BACKGROUNDS: Neoadjuvant chemoradiation (nCRT) is a standard treatment for rectal carcinoma that reduces tumor size and local recurrence while improving the rate of sphincter preservation. However, many patients remain insensitive to nCRT, with some exhibiting tumor progression. To date, there is still a lack of clinically available prognostic models to differentiate the sensitivity of patients with rectal carcinoma to nCRT. This study aimed to develop a genetic predictive model that predicts the effectiveness of nCRT in patients with rectal carcinoma, offering guidance for future treatments and studies on the underlying mechanisms. METHODS: Based on the NCBI GEO database datasets, key hub genes affecting the efficacy of neoadjuvant chemoradiotherapy in rectal carcinoma were identified using WCGNA. Subsequently, a consistency analysis of 101 model combinations constructed using ten different machine learning algorithms was performed in two independent cohorts, and a prognostic model (chemoradiation resistance score, CRTR score) was developed and validated. Moreover, the clinical applicability of CRTR in immunotherapy and drug selection was investigated using multi-omics analysis and public databases. Finally, the effect of KIF14 on the radiosensitivity of rectal carcinoma cells was studied using in vitro experiments. RESULTS: The CRTR model was composed of 13 genes impacting nCRT sensitivity, whereas six genes (KIF4, DBF4, UBL4A, SLC10A3, PRRG4, and PAPSS2) acted as protective factors and seven (BMS1, DSC2, PROM2, MNAT1, PPID, SMPDL3B, and TNFRSF14) served as risk factors. The CRTR model showed a significant negative correlation with the prognosis of patients with rectal carcinoma undergoing nCRT. Furthermore, patients with higher CRTR values displayed an increased potential to benefit from immunotherapy. Drug sensitivity analysis indicated that aurora kinase inhibitors, telomerase inhibitors, JAK1 inhibitors, and others may enhance the efficacy of nCRT. Finally, we identified KIF14 as the gene that contributed the most to the model and performed preliminary validation. Radiation significantly upregulated the expression of KIF14, and overexpression of KIF14 increased the radiosensitivity of rectal carcinoma cells. CONCLUSION: The CRTR score, based on 13 genes, was able to predict the prognosis of patients with rectal carcinoma undergoing neoadjuvant chemoradiotherapy and demonstrated immense potential in providing personalized risk assessments and recommendations for targeted immunotherapy. The core gene, KIF14, in the CRTR model may serve as a potential predictive biomarker of radiosensitivity in rectal carcinioma.

Hepatic fibrosis is a progressive pathology driven by hepatic stellate cell (HSC) activation and excessive extracellular matrix deposition. While mesenchymal stem cell (MSC) therapies show promise, their clinical translation is hindered by the inherent safety constraints of live cell transplantation. MSC-derived apoptotic vesicles (MSC-ApoVs), a structurally distinct class of extracellular vesicles, emerge as a compelling cell-free alternative. However, their specific therapeutic efficacy and mechanistic targets in hepatic fibrosis remain elusive. MSC-ApoVs were isolated from human umbilical cord MSCs and stringently characterized to exclude non-vesicular contaminants. Their anti-fibrotic efficacy was evaluated in vitro using TGF-β1-activated LX-2 cells and in vivo within a CCl₄-induced murine fibrosis model. To elucidate and functionally validate the underlying mechanisms, we integrated transcriptomic profiling (RNA-seq), dual-luciferase reporter assays, and dual-directional pharmacological interventions. Furthermore, human clinical liver biopsies were analyzed to determine the clinico-pathological relevance of the identified targets. We demonstrated that MSC-ApoVs were efficiently internalized by HSCs, significantly blunting TGF-β1-induced activation, proliferation, and migration, alongside a marked reduction in fibrotic markers (α-SMA, MMP2, and Collagen-I). Transcriptomic screening identified Insulin-like Growth Factor Binding Protein 3 (IGFBP3) as a crucial pro-fibrotic mediator. Mechanistically, MSC-ApoV-enriched miR-409-3p directly targeted and downregulated IGFBP3, thereby restricting the PI3K-AKT signaling cascade—a dependency unequivocally validated by targeted rescue and blockade assays. In vivo, systemic MSC-ApoV administration robustly ameliorated CCl₄-induced hepatic fibrosis and restored liver function. Crucially, clinical analyses revealed a strong positive correlation between elevated IGFBP3 expression and the severity of human fibrotic progression. This study delineates a novel cell-free therapeutic paradigm, demonstrating that MSC-ApoVs mitigate hepatic fibrosis largely through the miR-409-3p-mediated silencing of the IGFBP3/PI3K-AKT axis. By integrating robust in vitro, in vivo, and clinical evidence, these findings highlight MSC-ApoVs as a highly efficacious and translatable alternative to traditional live stem cell therapies for hepatic fibrosis.

