BackgroundCheckpoint inhibitor pneumonitis (CIP) is a rare but potentially fatal immune-related adverse event (irAE) that can interrupt immune checkpoint blockade in non-small cell lung cancer (NSCLC). With no validated pretreatment biomarkers and a diagnosis largely made by exclusion, upfront risk stratification is required. Recent advances in artificial intelligence (AI)-driven pathomics have made it feasible to infer tumor immune microenvironment (TIME)-relevant risk states in patients with NSCLC. Accordingly, we leveraged hematoxylin and eosin(H&E)-based digital pathomics combined with clinical variables to interrogate the TIME in patients who developed CIP and to enable pretreatment and early prediction of CIP.MethodsIn this retrospective study, 346 eligible patients from three hospitals were screened consecutively between January 2022 and January 2025. Patients were divided into CIP and non-CIP groups according to whether CIP occurred at a prespecified observation endpoint. We first developed a pathomics model that employed convolutional neural networks (CNNs) combined with multi-instance learning (MIL) to generate predictions at both the patch and whole slide image (WSI) levels on H&E-stained slides. Separately, we constructed a clinical model using logistic regression (LR) to process the structured clinical data accompanying each case. Subsequently, pathological and clinical information were integrated, where modeling was advanced from modality-specific feature learning to cross-modal representation learning, and final predictive modeling was completed. The predictive performance of different models was evaluated using the area under the Receiver Operating Characteristic (ROC) curve and benchmarked against unimodal models and standard ensemble methods.ResultsWhen the models were evaluated across both internal validation and external test datasets, the pathomics model demonstrated noticeably stronger performance than the clinical approach, achieving area under the curve (AUC) scores of 0.916, 0.875(test 1), and 0.843(test 2), respectively, while the clinical model posted more modest results of 0.880, 0.569(test 1), and 0.594(test 2). The most significant outcome, however, emerged from the multimodal fusion model, which produced the strongest results of all, with performance metrics of 0.930, 0.919(test 1), and 0.905(test 2) in the validation and test phases, respectively.ConclusionPretreatment H&E-derived pathomics, integrated with baseline clinical biomarkers, enable accurate prediction of CIP risk in locally advanced or metastatic NSCLC. This framework supports proactive surveillance and individualized immune checkpoint inhibitor (ICI) strategies and provides a scalable route to decode TIME-relevant states from routine pathology.

Neoadjuvant chemoimmunotherapy (nCIT) has improved outcomes in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, accessible and reliable biomarkers to predict survival and pathological response remain limited. This study assessed the prognostic and predictive value of the Global Immune-Nutrition Index (GINI), cytokeratin-19 fragment (CYFRA 21 − 1), fibrinogen–albumin ratio index (FARI), and a composite score combining these markers—the GINI–CYFRA 21 − 1–FARI (GCF) score. A retrospective analysis was conducted on 138 LA-ESCC patients who received nCIT followed by radical esophagectomy between 2021 and 2023. Optimal cut-off values for GINI, CYFRA 21 − 1, and FARI were determined using X-tile software. The composite GCF score was developed accordingly. Associations with disease-free survival (DFS) were evaluated using Kaplan–Meier analysis and multivariable Cox regression. Predictive performance was assessed via time-dependent ROC curves. Tumor regression grade (TRG) was analyzed using logistic regression, and a nomogram was constructed to predict pathological response. Elevated levels of GINI (median DFS: 20 vs. not estimable [NE] months; p = 0.001), CYFRA 21 − 1 (19 vs. NE months; p < 0.001), FARI (11 vs. 26 months; p < 0.001), and higher GCF scores (0 vs. 1 vs. ≥2: 18 vs. 22 vs. NE months; p < 0.001) were associated with worse DFS. The GCF score was independently predictive of DFS (low vs. high: HR = 0.264; p = 0.028) and demonstrated consistent discriminative capacity. For pathological response, the GCF score showed predictive value for TRG (AUC = 0.625; p = 0.004) and was independently associated with poor TRG (high vs. low: OR = 2.170; p = 0.048). A nomogram incorporating the GCF score outperformed models excluding it (AUC: 0.787 vs. 0.662; p < 0.05). The GCF score—a composite of GINI, CYFRA 21 − 1, and FARI—independently predicts DFS and pathological response following nCIT and surgery in LA-ESCC, and may hold potential as a practical, blood-based biomarker. Its integration significantly enhances predictive model performance and may aid in individualized patient risk stratification.

