Identification of subclusters and prognostic genes based on GLS-associated molecular signature in ulcerative colitis.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory disease that affects the colon and rectum. The response to treatment varies among individuals with UC. Therefore, the aim of this study was to identify and explore potential biomarkers for different subtypes of UC and examine their association with immune cell infiltration. We obtained UC RNA sequencing data from the GEO database, which included the training set GSE92415 and the validation set GSE87473 and GSE72514. UC patients were classified based on GLS and its associated genes using consensus clustering analysis. We identified differentially expressed genes (DEGs) in different UC subtypes through a differential expression analysis of the training cohort. Machine learning algorithms, including Weighted Gene Co-Expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine Recursive Feature Elimination (SVM-RFE), were utilized to identify marker genes for UC. The CIBERSORT algorithm was used to determine the abundance of various immune cells in UC and their correlation with UC signature genes. Finally, we validated the expression of GLS through in vivo and ex vivo experiments. The expression of GLS was found to be elevated in patients with UC compared to normal patients. GLS and its related genes were able to classify UC patients into two subtypes, C1 and C2. The C1 subtype, as compared to the C2 subtype, showed a higher Mayo score and poorer treatment response. A total of 18 DEGs were identified in both subtypes, including 7 up-regulated and 11 down-regulated genes. Four UC signature genes (CWH43, HEPACAM2, IL24, and PCK1) were identified and their diagnostic value was validated in a separate cohort (AUC > 0.85). Furthermore, we found that UC signature biomarkers were linked to the immune cell infiltration. CWH43, HEPACAM2, IL24, and PCK1 may serve as potential biomarkers for diagnosing different subtypes of UC, which could contribute to the development of targeted molecular therapy and immunotherapy for UC.

Causal effects of circulating glutamine on colitis, IBD, and digestive system cancers: a Mendelian randomisation study.

Backgrounds: There is growing evidence linking glutamine levels to the risk of gastrointestinal diseases, yet the presence of a causal relationship remains uncertain. In this study, we employed a Mendelian randomization (MR) approach to investigate potential causal associations between glutamine and colitis, inflammatory bowel disease (IBD), and digestive tumors. Methods: Genetic instrumental variables for glutamine exposure were identified from a genome-wide association study (GWAS) involving 114,751 participants. We pooled statistics from GWAS of gastrointestinal diseases in European populations, encompassing colitis (cases=1193, controls=461,740), IBD (cases=31,665, controls=33,977), Crohn's disease (cases=17,897, controls=33,977), ulcerative colitis (cases=1,239, controls=990), oesophageal cancer (cases=740, controls=372,016), gastric cancer (cases=6,563, controls=195,745), liver cell carcinoma (cases=168, controls=372,016), hepatic bile duct cancer (cases=418, controls=159,201), pancreatic cancer (cases=1,196, controls=475,049), and colon cancer (cases=1,494, controls=461,439). To ensure the validity of our findings, we utilized several analytical approaches including inverse variance weighted, weighted median, weighted mode, MR-Egger, and simple mode method. Results: Using the IVW method, we found that glutamine levels were inversely associated with colon cancer (OR = 0.998; 95% CI: 0.997-1.000; P = 0.027), colitis (OR = 0.998; 95% CI: 0.997-1.000; P = 0.020), and IBD (OR = 0.551; 95% CI: 0.343-0.886; P = 0.014). Subgroup analysis revealed a negative association between glutamine and Crohn's disease (OR = 0.375; 95% CI: 0.253-0.557; P = 1.11E-06), but not with ulcerative colitis (OR = 0.508; 95% CI: 0.163-1.586; P = 0.244). Glutamine levels showed no significant correlation with oesophageal cancer (OR = 1.000; 95% CI: 0.999-1.001; P = 0.566), gastric cancer (OR = 0.966; 95% CI: 0.832-1.121; P = 0.648), liver cell carcinoma (OR = 1.000; 95% CI: 0.999-1.000; P = 0.397), hepatic bile duct cancer (OR = 0.819; 95% CI: 0.499-1.344; P = 0.430), and pancreatic cancer (OR = 1.130; 95% CI: 0.897-1.423; P = 0.301). Sensitivity analyses also supports this finding, affirming the reliability and robustness of our study. Conclusions: This study suggests that blood glutamine levels in European populations may lower the risk of colon cancer, colitis, and IBD, particularly Crohn's disease. Nevertheless, additional research involving a diverse range of ancestries is imperative to corroborate this causal relationship.

Radiomics analysis based on CT for predicting lymph node metastasis and prognosis in duodenal papillary carcinoma.

