Persistent luminescence is a promising approach for photodynamic therapy (PDT) in deep-seated tumors, as it provides sustained light within tissues, eliminating the need for continuous external illumination. However, the uncontrollability of light within the body complicates precise spatiotemporal regulation. In this study, we report X-ray preactivated elimusertib-loaded tumor-targeted photodynamic nanoparticles (ETPNs), featuring reversible "on-off" afterglow properties. The excellent afterglow properties of X-ray-activated porous NaYF4:Er@NaGdF4 persistent luminescence nanoparticles enable the continuous activation of chlorin e6 (Ce6) to generate reactive oxygen species (ROS), leading to DNA damage. The integration of elimusertib potentiates ROS-induced DNA damage and activates the cGAS-STING pathway, thereby enhancing immuno-photodynamic therapeutic efficacy. All in vivo experiments were conducted using female mice. Our findings highlight the potential of ETPNs to advance the therapeutic landscape for deep-seated tumors, offering a robust and controllable platform for combined immuno-photodynamic therapy.

Radiation-induced liver disease (RILD) poses a major clinical challenge in radiotherapy, transplantation preconditioning, or radiation accidents, yet its pathogenesis is poorly understood due to limited animal models. Here, we establish a translational pig model recapitulating human RILD pathology within 4 weeks post-40 Gy irradiation, featuring veno-occlusive disease (VOD) and centrilobular necrosis. Single-cell atlas analyses identify ferroptosis as a key driver of hepatocyte death during RILD initiation. Ferroptosis inhibition with liproxstatin-1 (Lip-1) not only prevents RILD progression but also reverses histological damage and restores liver function. Mechanistically, Lip-1 treatment restores dysregulated gene expression profiles, particularly associated with hepatocyte ferroptosis, while stimulating hepatic regeneration via coordinated proliferation of hepatocytes and endothelial cells. Our findings establish ferroptosis inhibition as a therapeutic strategy for RILD, demonstrating its dual role in cytoprotection and regeneration. This large animal model provides a robust platform to optimize radiotherapy regimens, improve transplant conditioning, and develop targeted radioprotectants.

Background/Aims Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Recurrence and metastasis are the primary causes of mortality in hepatocellular carcinoma (HCC), primarily driven by an immunosuppressive tumor microenvironment. This study developed a multifunctional flexible patch (MnO2-P-ICG NFs) based on electrospun SiO2 gel fibers whose surface is modified with a layer of "nest-like" MnO2. The patch enables the co-delivery of indocyanine green (ICG) and pachymaran directly to the tumor site via a laparoscopic system. Under near-infrared light irradiation, ICG serves as a photosensitizer for photodynamic therapy (PDT), effectively ablating tumors and inducing immunogenic cell death (ICD), thereby activating antitumor immunity. Meanwhile, pachymaran, with its immunomodulatory effects, preferential activates natural killer (NK) cells to exert antitumor effects. Additionally, PDT further enhances this immune response by activating the cGAS-STING pathway. In mouse models, implantation of the patch significantly inhibited primary liver tumor progression and ascites formation. In a malignant liver tumor model, MnO2-P-ICG NFs prevented local recurrence in 80% of treated mice. Notably, both the depletion of NK cells and the blockade of the cGAS-STING pathway compromised the therapeutic efficacy of MnO2-P-ICG NFs. Clinically, tumors with higher NK cell infiltration were associated with improved patient outcomes. In conclusion, this versatile patch provides a promising therapeutic strategy for patients with advanced HCC.

Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver malignancy with a rising global incidence and limited therapeutic options. Vascular invasion (VI) is a hallmark of advanced disease, correlating with early recurrence and dismal prognosis, yet its tumor microenvironment (TME) drivers remain elusive. We analyzed single-cell RNA sequencing (scRNA-seq) data from 25 ICC samples to systematically characterize the cellular composition and molecular features related to VI. By integrating bulk RNA-seq data, spatial transcriptomics, and multiplex immunofluorescence, we identified a distinct subset of tumor-like cancer-associated fibroblasts (CAFs), termed tCAFs, enriched in VI-positive tumors. Functional enrichment analyses revealed that tCAFs were prominently associated with hypoxia and angiogenesis pathways, findings corroborated by the significant upregulation of tCAF markers (MME and NT5E) in ICC-derived CAFs under hypoxic conditions in vitro. Cell-cell communication analysis and spatial mapping uncovered that tCAFs might promote VI primarily through VEGF signaling interactions with endothelial cells. Integrative bioinformatics and RT-qPCR validation identified three key functional genes in tCAFs: SLC2A1, PTGS2, and PLOD2. In endothelial sprouting assays, pharmacological inhibition of SLC2A1 exerted a pronounced suppressive effect. Consistently, sprouting assays using ICC-derived CAFs with SLC2A1 knockdown confirmed that its downregulation significantly reduced endothelial sprouting capacity. Importantly, administration of the SLC2A1 inhibitor BAY-876 effectively suppressed tumor progression and intrahepatic metastasis in the orthotopic ICC mouse model. Our findings define a VI-associated cellular ecosystem and molecular landscape in ICC, unveiling a novel hypoxia-tCAFs-endothelial cells axis. Furthermore, we identify SLC2A1 as a clinically relevant therapeutic target, offering new insights into tumor VI.

Ribosome heterogeneity has emerged as a regulatory layer in gene expression, yet its biological roles in cancers remain poorly characterized. Here, we identify RPL22L1, a paralog of the ribosomal protein RPL22, as a key modulator of DNA damage response (DDR) in colorectal cancer cells. DNA damage induces RPL22L1 upregulation and ribosomal incorporation, forming RPL22L1-specific ribosomes. Ribosome profiling reveals that RPL22L1-containing ribosomes preferentially translate mRNAs with highly structured 5' untranslated region (5'UTR). In particular, RPL22L1 enhances the translation of ATRX through a cap-independent mechanism. ATRX subsequently recruits DNA-PKcs to DNA damage sites, thereby enhancing the DNA repair capacity. RPL22L1 loss creates exploitable DDR vulnerabilities, sensitizing cancer cells to cisplatin and PARP inhibitors in vitro and in vivo. Collectively, these findings uncover a specialized ribosome-mediated translational program in DDR and highlight RPL22L1 as a potential therapeutic target in DDR-based cancer therapy.

Background:Papillary thyroid carcinoma (PTC) is the most common type of primary endocrine malignancy. The tumor immune microenvironment (TIME) and genetic alterations play crucial roles in the progression of PTC. With the advance in research, there has been a heightened focus on re-evaluating molecular targeted therapies and identifying novel targets through molecular biology-based approaches. This study aimed to identify robust prognostic biomarkers and to construct a reliable risk model for patients with PTC by integrating multiomics data. Methods:RNA-sequencing (RNA-seq) data from six Gene Expression Omnibus (GEO) datasets and genome-wide association study (GWAS) data were integrated to identify differentially expressed genes (DEGs) and facilitate Mendelian randomization (MR) analysis for causal inference. The CIBERSORT algorithm was employed to evaluate immune cell infiltration. A prognostic risk model was constructed via least absolute shrinkage and selection operator (LASSO) Cox regression and validated in The Cancer Genome Atlas (TCGA) and GEO cohorts. Functional experiments, including Cell Counting Kit-8 (CCK-8), transwell, and wound-healing assays, were conducted to investigate the role of the key gene ALOX15B in PTC cells. Results:We identified seven PTC-associated genes (ALOX15B, TIAM1, TMC6, GPX3, RAP1GAP, JUN, and PAPSS2) through expression quantitative trait loci and MR analysis. A robust three-gene risk model (ALOX15B, RAP1GAP, and JUN) was established. Patients in the high-risk group exhibited significantly poorer progression-free survival (PFS), which was confirmed to be an independent prognostic factor by multivariate analysis [hazard ratio =1.355, 95% confidence interval (CI): 1.052-1.746; P=0.02]. The high-risk group was characterized by an immunosuppressive TIME-including decreased CD8+ T-cell and increased regulatory T-cell abundance-higher tumor mutational burden, and a higher frequency of BRAF mutations. Conversely, the low-risk group showed a higher prevalence of NRAS mutations. In addition, functional assays in vitro revealed that ALOX15B markedly enhanced the proliferative, migratory, and invasive capacities of PTC cells. Conclusions:A novel three-gene signature was developed and was demonstrated to be an independent prognostic indicator for patients with PTC. This model effectively reflects the intrinsic characteristics of the TIME and genomic instability and can inform risk stratification and therapeutic targeting. Due to its oncogenic activity, ALOX15B may represent a viable therapeutic target in PTC.