This study aims to investigate molecular mechanisms by which norepinephrine (NE) exposure influences lung cancer cell behavior, identify key factors and pathways involved in stress-related signaling in lung cancer cells. NE was used to treat lung cancer cells (H1975) to simulate a stress-related signaling environment. PFKFB3 mRNA expression and phosphorylation levels of epithelial-mesenchymal transition (EMT) markers and key proteins in NF-κB signaling pathway were evaluated. NE significantly enhanced lung cancer cell proliferation, specifically upregulated PFKFB3 mRNA expression, promoted EMT marker (N-cadherin and Vimentin) expression, and increased cell migration capacity. Knockdown of PFKFB3 or inhibition of glycolysis reduced cell viability, lactate production, ATP levels, and expression of glycolysis-related enzymes (LDHA and GLUT1) and EMT markers, while suppressing cell migration. Combined interventions exhibited synergistic inhibitory effects. Mechanistic studies revealed that PFKFB3 knockdown inhibited phosphorylation of NF-κB pathway proteins (IKKβ, IκBα, and p65), blocked pathway activation, and reduced histone lactylation levels, particularly at the H4K12la modification site. These effects were reversed by NE intervention. This study suggests a mechanism whereby NE upregulates PFKFB3, activates glycolysis, promotes lactate production to drive histone lactylation, and activates the NF-κB signaling pathway, which is associated with EMT and cell migration.

Modulating the immune system represents a pivotal mechanism through which the gut microbiome (GM) exerts influence over disease progression. However, Further investigation is necessary to ascertain the causal role of GM in Esophageal Adenocarcinoma (EAC) and the potential for immune cell mediation. Initially, a two-stage, two-sample Mendelian randomization (MR) analysis using the Inverse Variance Weighted (IVW) method was performed to assess the causal effects of GM conditions on EAC, while exploring the potential mediating role of immune cells in the GM-EAC association. A MR analysis identified 5 types of GM and 9 types of GM metabolic pathway abundances with potential causal relationships to EAC. Furthermore, 26 immune cell characteristics(ICTs) were identified as closely associated with EAC. Mediation MR analysis revealed that ICTs negatively influenced the relationship between Rothia and EAC. Our MR and mediation analyses suggest that specific gut microbes, microbial pathway abundances, and peripheral immune traits are associated with EAC susceptibility. Immune mediation was modest (-6–15

Carcinoembryonic antigen (CEA), a pan-cancer biomarker, holds critical clinical value in aiding diagnosis and prognostic assessment of various malignancies. The development of a facile, accurate, and selective CEA detection method remains an urgent need. Herein, we developed a facile colorimetric sandwich immunoassay based on a highly defective Fe-based single-atom nanozyme (dFeSA) for detecting CEA. The dFeSA with an Fe-N3-C active site exhibited remarkable oxidase-like activity, enabling the catalytic conversion of O2 to superoxide radicals and subsequent oxidation of chromogenic substrates. This method achieved high sensitivity and specificity for CEA detection over a wide range (0.05-300 ng mL-1) and a low detection limit of 0.017 ng mL-1. Notably, the immunoassay demonstrated exceptional performance for CEA detection in real serum samples with recovery rates of 92.7%-102.6%. This colorimetric immunoassay represents a robust analytical platform for CEA detection, offering a cost-effective alternative to conventional methods and holding significant potential for early cancer diagnosis and prognostic monitoring in clinical practice.

Functional vascularization is crucial for maintaining the long-term patency of tissue-engineered trachea and repairing defective trachea. Herein, we report the construction and evaluation of a novel cell-free tissue-engineered tracheal scaffold that effectively promotes vascularization of the graft. Our findings demonstrated that exosomes derived from endothelial progenitor cells (EPC-Exos) enhance the proliferation, migration, and tube formation of endothelial cells. Taking advantage of the angiogenic properties of EPC-Exos, we utilized methacrylate gelatin (GelMA) as a carrier for endothelial progenitor cell exosomes and encapsulated them within a 3D-printed polycaprolactone (PCL) scaffold to fabricate a composite tracheal scaffold. The results demonstrated the excellent angiogenic potential of the methacrylate gelatin/vascular endothelial progenitor cell exosome/polycaprolactone tracheal scaffold. Furthermore, in vivo reconstruction of tracheal defects revealed the capacity of this composite tracheal stent to remodel vasculature. In conclusion, we have successfully developed a novel tracheal stent composed of methacrylate gelatin/vascular endothelial progenitor exosome/polycaprolactone, which effectively promotes angiogenesis for tracheal repair, thereby offering significant prospects for clinical and translational medicine.

