Background Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy forwhich survival is hampered by late diagnosis, complex responses to treatment, and poor prognosis. Accurate ...prognostic tools are crucial for optimizing treatment strategies and improving patient outcomes. This study aimed to develop and validate a nomogram based on the Surveillance, Epidemiology, and End Results (SEER) database to predict cancer-specific survival (CSS) in patients with SBA and compare it to traditional American Joint Committee on Cancer (AJCC) staging. Methods We analyzed data from 2,064 patients diagnosed with SBA between 2010 and 2020 from the SEER database. Patients were randomly assigned to training and validation cohorts (7:3 ratio). Kaplan-Meier survival analysis, Cox multivariate regression, and nomograms were constructed for analysis of 3-year and 5-year CSS. The performance of the nomograms was evaluated using Harrell's concordance index (C-index), the area under the receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results Multivariate Cox regression identified sex, age at diagnosis, marital status, tumor site, pathological grade, T stage, N stage, M stage, surgery, retrieval of regional lymph nodes (RORLN), and chemotherapy as independent covariates associated with CSS. In both the training and validation cohorts, the developed nomograms demonstrated superior performance to that of the AJCC staging system, with C-indices of 0.764 and 0.759, respectively. The area under the curve (AUC) values obtained by ROC analysis for 3-year and 5-year CSS prediction significantly surpassed those of the AJCC model. The nomograms were validated using calibration and decision curves, confirming their clinical utility and superior predictive accuracy. The NRI and IDI indicated the enhanced predictive capability of the nomogram model. Conclusion The SEER-based nomogram offers a significantly superior ability to predict CSS in SBA patients, supporting its potential application in clinical decision-making and personalized approaches to managing SBA to improve survival outcomes. Keywords: Small bowel adenocarcinoma, Cancer-specific survival, SEER database, Nomogram, Neoplasm staging
Background Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with an increasing incidence and a high propensity for liver metastasis (LM). This study aimed to investigate the ...risk factors for synchronous LM and prognostic factors in patients with LM. Methods Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, this study analyzed data from 2,064 patients diagnosed with SBA between 2010 and 2020. Logistic regression was used to determine risk factors for synchronous LM. A nomogram was developed to predict the risk of LM in SBA patients, and its predictive performance was assessed through receiver operating characteristic (ROC) curves and calibration curves. Kaplan-Meier and Cox regression analyses were conducted to evaluate survival outcomes for SBA patients with LM. Results Synchronous LM was present in 13.4% of SBA patients ( n = 276). Six independent predictive factors for LM were identified, including tumor location, T stage, N stage, surgical intervention, retrieval of regional lymph nodes (RORLN), and chemotherapy. The nomogram demonstrated good discriminative ability, with an area under the curve (AUC) of 83.8%. Patients with LM had significantly lower survival rates than those without LM ( P < 0.001). Survival analysis revealed that advanced age, tumor location in the duodenum, surgery, RORLN and chemotherapy were associated with cancer-specific survival (CSS) in patients with LM originating from SBA. Conclusions This study highlights the significant impact of LM on the survival of SBA patients and identifies key risk factors for its occurrence. The developed nomogram aids in targeted screening and personalized treatment planning.
The activity of integrin-linked kinase (ILK) in cancerous cells is often oncogenic and associated with malignant properties, such as uncontrolled cell cycle progression and evasion from senescence. ...However, the role of ILK in cellular senescence in gastric cancer (GC) has not been previously examined. We generated single-cell clones of ILK knock-out using CRISPR-Cas9 in human GC lines with mesenchymal or epithelial histology. Cells with no residual ILK expression exhibited strong cellular senescence with diminished clathrin-mediated endocytosis, Surprisingly, ILK loss-induced cellular senescence appeared to be independent of its function in integrin signaling. The low dose of CPD22, a small molecule inhibitor of ILK activity-induced senescence in three GC cell lines with different histologies. Furthermore, senescent cells with ILK depletion transfected with N-terminal truncated ILK mutant remaining catalytic domains displayed the reduction of senescent phenotypes. RNA sequencing and cytokine array results revealed the enrichment of multiple pro-inflammatory signaling pathways in GC lines in the absence of ILK. Our study identified the important role and the potential mechanism of ILK in the cellular senescence of cancerous epithelial cells. The inhibition of ILK activity using small molecule compounds could have a pro-senescent effect as a therapeutic option for GC.
