Background The anatomical TNM staging system inadequately reflects the profound survival heterogeneity in gallbladder cancer (GBC), thereby limiting accurate risk stratification and contributing to suboptimal clinical decision-making. To overcome this limitation, we developed a multidimensional and dynamic prognostic framework integrating clinicopathological features, systemic inflammatory markers, and tumor biomarkers, leveraging large-scale multicenter real-world data. Methods A total of 1,354 patients with GBC from 44 medical centers were retrospectively analyzed and randomly assigned to training (n = 947) and validation (n = 407) cohorts. Independent prognostic factors were identified using LASSO and multivariable Cox regression to construct three risk scores: clinicopathological (C-score), blood-based inflammatory (B-score), and tumor marker (T-score). An integrated prognostic model was subsequently developed and evaluated through machine-learning–based benchmarking. Model performance was assessed using time-dependent ROC analysis (6–48 months), calibration curves, and decision curve analysis (DCA). Gene Set Enrichment Analysis (GSEA) was performed to explore the biological relevance of the scoring systems. Results Age, R0 resection status, TNM stage, CA19-9 (log1p), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-CRP ratio (LCR) were identified as independent prognostic factors. The integrated model consistently outperformed individual C-, B-, and T-scores across all follow-up intervals, demonstrating strong discriminative ability with a 12-month AUC of 0.857 in both cohorts. Calibration and decision curve analyses confirmed good model reliability and clinical utility. GSEA revealed distinct molecular associations underlying the three scores, including ECM–receptor interaction, immune-inflammatory signaling (JAK–STAT/NF-κB), and metabolic stress pathways (HIF-1/p53). A web-based dynamic prediction platform was further developed to enable individualized survival estimation. Conclusion This multidimensional framework provides a biologically interpretable and dynamically adaptable tool for prognostic stratification in gallbladder cancer. Implemented through a web-based platform, the model facilitates individualized risk assessment and supports data-driven clinical decision-making.

EVs-delivered OGA disrupts neuronal metabolic flux and glycosylation

BACKGROUND:A comprehensive preoperative assessment of the patient's physical condition is crucial for predicting the prognosis of patients undergoing radical cholecystectomy for gallbladder cancer (GBC). This study aimed to develop a prognostic model integrating preoperative hematological parameters and clinical information to predict postoperative survival in patients with GBC. METHODS:Patients who underwent radical cholecystectomy for GBC between 2000 and 2024 at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, and Shigatse People's Hospital were included in this study. Data on demographic features, clinical parameters, laboratory results, and clinical outcomes were collected. Univariate and multivariate Cox regression analyses, time-dependent ROC curve analysis, and the least absolute shrinkage and selection operator (LASSO) regression were used to identify the key factors for model development. Various machine learning models were constructed based on these findings. Internal validation assessed model stability, while clinical decision analysis evaluated its practical utility. RESULTS:A total of 184 patients were included, with a mean age of 67 years. Key predictors identified through univariate and multivariate Cox regression, time-dependent ROC, and LASSO analyses were the lymphocyte-to-C-reactive protein ratio (LCR) and tumor-node-metastasis (TNM) staging. The best-performing model was logistic regression, with the following area under the curve (AUC) values: for the training set, 0.785 at 1 year, 0.853 at 2 years, and 0.873 at 3 years; and for the test set, 0.800 at 1 year, 0.870 at 2 years, and 0.872 at 3 years. Clinical decision analysis confirmed the model's clinical applicability. CONCLUSION:The machine learning model incorporating LCR and TNM staging is a robust tool for predicting postoperative survival following radical resection for GBC.

