BMC Gastroenterology最新文献

Background: CD4⁺ T cells play an indispensable role in anti-tumor immunity and shaping tumor development. We sought to explore the characteristics of CD4⁺ T cell marker genes and construct a CD4⁺ T cell-related prognostic signature for stage III-IV colorectal cancer (CRC) patients.

Method: We combined scRNA and bulk-RNA sequencing to analyze stage III-IV CRC patients and identified the CD4⁺ T cell marker genes. Unsupervised cluster analysis was performed to divide patients into two clusters. The LASSO and multivariate Cox regression were performed to establish a prognostic-related signature. RT-qpcr and immunofluorescence staining were performed to examine the expression of ANXA2 in CRC tissue.

Result: We found a higher infiltration abundance of activated memory CD4⁺ T cells was associated with improved prognosis in stage III-IV CRC patients. Patients were divided into two subgroups with distinct clinical and immunological behaviors based on CD4⁺ T cell marker genes. And then a prognostic signature consisting of six CD4⁺ T cell marker genes was established, which stratified patients into high- and low-risk groups. Immune spectrum showed that the low-risk group had higher immune cell infiltration than the high-risk group. Furthermore, the risk score of this signature could predict the susceptibility of stage III-IV CRC patients to immune checkpoint inhibitors and chemotherapy drugs. Finally, we validated that ANXA2 was enriched in Tregs and was associated with infiltration of Tregs in CRC tumor microenvironment.

Conclusion: The CD4⁺ T cell-related prognostic signature established in the study can predict the prognosis and the response to immunotherapy in stage III-IV CRC patients. Our findings provide new insights for tumor immunotherapy of advanced CRC patients.

Background: The role of immune cell profiles at birth in determining the risk of celiac disease (CD) development is currently unestablished. This study aimed to determine the associations between T- and B-cell profiles at birth and pediatric CD.

Methods: This regional cohort study analyzed prospectively collected dried blood spots from 158 children with CD (median 7 years old at CD diagnosis) and two matched comparators each (n = 316). We quantified T-cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) as measures of thymic and bone marrow output at birth. Moreover, we used epigenetic cell counting to estimate the percentages of lymphocyte subsets: CD3+, CD4+, CD8 + T cells, CD4 + memory T, regulatory T, B, and NK cells.

Results: No associations were found between measured immune cell markers at birth and CD development (all p values > 0.26). The median number of copies was 120 for TRECs (IQR = 92-168) and 136 (IQR = 91-183) for CD patients and comparators, respectively, and for KRECs, it was 69 (IQR = 45-100) for CD patients and 66 for comparators (IQR = 44-93). Across the groups, there were similar median percentages of T cells (CD, 32.6% [IQR = 27.0-43.8%] vs. comparators, 33.9% [IQR = 26.3-45.7%]) and B cells (CD, 25.4% [IQR = 20.3-30.6%] vs. comparators, 24.7% [IQR = 19.9-30.8%]). The ratio of the lymphocyte subset estimates between CD patients and comparators approximated one; all p values were > 0.26. The results were consistent across strata defined by sex, HLA type, and age at diagnosis.

Conclusion: Genetic and epigenetic markers for B cells and T cells in immune cell profiles at birth did not impact susceptibility to childhood-onset CD.

Background: To analyze the expression patterns of circRNAs in metabolic associated fatty liver disease (MAFLD) and the regulation of m⁶A methylation on those circRNAs.

Methods: The expression profile of CircRNA in MAFLD and normal control liver tissues was analyzed by microarray. Predict the potential m⁶A sites of the differentially expression circRNAs (DECs) via the SRAMP website. The biological functions and molecular interactions of DECs were analyzed by GO and KEGG analyses. The selected DECs were verified by MeRIP-qPCR and RT-qPCR.

Results: There were 59 DECs in MAFLD liver tissues compared with normal control liver tissues. We found that m⁶A sites with high or very high confidence were present in 39 of these DECs. Four randomly selected DECs were validated by RT-qPCR, hsa-MLIP_0004, hsa-CHD2_0084 and hsa-FOXP1_0001 matched well with the microarray results. m⁶A qualification of them were conducted by MeRIP-qPCR, the m⁶A methylation levels are significantly different between the MAFLD and NC groups.

Conclusion: In MAFLD, the dysregulated expression of circRNAs may be influenced by m⁶A modifications. This study provides preliminary evidence suggesting that m⁶A-mediated regulation of circRNAs could play a role in the progression of MAFLD, laying the foundation for exploring the epigenetic regulation of circRNAs in MAFLD and offering potential avenues for future diagnostic and therapeutic strategies.

Trial registration: Not applicable.

Background: The incidence of early-onset colorectal cancer (EoCRC), defined as CRC diagnosed at < 50 years of age, is increasing globally. However, only a few studies are reported from Japan, and the clinicopathological features of EoCRC in Japanese patients remain unknown.

Methods: We retrospectively investigated consecutive Japanese patients who were pathologically diagnosed with invasive CRC at our hospital from January 2015 to December 2021. Patients were categorized into those who were diagnosed with CRC at < 50 years (early-onset group) and ≥ 50 years (late-onset group) of age. We compared the clinicopathological findings between the two groups.

