Digestive Diseases and Sciences最新文献

Introduction: Alcoholic hepatitis (AH) is a serious complication of alcohol consumption with high morbidity and mortality, particularly in the United States where alcohol-related liver diseases rank as one of the leading causes of preventable death. Our study aims to analyze the morbidity and mortality of AH across racial groups and project hospitalization trends up to 2028, thereby informing public health initiatives.

Methods: We conducted a cross-sectional study utilizing data from the Nationwide Inpatient Sample (NIS) spanning 2012 to 2021. The study population comprised hospitalizations identified using specific ICD-9-CM and ICD-10-CM codes for AH. We assessed hospitalizations, in-hospital mortality rates, length of stay (LOS), and morbidities related to alcoholic hepatitis adjusting for sociodemographic factors and hospital characteristics. Statistical analyses were performed using Stata and R software, employing logistic and linear regression analyses, and SARIMA models for forecasting.

Results: Our results indicated a predominantly White cohort (68%), with a notable increase in AH hospitalizations among Hispanics (129.1% from 2012 to 2021). Racial disparities were observed in inpatient mortality, liver transplant accessibility, and the occurrence of in-hospital complications. The study forecasts a continued rise in hospitalizations across all racial groups, with Hispanics experiencing the sharpest increase.

Conclusion: Our study reveals a disproportionate rise in the AH burden among Hispanics with projections indicating a persistent upward trend through 2028. These findings highlight the need for targeted public health strategies and improved healthcare access to mitigate the increasing AH burden and address disparities in care and outcomes.

Background

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an attractive target for the treatment of various malignancies; however, its therapeutic potential is limited because of the frequent occurrence of tumor cell resistance. In this study, we determined whether TRAIL resistance acquired by repeated administration could be overcome by HDAC inhibition in human colorectal cancer cells.

Methods

TRAIL-resistant HCT116 human colorectal cancer cells (HCT116-TR) were generated by repeated treatment with 10 and 25 ng/mL TRAIL twice weekly for 28 days.

Results

The resulting TRAIL-resistant cells were noncross-resistant to other chemotherapeutic agents. The levels of histone acetylation-related proteins, such as ac-histone H4 and HDAC1, were altered in HCT116-TR cells compared with the parental HCT116 cell line. The combined treatment with TRAIL and HDAC inhibitors significantly increased apoptosis in HCT116-TR cells and indicated a synergistic effect. The mechanism by which HDAC inhibition sensitizes HCT116-TR cells to TRAIL is dependent on the intrinsic pathway. In addition, we found that HDAC inhibition enhanced the sensitivity of cells to TRAIL through mitogen-activated protein kinases/CCAAT/enhancer-binding protein homologs of protein-dependent upregulation of death receptor 5.

Conclusion

These results suggest that histone acetylation is responsible for acquired TRAIL resistance after repeated exposure and acquired resistance to TRAIL may be overcome by combination therapies with HDAC inhibitors.

Introduction: Patients with cirrhosis are at risk for cardiac complications such as heart failure, particularly heart failure with preserved ejection fraction (HFpEF) due to left ventricular diastolic dysfunction (LVDD). The H2FPEF score is a predictive model used to identify patients with HFpEF. Our primary aim was to assess the H2FPEF score in patients with cirrhosis and determine its potential to identify patients at risk for heart failure after liver transplant.

Methods: This was a cohort study of patients undergoing liver transplant for cirrhosis from January 2010 and October 2018 who had a pre-transplant transthoracic echocardiogram.

Results: 166 cirrhosis subjects were included in the study. The majority were men (65%) and Caucasian (85%); NASH was the most common cause of cirrhosis (41%) followed by alcohol (34%). The median H2FPEF score was 2.0 (1.0-4.0). Patients with NASH cirrhosis had higher H2FPEF scores (3.22, 2.79-3.64) than those with alcohol induced cirrhosis (1.89, 1.5-2.29, p < 0.001) and other causes of cirrhosis (1.73, 1.28-2.18, p < 0.001). All subjects with a H2FPEF score > 6 had NASH cirrhosis. There was no association between the H2FPEF scores and measures of severity of liver disease (bilirubin, INR, or MELD score). Patients with heart failure after liver transplant had higher H2FPEF scores than those without heart failure (4.0, 3.1-4.9 vs. 2.3, 2.1-2.6, respectively; p = 0.015), but the score did not predict post-transplant mortality.

