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.

Sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction: a case report and literature review.

Immune checkpoint inhibitors could restore immune surveillance to attack tumor through targeting CTLA-4, PD-1 or PD-L1, and have achieved huge success. However, immune-related adverse events (irAEs) have been attracting attention as their application is expanding. Gastritis is relatively rare as a subtype of irAEs, particularly severe gastritis. Guidelines on its clinical management still remain undefined due to limited data. Sintilimab is a PD-1 inhibitor approved in China. Here we offer a case of sintilimab-induced severe erosive hemorrhagic gastritis and pyloric obstruction. Conventional proton pump inhibitors and mucosal protective agents did not take effect, so glucocorticoid was chosen. This severe gastritis was successfully cured finally. Our report describing its clinical performances, endoscopic characteristics and treatments, could assist clinicians to better know this rare irAE.

Immune checkpoint inhibitors are a type of drug which fight cancer through enhancing the body's immunity. They have significant anti-tumor effects. The side effects of these medications, called immune-related adverse events (irAEs), are becoming more obvious as more and more patients undergo immunotherapy. Sintilimab is an immune checkpoint inhibitor approved in China. This case report discusses an irAE in a patient treated with sintilimab. The patient suffered from gastritis, with severely erosive bloody inflammation and a narrow outflow tract of the stomach. Inhibiting stomach acid and protecting mucosa are classical methods to treat gastritis, but neither worked in this case. However, the patient was successfully treated with glucocorticoids, a type of steroid used to treat inflammation. Gastritis is an uncommon irAE for patients treated with immune checkpoint inhibitors and we are short of credible instructions to timely recognize and manage it. This case report might be valuable for other clinicians looking to treat patients with similar symptoms.

Biological functions of circRNA in regulating the hallmarks of gastrointestinal cancer (Review).

Circular RNA (circRNA) was first observed in the cytoplasm of eukaryotic cells in 1979, but it was not characterized in detail until 2012, when high­throughput sequencing technology was more advanced and available. Consequently, the mechanism of circRNA formation and its biological function have been progressively elucidated by researchers. circRNA is abundant in eukaryotic cells and exhibits a certain degree of organization, timing and disease­specificity. Additionally, it is poorly degradable, meeting the characteristics of an ideal clinical biomarker. In the present review, the recent research progress of circRNAs in digestive tract malignant tumors was primarily discussed. This included the roles, biological functions and clinical significance of circRNA, providing references for its research value and clinical potential in gastrointestinal cancer.

SERPINB5 promotes colorectal cancer invasion and migration by promoting EMT and angiogenesis via the TNF-α/NF-κB pathway.

This study aimed to investigate the role of SERPINB5 in colorectal cancer (CRC). We established knockdown and overexpression models of SERPINB5 in CRC cells and conducted bioinformatics analysis to assess the clinicopathological significance of SERPINB5 expression in CRC patients. Human CRC cells were transfected with LV-SERPINB5 and sh-SERPINB5 lentivirus for subsequent functional and mechanistic studies. Results showed that high SERPINB5 expression correlated positively with CEA levels, N stage and lymphatic infiltration, while displaying a negative correlation with progression-free survival. Overexpression of SERPINB5 in CRC cells upregulated the expression of TNF-α, p-NF-κB/p65, N-cadherin, MMP2 and MMP9, accompanied by decreased E-cadherin expression. In addition, SERPINB5 overexpression enhanced the migration, invasion, and proliferation of CRC cells. Furthermore, overexpression of SERPINB5 in CRC cells increased VEGFA expression, and the conditioned medium from SERPINB5-overexpressing CRC cells promoted tube formation of HUVECs. Conversely, overexpression of SERPINB5 in HUVECs decreased VEGFA expression and inhibited tube formation. Notably, these changes in CRC cells were reversed by QNZ, a specific inhibitor of the TNF-α/NF-κB pathway. In summary, our findings revealed that high SERPINB5 expression correlated with poor progression-free survival in CRC patients. Moreover, SERPINB5 could induce EMT and angiogenesis by activating the TNF-α/NF-κB pathway, thereby promoting the invasion and migration of CRC cells.