The limited efficacy of immunotherapy in hepatocellular carcinoma (HCC) is largely attributed to the formation of an immunosuppressive tumor microenvironment, in which abnormal cholesterol metabolism plays an important role. Here, we investigated the effects of signaling lymphocytic activation molecule family member 7 (SLAMF7) on the cholesterol metabolism of HCC. Metabolomics was performed in spontaneous HCC tissues with hepatocyte-specific Slamf7 knockout. An in vitro coculture system was constructed, and cytokine matrix, protein profiling, and transcriptome sequencing were applied to explore the function of SLAMF7 in HCC. Profiling of the metabolomics of spontaneous HCC with Slamf7 knockout and the proteomics of SLAMF7-overexpressing HCC cells clarified the inhibition of cholesterol synthesis by SLAMF7 in HCC cells. Furthermore, HCC cell-intrinsic SLAMF7 inhibited membrane cholesterol efflux and function reprogramming in macrophages. Mechanistically, SLAMF7 interacted with DHCR24 and enhanced the binding and ubiquitination degradation of DHCR24 by MARCH6 via its intracellular domain to inhibit cholesterol synthesis in HCC cells. Reduction of cholesterol content in lipid rafts impaired the AKT activation and promoted entry of dephosphorylated FOXO1 into nucleus for IL-7 transcription. Subsequently, IL-7 reduced membrane cholesterol efflux by inhibiting the NF-κB pathway and ABCA1 transcription in macrophages. Pharmacological enhancement of IL-7 signaling improved the efficacy of anti-PD-1 antibody in HCC mouse models with low SLAMF7 level. Our study molecularly identifies a key role of SLAMF7 in cholesterol metabolism and trafficking between HCC cells and macrophages and gives a rationale for targeting IL-7 signaling as an effective strategy to sensitize HCC to immunotherapy. A critical role of tumor cell-intrinsic SLAMF7 in cholesterol metabolism and trafficking between HCC cells and macrophages.

Infectious wounds induce a cycle of bacterial proliferation, oxidative stress accumulation, and dysregulated macrophage polarization, collectively hindering tissue repair. Conventional wound dressings typically address these pathological factors in isolation, resulting in suboptimal therapeutic outcomes. Here, we report the design of a biocompatible multifunctional hydrogel (GAPC). This system integrates self-assembled Proanthocyanidin/Chlorhexidine nanoparticles into a dual-network GelMA/ADM scaffold. Consequently, the hydrogel exhibits simultaneous antibacterial activity, ROS scavenging, and immunomodulatory capacity. In vitro, GAPC hydrogel has superb antibacterial, antioxidant, and anti-inflammatory effects. On the other hand, GAPC hydrogel promotes M1-to-M2 macrophage transition and preserved cellular viability under oxidative stress. Furthermore, in vivo it accelerated infected burn wound closure, enhanced collagen remodeling, and stimulated neovascularization. Collectively, GAPC hydrogel interrupts the “infection-oxidative stress-inflammation” loop, offering a safe and promising option for managing infected wounds.

Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a chronic, relapsing inflammatory disorder of the intestine driven by disruption of mucosal immune balance. In this context, mucosal inflammation, oxidative stress, and damage to the epithelial barrier reinforce one another and form a self-perpetuating cycle. Oral nanozymes that combine catalytic removal of reactive oxygen species with in vivo imaging readouts provide a potential platform for site-focused intervention and imaging-based evaluation of IBD. This review focuses on how oral nanozymes are designed to couple imaging and therapy and summarizes recent progress in two overarching directions: single-modality imaging-guided strategies and multimodal imaging-guided strategies. Within the single-modality group, current studies are discussed mainly as computed tomography (CT)-guided strategies and optical/photoacoustic (PA)-guided strategies according to their dominant signal-generation mechanisms. Multimodal imaging-guided strategies, by contrast, integrate structural and functional information on a single platform to support more informative preclinical assessment of IBD. This paper also discusses current limitations in oral delivery, characterization of enzyme-like activity, imaging assessment, and long-term biosafety, thereby outlining key design principles for the next generation of oral nanozymes for visual theranostics in IBD.

