Identification of glutamine metabolism-related gene signature to predict colorectal cancer prognosis.

Backgrounds: Colorectal cancer (CRC) is a highly malignant gastrointestinal malignancy with a poor prognosis, which imposes a significant burden on patients and healthcare providers globally. Previous studies have established that genes related to glutamine metabolism play a crucial role in the development of CRC. However, no studies have yet explored the prognostic significance of these genes in CRC. Methods: CRC patient data were downloaded from The Cancer Genome Atlas (TCGA), while glutamine metabolism-related genes were obtained from the Molecular Signatures Database (MSigDB) database. Univariate COX regression analysis and LASSO Cox regression were utilized to identify 15 glutamine metabolism-related genes associated with CRC prognosis. The risk scores were calculated and stratified into high-risk and low-risk groups based on the median risk score. The model's efficacy was assessed using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve analysis. Cox regression analysis was employed to determine the risk score as an independent prognostic factor for CRC. Differential immune cell infiltration between the high-risk and low-risk groups was assessed using the ssGSEA method. The clinical applicability of the model was validated by constructing nomograms based on age, gender, clinical staging, and risk scores. Immunohistochemistry (IHC) was used to detect the expression levels of core genes. Results: We identified 15 genes related to glutamine metabolism in CRC: NLGN1, RIMKLB, UCN, CALB1, SYT4, WNT3A, NRCAM, LRFN4, PHGDH, GRM1, CBLN1, NRG1, GLYATL1, CBLN2, and VWC2. Compared to the high-risk group, the low-risk group demonstrated longer overall survival (OS) for CRC. Clinical correlation analysis revealed a positive correlation between the risk score and the clinical stage and TNM stage of CRC. Immune correlation analysis indicated a predominance of Th2 cells in the low-risk group. The nomogram exhibited excellent discriminatory ability for OS in CRC. Immunohistochemistry revealed that the core gene CBLN1 was expressed at a lower level in CRC, while GLYATL1 was expressed at a higher level. Conclusions: In summary, we have successfully identified and comprehensively analyzed a gene signature associated with glutamine metabolism in CRC for the first time. This gene signature consistently and reliably predicts the prognosis of CRC patients, indicating its potential as a metabolic target for individuals with CRC.

Comparable long­term survival outcomes of endoscopic treatment versus surgical treatment for gastrointestinal stromal tumors with a diameter of 5-10 cm.

Currently, endoscopic treatment for small gastrointestinal stromal tumors (GIST) has been widely accepted. However, for tumors larger than 5 cm, endoscopic treatment has not been recognized by national guidelines as the standard therapy due to concerns about safety and adverse tumor outcomes. Therefore, this study compares the long-term survival outcomes of endoscopic treatment and surgical treatment for GIST in the range of 5-10 cm. We selected patients with GIST from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Kaplan-Meier analysis and the log-rank test were employed to compare the long-term survival outcomes between endoscopic treatment and surgical treatment. A multivariate Cox proportional hazards model was used for analysis to identify risk factors influencing patient prognosis. To balance baseline data, we performed 1:1 propensity score matching (PSM). A total of 1223 GIST patients were included, with 144 patients (11.8%) received endoscopic treatment and 1079 patients (88.2%) received surgical treatment. Before PSM, there was no significant difference in the long-term survival rates between the two groups [5-year OS (86.5% vs. 83.5%, P = 0.42), 10-year OS (70.4% vs. 66.7%, P = 0.42)]. After adjusting for covariates, we found that the overall survival (HR = 1.26, 95% CI 0.89-1.77, P = 0.19) and cancer-specific survival (HR = 1.69, 95% CI 0.99-2.89, P = 0.053) risks were comparable between the endoscopic treatment group and the surgical treatment group. In the analysis after PSM, there was no significant difference between the endoscopic treatment group and the surgical treatment group. Our study found that for GIST patients with tumor sizes between 5 and 10 cm, the long-term OS and CSS outcomes were similar between the endoscopic treatment group and the surgical treatment group.

Are Radiomic Spleen Features Useful for Assessing the Response to Infliximab in Patients With Crohn's Disease? A Multicenter Study.

INTRODUCTION: To develop and validate a radiomics nomogram for assessing the response of patients with Crohn's disease (CD) to infliximab. METHODS: Radiomics features of the spleen were extracted from computed tomography enterography images of each patient's arterial phase. The feature selection process was performed using the least absolute shrinkage and selection operator algorithm, and a radiomics score was calculated based on the radiomics signature formula. Subsequently, the radiomic model and the clinical risk factor model were separately established based on the radiomics score and clinically significant features, respectively. The performance of both models was evaluated using receiver operating characteristic curves, decision curve analysis curves, and clinical impact curves. RESULTS: Among the 175 patients with CD, 105 exhibited a clinical response, and 60 exhibited clinical remission after receiving infliximab treatment. Our radiomic model, comprising 20 relevant features, demonstrated excellent predictive performance. The radiomic nomogram for predicting clinical response showed good calibration and discrimination in the training cohort (area under the curve [AUC] 0.909, 95% confidence interval [CI] 0.840-0.978), the validation cohort (AUC 0.954, 95% CI 0.889-1), and the external cohort (AUC = 0.902, 95% CI 0.83-0.974). Accordingly, the nomogram was also suitable for predicting clinical remission. Decision curve analysis and clinical impact curves highlighted the clinical utility of our nomogram. DISCUSSION: Our radiomics nomogram is a noninvasive predictive tool constructed from radiomic features of the spleen. It also demonstrated good predictive accuracy in evaluating CD patients' response to infliximab treatment. Multicenter validation provided high-level evidence for its clinical application.