Nomogram for predicting electrocoagulation syndrome after endoscopic submucosal dissection of esophageal tumors.

BACKGROUND: Endoscopic submucosal dissection (ESD) was widely used for the removal of esophageal tumors, and post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) was one of the postoperative adverse events. The aim of this research was to develop and validate a model to predict electrocoagulation syndrome after endoscopic submucosal dissection of esophageal tumors. MATERIALS AND METHODS: Patients who underwent esophageal ESD in our hospital were retrospectively included. A predictive nomogram was established based on the results of multivariate logistic regression analysis, and bootstrapping resampling was used for internal validation. Besides, the clinical usefulness of the nomogram was evaluated using decision curve analysis (DCA) and clinical impact curve. RESULTS: A total of 552 patients who underwent esophageal ESD were included in the study, and the incidence of PPECS was 12.5% (69/552). Risk factors associated with PEECS (p < 0.1) were analyzed by multivariate logistic regression analysis, and the final model included four variables, namely gender, diabetes, tumor size and operation time. The predictive nomogram was constructed based on the above four variables, and the area under the ROC curve (AUC) was 0.811 (95% CI 0.767-0.855). The calibration curve of the nomogram presented good agreement between the predicted and actual probabilities. DCA showed that the model improved patient outcomes by helping to assess the risk of PEECS in patients compared to an all-or-no treatment strategy. In addition, the clinical impact curve of the model also indicates that the nomogram has a high clinical net benefit. CONCLUSION: In conclusion, we have developed a predictive nomogram for PEECS after ESD for esophageal tumors with good predictive accuracy and discrimination. This predictive nomogram can be effectively used to identify high-risk patients with PEECS, which will help clinicians in clinical decision-making and early intervention.

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.

Exploring the Molecular Targets and Therapeutic Potential of Coptisine in Colon Cancer: A Network Pharmacology Approach.

INTRODUCTION: Colon cancer is a frequent malignancy, and surgery is still the primary therapy for people with colon cancer. Other treatments, including radiation, chemotherapy, and biologic therapy, may be utilized as a supplement. Chemotherapy, a prominent treatment for colon cancer, has failed to provide positive outcomes. This necessitates the development of more effective and less harmful treatment drugs. Coptisine was discovered to inhibit the development of colon cancer cell line HCT-116 in vivo, decrease the growth of HCT-116 cells, and cause apoptosis in vitro in colon cancer. Coptisine (COP) has shown antitumor activity in colon cancer, but its molecular mechanism and its molecular targets have not been fully understood. METHODS: In this study, the biological behavior was verified in vitro. The targets of Huanglian alkaloids on colon cancer were predicted, and the protein-protein interaction (PPI) network was constructed. The core targets of safranine for colon cancer were extracted and analyzed by GO and KEGG enrichment to identify the possible molecular mechanisms of safranine treatment. Western blot was used to detect the changes of related pathway proteins in colon cancer cells. The differential expression of hub genes in colon cancer was analyzed using the GEPIA2 website. The binding ability of safranine to the target was verified by molecular docking. Finally, the targets were preliminarily verified by q-PCR analysis. RESULTS: Coptisine can inhibit the survival, migration, and proliferation of colon cancer cells DLD1 and HCT-116. Based on network pharmacology, ninety-one targets for colon cancer were screened. ESR1, ALB, AR, CDK2, PARP1, HSP90AB1, IGF1R, CCNE1, and CDC42 were found in the top 10. Enrichment analysis showed that these targets were mainly related to pathways in cancer, FC γ R-mediated phagocytosis, prostate cancer, progesterone-mediated oocyte maturation, the oestrogen signal pathway, proteoglycan in cancer and the PI3K-Akt signal pathway. WB results showed that after the treatment of colon cancer DLD1 cells with coptisine, the expression of P-AKT and AKT decreased, that of its downstream protein Bcl-2 decreased, and that of BAX increased. Differential expression analysis of hub genes showed that CCNE1, CDK2, HSP90AB1, and CHEK2 were upregulated in colon cancer samples, and molecular docking showed that these targets had a good ability to bind to coptisine. After the treatment of colon cancer DLD1 cells with coptisine, q-PCR results showed that CCNE1 and HSP90AB1 were significantly downregulated, while CDK2 and CHEK2 had no significant changes. CONCLUSION: Coptisine may be a candidate drug for the treatment of colon cancer, and its therapeutic effect may be related to the cancer pathway and PI3K-Akt signalling pathway. CCNE1 and HSP90AB1 may be potential targets of coptisine in the treatment of colon cancer.