Objective:Obesity is closely associated with an altered gut microbiota; however, the role of archaea in obesity remains unknown. We aimed to delineate the alterations in gut archaea in obese subjects and explore the changes in bariatric surgery-associated gut archaeal composition. Methods:Metagenomic sequencing data from 191 obese subjects and 184 lean controls were retrieved from three public cohorts. Of these, 23 obese patients who underwent bariatric surgery were followed up for 3 months. Results:The gut archaea of obese subjects showed significantly lower Shannon diversity index than those of lean controls. Principal component analysis of the gut archaea revealed distinct clusters in obese subjects and lean controls. A model using the 20 top archaeal genera discriminated obese from lean controls with an area under the receiver operating characteristic curve (AUC) of 0.79, 0.83, and 0.86 in three cohorts. Ecological analysis showed decreased trans-kingdom correlations between archaea and bacteria in obese subjects compared to those in lean controls, with partial restoration observed after bariatric surgery. Conclusion:This is the first study to demonstrate that obesity is characterized by gut archaeal dysbiosis across multiple cohorts. Bariatric surgery-induced weight loss is associated with significant changes in the gut archaea.

BACKGROUND:Neoadjuvant immune checkpoint blockade has shown remarkable activity in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H), locally advanced colorectal cancer. Preclinical studies suggest that COX-2 inhibition might modulate the inflammatory tumour microenvironment and augment the effect of PD-1 blockade. We aimed to investigate whether the addition of the COX-2 inhibitor celecoxib to neoadjuvant toripalimab would increase the pathological complete response in this population. METHODS:PICC-2 was a multicentre, open-label, randomised, controlled, phase 2 trial conducted at three academic hospitals in China. Eligible patients were aged 18-75 years; had histologically confirmed dMMR or MSI-H colorectal cancer, of clinical stage T3-T4 or any clinical T stage with lymph node positivity (N+); had an Eastern Cooperative Oncology Group performance status score of 0 or 1; and had adequate haematological, hepatic, and renal function. Participants were randomly assigned (1:1) via an interactive web response system, stratified by tumour location and clinical T stage, to receive neoadjuvant toripalimab plus celecoxib or toripalimab monotherapy every 14 days for 12 cycles, followed by surgery. Toripalimab 3 mg/kg was administered intravenously on day 1 in both groups; patients in the toripalimab plus celecoxib group also received celecoxib 200 mg orally twice daily on days 1-14. The primary endpoint was the proportion of patients with pathological complete response, defined as no presence of residual viable tumour in the primary tumour and all sampled lymph nodes at surgery, assessed by central blinded independent pathological review in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03926338, and is ongoing. FINDINGS:Between May 5, 2022, and Jan 20, 2025, 110 patients were randomly assigned to toripalimab plus celecoxib (n=55) or toripalimab monotherapy (n=55). Overall, 65 (59%) patients were male, all patients were Chinese, 76 (69%) had cT4 tumours, and 105 (95%) had clinically node-positive disease. At the data cutoff date (Oct 10, 2025), median follow-up was 18·1 months (IQR 11·5-25·3). 49 (89%) of 55 patients in each group completed all 12 planned cycles of neoadjuvant therapy. Surgery was done in 53 (96%) of 55 patients in the toripalimab plus celecoxib group and 51 (93%) of 55 in the monotherapy group. Pathological complete response was observed in 49 of 55 patients (89% [95% CI 78-96]) in the toripalimab plus celecoxib group versus 38 of 55 (69% [55-81]) in the monotherapy group (between-group difference 19 percentage points [95% CI 4-34]; p=0·014). Grade 3 treatment-related adverse events occurred in three (5%) patients and four (7%) patients, respectively; grade 3 treatment-related adverse events were tumour perforation (two [4%]) and bowel obstruction (one [2%]) in the toripalimab plus celecoxib group, and rash (one [2%]), tumour perforation (one [2%]), increased aminotransferase (one [2%]), and hypothyroidism (one [2%]) in the monotherapy group. No grade 4 or 5 treatment-related adverse events occurred. INTERPRETATION:In patients with dMMR or MSI-H locally advanced colorectal cancer, neoadjuvant toripalimab plus celecoxib significantly increased the proportion of patients attaining pathological complete response compared with toripalimab monotherapy, with a similar safety profile. These findings support further investigation of this combination strategy in larger phase 3 trials. FUNDING:The National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research, the National Key Clinical Discipline of China, the Program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and the Chinese Society of Clinical Oncology-Junshi Biosciences Oncology Immunity Research. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