Successful treatment of resectable intestinal diseases hinges on advanced intestinal anastomosis techniques and effective postoperative management. However, current postoperative adjuvant therapy remains limited to systemic administration of medications after conventional hand-sewn anastomosis, frequently leading to associated complications and potential recurrence. Here, we introduce a microneedle anastomotic stent (MAS) for postoperative intestinal healing and localized drug delivery in resectable intestinal diseases. This MAS integrates a biodegradable polyglycolic acid stent with a stimulus-responsive polyprodrug microneedle patch. This design provides robust mechanical properties, effective prevention of anastomotic leakage, and on-demand drug release at the anastomotic site. After intestinal resection, the MAS is implanted at the anastomotic site, where the microneedles penetrate the mucosal layer and release the anti-inflammatory drug in response to hyperinflammatory conditions, thereby attenuating local inflammation and facilitating anastomotic healing. In vitro assays verified the minimal cytotoxicity and good biocompatibility of the MAS and its degradation products. The efficacy of the MAS in tissue penetration and stimulus-responsive drug release was demonstrated using ex vivo patient samples. The in vivo therapeutic benefit and mechanism of the MAS were validated in the murine radiation colitis model, and its feasibility and safety were further confirmed in the minipig model of ischemic inflammatory injury. The MAS also exhibited versatility as a delivery platform for diverse therapeutics, suggesting potential applications in complex intestinal diseases. Compared with conventional methods, in preclinical studies, the MAS offered a sutureless approach for intestinal anastomosis and postoperative adjuvant therapy, holding potential for treating various resectable intestinal diseases.

Background: The prognostic factors for survival outcomes in patients with hepatocellular carcinoma (HCC) are not well defined. This study aimed to identify the prognostic factors for HCC and to construct a predictive nomogram model. Methods: A total 165 patients with HCC were identified between 25 January 2010 and 10 November 2021. Independent prognostic factors were identified using univariable and multivariable Cox regression analyses. A nomogram was constructed to predict the patient survival rate. The concordance index (C-index), area under the curve (AUC), and calibration curves were used to assess the predictive accuracy and discrimination of the model. Decision curve analysis was used to confirm the clinical utility of the nomogram. Results: A total of 165 patients were randomly selected retrospectively. Univariable and multivariable analyses revealed that body mass index, albumin, carbohydrate antigen 19-9 (CA19-9), tumor size, and tumor size, lymph node, metastasis (TNM) stage were independent factors for predicting patient survival. We constructed a 1-, 3-, and 5-year survival rate prediction clinical model by using these independent prognostic factors, which yielded C-indexes of 0.838, 0.798 and 0.725, respectively. On the basis of the AUCs and calibration curve and decision curve analyses, we concluded that the prognostic model for HCC exhibited excellent performance. Conclusions: The clinical model demonstrated good calibration, discrimination, clinical utility, and practical decision-making effects for the outcomes of patients with HCC. These findings may help oncologists and surgeons make better clinical decisions.

ABSTRACT Background Biliary tract cancer (BTC) is an aggressive malignancy characterized by a high recurrence rate and poor postoperative prognosis, despite advances in adjuvant therapy. This phase II study evaluated the efficacy and safety of a novel adjuvant regimen combining envafolimab, lenvatinib, and capecitabine in patients with BTC at high risk of recurrence following R0 resection. Methods This single‐center, open‐label, single‐arm phase II trial enrolled patients with high‐risk recurrence factors after curative resection. Patients received envafolimab (400 mg subcutaneously once every 3 weeks), Lenvatinib (8 mg orally once daily), and capecitabine (1000 mg/m2 orally twice daily, 2 weeks on/1 week off, continued without cycle limitation). The primary endpoint was disease‐free survival (DFS); secondary endpoints included overall survival (OS) and safety. Results 28 of 30 screened patients were included in the final analysis. The median DFS was 15.63 months, and the 1‐year DFS rate was 68.3%. Median OS was not reached but 1‐year OS was 91.4%. Treatment‐related adverse events (TRAEs) occurred in 17 patients, with grade 3/4 TRAEs observed in eight patients. No treatment‐related deaths were reported. Exploratory analysis suggested that baseline CA19‐9 levels were significantly associated with early recurrence. Conclusions The adjuvant combination of envafolimab, lenvatinib, and capecitabine demonstrates promising efficacy and a manageable safety profile in high‐risk BTC patients after R0 resection. However, these findings still require validation in larger, multicenter, randomized controlled trials.

