Clinical and Experimental Gastroenterology最新文献

Background: Pancreatic stellate cells (PSCs) are critical in the development of pancreatic fibrosis. In vitro, cell attachment itself can promote cell activation. Currently, there is a lack of methods for isolating activated PSCs that are unaffected by cell attachment. This study aims to identify effective methods for isolating quiescent and activated murine PSCs (mPSCs) and to evaluate the potential of caerulein in inducing mPSC activation in an ex vivo model.

Methods: Pancreatic tissue from mice was digested with collagenase P (1.17 U/mL), Pronase (0.5 mg/mL), and DNase I (0.01 mg/mL). Quiescent and activated mPSCs were isolated using a Nycodenz gradient. Immunostaining for α-smooth muscle actin (α-SMA), Desmin, glial fibrillary acidic protein (GFAP), vimentin, CK19, and CD68 was performed to confirm cell purity. Real-time quantitative PCR (RT-PCR) and RNA sequencing assessed the activation phenotype following caerulein treatment.

Results: Quiescent and activated mPSCs were successfully isolated using the Nycodenz gradient, with cells exhibiting typical stellate morphology and positive staining for α-SMA, Desmin and vimentin. Oil Red O staining confirmed lipid droplets in quiescent mPSCs. In the caerulein-treated group, mPSC activation was significantly greater than in the saline-treated control group. RT-PCR revealed progressive upregulation of acta2 (**p<0.01, d4 compared to d2, ^## p<0.01,d7 compared to d4,**p<0.01,d7 compared to d2), col1a (**p<0.01, d4 compared to d2,**p<0.01,d7 compared to d2), and actg2 (**p<0.01, d4 compared to d2, ^## p<0.01,d7 compared to d4, **p<0.01,d7 compared to d2) mRNA levels at 2, 4, and 7 days post-adhesion. Fibroblast markers were also upregulated, and KEGG and GO enrichment analyses identified key pathways involved in ECM-receptor interactions, cell cycle regulation, PI3K-Akt signaling, and extracellular matrix remodeling.

Conclusion: The Nycodenz gradient efficiently isolates quiescent mPSCs, and short-term caerulein treatment effectively activates mPSCs ex vivo, providing a valuable model for studying mPSC activation and related signaling pathways.

Purpose: Inflammatory bowel disease (IBD) is a grouping of chronic inflammatory diseases of the gastrointestinal tract that affects upwards of 2.4 million Americans. Despite its prevalence, the exact cause remains unknown. This study aims to identify geographical differences in IBD-related mortality.

Patients and methods: We utilized Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) database. IBD-related death and population size data over the span of 1999 to 2022 was extracted. Data was stratified by United States census regions, place of death, and gender. Crude and age-adjusted mortality rates (AAMR) were calculated and trends in mortality were modeled using the Join-point Regression Program, with statistically significant outcomes (p-value ≤ 0.05) denoted via an asterisk (*).

Results: During the interval from 1999 to 2022, there were a total of 71,628 deaths due to Inflammatory Bowel Disease (IBD) in the United States. All census regions showed an increase in AAMR over the study period. The Midwest had the highest AAMRs with 1.54 (95% CI 1.42 to 1.65) in 1999 and rising to 1.99 (95% CI 1.87 to 2.11) in 2022 with an AAPC of 1.57 (95% CI 0.75 to 2.14)* and an APC of 9.83 (95% CI 3.43 to 21.10)* from 2018 to 2022. More specifically, Midwestern males displayed the highest AAMR with 1.74 (95% CI 1.54 to 1.94) in 1999 and 2.09 (95% CI 1.9 to 2.27) in 2022, and an APC of 8.50 (95% CI 2.254 to 19.40)* between 2018 and 2022.

Conclusion: Persistent regional differences were seen in IBD mortality, with the Midwest having the highest AAMR and Southern states exhibiting the greatest regional increase in AAMR over the past two decades. IBD mortality worsened across all regions during the period of the COVID-19 pandemic.

Objective: Studies have indicated that cyclin dependent protein kinase inhibitor 2B (CDKN2B) deletion is one of the most common changes in esophageal cancer (EC) which affects its progression and prognosis. This study explored the association between CDKN2B deletion, immunophenotype, and the prognosis of EC.