OBJECTIVES: Radiomics has been demonstrated to be strongly associated with TNM stage and patient prognosis. We aimed to develop a model for predicting lymph node metastasis (LNM) and survival. METHODS: For radiomics texture selection, 3D Slicer 5.0.3 software and the least absolute shrinkage and selection operator (LASSO) algorithm were used. Subsequently, the radiomics model, computed tomography (CT) image, and clinical risk model were compared. The performance of the three models was evaluated using receiver operating characteristic (ROC) curves, decision curve analysis (DCA), calibration plots, and clinical impact curves (CICs). RESULTS: For the LNM prediction model, 224 patients with LNM information were used to construct a model that was applied to predict LNM. According to the CT data and clinical characteristics, we constructed a radiomics model, CT imaging model and clinical model. The radiomics model for evaluating LNM status showed excellent calibration and discrimination in the training cohort (AUC = 0.926, 95% CI = 0.869-0.982) and the validation cohort (AUC = 0.872, 95% CI = 0.802-0.941). DeLong's test demonstrated that the difference among the three models was significant. Similarly, DCA and CIC showed that the radiomics model has better clinical utility than the CT imaging model and clinical model. Our model also exhibited good performance in predicting survival-in line with the findings of the model built with clinical risk factors. CONCLUSIONS: CT radiomics models exhibited better predictive performance for LNM than models built based on clinical risk characteristics and CT imaging and had comparative clinical utility for predicting patient prognosis. CRITICAL RELEVANCE STATEMENT: The radiomics model showed excellent performance and discrimination for predicting LNM and survival of duodenal papillary carcinoma (DPC). KEY POINTS: LNM status determines the most appropriate treatment for DPC. Our radiomics model for evaluating the LNM status of DPC performed excellently. The radiomics model had high sensitivity and specificity for predicting survival, exhibiting great clinical value.

Risk factors and a nomogram for prediction of post-endoscopic submucosal dissection electrocoagulation syndrome for superficial colorectal lesions.

BACKGROUND: Post-endoscopic submucosal dissection electrocoagulation syndrome (PEECS) is an uncommon complication after colorectal endoscopic submucosal dissection (ESD). This study aimed to explore the risk factors of PEECS for superficial colorectal lesions based on the latest and consistent diagnostic criteria and to establish a predictive nomogram model. METHODS: This retrospective analysis included patients with superficial colorectal lesions who underwent endoscopic submucosal dissection (ESD) between June 2008 and December 2021 in our center. The independent risk factors of PEECS for superficial colorectal lesions were identified using least absolute shrinkage and selection operator (LASSO) logistic regression analysis, as well as univariate analysis and multivariate logistic regression, and derived predictive nomogram model was constructed. RESULTS: Among the 555 patients with superficial colorectal lesions enrolled, PEECS occurred in 45 (8.1%) patients. Multivariate logistic regression revealed that female sex (OR 3.94, P < 0.001), age > 50 years (OR 4.28, P = 0.02), injury to muscle layer (OR 10.38, P < 0.001), non-lifting sign (OR 2.20, P = 0.04) and inadequate bowel preparation (OR 5.61, P < 0.001) were independent risk factors of PEECS for superficial colorectal lesions. A predictive nomogram model was constructed based on the above five predictors. For this model, the area under the receiver operating characteristic (ROC) curve was 0.855, the calibration curve exhibited good consistency between the prediction and the actual observation, and the C-index was confirmed as 0.843 by bootstrap method. CONCLUSION: Female sex, age > 50 years, injury to muscle layer, non-lifting sign and inadequate bowel preparation were independent risk factors of PEECS for superficial colorectal lesions. The proposed nomogram could accurately predict the risk of PEECS for superficial colorectal lesions.

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.

Evaluation of ERCP-related perforation: a single-center retrospective study.

Background: Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation is a rare and serious adverse event. The aim of our study was to evaluate the risk factors and management of ERCP-related perforation, and to further determine the predictive factors associated with perforation outcome. Methods: A total of 27,018 ERCP procedures performed at the First Affiliated Hospital of Nanchang University (Nanchang, China) between January 2007 and March 2022 were included in the investigation of ERCP-related perforation. Medical records and endoscopic data were extracted to analyse the risk factors, management, and clinical outcome of ERCP-related perforation. Results: Seventy-six patients (0.28%) were identified as having experienced perforation following ERCP. Advanced age, Billroth II anatomy, precut sphincterotomy, and papillary balloon dilatation were significantly associated with ERCP-related perforation. Most patients with perforation (n = 65) were recognized immediately during ERCP whereas 11 were recognized later on. The delay in recognition primarily resulted from stent migration (n = 9). In addition, 12 patients experienced poor clinical outcome including death or hospice discharge (n = 3), ICU admission for >3 days (n = 6), and prolonged hospital stay for >1 month due to perforation (n = 3). Cancer and systemic inflammatory response syndrome (SIRS) are associated with a higher risk of poor outcome. Conclusions: Advanced age, Billroth II anatomy, precut sphincterotomy, and balloon dilation increase the risk of ERCP-related perforation whereas cancer and SIRS independently predicted poor clinical outcome.

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.

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.

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.

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.

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.

Treatment with antituberculosis agents after tuberculosis activation during ustekinumab treatment: Safety and effectiveness.

We report, for the first time, the safety and effectiveness of antituberculosis drugs after tuberculosis activation during ustekinumab treatment in Crohn's disease.

Incidence and risk factors for fever after endoscopic submucosal dissection and its derivative technology for gastric lesions.