NLRP3: A Promising Therapeutic Target for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is an intestinal disease with complicated pathological mechanisms. The incidence of IBD has been increasing in recent years, which has a significant negative impact on the lives of patients. Therefore, it is particularly important to find new therapeutic targets and innovative drugs for the development of IBD. Recent studies have revealed that NLRP3 inflammatory vesicles can play an important role in maintaining intestinal homeostasis and sustaining the intestinal immune response in IBD. On the one hand, aberrant activation of NLRP3 inflammatory vesicles may cause excessive immune response by converting caspase-1, proIL-18, and proIL-1ß to their active forms and releasing pro-inflammatory cytokines to stimulate the development and progression of IBD, and we can improve IBD by targeting blockade of NLRP3 activation. On the other hand, NLRP3 may also play an enter protective role by maintaining the homeostasis of the intestinal immune system. In this paper, we reviewed the activation mechanism of NLRP3 inflammasome, and the effects of NLRP3 inflammasome activation on IBD are discussed from two different perspectives: pathology and protection. At the same time, we listed the effects of direct inhibitors, indirect inhibitors, and natural inhibitors of NLRP3 inflammasome on IBD in combination with cutting-edge advances and clinical practice results, providing new targets and new ideas for the clinical treatment of IBD.

Exploring the Targets and Molecular Mechanisms of Thalidomide in the Treatment of Ulcerative Colitis: Network Pharmacology and Experimental Validation.

BACKGROUND: Ulcerative colitis (UC) is a chronic, nonspecific, inflammatory disease of the intestine with an unknown cause. Thalidomide (THA) has been shown to be an effective drug for the treatment of UC. However, the molecular targets and mechanism of action of THA for the treatment of UC are not yet clear. OBJECTIVES: Combining network pharmacology with in vitro experiments, this study aimed to investigate the potential targets and molecular mechanisms of THA for the treatment of UC. METHODS: Firstly, relevant targets of THA against UC were obtained from public databases. Then, the top 10 hub targets and key molecular mechanisms of THA for UC were screened based on the network pharmacology approach and bioinformatics method. Finally, an in vitro cellular inflammation model was constructed using lipopolysaccharide (LPS) induced intestinal epithelial cells (NCM460) to validate the top 10 hub targets and key signaling pathways. RESULTS: A total of 121 relevant targets of THA against UC were obtained, of which the top 10 hub targets were SRC, LCK, MAPK1, HSP90AA1, EGFR, HRAS, JAK2, RAC1, STAT1, and MAP2K1. The PI3K-Akt pathway was significantly associated with THA treatment of UC. In vitro experiments revealed that THA treatment reversed the expression of HSP90AA1, EGFR, STAT1, and JAK2 differential genes. THA was able to up- regulate the mRNA expression of pro-inflammatory factor IL-10 and decrease the mRNA levels of anti-inflammatory factors IL-6, IL-1ß, and TNF-α. Furthermore, THA also exerted anti-inflammatory effects by inhibiting the activation of the PI3K/Akt pathway. CONCLUSION: THA may play a therapeutic role in UC by inhibiting the PI3K-Akt pathway. HSP90AA1, EGFR, STAT1, and JAK2 may be the most relevant potential therapeutic targets for THA in the treatment of UC.

Identification of a Diagnosis and Therapeutic Inflammatory Response-Related Gene Signature Associated with Esophageal Adenocarcinoma.