Methods: We investigated CDKN2B status and RNA expression, identified differentially expressed immune-associated genes between wild-type CDKN2B (CDKN2B^WT) and deleted CDKN2B (CDKN2B^deletion) in Cancer Genome Atlas (TCGA) EC samples. We also a constructed an immune prognostic model (IPM) based on these genes. Thereafter, the effects of IPM on the immune microenvironment of EC were analyzed. Finally, we established a nomogram by integrating the IPM and other clinical factors.

Results: CDKN2B deletion leads to downregulation of the immune response in EC. A total of 136 immune-associated genes were identified based on the CDKN2B deletion status, and three genes with remarkable potential as individual targets were selected for model construction. An IPM was developed and validated, it showed good performance in differentiating patients with a low or high risk of poor prognosis, and its predictive ability was independent of traditional clinical features. High-risk patients with EC had increased T follicular helper cells (Tfh) and M0 macrophages, and lower infiltration levels of resting CD4 memory T cells resting, and naive B cells. The nomogram developed for clinical application showed good predictive performance.

Conclusions: Our results suggested that CDKN2B deletion was associated with the survival and immune microenvironment in EC. IPM is not only an effective indicator of the immune response and prognosis, but also suggest potential targets for immunotherapy in patients with EC.

Purpose: This study aimed to explore the role of CHAF1A in hepatocellular carcinoma (HCC) progression, focusing on its expression, co-expression genes, genomic alterations, promoter methylation, clinical relevance, prognostic value, and immune associations.

Methods: CHAF1A mRNA expression was analyzed using UALCAN. Co-expression genes and functions were explored via LinkedOmics. Genomic alterations were assessed using cBioPortal. Promoter methylation and clinical correlations were examined using GEO datasets. Prognostic significance was evaluated via Kaplan-Meier analysis. Immune cell infiltration and checkpoint gene associations were investigated.

Results: CHAF1A was significantly upregulated in HCC and involved in cancer-related pathways. Genomic alterations were prominent in T1-stage tumors, often linked to alcohol-related liver disease. Promoter methylation influenced HCC progression and prognosis. CHAF1A expression correlated with clinical characteristics (gender, stage, grade, etc.) and showed diagnostic potential (AUC = 0.795). High CHAF1A expression predicted poor prognosis across various subgroups and was positively associated with immune cell infiltration and checkpoint genes.

Conclusion: CHAF1A plays a critical role in HCC progression, with elevated expression linked to poor prognosis and immune modulation. These findings highlight its potential as a therapeutic target for HCC.

Objective: This study aims to investigate the correlation between the tumor-stroma ratio (TSR) and peritoneal metastasis (PM) in gastric cancer (GC) and constructs a diagnostic model based on preoperative examination data.

Methods: To determine the feasibility of obtaining TSR in GC patients through preoperative examinations, the consistency of TSR between endoscopic biopsy tissues and postoperative histopathological tissues was evaluated. Additionally, the correlation between TSR and PM in GC was analyzed using Gene Expression Omnibus (GEO) datasets. To validate TSR's clinical potential in diagnosing PM, 640 GC patients from two medical centers were enrolled. A training cohort of 330 patients evaluated TSR and synchronous PM correlation, and a validation cohort of 310 patients was used. An additional cohort of 510 patients was established to investigate TSR and metachronous PM. A diagnostic model based on preoperative data was developed and a nomogram constructed.

Results: The TSR shows good consistency between endoscopic biopsy tissues and postoperative histopathological tissues. A significant correlation between TSR and PM was observed. The TSR-based model, combined with CA125, CA724 and Borrmann type, exhibited strong diagnostic effectiveness and considerable predictive efficacy, with an Area Under the Curve (AUC) of 0.85 in the training cohort, 0.73 in the external validation cohort, and 0.72 in the metachronous PM cohort.

Conclusion: The TSR emerges as a crucial marker for PM in GC, with the developed model, based on TSR and preoperative examination data, demonstrating substantial diagnostic and predictive capabilities.