Verification after selective inhibition of OGA or addition of glycosylated substrates

Single cell analysis maker and proteomic PCA analysis

Peripheral nerve invasion (PNI) is an early and decisive step in gallbladder cancer progression that strongly predicts poor postsurgical outcome. The tumor-neuron interactions that drive PNI could represent potential targets and biomarkers to improve treatment of gallbladder cancer. In this study, we demonstrated that gallbladder cancer provoked necroptosis of neurons to enable PNI. Gallbladder cancer cells transferred extracellular vesicles (EV) containing O-GlcNAcase (OGA) to neurons, which activated RIPK1-dependent necroptosis. Mechanistically, EV-derived OGA suppressed RIPK1 glycosylation while enhancing its phosphorylation, thereby activating the RIPK1/RIPK3/MLKL axis to trigger neuronal necroptosis. Subsequent neuronal release of HMGB1 engaged RAGE on gallbladder cancer cells, establishing a loop that accelerated PNI. Moreover, the RAGE antagonist FPS-ZM1 synergized with gemcitabine to suppress tumor progression. Collectively, these findings uncover an EV-mediated cross-talk between gallbladder cancer cells and neurons in which RIPK1-dependent necroptosis and its effector HMGB1 drive PNI, positioning the HMGB1-RAGE axis as a tractable therapeutic target.Significance: Tumor-derived extracellular vesicles trigger neuronal necroptosis that fuels peripheral nerve invasion, creating a tumor-neuron signaling loop that could be leveraged for liquid biopsy and personalized therapy strategies in neurotropic cancers.

PURPOSE:The purpose of this study is to evaluate the efficacy and safety of nab-paclitaxel combined with gemcitabine (AG regimen) as a first-line chemotherapy for patients with unresectable gallbladder cancer (GBC). MATERIALS AND METHODS:A retrospective analysis was conducted on patients diagnosed with GBC via histological examination. Inclusion criteria included locally advanced or metastatic gallbladder cancer deemed unresectable by multidisciplinary team (MDT) consensus; age 18-75 years; ECOG performance status ≤ 2; and AG as first-line chemotherapy. Treatment response was assessed using RECIST 1.1 criteria. Primary endpoints were overall response rate (ORR) and progression-free survival (PFS); secondary endpoints included disease control rate (DCR), overall survival (OS), and adverse events incidence. RESULTS:Thirty-one patients were enrolled. The ORR was 48.4%, and DCR was 90.3%. The median PFS was 8.4 months (95% CI, 5.0-11.8), and the median OS was 20.9 months (95% CI, 16.8-24.9). Among the 11 patients with locally advanced disease, 7 patients (63.6%) successfully converted to a resectable state and underwent surgery. Grade 3/4 treatment-related adverse events occurred in 11 patients (35.5%), predominantly hematologic toxicities, and no treatment-related deaths or treatment discontinuations due to adverse events were observed. CONCLUSION:First-line AG chemotherapy demonstrated promising efficacy and manageable safety for patients with unresectable GBC, with a substantial portion achieving disease control and some converting to resectable status.

BACKGROUND:Gallbladder cancer (GBC) is a leading cause of cancer-related death worldwide, and its prognosis remains poor, with 5-year survival of approximately 5%. In this study, we analyzed the involvement of a novel proteoglycan, Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1), in the tumor progression and prognosis of human GBC. METHODS:SPOCK1 expression levels were measured in fresh samples and stored specimens of GBC and adjacent nontumor tissues. The effect of SPOCK1 on cell growth, DNA replication, migration and invasion were explored by Cell Counting Kit-8, colony formation, EdU retention assay, wound healing, and transwell migration assays, flow cytometric analysis, western blotting, and in vivo tumorigenesis and metastasis in nude mice. RESULTS:SPOCK1 mRNA and protein levels were increased in human GBC tissues compared with those in nontumor tissues. Immunohistochemical analysis indicated that SPOCK1 levels were increased in tumors that became metastatic, compared with those that did not, which was significantly associated with histological differentiation and patients with shorter overall survival periods. Knockdown of SPOCK1 expression by lentivirus-mediated shRNA transduction resulted in significant inhibition of GBC cell growth, colony formation, DNA replication, and invasion in vitro. The knockdown cells also formed smaller xenografted tumors than control GBC cells in nude mice. Overexpression of SPOCK1 had the opposite effects. In addition, SPOCK1 promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of relevant genes. We found that activation of the PI3K/Akt pathway was involved in the oncogenic functions of SPOCK1 in GBC. CONCLUSIONS:SPOCK1 activates PI3K/Akt signaling to block apoptosis and promote proliferation and metastasis by GBC cells in vitro and in vivo. Levels of SPOCK1 increase with the progression of human GBC. SPOCK1 acts as an oncogene and may be a prognostic factor or therapeutic target for patients with GBC.

