Background: Survival outcomes are significantly different in stage II colorectal cancer (CRC) patients with diverse clinicopathological features. The objective of this study is to establish a credible prognostic nomogram incorporating easily obtained parameters for stage II CRC patients. Methods: A total of 1708 stage II CRC patients seen at Fudan University Shanghai Cancer Center (FUSCC) from 2008 to 2013 were retrospectively analyzed in this study. Cases were randomly separated into a training set (n = 1084) and a validation set (n = 624). Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors that were subsequently incorporated into a nomogram. The performance of the nomogram was evaluated by the predicted concordance index (C-index) and ROC curve to calculate the area under the curve (AUC). The clinical utility of the nomogram was evaluated using decision curve analysis (DCA). Results: In univariate and multivariate analyses, eight parameters were correlated with disease-free survival (DFS), which were subsequently selected to generate a prognostic nomogram based on DFS. For DFS predictions, the C-index values of the nomogram were 0.842 (95% confidence interval (CI) 0.710–0.980), and 0.701 (95% CI 0.610–0.770) for the training and validation sets, respectively. The AUC values of the ROC curves for the nomogram to predicted 1, 3 and 5-year survival were 0.869, 0.858, and 0.777 (training group) and 0.673, 0.714, and 0.706 (validation group), respectively. The recurrence probability calibration curve showed good consistency between actual observations and nomogram-based predictions. DCA showed better clinical application value for the nomogram than the TNM staging system. Conclusion: A novel nomogram was established and validated in a large population, and the nomogram is a simple-to-use tool for physicians to facilitate postoperative personalized prognostic evaluation and determine therapeutic strategies for stage II CRC patients.

Mitral valve prolapse is a common valvular abnormality that is caused by myxomatous degeneration, characterized macroscopically by leaflet thickening and redundancy accompanied with histologically marked proliferation of the spongiosa and mucopolysaccharide acid replacement of leaflet collagen in the prolapse leaflets. Nevertheless, the discrepant natural history and various concomitant syndromes cannot be explained completely by the current genetic autosomal dominant inheritance theory. In addition, autonomic dysregulation has been commonly reported in mitral valve prolapse, but has never been indicated as a major underlying cause. This article attempts to interpret the occurrence of primary pathology and progression in mitral valve prolapse on a common basis of improper autonomic tone. The imbalanced background of autonomic nervous firing leads to disharmonized synthetic/catabolism balance in the extracellular matrix, disrupted transition in the interstitial cellular component and invalided anti-inflammatory pathway in the endothelium, which trigger and accelerate the progression of this condition. Such a hypothesis not only unifies the seemingly disparate syndromes and valvular disorder, but also has implications for future biopharmaceutical and mechanical treatment.

Seldom have the associations of preoperative CEA (p-CEA) and recurrent CEA (r-CEA) levels as well as changes in p-CEA and r-CEA with survival in patients with stage I–III colorectal cancer (CRC) who have experienced metastatic relapse, been thoroughly examined. 241 consecutive patients with stage I–III CRC who experienced metastatic relapse at Fudan University Shanghai Cancer Center (FUSCC) between January 2008 and January 2016 were investigated. The influence of p-CEA, r-CEA and CEA alteration on the overall survival (OS) and relapse-to-death survival (RDS) was evaluated. The restricted cubic spline regression model was employed to explore the optimal cut-off value of CEA. All 241 patients were categorized into four groups built on their CEA alteration patterns as follows: A, patients presenting elevated p-CEA levels but normal r-CEA levels (P–N); B, patients displaying normal levels of both p-CEA and r-CEA (N–N); C, patients exhibiting elevated levels of both p-CEA and r-CEA (P–P); D, patients with normal p-CEA levels but elevated r-CEA levels (N–P). The correlation between p-CEA and OS (P = 0.3266) and RDS (P = 0.2263) was insignificant. However, r-CEA exhibited a significant association with both OS (P = 0.0005) and RDS (P = 0.0002). Group A demonstrated the longest OS and RDS, whereas group D exhibited the poorest OS and RDS outcomes. For both OS and RDS, the CEA alteration groups served as an independent prognostic indicator. The optimal cut-off threshold for CEA was determined to be 5.1 ng/ml via the restricted cubic spline regression model. r-CEA has a stronger correlation with OS and RDS in individuals with stage I–III CRC who have experienced metastatic relapse. The change between p-CEA and r-CEA could further indicate post-relapse survival, thereby facilitating the assessment of mortality risk stratification in stage I-III CRC patients experiencing metastatic relapse.