Results: The analysis included 731 patients. EoCRC was diagnosed in 46 patients　(6.3% of all patients). Of them, 41.3% demonstrated a positive fecal immunochemical test (FIT) for CRC screening as a diagnostic opportunity, which was significantly higher than that in the late-onset group (p = 0.032). Rectal cancer was significantly more prevalent in the early-onset group compared to the late-onset group (45.7% vs. 26.4%, p < 001). No significant difference in the rate of clinical stage at presentation was found between the two groups. Furthermore, patients with positive FIT were more likely diagnosed at an earlier stage.

Conclusions: EoCRC among Japanese patients tends to occur on the rectum and is more frequently diagnosed with FIT screening compared to late-onset CRC. Patients with advanced stage were diagnosed by symptoms, indicating the usefulness of FIT screening in diagnosing EoCRC at an early stage.

Background: To evaluate the prognostic value of the presence and number of tumor deposits (TDs) and the combination of TDs and number of positive lymph nodes (PLNs) in patients undergoing colorectal cancer (CRC) surgery, and to modify N staging.

Method: The clinical data of 1470 patients with stage I-IV CRC who underwent surgery in Wuhan Union Hospital from February 2014 to May 2018 were collected. The optimal cutoff value for TD + PLNs was obtained using X-tile software, and patients were regrouped accordingly. Cox univariate and multivariate analysis were used to screen the factors affecting the prognosis of patients. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the predictive ability of independent prognostic factors for overall survival (OS) and disease-free survival (DFS) of patients.

Result: The presence of TD was associated with poor OS (HR = 2.478, 95%CI: 1.794-3.422, P<0.001) and DFS (HR = 2.516, 95%Cl: 1.874-3.377, P<0.001). Combined with TD and PLNs, a total of 128 of 395 N1 patients were reclassified re-staged as N2(TD + PLNs ≥ 3), which had a worse prognosis than those diagnosed with N1. Compared with Tumor Node Metastasis stage and TD number, the multivariate model constructed using independent prognostic factors showed better predictive power for OS (AUC:0.769 vs. 0.681 vs. 0.650) and DFS (AUC:0.757 vs. 0.702 vs. 0.650).

Conclusion: TD significantly affects the long-term prognosis of CRC patients. Combining TD and PLNs to redefine the tumor staging of CRC patients can improve the accuracy of long-term prognosis of surgical patients.

Background: The management of patients with concomitant gallbladder stones with silent CBDS still involves a wide range of debates, and there is little evidence regarding the recommendation of CBD clearance either before cholecystectomy or in the same session. In this study, we aimed to discuss the feasibility of performing LC with a wait-and-see strategy for patients with silent CBS.

Method: Patients with silent CBDS identified during preoperative examinations for gallbladder stones were studied for the feasibility of performing LC with a wait-and-see strategy for silent CBS.

Results: Sixty patients who presented with gallbladder stones with silent CBDS underwent LC between February 2023 and July 2023. Seventeen patients (28.3%) underwent laparoscopic acute cholecystectomy, and 43 (71.7%) patients underwent laparoscopic elective cholecystectomy; all of these procedures were completed laparoscopically. Two patients (3.3%) developed symptomatic CBDS, both of whom were treated medically without intervention. Sixteen patients (26.7%) experienced spontaneous CBDS during the follow-up period.

Conclusion: Patients who present with symptomatic gall bladder stones either acutely or electively with asymptomatic CBDS can undergo laparoscopic cholecystectomy without suffering from CBDS with acceptable short-term outcomes.

Trial registration: This study was registered at Suez med - IRB office under trial registration no. 6 and registered at clinicaltrials.gov (NCT06349876) in 31/3/2024.

Background: The metabolic dysfunction-associated steatotic liver disease (MASLD) paradigm represents a significant departure from the previous nonalcoholic fatty liver disease (NAFLD) framework, offering a non-stigmatizing approach that enhances awareness and accelerates patient understanding. Our primary aim was to investigate the potential relationship between blood lead and manganese exposure and the onset of MASLD.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2017 to 2020, a cross-sectional study included 4,475 participants was performed to assess the relationship. The statistical analysis used throughout the study included multivariable linear regression and multiple logistic regression models, adjusted for potential confounders to ensure robust and reliable results. We applied a thorough multivariable analysis, examining various factors including age, sex, and ethnicity to enhance the robustness of our findings.

Results: Employing linear regression models in our study, we observed a clear positive correlation between elevated levels of blood lead and manganese and Controlled attenuation parameter (CAP). Additionally, employing multiple logistic regression models for detailed analysis, we noted a significant increase in the likelihood of MASLD with higher levels of blood lead and manganese.

Conclusion: The findings of this study strongly suggest a notable correlation between increased levels of blood lead and manganese with both CAP and the presence of MASLD. This study represents a population-based approach, enhancing the generalizability of the findings to the broader U.S.

Population:

Background: The aim of this study was to develop and internally validate an interpretable machine learning (ML) model for predicting the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) infection.

