This study introduces the Sono@NAT10 nanorobot for colorectal cancer (CRC) immunotherapy, designed to target NAT10 condensates in macrophages. Sono@NAT10, enclosed in a macrophage membrane using a metal–organic framework, shows stability under acidic conditions and releases NAT10 siRNA upon ultrasound activation. Flow cytometry and confocal imaging confirm effective macrophage targeting. Sequencing and proteomics reveal that NAT10 regulates SRSF2 protein stability, thereby promoting the transition of macrophages from the M2 to the M1 phenotype. In a CRC mouse model, Sono@NAT10 combined with anti‐PD‐1 (CD279) antibody inhibited tumor growth and enhances survival. These findings demonstrate the potential of Sono@NAT10 as a novel immunotherapeutic strategy for CRC by modulating NAT10 phase separation, providing a foundation for further exploration of its clinical application.

Background: The prognostic value of systemic inflammatory biomarkers in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. This study aimed to compare their predictive performance and identify the most effective indicator. Methods: We retrospectively analyzed 312 iCCA patients who underwent curative resection at three medical centers (2014– 2022). Twelve systemic inflammatory biomarkers, derived from routine blood parameters (neutrophils, lymphocytes, monocytes, platelets, albumin), were assessed for overall survival (OS) and disease-free survival (DFS). Prognostic accuracy was evaluated using the concordance index (C-index), time-dependent area under the ROC curve (time-AUC), and Brier score. Independent predictors identified by multivariate Cox regression were incorporated into nomograms to estimate survival. Results: The median patient age was 63 years, 71.8% were male, 38.8% had stage III disease, and 37.5% had poorly differentiated tumors. Median follow-up was 24 months. Among the twelve biomarkers, the pan-immune-inflammation value (PIV) demonstrated the strongest prognostic performance. For OS, PIV achieved a C-index of 0.682, time-AUC of 0.695, and Brier score of 0.180; for DFS, C-index was 0.679, time-AUC 0.681, and Brier score 0.192. Unlike single-ratio indices, PIV integrates neutrophil, monocyte, platelet, and lymphocyte counts, providing a multidimensional view of systemic inflammation and immunity. Multivariate analysis confirmed high PIV as an independent predictor of poor OS (HR = 2.488; 95% CI: 1.745– 3.546; P < 0.001) and DFS (HR = 2.353; 95% CI: 1.701– 3.247; P < 0.001). Nomograms combining PIV with clinicopathological factors (CEA, CA19-9, perineural invasion, TNM stage) demonstrated improved discrimination and calibration at 12, 36, and 60 months. Conclusion: PIV provides superior prognostic value compared with traditional inflammatory indices, offering a cost-effective and readily available biomarker for iCCA. While promising, these results are based on a retrospective multicenter cohort without independent validation, and should be confirmed in prospective external studies.

Objective: To investigate the impact of diagnostic and treatment delays on the prognosis of patients with locally advanced rectal cancer (LARC). Methods: Retrospective analyses were performed in Chinese and American cohorts. The intervals from symptom onset to diagnosis and from diagnosis to initial treatment were defined as diagnostic and treatment delays. A univariate and multivariable Cox regression model was conducted for overall survival (OS), cancer‐specific survival (CSS), and disease‐free survival (DFS). Results: A total of 450 Chinese and 5810 American patients were included in this study. Multivariable analysis revealed that a prolonged diagnostic delay (> 5 months) was significantly associated with decreased OS (hazard ratio [HR]: 1.50, p = 0.041) and DFS (HR: 1.36, p = 0.047). Additionally, an extended treatment delay (> 2 months) was closely associated with reduced OS (> 1 and ≤ 2 months vs. ≤ 1 month, HR: 1.06, p = 0.386; > 2 months vs. ≤ 1 month, HR: 1.52, p < 0.001) and CSS (> 1 and ≤ 2 months vs. ≤ 1 month, HR: 1.03, p = 0.693; > 2 months vs. ≤ 1 month, HR: 1.58, p = 0.001) in patients with LARC. Conclusion: Diagnostic intervals exceeding 5 months and treatment delays of more than 2 months are significantly associated with unfavorable survival outcomes in LARC patients. These findings underscore the importance of timely diagnostic pathways and treatment initiation and may serve as clinically meaningful benchmarks for healthcare systems to optimize referral processes, resource allocation, and quality‐of‐care assessment in rectal cancer management.