Background: The optimal choice of chemotherapy regimen for resectable colorectal liver metastases (CRLM) is still undetermined. The study aimed to estimate the impact of perioperative or adjuvant chemotherapy on disease-free survival (DFS), and explore the underlying mechanisms which influence chemotherapy efficacy. Methods: Eight hundred twenty-two patients undergoing curative resection of CRLM were retrospectively collected from May 2018 to December 2023. Treatment effects between perioperative and adjuvant chemotherapy were compared in full subgroup analyses by Kaplan–Meier and Cox proportional hazards methods. Single-cell RNA sequencing and tumor derived organoids were used to explore the molecular mechanisms. Results: After propensity score matching, 630 patients were enrolled with ratio 1:1 in adjuvant and perioperative chemotherapy group. The median DFS in adjuvant and perioperative group was comparable with 28 and 32.5 months, respectively (HR = 0.99, P = 0.945). Perioperative chemotherapy was associated with improved DFS (25 vs. 13 months, P = 0.039) in patients with a clinical risk score (CRS) of 5. Notably, within the high-risk CRS 4-5 population receiving perioperative chemotherapy, patients with chronic hepatitis B (CHB) had significantly worse DFS (HR = 4.31, 95% CI 1.93–9.64; P < 0.001). Single-cell analyses revealed TSPAN8 ⁺ stem-like epithelial cells were enriched in sample with CHB. TSPAN8 knockdown sensitized colorectal cancer cells to 5-fluorouracil, and anti-TSPAN8 antibody showed synergistic efficacy with 5-fluorouracil in patient-derived liver metastasis organoids. In addition, the enhanced SPP1-CD44 signaling between TSPAN8 ⁺ epithelial cells and SPP1 ⁺ macrophages also contributed to 5-fluorouracil resistance. Conclusions: Higher CRS identify a subgroup of CRLM patients who may derive greater benefit from perioperative chemotherapy. HBV-related serological profiles is a potential predictor of chemotherapy resistance. The exploratory findings warrants further validation.

Colorectal cancer (CRC) is characterized by aberrant mucin expression, but the full spectrum of mucin profiles and their clinical relevance remain unclear. Here, we developed a novel mucin-based CRC subtyping using multiple datasets to tailor therapeutic strategies. Mucin-related signatures were used to stratify CRC into four novel mucin-based subtypes: metabolism initiated, inflammatory, immune activated, and progressing. Highly accurate predictions were achieved, with under the curve (AUC) values of 0.977 for PC1 and 0.997 for PC2. The novel subtypes demonstrated prognostic potential in predicting CRC patient survival outcomes. We identified interactions between mucin-based subtypes and tumor-associated macrophages (TAMs). Mechanistic research revealed that MUC20 overexpression promoted M2 macrophage-dependent tumor glycolysis and hypoxia. Specifically, M2 phenotype TAMs secreted TNF-α, which enhanced tumor glycolysis and upregulated MUC20 expression in cancer cells. This established a MUC20/glycolysis positive feedback loop that exacerbated hypoxia and aerobic glycolysis in CRC. Additionally, chemotherapy responses in patient organoids were highly matched to these subtypes. Patients in cluster 2 were sensitive to 5-Fu or CPT-11 but potentially resistant to routine FOLFOX treatment. We identified a novel four mucin-characterized subtypes, which advance precision medicine by refining chemotherapy regimen selection. Our study provides valuable insights for tailoring therapeutic strategies.