Immune checkpoint inhibitors（ICIs） have reshaped the therapeutic landscape of biliary tract cancer（BTC）, yet both primary and acquired resistance substantially limit their clinical impact.These resistance phenomena reduce overall response rates and restrict the population of BTC patients who can derive durable benefit. Understanding the multifactorial mechanisms underlying immunotherapy failure is therefore a pressing clinical and scientific priority.This article systematically summarizes the multi‑level causes of immunotherapy resistance in BTC and discusses corresponding countermeasures, and proposes integrated directions for future research to provide a theoretical basis and ideas for developing precise and effective combination treatment regimens.

Biliary tract cancer（BTC）, which encompasses intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, is a biologically heterogeneous, highly invasive malignancy with generally poor outcomes.Although immune checkpoint inhibitors and other immunotherapies have revolutionized treatment for many solid tumors, responses in BTC are highly variable and overall response rates remain modest.This discrepancy is largely attributed to the complex and diverse tumor immune microenvironment（TIME） in BTC. The BTC TIME is a dynamic, interactive network formed by malignant cells, multiple immune cell populations, stromal elements, the vascular network, and a milieu of cytokines and chemokines. Its composition and functional state are shaped by multiple, interdependent factors, including tumor anatomical origin, molecular and genetic subtype, underlying etiology, host immune status, and prior therapies, leading to pronounced intra-and inter-tumoral heterogeneity. Here, we systematically review current knowledge on BTC TIME heterogeneity, dissecting its manifestations across cellular composition, spatial organization, molecular signatures, and functional phenotypes; we discuss how this heterogeneity influences tumor progression, clinical prognosis, and differential responses to immunotherapy; and we consider pathways to translate basic discoveries into clinically actionable strategies to provide a theoretical rationale and actionable translational pathways to enhance the efficacy of immunotherapy for BTC.

Biliary tract cancer（BTC） is characterized by insidious onset and high invasiveness, with most patients diagnosed at an advanced stage, thereby losing the opportunity for curative resection. The distinct biological features of BTC significantly contribute to the limited efficacy of targeted and immunotherapeutic approaches. Enhancing early diagnosis and treatment rates, as well as improving R0 resection rates, represents a critical strategy to overcome current therapeutic challenges. With advancing research into tumor biology and resistance mechanisms, future efforts should focus on harnessing the synergistic effects of targeted therapy,immunotherapy,and chemotherapy.This will facilitate the development of combined regimens with more precise patient selection,improved efficacy, and reduced toxicity, ultimately leading to better long-term survival outcomes for patients with biliary tract malignancies.

Biliary tract cancer（BTC） remains a formidable clinical problem due to its aggressive biology, low rates of curative resection, high recurrence, and poor prognosis. Chemotherapy combined with immunotherapy has emerged as a cornerstone for patients with advanced or initially unresectable BTC. Immune checkpoint inhibitors（ICIs） have produced important breakthroughs in advanced disease, and their application in the perioperative setting, including neoadjuvant and adjuvant approaches, and in conversion（downstaging） therapy is increasingly the focus of investigation.This review synthesizes evidence on： the unmet needs in perioperative BTC management; immunotherapy mechanisms relevant to the perioperative context; neoadjuvant and adjuvant immunotherapeutic strategies; immunotherapy-driven conversion regimens; predictive biomarkers of response; and future research directions. Preliminary data suggest that neoadjuvant immunotherapy combined with chemotherapy may raise complete/pathologic complete response rates and lower recurrence risk among initially resectable patients, although confirmation in high-level randomized trials is needed. In the conversion setting,intensified regimens（triplet or four‑drug combinations incorporating ICIs） can render some initially unresectable tumors operable and appear to markedly improve survival.As phase Ⅲ trial results emerge, novel biomarkers are validated,and combination strategies are optimized, perioperative chemotherapy plus immunotherapy is expected to further enhance long-term outcomes in BTC.