Background
Microsatellite instability‐high (MSI‐H) subgroup of gastric cancer (GC) is characterized by a high tumor mutational burden, increased lymphocytic infiltration, and enhanced inflammatory ...cytokines. GC patients with MSI‐H status have a good response to immune checkpoint blockade management. However, heterogeneity within the subtype and the underlying mechanisms of shaping tumor microenvironments remain poorly understood.
Methods
RNA expression levels and clinical parameters of GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The data were analyzed using single‐sample Gene Set Enrichment Analysis (ssGSEA), univariate Cox regression, multivariate Cox regression, and Least Absolute Shrinkage Selection Operator (LASSO) regression. In addition, multiplex immunohistochemistry (mIHC) was used in our clinical cohort for the tumor microenvironment study.
Results
By ssGSEA and survival analysis, the EMT signaling pathway was identified as a representative pathway, which can stratify the patients with MSI‐H GC with significant survival predictive power. Then, a novel representative EMT‐related five‐gene signature (namely CALU, PCOLCE2, PLOD2, SGCD, and THBS2) was established from EMT signaling gene set, which sensitivity and specificity were further validated in the independent GEO database (GSE62254) cohort for disease outcome prediction. Based on public single‐cell data and in situ immunohistochemistry, we found that most of these five genes were abundantly expressed in cancer‐associated fibroblasts. Furthermore, patients with high or low risk divided by this five‐gene signature exhibited a strong correlation of the distinct patterns of tumor immune microenvironment. By mIHC staining of sections from 30 patients with MSI‐H status, we showed that the patients with better prognoses had the increased infiltration of CD8+ cells in the primary tumoral tissue.
Conclusion
Our study developed a simple five‐gene signature for stratifying MSI‐H GC patients with survival predictive power.
Zhang et al. developed a simple five‐gene signature for stratifying MSI‐H GC patients. The gene signature based on EMT‐related genes is helpful in predicting the prognosis of MSI‐H GC patients and, to some extent, reflects the immune microenvironment of patients.
The KRAS genotype status is strongly associated with a prothrombotic state in colorectal cancer, and hypercoagulability and cancer-related thrombosis are among the significant events leading to poor ...prognosis. However, this correlation has not been confirmed at the cellular level. This study aimed to assess the maximum platelet aggregation rate and thrombin expression induced by colorectal cancer cells under different KRAS genotypes.
Platelet aggregation rate assay and western blotting analysis were used to detect platelet aggregation and thrombin expression induced by four colorectal cancer cells with different KRAS genotypes, including RKO, HCT116, SW480, and SW620. FVIIa/tissue factor and thrombin inhibitors were added to explore changes in platelet aggregation rates induced by colorectal cancer cells and the association between KRAS genotype status and hypercoagulable state.
KRAS-mutant cells were more likely to increase maximal platelet aggregation, with RKO, HCT116, SW480, and SW620 inducing 34.7%, 55.4%, 44.4%, and 63.8% of platelet aggregation, respectively. The maximum platelet aggregation rate was higher in the metastatic rectal cancer tumour strain SW620 than in the primary rectal cancer strain SW480. RKO cells had lower thrombin expression than the other three cells. Furthermore, the addition of thrombin inhibitors caused a more significant decrease in the platelet aggregation rate in KRAS-mutant cell lines compared to KRAS wild-type cell lines.
Compared to KRAS wild-type colorectal cancer cells, KRAS-mutant colorectal cancer cell lines were more likely to be hypercoagulable through the upregulation of thrombin expression, which was mainly achieved through the TF-thrombin pathway.
Colorectal cancer (CRC), one of the most prevalent types of cancer, is accompanied by a notably high incidence of thrombotic complications. The present study aimed to elucidate the association ...between
mutations and hypercoagulability in operable CRC. The prognostic value of preoperative D-dimer levels was also investigated, thus providing novel insights into the development of therapeutic strategies to enhance patient survival and diminish morbidity. Therefore, a prospective analysis of 333 CRC cases post-surgery at Yan'an Hospital Affiliated to Kunming Medical University, between May 2019 and October 2022 was performed. Data on demographics, tumor characteristics and D-dimer levels were compiled from the electronic health records. Venous thromboembolism (VTE) was diagnosed by doppler or computed tomography angiography, with D-dimer thresholds set at 550 and 1,650 µg/l.