Gallbladder cancer (GBC), the most common malignancy of the bile duct, is highly aggressive and has an extremely poor prognosis, which is a result of early metastasis. As it is regulated being at multiple levels, the metastatic cascade in GBC is complex. Recent evidence suggests that microRNAs (miRNAs) are involved in cancer metastasis and are promising therapeutic targets. In this study, miR-101 was significantly downregulated in tumor tissues, particularly in metastatic tissues. In GBC patients, low miR-101 expression was correlated with tumor size, tumor invasion, lymph node metastasis, TNM stage, and poor survival. Moreover, miR-101 was an independent prognostic marker for GBC. Additionally, miR-101 inhibited GBC cell proliferation, migration, invasion, and TGF-β-induced epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, the gene encoding the zinc finger protein X-linked (ZFX) was identified as a direct target of miR-101. More importantly, miR-101 significantly reduced activation of the MAPK/Erk and Smad signaling pathways, resulting in inhibition of TGF-β-mediated induction of EMT. Altogether, our findings demonstrate a novel mechanism by which miR-101 attenuates the EMT and metastasis in GBC cells and suggest that miR-101 can serve as a potential biomarker and therapeutic target for GBC management.

The journal retracts the article, titled “Schisandrin B induces apoptosis and cell cycle arrest of gallbladder cancer cells” [...]

Background: Pancreatic fistula (PF) is the main complication in patients undergoing pancreaticoduodenectomy. Computed tomography (CT) value can reflect pancreatic tissue characteristics which is related to PF. This study was designed to study the relationship between the preoperative CT value and pancreatic fistula. Methods: We retrospectively reviewed the clinical and medical data of patients undergoing pancreaticoduodenectomy from 2017 to 2021. The pancreatic CT value and the CT value ratios of the pancreas and abdominal aorta (PCT/ACT) were measured and compared between the PF group and non-PF group. The values in different PF severity groups were compared using variance analysis. A cut-off value was selected by receiver operating characteristic (ROC) curve. Single-factor and multiple-factor analysis were performed to evaluate Correlation between PF and CT. Results: One hundred and twenty-seven cases were included in this study. The PCT/ACT in the PF group was significantly lower than that in the non-PF group (P<0.001), and the PCT/ACT value was correlatively lower in the severe PF group than in the mild PF group (P=0.008). A cutoff value of 0.99 was selected by ROC curves analysis. Further multifactor analysis identified PCT/ACT <0.99 to be an independent preoperative predictor [odds ratio (OR): 11.3, P<0.01]. Conclusions: The preoperative pancreatic CT value can indirectly reflect the histological condition of the pancreas and thus may related to postoperative PF after pancreaticoduodenectomy and provide useful information for surgeons in deciding upon the pancreaticojejunostomy method.

BackgroundGallbladder cancer (GBC) is highly lethal and resistant to most chemotherapeutic drugs. GBC was reported to carry multiple genetic mutations such as TP53, K-RAS, and ERBB2/3. Here, we unexpectedly identified a patient with GBC harboring germline BRCA1 p.Arg1325Lys heterozygous mutation. We sought to determine if olaparib, the poly ADP-ribose polymerase inhibitor (PARPi) commonly treated for BRCA mutation, can inhibit cancer development via a therapeutic trial on this patient. Case presentationThe patient received GBC R0 resection after an 8-week olaparib treatment. After surgery and 6-month follow-up treatment with olaparib, the patient's blood carbohydrate antigen 19-9 (CA19-9) level declined from 328 to 23.6 U/ml. No recurrence in CT scanning was observed, indicating a disease-free survival of 6 months with conventional therapy. Two months later, CT examination and CA19-9 level showed cancer relapse. A blood biopsy revealed a new ERBB3 p.Gly337Arg mutation. GBC cell lines ectopically expressing BRCA1 p.Arg1325Lys together with ERBB3 p.Gly337Arg mutations were challenged with olaparib and/or afatinib, an ERBB2/3 inhibitor. The dual mutation cells were more responsive to the combined olaparib with afatinib than a single drug in the cell proliferation assay. ConclusionOlaparib is effective in a GBC patient with a BRAC1 mutation. The efficacy of olaparib and afatinib in both cultured BRAC1 and ERBB3 mutation cell lines suggests that a combined regimen targeting BRCA1/2 and ERBB2/3 mutations may be an optimal strategy to treat GBC patients who carry both gene mutations.