Cholangiocarcinoma（CCA）, a highly aggressive malignancy arising from biliary epithelium, is characterized by insidious clinical presentation and poor therapeutic outcomes. The tumor's limited responsiveness to current treatments is tightly linked to its distinctive immune microenvironment. Within CCA tumors, diverse tumor‑associated cells produce an array of immunomodulatory factors and interact through complex networks to facilitate immune escape and drive tumor progression and invasion. Although immunotherapy has transformed oncology, immune checkpoint inhibitor monotherapy yields modest results in CCA; greater clinical benefit has been observed with rational combinations of ICIs with chemotherapy or targeted agents. Emerging approaches, such as chimeric antigen receptor （CAR）‑T cell therapy and tumor vaccines, also show early promise. Because of the complexity and context‑dependence of the CCA immune milieu, future research must prioritize detailed characterization of the microenvironment, identification and validation of novel immunotherapeutic targets, and the development of biomarker‑driven, personalized combination strategies to improve patient outcomes. This review outlines the key features of the CCA immune microenvironment, examines its implications for immunotherapy, and surveys emerging therapeutic directions.

Advances in systemic and multimodal therapies have materially improved outcomes for primary liver cancer. Consequently, clinicians are increasingly challenged to define the appropriate role and timing of surgical resection within whole‑course management so as to maximize survival benefit. Certain adverse oncologic features, including multifocal disease, tumor thrombus involving hepatic or portal veins or the bile duct, markedly elevated serum tumor markers, positive circulating tumor biomarkers （for example, circulating tumor cells or circulating tumor DNA）, or tumors immediately adjacent to essential hepatic structures to be preserved, are associated with aggressive biology and a high risk of recurrence. When such features coexist with lesions that are technically resectable or can be rendered resectable through conversion （downstaging） therapy, the central clinical question is whether immediate aggressive resection （or aggressive resection following successful conversion） will reliably yield superior survival outcomes. This question remains contested. Based on the author's clinical experience, this paper outlines a structured approach to clinical reasoning for individualized surgical decisions： it analyzes the oncologic principles and the surgical trade‑offs that drive the controversy and proposes a decision‑making framework adaptable to different clinical contexts. The goal is to support precision, patient‑tailored surgical strategies that appropriately balance technical feasibility, oncologic benefit, and overall patient outcome.

Objective To explore the feasibility of day-care laparoscopic appendectomy in college students with acute appendicitis and to develop a nomogram to predict the probability of achieving this model. Methods A prospective cohort study design was adopted, and 82 college students with acute appendicitis admitted from December 2023 to December 2024 were included. All patients underwent laparoscopic appendectomy and integrated traditional Chinese and Western medicine management of enhanced recovery after surgery （ERAS）. They were grouped according to the achievement of the day surgery model. Independent predictors were screened by multivariate logistic regression, and a nomogram was constructed and validated through a triple validation （discrimination-calibration-clinical utility）. Results Among the 82 patients, 46 （56.0%） cases achieved the day surgery model. The hospital stay was 41.37±6.33 hours, and no serious complications were observed during the 30-day postoperative follow-up. The independent influencing factors for achieving this model were C-reactive protein≤13.9 mg/L （OR=1.100, 95% CI：1.005-1.204, P<0.05）, abdominal pain duration≤22 hours （OR=1.160, 95% CI：1.022-1.316, P<0.05）, appendiceal diameter≤10 mm （OR=13.683, 95% CI：1.671-112.073, P<0.05）, no drainage tube placement （OR=6.058,95%CI：1.066-34.428, P<0.05）, and postoperative visual analogue scale （VAS） score≤2.5 points （OR=10.493,95%CI：2.696-40.835, P<0.05）. Based on the logistic regression analysis, these five independent predictive factors were selected to construct a nomogram. The area under the curve （AUC） of this nomogram was 0.905 （95% CI：0.845-0.966）. The calibration curve showed high consistency, and the decision curve confirmed significant clinical net benefit. Conclusion The day-care laparoscopic appendectomy model is safe and feasible for college students. The created nomogram has good predictive ability and can assist in early identification of eligible patients and timely intervention to improve the achievement rate of this model.