Postoperative leaks after sleeve gastrectomy are a troublesome complication that occur in 0.7-5.3% of cases depending on the referenced source. These complications cause significant morbidity for patients requiring prolonged hospitalizations, nutritional support, intravenous antibiotics, and at times additional operations and procedures that risk further downstream complications. The patient presentation varies from relatively benign with minimal or no symptomatology, to the acutely ill with life-threatening sepsis. The management of gastric leak is dependent on a multitude of factors, including the initial presentation as well the surgeon's experience and preference. Here, we will summarize the current literature and discuss the different options that exist for the management of gastric leaks after sleeve gastrectomy including laparoscopic lavage, endoscopic stenting, endoscopic pigtail catheters, endoscopic vacuum therapy, and salvage surgical operations such as fistula jejunostomy and total gastrectomy. The aim is to provide a source for surgeons to reference when they encounter this disease pathology and to shed light on a daunting challenge for the modern bariatric surgeon.

Objective: Psychiatric disorders have been associated with Constipation in observational studies, although their causal relationships remain uncertain. We used Mendelian randomization analysis to infer causality between Schizophrenia and Major Depressive Disorder with Constipation.

Methods: The exposure of interest was Psychiatric disorders, including Schizophrenia (SCZ) and Major Depressive Disorder (MDD). Summary statistics for psychiatric disorders were recruited from the PGC, SCZ (30,490 cases and 312,009 controls), MDD (170,756 cases and 329,443 controls), whereas Constipation summary genetic data were obtained from a FinnGen involving 17,246 cases and 201,546 controls. The inverse variance weighted (IVW) method was used as the primary analysis to assess the causal relationship between SCZ and MDD with Constipation.

Results: LDSC indicated that Constipation was genetically correlated with Psychiatric disorders (r _g range: |0.04-0.05). The Mendelian randomization analysis indicated that there was significant evidence that genetically determined SCZ (OR = 1.05, 95% CI = 1.02-1.07, P<0.01) and MDD (OR = 1.21, 95% CI = 1.10-1.33, P<0.01) were statistically significantly causally associated with the risk of Constipation. SCZ effects remained within the range of practical equivalence (ROPE).

Conclusion: The Mendelian randomization analysis suggested that SCZ and MDD increase the risk of Constipation. However, the association between SCZ and constipation, predominantly within the ROPE range, suggested only limited clinical implications.

[This corrects the article DOI: 10.2147/CEG.S464375.].

Etrasimod is a sphingosine 1 phosphate (S1P) receptor modulator approved for the treatment of moderate to severely active ulcerative colitis (UC). Etrasimod selectively activates S1P_1,4,5 receptors with no detectable activity on S1P_2,3. The ELEVATE clinical trials evaluated the efficacy and safety of etrasimod for UC. Etrasimod showed clinically significant improvement in clinical remission at weeks 12 and 52 compared to placebo. Etrasimod showed greater efficacy in patients who were biologic naive. Etrasimod was also effective in a subgroup of patients with isolated proctitis. The medication should be avoided in pregnancy and lactation, certain cardiac conditions including brady-arrythmias, and those with a history of skin cancer. Etrasimod has a shorter half-life and fewer drug-drug and food interactions as compared to the S1P receptor modulator ozanimod. In addition, no dosing titration is required. Etrasimod is a promising treatment option for UC patients with moderate to severe inflammation, particularly those who have no prior biologic exposure, are not considering pregnancy, and prefer oral therapy.

Aim: Correlation of Survivin expression levels in tumor tissues and degree of tumor outgrowth with colorectal cancer characteristics.

Methods: The pathological tissues of 90 cases of colorectal cancer were observed by HE staining, and the tumor budding was judged by Ueno standard, and the expression of Survivin was detected by immunohistochemistry (IHC) technique (EnVision method), so as to analyze the correlation between tumor budding, the expression level of Survivin and the degree of tumor budding, and the correlation between the tumor budding and the patients' clinical characteristics.

Results: The expression level of Survivin was significantly correlated with TNM stage, lymph node metastasis and distant metastasis in patients with colorectal cancer; tumor outgrowth was significantly correlated with TNM stage, lymph node metastasis and distant metastasis in patients with colorectal cancer (P < 0.05); the expression level of Survivin was significantly correlated with the degree of tumor budding in patients with colorectal cancer (P < 0.05).

Conclusion: In this paper, we tested the relationship between Survivin and tumor budding in colon cancer, and analyzed its relationship with clinicopathological features, with a view to providing a reference for the mechanism related to colorectal cancer.