Development and validation of a preoperative risk nomogram prediction model for gastric gastrointestinal stromal tumors.

BACKGROUND AND STUDY AIMS: Gastrointestinal stromal tumors (GIST) carry a potential risk of malignancy, and the treatment of GIST varies for different risk levels. However, there is no systematic preoperative assessment protocol to predict the malignant potential of GIST. The aim of this study was to develop a reliable and clinically applicable preoperative nomogram prediction model to predict the malignant potential of gastric GIST. PATIENTS AND METHODS: Patients with a pathological diagnosis of gastric GIST from January 2015 to December 2021 were screened retrospectively. Univariate and multivariate logistic analyses were used to identify independent risk factors for gastric GIST with high malignancy potential. Based on these independent risk factors, a nomogram model predicting the malignant potential of gastric GIST was developed and the model was validated in the validation group. RESULTS: A total of 494 gastric GIST patients were included in this study and allocated to a development group (n = 345) and a validation group (n = 149). In the development group, multivariate logistic regression analysis revealed that tumor size, tumor ulceration, CT growth pattern and monocyte-to- lymphocyte ratio (MLR) were independent risk factors for gastric GIST with high malignancy potential. The AUC of the model were 0.932 (95% CI 0.890-0.974) and 0.922 (95% CI 0.868-0.977) in the development and validation groups, respectively. The best cutoff value for the development group was 0.184, and the sensitivity and specificity at this value were 0.895 and 0.875, respectively. The calibration curves indicated good agreement between predicted and actual observed outcomes, while the DCA indicated that the nomogram model had clinical application. CONCLUSIONS: Tumor size, tumor ulceration, CT growth pattern and MLR are independent risk factors for high malignancy potential gastric GIST, and a nomogram model developed based on these factors has a high ability to predict the malignant potential of gastric GIST.

The E3 ubiquitin ligase RNF31 mediates the development of ulcerative colitis by regulating NLRP3 inflammasome activation.

Ulcerative colitis (UC) is characterized by dysregulated inflammation and disruption of the intestinal barrier. The NLRP3 inflammasome, which is composed of NLRP3, ASC, and caspase-1, plays a crucial role in UC pathogenesis by triggering the production of proinflammatory cytokines. In this study, we investigated the regulatory role of RNF31 in NLRP3 inflammasome activation during UC development. Through comprehensive analysis of ulcerative colitis tissues using the GEO database and immunohistochemistry, we found that RNF31 expression was elevated in UC tissues, which prompted further investigation into its function. We constructed an RNF31 knockdown cell model and observed a significant reduction in NLRP3 inflammasome activation, indicating the involvement of RNF31 in regulating NLRP3. Mechanistically, RNF31 could interact with NLRP3 through the RBR structural domain, leading to increased K63-linked ubiquitination of NLRP3 and consequent stabilization. Coimmunoprecipitation experiments revealed a mutual interaction between RNF31 and NLRP3, substantiating their functional association. Finally, an in vivo mouse model with RNF31 knockdown showed a notable reduction in NLRP3 expression, which was accompanied by a decrease in the proinflammatory cytokines IL-18 and IL-1ß. The successful attenuation of DSS-induced tissue inflammation by this treatment confirmed the physiological relevance of RNF31-mediated regulation of NLRP3. This study unveils a novel regulatory pathway by which RNF31 affects NLRP3 inflammasome activation, providing new insights into UC pathogenesis and potential therapeutic targets for UC treatment.

Comparable long-term survival outcomes of endoscopic therapy versus surgical therapy for T1-2N0M0 duodenal neuroendocrine tumors.