The purpose of this study is to identify the key regulatory genes related to the inflammatory response of esophageal adenocarcinoma (EAC) and to find new diagnosis and therapeutic options. We downloaded the dataset GSE72874 from the Gene Expression Omnibus database for this study. Weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) analysis were used to find common inflammatory response-related genes (IRRGs) in EAC. The relationship between normal and tumor immune infiltration was analyzed using an online database of CIBERSORTx. Finally, 920 DEGs were identified, of which 5 genes were key IRRGs associated with EAC, including three down-regulated genes GNA15, MXD1, and NOD2, and two down-regulated genes PLAUR and TIMP1. Further research found that GNA15, MXD1, and NOD2 were down-regulated, PLAUR and TIMP1 were up-regulated in Barrett's esophagus (BE). In addition, we found that the expression of GNA15 and MXD1 in normal esophageal squamous epithelial cells decreased after ethanol treatment, while the expression of PLAUR and TIMP1 increased after ethanol treatment. Compared with normal esophageal tissue, immune cells infiltrated such as plasma cells, macrophages M0, macrophages M1, macrophages M2, dendritic cells activated, and mast cells activated were significantly increased in EAC, while immune cells infiltrated such as T cells CD4 memory resting, T cells follicular helper, NK cells resting, and dendritic cells resting were significantly reduced. The receiver operating characteristic curve indicated that GNA15, MXD1, NOD2, PLAUR and TIMP1 expression had a performed well in diagnosing EAC from healthy control. GNA15, MXD1, NOD2, PLAUR and TIMP1 were identified and validated as novel potential biomarkers for early diagnosis and may be new molecular targets for treatment of EAC.

Prediction model for lymph node metastasis in superficial colorectal cancer: a better choice than computed tomography.

BACKGROUND: Risk evaluation of lymph node metastasis (LNM) in superficial colorectal cancer resected by endoscopic surgery is critical for determining subsequent therapeutic strategies, but the role of existing clinical methods, including computed tomography, remains limited. METHODS: Features of the nomogram were determined by logistic regression analysis, and the performance was validated by calibration plots, ROC curves and DCA curves in both the training set and the validation set. RESULTS: A total of 608 consecutive superficial CRC cases were randomly divided into 426 training and 182 validation cases. Univariate and multivariate logistic regression analyses revealed that age < 50, tumour budding, lymphatic invasion and lower HDL levels were risk factors for LNM. Stepwise regression and the Hosmer‒Lemeshow goodness of fit test showed that the nomogram had good performance and discrimination, which was validated by ROC curves and calibration plots. Internal and external validation demonstrated that the nomogram had a higher C-index (training group, 0.749, validation group, 0.693). DCA and clinical impact curves graphically show that the use of the nomogram to predict LNM had remarkable predictive power. Finally, in comparison with CT diagnosis, the nomogram also visually showed higher superiority, as demonstrated by ROC, DCA and clinical impact curves. CONCLUSION: Using common clinicopathologic factors, a noninvasive nomogram for individualized prediction of LNM after endoscopic surgery was conveniently established. Nomograms have great superiority in the risk stratification of LNM compared with traditional CT imaging.

A comparative study on the application of different endoscopic diagnostic methods in the differential diagnosis of benign and malignant bile duct strictures.

Objective: To compare the diagnostic value of cytobrush, ERCP-guided biopsy, SpyGlass direct visual impression and SpyGlass-guided biospy (SpyBite) in the differential diagnosis of benign and malignant bile duct strictures. Methods: The data of 1,008 patients who were clinically diagnosed with indeterminate biliary strictures and underwent ERCP-guided biopsy, cytobrush, SpyGlass direct visual impression or SpyBite at the First Affiliated Hospital of Nanchang University between January 2010 and December 2019 were collected and analyzed retrospectively. The final diagnose was determined by surgical pathological specimen or follow-up (Malignant stricture can be identified if the stricture showed malignant progression during one year of follow-up). The differential diagnostic value of the above endoscopic diagnostic methods was evaluated by means of sensitivity, specificity, accuracy, positive predictive value, negative predictive value, etc. and safety was evaluated by the incidence rate of adverse events. Results: In terms of sensitivity, standard biopsy group (48.6%) and SpyBite group (61.5%) were significantly higher than cytobrush group (32.0%), and visual impression group (100%) was significantly higher than any other group. As far as specificity was concerned, cytobrush group (99.0%), standard biopsy group (99.3%) and the SpyBite group (100%) were significantly higher than visual impression (55.6%), but there was no statistical difference among the three groups above. As far as accuracy was concerned, standard biopsy group (65.3%), and SpyBite group (80.0%) were significantly higher than cytobrush group (44.4%), and SpyBite group (80.0%) was significantly higher than visual impression group (54.8%). In terms of safety, visual impression group and SpyBite group were significantly higher than cytobrush group and standard biopsy group in post-ERCP cholangitis. Conclusion: SpyBite combined with SpyGlass-guided visual impression was better for differential diagnosis of benign and malignant bile duct strictures in terms of sensitivity and accuracy compared with conventional endoscopic diagnostic methods such as cytobrush and standard biopsy. Furthmore, the incidence rates of adverse events after SpyGlass examination was similar to those after conventional endoscopic diagnostic methods except for higher cholangitis, which could be controlled by antibiotics and might be avoided by adequate biliary drainage.