BACKGROUND:The efficacy of neoadjuvant chemotherapy combined with dual immune checkpoint blockade in proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced colorectal cancer (LACRC) remains uncertain. METHODS:In this open-label, randomized phase 2 trial (ClinicalTrials.gov: NCT05571644), eligible patients were randomly assigned (1:1:1) to receive 6 cycles of neoadjuvant mFOLFOXIRI plus cadonilimab, mFOLFOXIRI, or mFOLFOX6, followed by surgery and adjuvant chemotherapy. The primary endpoint was pathological complete response (pCR) in the intention-to-treat population. Secondary endpoints included major pathological response (MPR), safety, locoregional recurrence, disease-free survival, and overall survival. FINDINGS:Between July 2023 and August 2024, 123 patients were randomly assigned (41 per group). Neoadjuvant mFOLFOXIRI plus cadonilimab significantly improved pCR compared with mFOLFOX6 (26.8% versus 9.8%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.04 to 13.24; p = 0.046), whereas mFOLFOXIRI alone did not (14.6% versus 9.8%; OR, 1.6; 95% CI, 0.4 to 6.7; p = 0.50). MPR rates were 68.3%, 46.3%, and 43.9%, respectively, and were significantly higher with mFOLFOXIRI plus cadonilimab than with mFOLFOX6 (p = 0.026). Downstaging to ypStage 0-I occurred in 66%, 45%, and 41% of patients in the three groups, respectively, and was significantly higher in the mFOLFOXIRI plus cadonilimab group (p = 0.027). Grade ≥3 adverse events were manageable, with liver enzyme elevation and neutropenia being the most common. CONCLUSIONS:Neoadjuvant mFOLFOXIRI plus cadonilimab significantly improved pCR compared with mFOLFOX6 in LACRC, with a manageable safety profile, supporting further investigation. FUNDING:This work was funded by the National Science Fund for Distinguished Young Scholars (82425045) and the National Natural Science Foundation of China (82272800).

BACKGROUND:A novel bacterial gene marker, Lachnoclostridium (m3), has potential for non-invasive diagnosis of colorectal cancer (CRC) and adenoma. AIM:This study aims to determine the diagnostic performance of m3 in a multi-center cohort and to examine the effect of diet and drugs on fecal m3 in subjects with colorectal neoplasia. METHODS:In a prospective cohort study, we included 2563 subjects (330 CRC, 1119 adenomas, and 1114 controls) from two independent cohorts from Hong Kong and five cities in the Chinese mainland. Stool samples were collected before colonoscopies and bowel preparation. Dietary information was collected using a qualitative dietary questionnaire. Fecal m3 was measured using quantitative PCR (qPCR). Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of fecal m3. The impact of diet and drugs on fecal m3 was investigated using in vitro experiments and multivariate analysis by logistic regression. RESULTS:Fecal m3 could significantly discriminate CRC and advanced adenoma (AA) from normal controls, with areas under the receiver operating characteristic curve (AUROC) of 0.701 and 0.604 (both p < 0.001), respectively. Three types of dietary components (meat, vegetables, and oil) and 15 drugs did not affect fecal m3 levels in vitro. In multivariate analysis, after adjusting for clinical factors, diet and drugs did not have a significant impact on fecal m3 levels in subjects with colorectal neoplasia. CONCLUSION:Fecal m3 levels and diagnostic performance were not influenced by diet and drugs. It can be considered a promising and reliable non-invasive diagnostic biomarker for colorectal neoplasia.