BACKGROUND AND STUDY AIMS: The optimal treatment modality for T1-2N0M0 duodenal neuroendocrine tumors (DNETs) is still controversial. In this study, long-term survival outcomes were compared between the endoscopic therapy and surgical therapy for T1-2N0M0 DNETs using the Surveillance, Epidemiology, and End Results (SEER) database. PATIENTS AND METHODS: Patients with DNETs from the SEER database were selected from 2004 to 2015. We used the Kaplan-Meier method and log-rank test to compare long-term survival results between the endoscopic therapy and surgical therapy. An analysis of the multivariable Cox proportional hazards model was performed to identify risk factors for patient prognoses. The 1:1 propensity score matching (PSM) was performed to balance baseline data. RESULTS: A total of 816 patients with DNETs were included, of which 578 patients (70.8%) received endoscopic therapy and 238 patients (29.2%) received surgical therapy. Before the PSM, there was no difference between the two groups of patients with DNETs on long-term survival [5-year OS (86.1% vs. 87.9%, P = 0.45), 10-year OS (72.5% vs. 72.3%, P = 0.45)]. After adjusting covariates, we found endoscopic therapy and surgical therapy groups had comparable risks of overall survival (HR 0.86, 95% CI 0.60-1.23, P = 0.409) and cancer-specific survival (HR 1.68, 95% CI 0.74-3.83, P = 0.214). In the post-PSM analysis, there was no discernible difference between the endoscopic therapy and surgical therapy group. CONCLUSIONS: Our study found that for T1-2N0M0 DNETs patients, whose long-term OS and CSS results were similar for the endoscopic and surgical therapy groups. For these patients, endoscopic resection might be an optimal therapy modality.

A Novel Motor Structure with Extended Particle Swarm Optimization for Space Robot Control.

This paper studies motor structures and optimization methods for space robots, proposing an optimized stepped rotor bearingless switched reluctance motor (BLSRM) to solve the poor self-starting ability and significant torque fluctuation issues in traditional BLSRMs. Firstly, the advantages and disadvantages of the 12/14 hybrid stator pole type BLSRM were analyzed, and a stepped rotor BLSRM structure was designed. Secondly, the particle swarm optimization (PSO) algorithm was improved and combined with finite element analysis for motor structure parameter optimization. Subsequently, a performance analysis of the original and new motors was conducted using finite element analysis software, and the results showed that the stepped rotor BLSRM had an improved self-starting ability and significantly reduced torque fluctuation, verifying the effectiveness of the proposed motor structure and optimization method.

Taraxasterol acetate targets RNF31 to inhibit RNF31/p53 axis-driven cell proliferation in colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. Several studies have suggested that taraxasterol acetate (TA) can inhibit the growth of tumor cells. However, to date, it remains unclear how TA inhibits cell growth and how RNF31 functions as an oncogene. We examined the expression of RNF31 in CRC tissue samples via immunohistochemistry and elucidated the function of RNF31 in CRC cells by constructing a cell model with RNF31 depletion. A cycloheximide (CHX)-chase analysis and immunofluorescence assays were conducted to demonstrate that TA can promote RNF31 degradation by activating autophagy. We used the PharmMapper website to predict targets of TA and identified RNF31. CHX-chase experiments showed that TA could facilitate RNF31 degradation, which was inhibited by the administration of chloroquine. Immunofluorescence assays showed that RNF31 protein was colocalized with LC3I/II and p62, suggesting that TA promoted RNF31 degradation by activating autophagy. We also found that CRC patients with RNF31 overexpression had poorer survival than those with low RNF31 expression. The results of the CHX-chase experiment showed that depletion of RNF31 alleviated p53 degradation, which was inhibited by MG132. A series of co-immunoprecipitation (Co-IP) assays revealed that RNF31 interacts with p53 and promotes p53 ubiquitination and degradation. A Co-IP assay performed with a truncated RNF31 plasmid showed that the PUB domain interacts with p53. Moreover, the PUB domain is the key structure in the induction of p53 ubiquitination. Our findings reveal a key role of RNF31 in CRC cell growth and indicate a mechanism through which TA inhibits cell growth.

Persistence of the protective immunity to Schistosoma japonicum in Chinese yellow cattle induced by recombinant 26kDa glutathione-S-transferase (reSjc26GST).

To observe the long lasting effect of the recombinant Sj26GST sub-unit vaccine against Schistosoma japonicum in cattle, animals aged from 5 to 12 months were vaccinated with reSjc26GST, and were challenged by natural infection 6 months or 12 months after vaccination. Worm burdens per cattle and egg burden in tissue (per gram) of cattle with or without vaccination were compared. The results showed that anti-reSjc26GST antibodies were produced in vaccinated cattle. Following natural infection, the vaccinated and the control non-vaccinated cattle were all found to be infected with S. japonicum. A 30% reduction in worm number was observed in the vaccinated cattle when compared with the control cattle. The anti-fecundity effect was characterized by an average of 60% decrease in eggs deposited in the liver of vaccinated cattle; such a decrease is obviously very significant. In addition to the anti-fecundity effect induced in the vaccinated cattle, the number of miracidum hatched per 50 g faeces and the number of eggs released in intestinal tissues per gram were reduced or decreased. Results suggested that the immune responses induced by reSjc26GST in cattle were similar to that in buffaloes and in pigs. In addition, our result demonstrated that the lasting effect of immunity to S. japonicum induced in cattle after vaccination with reSjc 26 GST could persist at least 12 months.