Objective To characterize the clinicopathological features of malignant tumors in family members with Lynch syndrome（LS）. Methods Malignant cancer occurrence within a single LS pedigree（14 affected individuals in four generations） were retrospectively analyzed. Six patients were treated in the Colorectal Tumor Center, the Affiliated Hospital of Guizhou Medical University, and the remaining cases were treated in other medical institutions. Family history was systematically collected to construct the intrafamilial malignancy distribution across four generations. Continuous variables that did not meet normality assumptions were summarized as median （Q₁,Q₃）. Results Among the 14 affected individuals （male-to-female ratio,1∶1）, age at onset declined markedly across generations by 45.3 years （generation Ⅱ：69.0 years; generation Ⅲ：23.7 years）. Colorectal cancer was the predominant type of malignant tumors（8/14）, and the proportion of multiple primary cancers was unusually high（5/14）.Of the six patients treated in our center,five exhibited a microsatellite instability-high（MSI-H） phenotype, strongly supporting germline mismatch repair （MMR） gene mutations. Together with LS-spectrum tumors such as endometrial carcinoma （n=2） and glioma, the family members fulfilled the Amsterdam II criteria and exceeded the molecular testing threshold of the Bethesda guidelines. Survival was significantly longer for colorectal cancer than for extracolonic tumors （102.0[36.3,141.0] months vs 12.00[9.80,13.50] months,P<0.001）. Extracolonic tumors showed a higher case-fatality rate （4 deaths among 6 patients）, indicating heterogeneous progression risks among MMR-deficient malignancies. Conclusion This LS pedigree shows a high frequency of multiple primary cancers, a characteristic tumor spectrum, and a trend toward earlier onset across generations.With successive generations, age at onset decreased and the proportion of multiple primaries increased. Overall, the family was characterized by MSI-H. Notably,colorectal cancer outcomes were significantly better than those of extracolonic tumors, which may relate to improved health awareness, regular surveillance,and earlier diagnosis and treatment.The elevated incidence of multiple primaries highlights the need for strengthened dynamic management of high-risk family members.

Objective To identify clinical factors associated with postoperative complications after laparoscopic common bile duct exploration（LCBDE） using the Clavien-Dindo grading system, and to develop and validate a practical prediction model. Methods In this prospective study, 285 consecutive patients undergoing LCBDE at the First People's Hospital of Taicang（January 2023-May 2025） were randomly allocated 2∶1 to a training set（n=190） and a validation set（n=95）.Postoperative complications were recorded and graded by the Clavien-Dindo classification.In the training set, patients who developed Clavien-Dindo grade≥Ⅱ complications formed the even group（n=26）;the remainder constituted the complications grade 0~Ⅰ group（n=164）.Baseline characteristics, comorbidities, laboratory values, and intraoperative variables were compared. Independent predictors of grade≥Ⅱ complications were identified by multivariable logistic regression and used to construct a predictive model. Model discrimination was assessed by receiver operator characteristic（ROC） curve; calibration was evaluated with calibration plots and the Hosmer-Lemeshow test. Results Compared with complications grade 0~Ⅰ patients, those who developed grade≥Ⅱ complications had higher rates of ASA≥Ⅲ, more frequent moderate/severe acute cholangitis, higher Charlson comorbidity index（CCI） scores, and greater intraoperative blood loss; they also had lower serum albumin （all P<0.05）.Multivariable analysis showed ASA≥Ⅲ（OR=3.550, 95%CI： 1.271-9.915）, CCI（OR=2.617, 95%CI： 1.151-5.949）, moderate/severe acute cholangitis（OR=2.171, 95%CI：1.296-3.635）, and intraoperative blood loss（OR=2.872, 95%CI：1.322-6.241） were independent risk factors, while higher albumin was protective（OR=0.426, 95%CI：0.200-0.904）.The final logistic model：logit [P（complication≥Ⅱ）] = -12.874-0.854X₁（albumin） + 1.267X₂（ASA≥Ⅲ） +0.962X₃（CCI） +0.775X₄（moderate/severe cholangitis） + 1.055X₅（intraoperative blood loss）.（For binary predictors, code 1 if present, 0 if absent; continuous predictors are entered as measured.） Model performance was strong： training set area under the curve（AUC）=0.929 （sensitivity 84.62%, specificity 98.17%）; validation set AUC= 0.920 （sensitivity 92.31%, specificity 81.71%）.Hosmer-Lemeshow tests showed good calibration in both sets （training χ²=6.036, P=0.702;validation χ²=7.254, P=0.512）. Conclusion Higher ASA class（≥Ⅲ）, greater comorbidity burden（CCI）, concomitant moderate/severe acute cholangitis, and larger intraoperative blood loss increase the risk of postoperative Clavien-Dindo grade≥Ⅱ complications after LCBDE;higher serum albumin is protective.The internally validated prediction model demonstrates excellent discrimination and calibration and may help identify high-risk patients who would benefit from intensified postoperative management.