Methods: We retrospectively collected clinical data from patients with HCC and CHB treated at the Fourth Affiliated Hospital of Guangxi Medical University from January 2022 to December 2022, including demographics, comorbidities, and laboratory parameters. The datasets were randomly divided into a training set (361 cases) and a validation set (155 cases) in a 7:3 ratio. Variables were screened using Least Absolute Shrinkage and Selection Operator (LASSO) and multifactor logistic regression. The prediction model of HCC risk in CHB patients was constructed based on five machine learning models, including logistic regression (LR), K-nearest neighbour (KNN), support vector machine (SVM), random forest (RF) and artificial neural network (ANN). Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the predictive performance of the model in terms of identification, calibration and clinical application. The SHapley Additive exPlanation (SHAP) method was used to rank the importance of the features and explain the final model.

Results: Among the five ML models constructed, the RF model has the best performance, and the RF model predicts the risk of HCC in patients with CHB in the training set [AUC: 0.996, 95% confidence interval (CI) (0.991-0.999)] and internal validation set [AUC: 0.993, 95% CI (0.986-1.000)]. It has high AUC, specificity, sensitivity, F1 score and low Brier score. Calibration showed good agreement between observed and predicted risks. The model yielded higher positive net benefits in DCA than when all participants were considered to be at high or low risk, indicating good clinical utility. In addition, the SHAP plot of the RF showed that age, basophil/lymphocyte ratio (BLR), D-Dimer, aspartate aminotransferase/alanine aminotransferase (AST/ALT), γ-glutamyltransferase (GGT) and alpha-fetoprotein (AFP) can help identify patients with CHB who are at high or low risk of developing HCC.

Conclusion: ML models can be used as a tool to predict the risk of HCC in patients with CHB. The RF model has the best predictive performance and helps clinicians to identify high-risk patients and intervene early to reduce or delay the occurrence of HCC. However, the model needs to be further improved through large sample studies.

Objective: To investigate whether preoperative biliary drainage is beneficial for patients undergoing pancreaticoduodenectomy.

Methods: The PubMed, Cochrane Library and the Web of Science were systematically searched for relevant trials that included outcome of pancreaticoduodenectomy with and without preoperative biliary drainage from January 2010 to May 2024. The primary outcomes are postoperative pancreatic fistula and intra-abdominal infection. Data is pooled using the risk ratio or standardized mean difference with 95% confidence interval. The study protocol was registered prospectively with PROSPERO (CRD42022372584).

Results: A total of 39 retrospective cohort studies with 33,516 patients were included in this trial. Compared with no preoperative biliary drainage, the preoperative biliary drainage group had a longer hospital stay (SMD, 0.14). Performing preoperative biliary drainage significantly increases the risk of postoperative pancreatic fistula (RR, 1.09), intra-abdominal infection (RR, 1.09), surgical site infection (RR, 1.84), and sepsis (RR, 1.37). But preoperative biliary drainage lowers risk of bile leak (RR, 0.74).

Conclusion: Preoperative biliary drainage before pancreaticoduodenectomy increases the risk of postoperative complications without clear overall benefits. Routine PBD is not recommended for younger patients with mild to moderate jaundice but may be considered for high-risk patients, such as those with severe infections or progressive jaundice. Optimizing preoperative biliary drainage duration and timing may help reduce complications. Further research is needed to refine patient selection and perioperative strategies.

Background: Gastrointestinal neuroendocrine tumors (GI-NETs) are slow-growing tumors with the potential for malignancy that originate from neuroendocrine cells. Therefore, early diagnosis and treatment of GI-NETs are necessary to prevent metastasis. The widespread use of colonoscopy, which allows early detection of rectal neuroendocrine tumors (rNETs) that are small enough to be treated endoscopically, has resulted in an increasing rate of endoscopic resection of rNETs. However, whether the long-term prognosis of endoscopically resected rNETs is favorable has not yet been determined. This study aimed to assess whether endoscopically resected rNETs affect the long-term prognosis of patients.

Methods: We retrospectively reviewed the medical records of 163 consecutive patients with rNETs who underwent endoscopic resection at 11 hospitals in Japan between 1999 and 2012. The primary analysis focused on 47 patients with 51 rNETs who underwent ≥ 10 years of follow-up. The secondary analysis focused on patients who underwent less than 10 years of follow-up.

Results: The median follow-up period of patients included in the primary analysis was 12.3 years (range, 10-19.1 years). The median lesion size was 5 mm (range, 2-12). Three lesions were treated using conventional endoscopic mucosal resection (EMR). Twenty-nine lesions were treated using modified EMR. Nineteen lesions were treated using endoscopic submucosal dissection. The R1 resection rate and lymphovascular invasion rate were 15.7% and 25.5%, respectively. The curative resection (CR) rate and non-CR rate were 66.7% and 33.3%, respectively. Two patients with lesions treated with non-CR underwent radical surgery. None of the 47 patients experienced lesion recurrence during the 10-year follow-up period. Two patients whose lesions were treated with CR died of other diseases.

Conclusions: Death attributable to rNETs did not occur among patients who underwent at least 10 years of follow-up after endoscopic resection.