Introduction: Fever is one of the postoperative complications of endoscopic submucosal dissection (ESD) and its derivative technology. However, there are few studies on risk factors for fever after ESD and its derivative technology. The aim of this study was to determine the incidence and related risk factors after ESD and its derivative technology for gastric lesions. Materials and methods: A retrospective review of patients with gastric lesions who were treated by ESD and its derivative technology in our hospital from January 2014 to January 2019 was conducted. Results: A total of 1955 patients were included in the present study. A total of 451 (23.1 %) patients presented with fever after ESD and its derived techniques. The highest fever temperature was 37.6 ± 3.12 °C, and the number of days with fever was 1.48 ± 0.85. Through single factor and multiple factor analysis, age (OR: 1.261, 95% CI: 1.009-1.576, p < 0.05), procedure time (OR: 1.457, 95% CI: 1.053-2.016, p < 0.05), postoperative gastric tube placement (OR: 2.098, 95% CI: 1:616-2.723, p < 0.05), intraoperative hemorrhage (OR: 1.537, 95% CI: 1.196-1.974, p < 0.05) and perforation (OR: 1.970, 95% CI: 1.531-2.535, p < 0.05) were independent risk factors for postoperative fever. Conclusion: Age ≥56 years old, procedure time ≥60 min, gastric tube placement, intraoperative hemorrhage and perforation were independent risk factors for postoperative fever after gastric ESD and its derivative technology. Attention should be given to such patients to minimize the risk of postoperative fever.

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.

Optimal dilation duration of 10 mm diameter balloons after limited endoscopic sphincterotomy for common bile duct stones: a randomized controlled trial.

Limited endoscopic sphincterotomy (EST) combined with endoscopic papillary balloon dilation (EPBD) is widely used. However, the optimal duration of small balloon dilation in choledocholithiasis remains controversial. We aimed to determine the optimal duration for 10 mm diameter balloon dilation after limited EST in choledocholithiasis. In this randomized controlled clinical trial, 320 patients were randomly assigned to receive small balloon dilation (10 mm in diameter) for 1 min (n = 160) or 3 min (n = 160) after deep bile duct cannulation. No significant difference in success rate of stone extraction between the two groups was observed. The incidence of post-ERCP pancreatitis (PEP) was higher in the 1 min group (10.6%) than in the 3 min group (4.4%) (P = 0.034). The logistic regression analysis showed that guidewire into the pancreatic duct, cannulation time > 5 min and 1 min balloon dilation were independent risk factors for PEP. There were no significant differences in other post-ERCP adverse events such as acute cholangitis, bleeding, perforation, etc. between the two groups. In conclusion, 3 min in duration was determined to be the optimal dilation condition for the removal of common bile duct stones.

Moderately severe acute pancreatitis after snake bite: a case report from Southern China.

Venomous snakebites are not rare worldwide, and this is also the situation in the mountainous regions of southern China, where they pose a serious health risk to the local population. Snake venom usually causes a variety of clinical symptoms, such as local pain and swelling, systemic coagulation system abnormalities, and shock, but rarely leads to acute pancreatitis. In this report, we presented a rare case of moderately severe acute pancreatitis caused by snake venom even after prompt antivenom treatment. The patient was relieved, obviously, with effective treatment of acute pancreatitis and was discharged without severe complications. Although acute pancreatitis after snake bite is a rarity, its serious complications and lethality still deserve our utmost attention, and timely and standardized treatment of acute pancreatitis is needed in addition to antivenom treatment.

Etiological Changes and Prognosis of Hospitalized Patients with Acute Pancreatitis Over a 15-Year Period.

BACKGROUND: The worldwide incidence of acute pancreatitis (AP) is increasing, but the dominant etiology of AP may vary by country. Mixed etiologies are involved in the increase in the number of AP patients. AIMS: This study was to analyze the etiological changes and prognosis of AP patients and explore the prognosis of AP patients with mixed etiologies. METHODS: Using a retrospective analysis method, AP patients hospitalized from January 2007 to December 2021 were selected from a pancreatic center in Nanchang, China. Trends in the main etiologies were analyzed, and the severity and prognosis of different etiologies were compared. RESULTS: A total of 10,071 patients were included. Cholelithiasis (56.0%), hyperlipidemia (25.3%), and alcohol (6.5%) were the top three etiologies. The proportion of acute biliary pancreatitis (ABP) showed a decreasing trend, while the proportion of hypertriglyceridemic pancreatitis (HTGP) and alcoholic AP showed an increasing trend (all ptrend < 0.001). The incidence of organ failure and necrotizing pancreatitis was higher in patients with HTGP than in those with AP induced by other etiologies (all p < 0.05). There was no statistically significant difference in mortality among patients with different etiologies. Patients with AP due to a mixed hypertriglyceridemia-alcoholic etiology had higher ICU admission rates and were more severe than those with AP induced by other mixed etiologies. CONCLUSION: In the past 15 years, the proportion of ABP has trended downward, while those of HTGP and alcoholic AP have risen. Among patients with mixed etiologies, those with a mixed hypertriglyceridemia-alcoholic etiology had a worse prognosis.

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.