Radiotherapy is an essential component of multimodal treatment for solid tumors, and more than half of patients with cancer receive radiation during their disease course. Because of the unique anatomical and physiological features of the intestine, radiation enteritis (RE) remains a common and clinically challenging complication of abdominal and pelvic irradiation, with limited effective treatment options. In this review, we re-examine RE from a host-microbiome perspective. We summarize classical pathophysiological mechanisms and discuss how radiotherapy reshapes gut microbial composition and metabolism. We also highlight the roles of microbial metabolites, including short-chain fatty acids, bile acids and tryptophan derivatives, in barrier repair, immune homeostasis and stem-cell regeneration. Finally, we discuss microbiome heterogeneity across disease phases, tumor types and host factors, as well as microbiota-mediated gut-brain, gut-cardiopulmonary, gut-skin and gut-bone-marrow axes involved in systemic radiation injury. We further outline microbiome-based strategies for individualized risk stratification and early prediction, and recent advances and limitations of probiotics and synbiotics, fecal microbiota transplantation, dietary and lifestyle interventions, drugs and natural products, engineered microbes and novel delivery systems, highlighting the gut microbiome as a promising entry point to improve prevention and treatment of RE and systemic radiation toxicity.

The Tianhe Procedure is a functional sphincter-preserving surgical approach developed for patients with rectal cancer following radiotherapy. This technique involves proximal extended resection of the colon beyond the pelvic cavity, followed by anastomosis of the non-irradiated proximal colon to the distal rectum or anal canal. This strategy aims to reduce the incidence of anastomotic complications and postoperative bowel dysfunction. However, there is currently a lack of standardized practice guidelines for implementing the Tianhe Procedure in China. Therefore, the Chinese Radiation Intestinal Injury Research Group, the Colorectal Surgery Group of Surgery Branch of the Chinese Medical Association, the Anorectal Branch of Chinese Medical Doctor Association, the Colorectal Cancer Committee of the Chinese Medical Doctor Association, the Colorectal Cancer Committee of China Anti-cancer Association, and the Gastrointestinal Surgical Branch of Guangdong Medical Doctor Association have jointly convened a panel of national experts to discuss and establish this standardized surgical procedure. This standard, based on the latest evidence from literature, research advancements, and expert experience, focuses on key aspects of the Tianhe Procedure, including its precise definition, indications, critical procedural steps, postoperative complications, and functional rehabilitation strategies. It aims to promote standardized implementation and broader clinical adoption of this innovative surgical technique.

Despite advances in systemic therapies, metastatic colorectal cancer (mCRC) remains largely incurable, underscoring persistent gaps in our understanding of metastatic progression and therapeutic resistance. Emerging evidence suggests that gut and tumor-associated microbial communities may contribute to metastatic progression by shaping organ-specific niches, disrupting intestinal and vascular barriers, remodeling immune and stromal microenvironments, and altering host–microbial metabolism. This review synthesizes current evidence on the involvement of gut and intratumoral microbial communities in colorectal cancer metastasis, with emphasis on liver, lung, lymphatic, and peritoneal metastatic patterns; microbial translocation and barrier dysfunction; microbiome–tumor microenvironment interactions; and metabolic pathways such as bile acid, short-chain fatty acid, and tryptophan metabolism. Furthermore, distinct microbial signatures have been associated with responses to chemotherapy, radiotherapy, immunotherapy, and targeted therapies, supporting their potential value as candidate biomarkers for treatment stratification and prognosis, particularly when interpreted alongside treatment exposure and longitudinal microbiome dynamics. Finally, we discuss microbiome-targeted interventions as emerging adjunctive strategies that may help modulate treatment response, while emphasizing the need for standardized, longitudinal, and mechanistically validated studies before clinical translation in mCRC.