Comparison of the efficacy and safety of an oral sulfate solution and 3-L polyethylene glycol on bowel preparation before colonoscopy: a phase III multicenter randomized controlled trial.

BACKGROUND AND AIMS: Adequate bowel preparation is crucial for clear mucosal visualization during colonoscopy. We aimed to comprehensively compare oral sulfate solution (OSS) and 3-L split-dose polyethylene glycol (PEG) for bowel preparation before colonoscopy. METHODS: This randomized, active-controlled, noninferiority study was performed in 10 medical centers. Eligible subjects were enrolled to receive OSS or 3-L PEG in a split-dose regimen. The quality of bowel preparation, adverse reactions, and acceptability were evaluated. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. Safety was evaluated by adverse reactions. The study population was divided into the full analysis set (FAS), the safety set, the modified FAS (mFAS), and the per-protocol set (PPS). RESULTS: Three hundred forty-eight potentially eligible subjects were enrolled. Three hundred forty-four subjects were included in the FAS and safety set, 340 subjects were included in the mFAS, and 328 subjects were included in the PPS. Adequate bowel preparation of the OSS was not inferior to 3-L PEG in the mFAS (98.22% vs 97.66%) and the PPS (98.17% vs 98.78%). There was no significant difference in acceptability between the 2 groups (94.74% vs 94.80%, P = .9798). Overall adverse reactions were similar (50.88% vs 44.51%, P = .2370) between the 2 groups. CONCLUSIONS: The split-dose OSS regimen was not inferior to the split-dose 3-L PEG regimen for the quality of bowel preparation in a Chinese adult population. The safety and acceptability of the 2 groups were similar. (Clinical trial registration number: NCT05465889.).

Risk factors for inadequate bowel preparation before colonoscopy: a retrospective cohort study.

BACKGROUND: Colonoscopy is the standard and most effective screening tool for colonic diseases and the accuracy of colonoscopy depends on the quality of bowel preparation. The aim of this study was to analyze the risk factors for inadequate bowel preparation before colonoscopy. METHODS: In this retrospective study, patients who underwent colonoscopy in 2018 and received 3 L of Polyethylene Glycol Electrolytes powder were included. They were instructed to drink 1.5 L the night before the colonoscopy and 1.5 L 4-6 h before the procedure given in doses of 250 ml every 10 min with 30 ml of simethicone given 4-6 h before the colonoscopy. Patient- and procedure-related parameters were recorded. An adequate bowel preparation was defined as all 3 segments rated 2 or 3 on the Boston Bowel Preparation scale. Risk factors for inadequate bowel preparation were identified using multivariate logistic regression analysis. RESULTS: A total of 6720 patients were included in the present study. The mean age of these patients was 49.7 ± 13.0 years old. Inadequate bowel preparation was found in 233 (12.4%), 139 (6.4%), 131 (7%), 68 (8.6%) patients in spring, summer, autumn and winter respectively. On the multivariate analysis, male gender (OR: 1.295; 95% CI: 1.088-1.542; P = 0.005), inpatient status (OR: 1.377; 95% CI: 1.040-1.822; P = 0.025) and season (spring vs. winter, OR: 1.514; 95% CI: 1.139-2.012; P = 0.004) were the independent risk factors for inadequate bowel preparation. CONCLUSIONS: Male gender, inpatient status and spring season were the independent risk factors for inadequate bowel preparation. For patients with risk factors for inadequate bowel preparation, enhanced bowel preparation and instructions may help to optimize the quality of bowel preparation.

