-shaped SIS patch was placed posterior to the esophagus to reinforce the crura and fixed with medical glue.In the 3D-SIS patch group,an intraoperatively assembled three-dimensional patch was applied,consisting of an upper keyhole-shaped layer for circumferential diaphragmatic reinforcement,a tubular middle part encircling the abdominal esophagus,and a lower small keyhole-shaped patch covering the gastroesophageal junction,all fixed with medical glue.After 3 months,laparotomy was performed to assess recurrence,patch integration,and complications,followed by biomechanical and histological evaluations.Results:All procedures were completed successfully with no deaths or major complications.Operative time was slightly longer in the patch groups,while blood loss was similar.No hernia recurrence or patch migration was observed at 3 months.Biomechanical testing revealed higher ultimate load and Young's modulus in both SIS groups than in the non-mesh group.Histological analysis demonstrated neovascularization and collagen deposition in the patch groups,with the 3D-SIS patch showing more complete circumferential integration and ligament-like tissue formation.Conclusion:The 3D-SIS patch is feasible and safe in porcine LHHR.It provides circumferential diaphragmatic reinforcement and promotes phrenoesophageal ligament-like regeneration,offering a new concept for reducing postoperative recurrence and reconstructing the anti-reflux barrier.

Corynebacterium pseudotuberculosis(C.pseudotuberculosis)is a group of intracellular Gram-positive bacteria that can cause zoonotic diseases.This study investigated the mechanisms of inflammatory mediator secretion and the phagocytic and bactericidal functions of mouse peritoneal macrophages following C.pseudotuberculosis infection.Initially,transcriptomic sequencing was em-ployed to identify genes critical for C.pseudotuberculosis infection in macrophages.Subsequently,gene knockout mice were utilized to assess the impact of these key genes on inflammatory media-tor secretion,activation of inflammatory signaling pathways,and the phagocytic and bactericidal functions of macrophages infected with C.pseudotuberculosis.Techniques such as ELISA,Western blot,and immunofluorescence were employed in this analysis.Further,transcriptomic sequencing was conducted to identify key downstream genes.Following C.pseudotuberculosis infection,GO enrichment analysis was performed,and TLR2 was identified as the focal point of the study.Perito-neal macrophages from C57BL/6J and TLR2 knockout(TLR2-/-)mice were infected with C.pseudotuberculosis.ELISA results revealed that the levels of TNF-α,IL-1β,and IL-10 were signifi-cantly downregulated in TLR2-/-macrophages compared to C57BL/6J macrophages post-infec-tion.Western blot demonstrated that the absence of TLR2 led to a marked decrease in M APK(p38 and ERK)signaling pathway phosphorylation following C.pseudotuberculosis infection.Immuno-fluorescence results indicated that the phagocytic rate of TLR2-/-macrophages was significantly higher than that of C57BL/6J macrophages after infection.Subsequently,transcriptomic analysis of C57BL/6J and TLR2-/-macrophages infected with C.pseudotuberculosis was performed,followed by GO enrichment analysis of differential genes.IL-36a,Cx3cr1,TLR1,and TLR2 were identified as key differential genes.TLR2 plays a crucial role in the inflammatory response induced by C.pseudotuberculosis infection in mice,influencing the progression of the inflammatory response and host outcomes through the secretion of inflammatory mediators,activation of signaling pathways,and modulation of phagocytic and bactericidal functions.IL-36a and Cx3cr1 were identified as key downstream factors in this process.