ABSTRACT Injectable wet‐adhesive hydrogels represent a promising approach for managing traumatic hemorrhage, yet their clinical translation is often hindered by excessive swelling and inadequate sealing stability. Herein, we report an injectable hydrogel (denoted as PACmC) with rapid coagulation, ultrahigh burst pressure tolerance, and low swelling properties for emergency hemostasis and long‐term wound management. PACmC hydrogel is formed by electrostatic self‐assembly of aminated carboxymethyl chitosan (ACmCS) into nanoparticles, which are then crosslinked with NHS‐activated tetra‐arm polyethylene glycol (Tetra‐PEG‐SS) via rapid NHS‐amine coupling, yielding gelation within 22.3 s. The positively charged ACmCS nanoparticles actively aggregate blood components to accelerate hemostasis, while their densely packed network physically restricts water infiltration, resulting in low swelling ratio of only 49.2% within 7 d. For tissue adhesion, the NHS‐ester groups on Tetra‐PEG‐SS covalently bond with amino groups on the wound surface, and ACmCS nanoparticles serve as multivalent crosslinking centers that enhance cohesive strength, together enabling robust wet‐tissue adhesion (46.5 kPa) and an ultrahigh burst pressure tolerance of 701 mm Hg. In rabbit and porcine models of hepatic and splenic hemorrhage, PACmC hydrogel achieves rapid hemostasis and maintains long‐term sealing compared to clinical hemostats (thrombin powder and gauze), providing a new direction in developing novel hemostatic materials.

The oncologic safety of laparoscopic-assisted surgery for synchronous colorectal cancer (SCRC), a distinct high-risk subgroup, remains under-investigated. This study aimed to compare the short-term and long-term outcomes of laparoscopic-assisted versus open surgery for SCRC. A retrospective analysis of a cohort of 178 consecutive patients undergoing curative-intent surgery for SCRC between June 2007 and April 2019 was performed. To balance baseline covariates for the primary analysis, overlap weighting (OW) was applied to the cohort (133 laparoscopic, 45 open). A 1:1 propensity score matching (PSM) analysis was conducted as a sensitivity analysis. The primary outcomes were 5-year overall survival (OS) and 5-year disease-free survival (DFS). In the primary OW analysis, the laparoscopic group showed significantly less estimated blood loss (median, 100 mL vs. 200 mL; P = 0.003) and shorter time to first liquid diet (median, 4 vs. 5 days; P = 0.005) than the open surgery group. The two groups did not differ significantly in terms of 5-year OS (75.1

Objective: The objective of this study was to develop and validate an innovative risk-stratification tool that integrates Traditional Chinese Medicine (TCM) constitution with clinical factors to enhance colorectal cancer (CRC) screening among asymptomatic Chinese adults. Methods: Conducted as a multicenter investigation, the study involved the randomization of 1430 asymptomatic participants into a derivation cohort (n=953) for model development and a validation cohort (n=477). Data on demographics, TCM constitution, and colonoscopy results were gathered using the TCM-Asia-Pacific Colorectal Screening (TCM-APCS) Questionnaire. A risk score was constructed through multivariable logistic regression analysis and its performance was assessed using receiver operating characteristic (ROC) analysis. Results: The TCM-APCS model proficiently stratified participants into low-, medium-, and high-risk categories. Among individuals classified within the high-risk group, there was a significantly elevated prevalence of both low-grade adenoma (44.1% compared to 7.3%, p< 0.001) and advanced colorectal neoplasia (17.2% compared to 3.6%, p< 0.001) when contrasted with the low-risk group. The model demonstrated strong discriminatory capability for advanced neoplasia, exhibiting enhanced predictive performance relative to the original Asia-Pacific CRC Screening score. Additionally, at the optimal threshold, the model accurately identified 71.1% of advanced neoplasia cases within the validation cohort. Conclusion: The TCM-APCS score is an effective, validated tool for risk-stratified CRC screening in China, enabling targeted resource allocation and enhanced screening efficiency in resource-constrained settings. Further external validation in diverse populations is warranted.