目的:探讨细管状胃(宽度4～<5 cm)的安全性以及对吻合口瘘发生率的影响,为临床选择最佳管状胃宽度提供理论依据.方法:回顾性分析扬州大学附属苏北人民医院2015年7月—2021年6月收治的胸腹腔镜三切口食管癌根治术患者791例,其中2015年7月—2018年12月采用粗管状胃(宽度5～6 cm)代食管手术患者446例作为A组,2019年1月—2021年6月采用细管状胃(宽度4～<5 cm)代食管手术患者345例作为B组.比较两组患者手术一般情况及术后吻合口瘘发生的情况.结果:两组患者术中出血量、术后引流

Evidence suggests that Tripartite Motif Containing 11 (TRIM11) has pro-tumor activity in human non-small cell lung cancer (NSCLC). However, the roles and underlying mechanisms of TRIM11 in NSCLC have not yet been fully elucidated. In this work, human lung cancer cell lines (A549, H446, and H1975) were transfected with siRNA or lentiviruses to knockdown or overexpress TRIM11 and dual-specificity phosphatase 6 (DUSP6). The cell tumor response was assessed by determining the rate of proliferation, apoptosis, the uptake of 2-[N-(7-nitrobenz-2-oxa-1, 3-diaxol-4-yl) amino]-2-deoxyglucose (2-NBDG), and the secretion of lactic acid (LD). Dominant-negative (dn)-MEK1 was used to block the ERK1/2 pathway. The mechanism was investigated by assessing the protein levels of pyruvate kinase isozymes M2 (PKM2) and DUSP6, as well as the activation of ERK1/2 pathway. Our data confirmed the anti-cancer effect of siTRIM11 in human lung cancer by demonstrating inhibition of cancer cell proliferation, induction of apoptosis, prevention of 2-NBDG uptake, suppression of LD production, and prevention of lung cancer cell (A549) tumorigenicity in nude mice. The underlying mechanism involved the up-regulation of DUSP6 and the inhibition of ERK1/2 activity. Overexpression of TRIM11 induced tumorigenesis of NSCLC in vitro, and the activation of ERK1/2 was significantly reversed by DUSP6 overexpression or additional dn-MEK1 treatment. Interestingly, we confirmed TRIM11 as a deubiquitinase that regulated DUSP6 accumulation, indicating that lung cancer progression is regulated via the DUSP6-ERK1/2 pathway. In conclusion, TRIM11 is an oncogene in NSCLC, likely through the DUSP6-mediated ERK1/2 signaling pathway.

Objective To establish a mathematical prediction model of mediastinal lymph node metastasis in early or mid-term non-small cell lung cancer (NSCLC) with diameter ≤5 cm and improve the accuracy of preoperative staging of lung cancer.Methods A retrospective analysis of 608 patients with NSCLC meeting the inclusion criteria in the Department of Thoracic Surgery,Clinical Medical College of Yangzhou University from January 2012 to August 2017 was randomly divided into modeling and validation groups according to a 3 ∶ 1 ratio by SPSS random number generator method.Using the data of the model group,the independent risk factors of mediastinal lymph node metastasis were screened by single factor and multivariate analysis to establish the mathematical prediction model.External validation of the model was performed using validation group case data and compared with previous models.Results Multivariate tumor size,tumor location (central or peripheral),pathological type and pleural traction were independent risk factors for mediastinal lymph node metastasis.The mathematical predictive model established was P =ex/(1+ex),x=-2.831 + (0.825 × tumor diameter) + (1.53 × central type) + (0.779 × pleural traction sign) + (1.883 × pathological type)-(0.06 × age).The Hosmer-Lemeshow test showed no significant difference between the predicted and observed values.The area under the curve for the receiver operating characteristic curve was 0.763 (95 ％ CI:0.697 ～ 0.829).External verification results show that compared with the VA model and the Fudan model,the proposed model is applicable to a wider range and higher accuracy.Conclusions The mathematical model established in this study has high sensitivity and specificity for the diagnosis of mediastinal lymph node metastasis of NSCLC ≤ 5 cm in diameter,and its prediction ability and accuracy are higher than other similar models.This model allows for more rational clinical decisons on whether to perform further mediastinal lymph node.