Liver fibrosis is a major contributor to global mortality due to its progressive disruption of hepatic architecture and function, and it remains a critical unmet medical need. Hepatic stellate cells (HSCs) are considered a key therapeutic target owing to their central role in fibrosis progression, primarily mediated through the TGF-β1/Smad2/3 signaling pathway. Pirfenidone (PFD), a clinically approved broad-spectrum antifibrotic agent, shows potential for repurposing in liver fibrosis therapy. However, its clinical translation is limited by poor aqueous solubility and a lack of cellular targeting specificity. To address these limitations, we developed a vitamin A–conjugated liposomal delivery system (P@GB-Lipo-VA) to enhance the liver-specific accumulation of PFD. In vitro studies demonstrated that P@GB-Lipo-VA significantly increased cellular uptake in TGF-β1–stimulated LX-2 cells and reduced oxidative stress. In a bile duct ligation (BDL)–induced mouse model of liver fibrosis, P@GB-Lipo-VA effectively alleviated collagen deposition, improved liver function, and suppressed activation of the TGF-β1/Smad signaling pathway. These findings support P@GB-Lipo-VA as a promising targeted nanotherapeutic platform for enhancing the efficacy and safety of PFD in the treatment of liver fibrosis.

Tumor evolution enables liver cancer cells to acquire survival advantages and evade therapy-induced cell death. However, the role of natural killer (NK) cells in liver cancer evolution remains unclear. Here, we establish immune-humanized spatiotemporal liver cancer models and integrate single-cell, spatial transcriptomic, and CRISPR/Cas9 screening analyses to investigate this process. We demonstrate that early NK cell-mediated immunosurveillance promotes tumor cell state transition and impairs subsequent adaptive immune responses. Mechanistically, NK cells induce lipid metabolic reprogramming, particularly cholesterol accumulation, and enhance tumor stemness, both of which promote liver cancer evolution. Furthermore, combined anti-LAG-3 treatment and liver X receptor activation suppress tumor evolution and improve the efficacy and durability of immune checkpoint blockade in advanced liver cancer. Collectively, our findings identify that NK cell-mediated early immunosurveillance promotes liver cancer evolution and suggest immunometabolic therapy as a potential strategy for advanced liver cancer.

To compare the effects of multikinase inhibitors (sorafenib/lenvatinib) and immune checkpoint inhibitors (PD-1/PD-L1) on anxiety, depression, and quality of life (QoL) in patients with advanced hepatocellular carcinoma (HCC) and to analyse their correlations with clinical indicators. This retrospective cohort study included 304 patients with advanced HCC (BCLC stage B/C) who received first-line monotherapy between 2018 and 2023. Propensity score matching (1:1) was used to categorize patients into two groups: those treated with multikinase inhibitors (n = 152) and those treated with PD-1/PD-L1 inhibitors (n = 152). Anxiety and depression (Hospital Anxiety and Depression Scale (HADS)), and QoL (EORTC QLQ-C30) were assessed at baseline and during follow-up (every 3 months). Correlations between the treatment duration, survival outcomes, and adverse events (AEs) were analysed. The PD-1/PD-L1 group presented significant reductions in anxiety (HADS-A: mean difference [MD] = − 2.4) and depression (HADS-D: MD = − 2.3) at 6 months (both *p < 0.001), with lower rates of clinically significant anxiety (28.3% vs. 42.1%) and depression (24.3% vs. 38.8%; p < 0.05). QoL improved markedly (6-month MD = + 10.3, p < 0.001), particularly when the treatment was administered as the first-line therapy (MD = + 14.2 vs. second-line MD = + 3.8; interaction p < 0.001). PD-1/PD-L1 inhibitors were associated with longer treatment durations (median 9.5 vs. 5.8 months, p < 0.001) and superior overall survival (median 18.2 vs. 12.5 months; HR = 0.62, p = 0.002). Fatigue (grade ≥ 2) independently predicted depression (OR = 1.82, p = 0.002), whereas immune-related AEs were correlated with a reduced QoL (ρ=−0.22, p = 0.004). Compared with multikinase inhibitors, PD-1/PD-L1 inhibitors significantly improve the psychological outcomes, QoL, and survival of patients with advanced HCC, especially when administered as first-line therapies. Fatigue is a critical modifiable risk factor for depression. These findings support prioritizing immunotherapy when treating atients with advanced hepatocellular carcinoma.