Background: Limited research exists on colorectal cancer (CRC) patients with bladder invasion, with survival outcomes post-cystectomy underexplored and a debate between partial and total cystectomy ongoing. Objective: The study aimed to evaluate the effect of pathological bladder invasion on the long-term tumour prognosis of patients with clinically diagnosed bladder invasion in CRC after cystectomy. Design: Retrospective, cohort study. Methods: Our study involving 105 CRC patients with bladder invasion who had partial or total cystectomy from 2012 to 2020 collected surgical and pathological data. Groups were divided by pathological bladder invasion presence and compared for 3-year overall survival (OS) and recurrence-free survival (RFS) rates. Multiphoton imaging assessed collagen features in some samples. Results: Pathological bladder invasion was confirmed in 50 patients (48%). Of 94 who had partial cystectomy, 41 were in the bladder invasion (+) group. The 3-year OS and RFS rates were 62.97% and 57.35% for the bladder invasion (+) group, and 77.16% and 58.68% for the bladder invasion (−) group, with no significant differences in recurrence rates between groups ( p > 0.05). There are also no significant differences in 3-year local recurrence and intravesical recurrence rates between the two groups (18.62% vs 25.83%, 7.73% vs 11.82%, p > 0.05). Distant metastasis was identified as an independent risk factor for OS and RFS by univariate and multivariate Cox regression analyses. Of the 24 samples that underwent multi-photon imaging, 142 collagen features extracted did not show statistical differences. Conclusion: Pathological bladder invasion impacts CRC patients’ post-cystectomy survival may be less than what clinical practice implies. Partial cystectomy in cases with pathological bladder invasion might offer similar survival rates to total cystectomy. Trial registration: ChiCTR2300077861.

BACKGROUND AND AIMS:The relationship between gut microbiota and biological treatment response in inflammatory bowel disease (IBD) remains incompletely understood. We sought to characterize microbial signatures associated with clinical remission and develop a prediction model for clinical remission. METHODS:We analyzed 16 S rRNA gene sequencing data from two independent public cohorts (n = 231) treated with biologics (infliximab: n = 23; adalimumab: n = 22; ustekinumab: n = 186). Microbial diversity and taxonomic compositions were compared between the remission and non-remission groups. Random Forest algorithm was employed to construct a prediction model using differential genera and clinical features, with performance evaluated through cross-validation. The model was further validated in a local cohort (n = 29). RESULTS:Significant differences in alpha and beta diversity were observed between the remission and non-remission groups (p < 0.05). MaAsLin2 analysis identified 25 differentially abundant genera (p < 0.05). Among these, we selected the top 10 genera with highest importance scores (Parabacteroides_B_862066, Agathobaculum, Ruminococcus_E, Sutterella, Clostridium_R_135822, Hominilimicola, Onthenecus, Butyricimonas, Bariatricus, Hominenteromicrobium) to build the Random Forest model, notably all enriched in remission patients. The model demonstrated robust predictive performance for clinical remission (AUC: 0.895), which was further validated in the local cohort (AUC: 0.750). CONCLUSION:There is a relationship between gut microbial signatures and biological treatment outcomes in IBD patients. A predictive model based on gut microbiota composition may help stratify patients for treatment response. Further investigation of microbiome modulation strategies may enhance therapeutic efficacy.