Efficacy and safety of covered versus uncovered self­expandable metal stents for the palliative treatment of malignant distal biliary stricture: A long­term retrospective study.

Both covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (USEMSs) have been tried in the palliation of malignant distal biliary strictures by means of endoscopic retrograde cholangiopancreatography (ERCP); however, the comparison of efficacy and safety between them remains contested. To the best of our knowledge, no similar studies have assessed this in the Chinese population. In the present study, the clinical and endoscopic data of 238 patients (CSEMSs, n=55; USEMSs, n=183) with malignant distal biliary strictures from 2014 to 2019 were collected. The efficacy indicated by mean stent patency, stent patency rate, mean patient survival time and survival rate, and the safety indicated by adverse events after CSEMS or USEMS placement were retrospectively analyzed and compared. The mean stent patency time was significantly longer in the CSEMSs group than that in the USEMSs group (262.8±195.3 days vs. 169.5±155.7 days, P=0.002). The mean patient survival time was significantly longer in the CSEMSs group than that in the USEMSs group (273.9±197.6 days vs. 184.9±167.6 days, P=0.003). The stent patency rate and patient survival rate were significantly higher in the CSEMSs group than those in the USEMSs group at 6 and 12 months, but not at 1 and 3 months. There was no significant difference in stent dysfunction and adverse events between the two groups, although post-ERCP pancreatitis (PEP) occurred more frequently in the CSEMSs group than in the USEMSs group (18.1% vs. 8.8%, P=0.049). In conclusion, CSEMSs were better than USEMSs for malignant distal biliary strictures in terms of stent patency time and patient survival time as well as stent patency rate and patient survival rate in the long term (>6 months). Adverse events in the two groups occurred at a similar rate, although the incidence of PEP was higher in the CSEMSs group.

Prepackaged formula low-residue diet vs. self-prepared low-residue diet before colonoscopy: A multicenter randomized controlled trial.

Background and aims: Compared with self-prepared LRD, a prepackaged low-residue diet (LRD) can improve patient compliance, but whether it can further improve the quality of bowel preparation is uncertain. The study aimed to compare the application of the prepackaged formula LRD with self-prepared LRD in bowel preparation for colonoscopy. Methods: A multicenter randomized controlled trial was conducted in 15 centers. The eligible subjects were randomly assigned to one of two groups: the formula LRD group and the self-prepared LRD group. On the day before the colonoscopy, subjects in the self-prepared LRD group were instructed to consume a restricted LRD prepared by themselves, while subjects in the formula LRD group were given six bags of prepackaged formula LRD and instructed to consume them according to their individual need. The primary outcome was an adequate bowel preparation rate. Secondary outcomes mainly included Boston Bowel Preparation Scale (BBPS) scores, dietary restriction compliance rate, tolerance, satisfaction, adenoma detection rate (ADR), and adverse reactions. The trial was registered at ClinicalTrials.gov under the identifier NCT03943758. Results: A total of 550 subjects were recruited. Compared with the self-prepared LRD group, the formula LRD group showed a higher adequate bowel preparation rate (94.5 vs. 80.4%; P < 0.01), BBPS scores (7.87 ± 1.13 vs. 6.75 ± 1.47; P < 0.01), dietary compliance rate (92.4 vs. 78.9%; P < 0.01), tolerance (P < 0.01 in degree of hunger, intensity of physical strength, and negative influence on daily activities), satisfaction (8.56 ± 1.61 vs. 7.20 ± 2.02; P < 0.01), and ADR (25.6 vs. 16.0%; P < 0.01). There was no significant difference in adverse reactions. Conclusion: Compared with self-prepared LRD, the formula LRD showed similar safety and higher bowel preparation quality, compliance, and tolerance in bowel preparation. More formula LRDs could be designed according to different dietary habits and ethnic populations, and further researches are warranted to confirm their effect. Clinical trial registration: https://register.clinicaltrials.gov, identifier: NCT03943758.