Background: A significant portion of primary liver cancer patients in China are diagnosed at intermediate-to-advanced stages, often making them ineligible for curative surgery. Furthermore, high postoperative recurrence rates, reaching up to 70%, pose a major challenge for long-term survival. The emergence of novel systemic treatments, such as immune checkpoint inhibitor combinations, and advancements in locoregional therapies have created new opportunities for conversion and perioperative strategies. This updated consensus aims to standardize the clinical application of these therapies based on the latest evidence, with the objective of improving patient prognosis. Methods: A multidisciplinary committee of 97 experts was convened to revise previous guidelines. The process involved a comprehensive search of medical databases and conference proceedings, with evidence graded according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Consensus statements were finalized through a formal electronic voting process, requiring at least 80% agreement for approval, resulting in 18 updated statements. Results: The consensus provides refined definitions for conversion and perioperative therapy. It recommends various strategies for oncological conversion, including systemic therapy with anti-angiogenic drugs plus immunotherapy, and locoregional approaches like precision transarterial chemoembolization (TACE) and hepatic artery infusion chemotherapy (HAIC). The document strongly affirms surgical resection as a crucial step for achieving long-term survival after successful conversion and offers guidance on surgical timing and adjuvant therapy. For resectable patients with high-risk features, neoadjuvant and adjuvant treatments are outlined to mitigate recurrence. The consensus also advocates for using dynamic enhanced magnetic resonance imaging ( MRI) and the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria for efficacy assessment and underscores the essential role of a multidisciplinary team in management. Conclusions: This updated consensus offers standardized, evidence-based guidance for clinicians on implementing conversion and perioperative strategies to optimize patient-centered care and highlights the need for continued research to further refine these promising approaches.

e16289 Background: Surgery remains the cornerstone of curative treatment for cholangiocarcinoma. However, recurrence rates remain high (60-70%) even after R0 resection, particularly in high-risk patients This study aimed to evaluate the efficacy and safety of an adjuvant regimen combining capecitabine, lenvatinib, and envafolimab for high-risk patients following R0 resection of cholangiocarcinoma. Methods: This open-label, single-arm, phase II trial was conducted at the Sir Run Run Shaw Hospital. Patients with histologically confirmed R0-resected cholangiocarcinoma and at least one of high-risk features (e.g., lymph node positivity, nerve invasion, or vascular invasion) were consecutively enrolled. The treatment protocol included envafolimab (400 mg subcutaneous injection every three weeks for up to 35 cycles), capecitabine (oral administration of 1000 mg/m² for two weeks followed by one week off, every three weeks, without cycle limit), and lenvatinib (oral administration of 8 mg every three weeks for up to eight cycles). The primary endpoint was disease-free survival (DFS), and secondary endpoints were overall survival (OS) and safety. Results: Between July 2023 and May 2024, a total of 30 patients were recruited, with 28 included in the efficacy and safety analysis. As of January 2025, the median follow-up period was 16.9 months. Notably, the median DFS was observed to be 16.3 months, while the median OS data remain immature with a 1-year OS rate of 92.9%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with grade ≥3 TRAEs reported in 68%. Treatment discontinuation due to TRAEs affected 10% of participants, and no treatment-related mortalities were recorded. Conclusions: The combination of envafolimab, lenvatinib, and capecitabine demonstrated promising DFS with acceptable toxicity in the adjuvant setting for high-risk cholangiocarcinoma patients post R0 resection. These results highlight the potential of this therapeutic approach and warrant further investigation through randomized controlled trials. Clinical trial information: ChiCTR2300074241 .

Appropriate suture tension is crucial for effective wound healing, as improper tension may lead to wound dehiscence or ischemia. Advances in bioelectronic sutures enable monitoring and therapy, but reliance on external power or complex circuits limits their use in long-term and minimally invasive applications. Herein, a self-powered bioelectronic suture (B-suture) is reported that enables real-time tension monitoring during suturing. The B-suture integrates a conductive composite within a capillary structure. Hybrid laser processing, combining continuous wave laser-induced phase separation and femtosecond laser-engraved microstructures, greatly enhances electro-mechanical properties and triboelectric sensing performance. The triboelectric nanogenerator-based principle enables tension detection in the 0-2 N range. In vitro and in vivo evaluations demonstrate biocompatibility and precise monitoring of suturing tightness. By providing real-time quantitative feedback, the proposed B-suture affords to improve wound closure quality, reduce postoperative complications, and advance bioelectronic applications in surgical practice.