Exudate management and cell activity enhancement are vital to complicated wound healing. However, current exudate management dressings indiscriminately remove exudate, which is detrimental to cell activity enhancement. Herein, a novel class of electroactive bilayer (cMO/PVA) dressing is developed by constructing manganese oxide nanoneedle-clusters decorated commercial carbon cloth (MO), in situ casting polyvinyl alcohol (PVA) hydrogel, and finally charging. Benefitting from the hierarchical nanoneedle-cluster structure of MO, abundant active sites are sufficiently exposed to achieve high area-specific capacitances (e.g., 1881.3 mF cm-2), thereby establishing the long-lasting electric field for cMO/PVA dressing. Such a unique cMO/PVA dressing can realize extraordinary selective sorption toward noxious substances over nutrient substances during exudate management. Meanwhile, its long-term electrical stimulation therapy can promote cell proliferation and migration and enhance antibacterial property. As a result, our multifunctional cMO/PVA dressing can rapidly repair full-thickness wounds in type II diabetic rats, offering an advanced strategy for the treatment of complicated wounds.

This article discusses Wang et al ’s essay. Endoscopic biliary stenting, a less invasive alternative to surgery, is effective for malignant obstructive jaundice. This article summarizes the pathophysiology of biliary obstruction, the technical aspects of stenting, and the clinical outcomes. By comparison of endoscopic stenting with percutaneous biliary drainage, improvements and complications are focused on. Additionally, patient selection for stenting and future advancements in stent technology are important. Overall, endoscopic biliary stenting is a valuable palliative option for patients with malignant jaundice, especially those ineligibles for surgery.

In situ therapies show significant promise for the treatment of unresectable tumors that lack tumor supply vessels. However, it remains a tremendous challenge to achieve precise delivery and sustained release of anti-tumor agents with synergistic anti-tumor efficacy. Here, a novel in situ injectable hydrogel (denoted as CFe/βCP+Cis hydrogel) has been designed by integrating β-CD-g-PEGMA (βCP) molecular brush hydrogel with functional carbon nanozyme (CFe) and cisplatin. The reversible gel network of βCP hydrogel and the rigid nanoscale architecture of CFe endow CFe/βCP+Cis hydrogel with properties conducive to injectability and long-term retention (more than 63 days). CFe and cisplatin mixed in hydrogel are both gradually released into the tumor tissue, facilitating the synergistic anti-tumor efficacy via ferroptosis and cytotoxicity. In addition, CFe/βCP hydrogel can reduce the M2-like/M1-like ratio of macrophages and promote the infiltration of CD8+ T cells in the tumor microenvironment to enhance anti-tumor immunity. As a result, the CFe/βCP+Cis hydrogel demonstrates significant potential for precise and sustained tumor treatment through chemodynamic therapy, chemotherapy, immunoregulation, and long-term retention properties.

BACKGROUND:Individualized postoperative management of colorectal ovarian metastases demands precision medicine tools, yet current approaches lack consideration of prognostic heterogeneity and targeted therapy benefit guidance and suffer from high costs and long turnaround times of genetic testing. METHODS:In this retrospective, prospective multicohort study, we developed and validated an interpretable transformer-based transfer learning model to predict patient prognosis, targeted therapy benefits and molecular mutations by integrating digital pathology with RNA data. The performance of the model was assessed with the AUC, accuracy, sensitivity, specificity, PPV and NPV. RESULTS:The model accurately predicted peritoneal recurrence, with AUCs of 0.90, 0.74, and 0.83 across patient cohorts. It also achieved precise prognostic stratification for peritoneal recurrence-free survival in the training (HR = 107.22, 95% CI 24.18-475.52; p<0.001), external test (HR = 4.97, 95% CI 1.16-21.37; p = 0.03), and prospective test (HR = 10.53, 95% CI 2.02-54.94; p = 0.01) sets. The model revealed a significant association between prognostic stratification and tumor microenvironment heterogeneity (p < 0.05), thereby enhancing its biological interpretability. Further analysis revealed that only patients classified as high risk with BRAF/RAS mutations could benefit from the addition of targeted therapy to adjuvant chemotherapy (HR 0.38, 95% CI 0.18-0.79; p = 0.007). Moreover, the model predicted BRAF/RAS mutations with AUCs of 0.96/0.94 in the training set, maintaining cross-cohort generalizability with AUCs of 0.64-0.83. CONCLUSIONS:This pathobiology-based deep learning model can robustly detect prognosis and mutation and identify targeted therapy beneficiaries, serving as a potential precision tool in clinical decision-making for the management of colorectal ovarian metastases.