Objective To prepare 3D printed porous tracheal graft fabricated by PCL and to select the appropriate pore size and surface modification techniques,in order to explore its effect on cell behavior.Methods The PCL porous tracheal graft was prepared by 3D printing technology and biomechanical properties of the graft were measured by means of longitudinal tension,radial compression and three-point bending test.The porous grafts were surface-modified through hydrolysis,amination and nanocrystallization treatment and then characterized by energy dispersive spectroscopy(EDS).The effect of different pore sizes and surface modifications on the cell proliferation behavior was evaluated by CCK-8 and scanning electron microscopy (SEM).Results The 3 D printed porous tracheal graft had similar morphology with the native tracheas(P ＞ 0.05) and better biomechanical properties(P ＜0.05).It was more suitable for cell adhesion and proliferation when the pore size is 200 μm (P ＜ 0.05).Compared to hydrolysis and amination,nanocrystallization treatment successfully improved the cytotropism of the 3D printed tracheal graft(P ＜ 0.05).Conclusion 3 D printed porous tracheal graft shows favorable biomechanical properties.The appropriate pore size of the 3D printed porous tracheal graft is 200 μm and the appropriate surface modification techniques is nanocrystallization.

Objective To investigate the treatment and managment for cervical anastomotic fistula after thoracic laparoscopic combined with esophageal cancer resection. Methods The data of 41 cases of cervial anastomotic fistula after thoracic laparoscopie combined with esophageal cancer resection in the Department of Thoracic Surgery of Medical College of Yangzhou University from January 2015 to March 2017 were reviewed. Results In the 41 cases of cervial anastomotic fistula,26 cases started to take liquid food within 4 to 14 days after anastomotic and no abnormal symptoms such as incisional leakage, chest distress or asthma occurred. While 11 cases started to take liquid food within 15 to 28 days after anastomotic fistula without abnormal manifestation. And 4 cases began to take liquid food after anastomotic fistula within 29 to 60 days later after anastomotic fistula, and upper gastrointestinal contrast examination suggested that anastomotic stoma healed. No one died or underwent the second operation during hospitalization. Conclusions Fasting, smooth drainage around the anastomosis, and enteral nutrition support are the keys to treatment cervical anastomotic fistula after thoracic laparoscopic combined with esophageal cancer resection. Early detection and active treatment contribute to promoting rapid cervical anastomotic fistula healing.

病例 1,男,23 岁.咳嗽 4 个月余,体检发现纵隔占位 4天.胸部增强 CT&nbsp;检查提示右侧中上纵隔内占位(图 1),术前诊断为右中上纵隔内占位,行开胸手术治疗.术中探查:肿瘤位于右中上纵隔内,大小约 6 cm × 5 cm.肿瘤表面外覆血管,与奇静脉弓、膈神经及上腔静脉关系密切.沿肿瘤包膜将肿瘤作完整切除,肿瘤与周围组织关系密切,触之易出血.肿瘤完整切除.术中出血 800&nbsp;ml.术后病理检查,诊断为血管滤泡性淋巴结增生(图 2).

通信作者:史宏灿,E-mail:shihongcan@hotmail. com 气管腺样囊性癌( tracheal adenoid cystic carci-noma,TACC)是一种罕见病,其发病率低,症状不典型,很容易错过早期诊断,而导致治疗的延误.本文回顾性分析我科收治的1例气管腺样囊性癌患者的临床及术后随访资料,并结合文献,对该病的诊断及治疗进行探讨.

Objective To investigate the prevalence and related factors of primary palmar hyperhidrosis in adolescents in Yangzhou.Methods On-site questionnaire survey was performed on students selected by cluster random sampling from the two colleges and two high or middle schools,with each class as a unit.Data were collected through the questionnaire to make the diagnosis and severity grading.Results A total of 3 487 copies of the questionnaire were distributed in the survey and 3 299 were finished,among which 3 083 were effective with an effective rate of 88.41％.Among them,1 358 respondents were males and 1 725 were females;933 were middle school students,809 high school students,and the remaining 1 341 college students.According to the diagnostic criteria,104 respondents were diagnosed with palmar hyperhidrosis with an overall prevalence of 3.37％.There were 60 (4.41％) males and 44 (2.55％) females.Although the prevalence ofpalmar hyperhidrosis in males was higher than that of females (x2=8.130,P＜0.05),severe palmar hyperhidrosis was more often to be observed in females than in males,and females were also more likely to have hyperhidrosis in other parts of the body.In addition,the age of the first onset of the disease was mainly 10 to 20 years old and 36.54％ of the patients had a family history.Conclusion The prevalence of palmar hyperhidrosis in adolescents in Yangzhou was 3.37％,and there is a significant difference in the gender.The palmar hyperhidros is often accompanied by hyperhidrosis symptoms of other parts of body,and the disease shows an obvious genetic predisposition.