mutations at codons 12 and 13 were assessed in a subset of 56 cases. Subsequently, the factors affecting the hypercoagulable state in these patients were prospectively analyzed, focusing on the pivotal role of
. The results showed that
mutations were associated with elevated preoperative D-dimer levels, with 1,076 µg/l compared with 485 µg/l in the wild-type cohort, indicative of a hypercoagulable state. Increased D-dimer levels were also associated with vascular invasion, distant metastases and a heightened risk of postoperative VTE. Furthermore, multivariate analyses identified
mutations, distant metastases and vascular invasion as independent predictors of elevated D-dimer levels, with relative risk values of 2.912, 1.884 and 1.525, respectively. Conversely, sex, age, tumor location, differentiation grade, Ki67 index and tumor stage could not significantly affect D-dimer levels, thus indicating a complex interplay between tumor genetics and coagulation dysfunction in CRC. The current study suggested that the
mutation status, distant metastasis and vascular invasion could be considered as independent risk factors of blood hypercoagulability in patients with CRC, potentially serving as prognostic factors for VTE risk.
Optic neuropathy is the leading cause of irreversible blindness and is characterized by progressive degeneration of retinal ganglion cells (RGCs). Several studies have demonstrated that ...transplantation of Schwann cells (SCs) is a promising candidate therapy for optic neuropathy and that intravitreally transplanted cells exert their effect via paracrine actions. Extracellular vesicle (EV)-based therapies are increasingly recognized as a potential strategy for cell replacement therapy. In this study, we aimed to investigate the neuroprotective and regenerative effects of SC-EVs following optic nerve injury. We found that SC-EVs were internalized by RGCs in vitro and in vivo without any transfection reagents. Intriguingly, SC-EVs significantly enhanced the survival and axonal growth of primary RGCs in a coculture system. In a rat optic nerve crush model, SC-EVs mitigated RGC degeneration, prevented RGC loss, and preserved the thickness of the ganglion cell complex, as demonstrated by the statistically significant improvement in RGC counts and thickness measurements. Mechanistically, SC-EVs activated the cAMP-response element binding protein (CREB) signaling pathway and regulated reactive gliosis in ONC rats, which is crucial for RGC protection and axonal regeneration. These findings provide novel insights into the neuroprotective and regenerative properties of SC-EVs, suggesting their potential as a cell-free therapeutic strategy and natural biomaterials for neurodegenerative diseases of the central nervous system.
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Objective To analyze the association of coagulation with clinical parameters in patients with colorectal cancer. Methods Clinical and pathological data in the patients with colorectal cancer and ...surgical treatment were collec-ted from August 2018 to December 2019 in the Department of Gastrointestinal Surgery in our hospital. Retrospective analysis was performed to study the related factors to hypercoagulability with preoperative D-dimer value as index. Results A total of 104 from 249 (41.8%) cases exhibited elevated D-dimer (>550 μg/ L) in serum preoperatively. Twenty-seven (10.8%) cases had a significant elevation of D-dimer(>1 650 μg/ L) three times higher than normal limit. There were 7 cases with venous thromboembolism(VTE) postoperatively. Multivariate analysis showed that the preoperative elevated D-dimer in serum was associated with far metastasis and intraluminal invasion. Elevated D-dimer was found 73.3% cases with metastasis and 37.6% cases without metastasis(P<0.01), and 51.9% cases with intralumin
This paper describes the 600 MW Supercritical Boiler's Main Steam Temperature Control method and analysis the characteristic of the method. Operation information show that the main steam temperature ...overheating appears commonly in actual operation process. In this paper, 600MW super-critical boiler's flue gas tube wall temperature was tested by setting probes in the furnace. The experimental results shown that the tube wall temperature changes swiftly with the load variation. There is significant temperature bias between testing cells at same super-heater stage. On this basis, a new control strategy was derived for 600 MW Supercritical Boiler's Main Steam.
Superheater and reheater tube failures were mostly due to excessive temperature, the inner-flue tube wall temperature of superheater make certain of tube thermal stress, material creep status and ...residual lifespan of tubes. So investigation of superheater safety began with experimentation of inner-flue tube wall temperature of superheater. In order to precisely learn inner-flue tube wall temperature of superheater of 600MW supercritical boiler, new measuring points are set on the superheater tube wall inner the flue. Since the working condition of 600MW supercritical boiler is quite severe, the temperature measuring points can only be used for short-term test. The data acquisition can be carried out automatically and a data storage system is required. The testing method in this paper transmit the measuring signal to the database of the thermal power control system through the redundant channel of the system. This method only requires new measuring points (thermocouple). The test data can be loaded directly from the SIS database, which saves not only money but also the work.