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.

Clinical significance of peripheral blood-derived inflammation markers combined with serum eotaxin-2 in human colorectal cancer.

To investigate the value of serum eotaxin-2, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) in the diagnosis and prognosis of colorectal cancer (CRC). The association between different clinicopathological characteristics and eotaxin-2, NLR, and PLR in different patient groups was evaluated. The combined detection indicator and the combined detection's predictive effect on distant metastasis were examined. The receiver operating characteristic (ROC) curve was drawn to evaluate the efficacy of combined detection. The association between eotaxin-2, inflammation markers, and postoperative complications was assessed. Multivariate analysis to investigate the factors affecting the prognosis of patients with CRC. We detected a marked positive correlation between NLR and PLR (p < 0.05, r= 0.209). The AUC of serum eotaxin-2 combined with inflammation markers was 0.889, which was higher than single diagnosis. Compared with the single eotaxin-2 test, the combined detection of eotaxin-2 and inflammation markers might improve the specificity of CRC assessment. In univariate analysis, age, surgical method, high eotaxin-2, and high NLR were associated with postoperative complications. In multivariate analysis, age (≥ 60 years), high eotaxin-2, and high NLR were independent risk elements influencing postoperative complications of CRC. The distant metastasis, TNM staging -Ⅳ stage, NLR ≥ 3.18, and PLR ≥ 193 were independent factors affecting the prognosis of patients with CRC. The combined detection of eotaxin-2 and inflammatory markers has a particular value in improving the diagnosis of CRC, predicting distant metastasis, and guiding the frequency of reexamination after radical resection of CRC.

USP20 is a predictor of poor prognosis in colorectal cancer and associated with lymph node metastasis, immune infiltration and chemotherapy resistance.

Background: Colorectal cancer (CRC) is a highly prevalent malignancy with a poor prognosis. USP20 can support progression of variety of tumors. USP20 was shown to promote breast tumor metastasis, and proliferation of oral squamous carcinoma cells. However, the role of USP20 in CRC remains unclear. Methods: We used bioinformatics to analyze the expression and prognosis of USP20 in pan-cancer and explore the relationship between USP20 expression and immune infiltration, immune checkpoints, and chemotherapy resistance in CRC. The differential expression and prognostic role of USP20 in CRC was validated by qRT-PCR and immunohistochemistry. Cox univariate and multivariate analyses were performed to assess risk factors for poor prognosis of CRC, and new prognostic prediction models were constructed and evaluated by decision curve analysis (ROC) and receiver operating characteristic (DCA). USP20 was overexpressed in CRC cell lines to explore the effect of USP20 on the functionalities of CRC cells. Enrichment analyses were used to explore the possible mechanism of USP20 in CRC. Results: The expression of USP20 was lower in CRC tissues than adjacent normal tissues. Compared with low USP20 expression patients, CRC patients with high USP20 expression level had shorter OS. Correlation analysis showed that USP20 expression was associated with lymph node metastasis. Cox regression analysis revealed USP20 as an independent risk factor for poor prognosis in CRC patients. ROC and DCA analyses showed that the performance of the newly constructed prediction model was better than the traditional TNM model. Immune infiltration analysis shown that USP20 expression is closely associated with T cell infiltration in CRC. A co-expression analysis showed that USP20 expression was positively correlated with several immune checkpoint genes including ADORA2A, CD160, CD27 and TNFRSF25 genes and positively associated with multiple multi-drug resistance genes such as MRP1, MRP3, and MRP5 genes. USP20 expression positively correlated with the sensitivity of cells to multiple anticancer drugs. Overexpression of USP20 enhanced the migration and invasive ability of CRC cells. Enrichment pathway analyses showed the USP20 may play a role via the Notch pathway, Hedgehog pathway and beta-catenin pathway. Conclusion: USP20 is downregulated in CRC and associated with prognosis in CRC. USP20 enhances CRC cells metastasis and is associated with immune infiltration, immune checkpoints, and chemotherapy resistance.