Acute lung injury(ALI), which caused by a variety of direct and indirect factors, is a kind of acute hypoxic respiratory insufficiency. ALI can develop to acute respiratory distress syndrome when it becomes worse. Ischemic preconditioning and remote ischemic preconditioning which was discovered in recent years play a protective role in preventing ischemic organ damage. Especially remote ischemic preconditioning, it has won the attention because it′s convenient to use, easy to operate and undamaged to body. This review focuses on the protective effects and possible mechanism of preoperative ischemia on acute lung injury. Key words: Ischemic preconditioning; Acute lung injury; Protective effects

Tissue engineering can regenerate damaged tissues and restore the biological functions by cell or tissue reconstruction,and is becoming a promising method for trachea replacement.Seed cells,cell growth factors and tracheal scaffolds are the three major elements of tissue engineering trachea,as a result researchers have paid a lot of attention to find ideal seed cells.Mesenchymal stem cells (MSCs) are a kind of stem cells with high self-renewal ability and muhi-directional differentiation potential.MSCs are widely distributed in bone marrow,umbilical cord,adipose tissue,myocardial tissue,brain,muscle and skin,and can differentiate into a variety of cells,including osteocytes,chondrocytes,adipocytes and neurocytes.MSCs have the characteristics of high proliferation ability,wide differentiation range and immunomodulatory function,which can be used to repair damaged tissue.These advantages make the MSCs an ideal candidate of seed cells for tissue engineering trachea.This review mainly summarized the application of MSCs in tissue engineering trachea.

In recent years,the incidence of lung cancer,high mortality,become one of the main diseases that threaten human health and life.Preoperative staging of non-small cell lung cancer,especially mediastinal lymph node staging is the key to determine whether surgery and judge tne prognosis of patients.Therefore,how to achieve accurate staging of mediastinal lymph node before surgery is a clinical problem to be solved urgently.The traditional methods of preoperative staging of mediastinal lymph nodes include imaging,minimally invasive biopsy and surgery.In recent years,the development of relevant serum tumor markers,serum miRNAs and clinical prediction models provide some new references for the preoperative diagnosis and assessment of mediastinal lymph node metastasis.This paper reviews the methods of preoperative diagnosis of mediastinal lymph node metastasis of non-small cell lung cancer in recent years,and summarizes and analyzes the advantages and disadvantages of various methods.

In recent years,the detection rate of early lung cancer with microscopic lesions such as ground-glass nodules and sub-centimeter nodules (≤ 1 cm) has been significantly higher.For such lesions,early surgical intervention can effectively prolong the survival time of patients.But in the actual operation of these small lesions difficult to detect,which brought great difficulties to surgery.At present,clinically for such small lesions,usually in the preoperative CT-guided puncture positioning based on the implementation of surgical resection.This method of location there are trauma,complications and other shortcomings,so how to more precise positioning and labeling of lung lesions is a clinical problem to be solved urgently.In this paper,the localization and localization of lung lesions in recent years are reviewed,and the advantages and disadvantages of various methods and materials are summarized and analyzed.

The goals of our study were to evaluate the biomechanical properties and cellular biocompatibility of 3D printed tracheal graft fabricated by polycaprolactone (PCL). Compared with native tracheal patch, there was a significant increase in maximum stress and elastic modulus for 3DP tracheal graft (p < 0.05). BMSCs were co-cultured under four different conditions to investigate cytotoxicity of the graft: (1) co-cultured with normal culture medium, as blank control; (2) co-cultured with perfluoropropylene, as negative control; (3) co-cultured with 3DP tracheal graft; and (4) co-cultured with polyvinyl chloride, as positive control. Moreover, the results of SRB assay showed that compared with blank and negative control group, there was no significant difference in the cell proliferation of 3DP tracheal graft group for 21 days (p > 0.05). These results revealed that 3DP tracheal graft in our study has favorable cellular biocompatibility and biomechanical properties, and, therefore, will be a promising alternative for tissue-engineered trachea.