Objective To investigate the expression patterns, prognostic value, and immune relevance of cuproptosis-related genes （CRGs） in colon cancer. Methods Bioinformatics analysis was performed to assess differentially expressed CRGs between colon cancer and normal tissues and their functional enrichment.A risk scoring model was constructed using least absolute shrinkage and selection operator（LASSO） and Cox regression, and the prognostic performance was assessed. The association between CRGs and immune cell infiltration/checkpoints was explored via the Tumor Immune Estimation Resource（TIMER） database. Key CRGs were validated by quantitative reverse transcription-polymerase chain reaction （qRT-PCR）. Results Thirty-five differentially expressed CRGs in colon cancer were identified via analyzing the transcriptome of colon cancer （P<0.05）.The CDKN2A gene exhibited the highest mutation frequency （17%）. Based on LASSO regression, independent risk factors were screened as follows： DAXX（HR=1.523,95% CI：1.075-2.158,P<0.05）, PRNP（HR=1.523,95% CI：1.075-2.158,P<0.05）, COX19（HR=1.523,95% CI：1.075-2.158,P<0.05）,CDKN2A（HR=1.523,95% CI：1.075-2.158,P<0.05）, and DLAT（HR=1.523,95% CI：1.075-2.158,P<0.05）. A CRGs-based risk scoring model for the prognosis of colon cancer incorporating the above independent risk factors was created. Based on the median score, patients were divided into the high-risk and low-risk groups. Those in the high-risk group had a significantly shortened survival. This model had a good prognostic value, with an area under the curve （AUC） exceeding 0.7. It was significantly correlated with immune cell infiltration/checkpoints.qRT-PCR confirmed upregulation of DAXX, COX19, and CDKN2A, and downregulation of PRNP and DLAT in colon cancer cells. Conclusion The CRGs-based risk scoring model effectively predicts colon cancer prognosis, and its close association with the tumor immune microenvironment suggests potential therapeutic targets for immunotherapy.These findings provide a theoretical foundation for prognostic assessment and personalized treatment strategies.

Hirschsprung's disease（HD）, or congenital megacolon, is a relatively common congenital malformation of the gastrointestinal tract.The condition, characterized by severe constipation,abdominal pain, and complications such as necrotizing enterocolitis, causes substantial morbidity for affected children and distress for their families.Because early surgical intervention is the treatment of choice, timely diagnosis and accurate identification of the diseased（aganglionic） bowel segment are critical.Rapid advances in artificial intelligence, medical imaging, and related technologies have produced a variety of novel diagnostic approaches for HD with promising performance. This review systematically summarizes the application of machine learning to HD diagnosis across multiple data modalities, including histopathology from rectal biopsy, body‑fluid biomarkers, imaging data, and intraoperative signals, and examines emerging methods for intraoperative identification of aganglionic segments, aiming to inform future research priorities and support translation of machine‑learning tools into clinical practice.