Abstract Background Three‐dimensional visualization preoperative evaluation (3D‐VPE) and enhanced recovery after surgery (ERAS) have been suggested to improve outcomes of cancer surgery in patients, yet little is known regarding their clinical benefit in patients with gallbladder cancer (GBC). We hypothesized that the combination of 3D‐VPE and ERAS would improve the outcome of patients undergoing surgery for GBC. Objective This study aimed to determine if 3D‐VPE and ERAS can improve the outcomes and overall survival in patients with GBC, establishing a novel patient management strategy for GBC. Methods A total of 227 patients with GBC were recruited and divided into two groups: those who received traditional treatment between January 2000 and December 2010 (n = 86; the control group) and those who underwent 3D‐VPE and ERAS between January 2011 and December 2017 (n = 141). Univariate and multivariate analyses were employed to assess the relationship among disease stages, lymph node invasion, and cell differentiation between the two groups. Cox regression analysis was used to investigate patient survival in these groups. Results Patients who underwent 3D‐VPE and ERAS showed a significantly higher R0 resection rate (67.4% vs. 20.9%, p < 0.001) and dissected lymph node number (26.6 ± 12.6 vs. 16.3 ± 7.6 p < 0.001) compared to the control group. The median survival was 27.4 months, and the 1‐ and 3‐year survival rates were 84.4% and 29.8%, respectively, in patients who received combined management; in the control cohort, the median survival was 12.7 months, and the 1‐ and 3‐year survival rates were 53.5% and 15.1%, respectively. In addition, some postoperative complications and risk factors were diminished relative to the traditionally treated patients. Conclusion The implementation of 3D‐VPE and ERAS can significantly improve the prognosis and outcomes of patients with GBC and should be considered for wide use in clinical practice.

文章以新冠肺炎疫情防控期间,上海交通大学医学院附属新华医院普外科2022届研究生毕业论文线上"云答辩"为例,阐述了医学院校线上"云答辩"的组织流程,并总结经验,论述"云答辩"优势,即符合疫情管控要求、节约答辩成本、答辩参与度广,最后提出了更好开展"云答辩"的几点建议,包括统一组织答辩秘书培训、规范答辩流程、加强检查督导,以期推动医学院校研究生毕业论文答辩形式的改革和创新.

目的 总结上海市开展外科住院医师规范化培训10年的实践与经验,为今后进一步提高外科住院医师规培化培训质量提供理论依据.方法 统计2010-2021年上海市32家外科住院医师规范化培训基地的基本情况、外科床位数、带教师资人数、研究生导师人数,招录及出站人数、性别、年龄、学历背景、培训年限,结业综合考合格率、申请课题及发表论文情况、就业情况等信息.结果 上海市共有32家外科专业基地,以三级甲等综合性医院为主,目前累计招录了住培医师4597名,已结业3162名,绝大多数外科住培医师达到培训要求并通过考核结业.上海市外科住院医师规范化培训工作在建立健全制度建设,开展教学活动,推广信息化管理,师资培训与督导检查,临床科研培养等方面取得了满意的成效.同时现阶段工作中仍有不足之处,包括规范教学活动、加强医学人文及思政教育、落实外科培训细则、待遇保障等方面.结论 外科住院医师规范化培训已成为培养高水平外科医学人才的重要途径,后续住院医师规范化培训重点应进一步加强各外科基地培训效果的同质化、标准化、规范化,注重内涵建设和质量建设.