Conclusion: H2FPEF scores are higher in cirrhosis patients with NASH and appear to be associated with post-transplant heart failure, but not death.

Background: Colorectal cancer (CRC) is a malignant tumor within the digestive tract with both a high incidence rate and mortality. Early detection and intervention could improve patient clinical outcomes and survival.

Methods: This study computationally investigates a set of prognostic tissue and cell features from diagnostic tissue slides. With the combination of clinical prognostic variables, the pathological image features could predict the prognosis in CRC patients. Our CRC prognosis prediction pipeline sequentially consisted of three modules: (1) A MultiTissue Net to delineate outlines of different tissue types within the WSI of CRC for further ROI selection by pathologists. (2) Development of three-level quantitative image metrics related to tissue compositions, cell shape, and hidden features from a deep network. (3) Fusion of multi-level features to build a prognostic CRC model for predicting survival for CRC.

Results: Experimental results suggest that each group of features has a particular relationship with the prognosis of patients in the independent test set. In the fusion features combination experiment, the accuracy rate of predicting patients' prognosis and survival status is 81.52%, and the AUC value is 0.77.

Conclusion: This paper constructs a model that can predict the postoperative survival of patients by using image features and clinical information. Some features were found to be associated with the prognosis and survival of patients.

Objective: Krüppel-like factor 4 (KLF4) has been demonstrated to exert a pro-carcinogenic effect in solid tissues. However, the precise biological function and underlying mechanisms in colorectal cancer (CRC) remains elucidated.

Aims: To investigate whether KLF4 participates in the proliferation and invasion of CRC.

Methods: The expression of KLF4 was investigated using immunohistochemistry and immunoblotting. The clinical significance of KLF4 was evaluated. Furthermore, the effect of inhibiting or overexpressing KLF4 on tumor was examined. Immunoblotting and qPCR were used to detect Epithelial-mesenchymal transition-related proteins levels. Additionally, the molecular function of KLF4 is related to the STAT3 signaling pathway and was determined through JASPAR, GSEA analysis, and in vitro experiments.

Results: KLF4 exhibits down-regulated expression in CRC and is part of the vessel invasion, TNM stage, and worse prognosis. In vitro studies have shown that KLF4 promotes cellular proliferation and invasion, as well as EMT processes. Xenograft tumor models confirmed the oncogenic role of KLF4 in nude mice. Furthermore, GSEA and JASPAR databases analysis reveal that the binding of KLF4 to the signal transducer and activator of transcription 3 (STAT3) promoter site induces activation of p-STAT3 signaling. Subsequent targeting of STAT3 confirmed its pivotal role in mediating the oncogenic effects exerted by KLF4.

Conclusion: The study suggests that KLF4 activates STAT3 signaling, inducing epithelial-mesenchymal transition, thereby promoting CRC progression.

Background: Insights into (poly)phenol exposure represent a modifiable factor that may modulate inflammation in chronic pancreatitis (CP), yet intake is poorly characterized and methods for assessment are underdeveloped.

Aims: The aims are to develop and test a method for estimating (poly)phenol intake from a 90-day food frequency questionnaire (FFQ) using the Phenol-Explorer database and determine associations with dietary patterns in CP patients versus controls via analysis of previously collected cross-sectional data.

Methods: Fifty-two CP patients and 48 controls were recruited from an ambulatory clinic at a large, academic institution. To assess the feasibility of the proposed methodology for estimating dietary (poly)phenol exposure, a retrospective analysis of FFQ data was completed. Mann-Whitney U tests were used to compare (poly)phenol intake by group; Spearman correlations and multivariable-adjusted log-linear associations were used to compare (poly)phenol intakes with dietary scores within the sample.

Results: Estimation of (poly)phenol intake from FFQs was feasible and produced estimates within a range of intake previously reported. Total (poly)phenol intake was significantly lower in CP vs controls (463 vs. 567mg/1000kcal; p = 0.041). In adjusted analyses, higher total (poly)phenol intake was associated with higher HEI-2015 (r = 0.34, p < 0.001), aMED (r = 0.22, p = 0.007), EDIH (r = 0.29, p < 0.001), and EDIP scores (r = 0.35, p < 0.001), representing higher overall diet quality and lower insulinemic and anti-inflammatory dietary potentials, respectively.

Conclusions: Using enhanced methods to derive total (poly)phenol intake from an FFQ is feasible. Those with CP have lower total (poly)phenol intake and less favorable dietary pattern indices, thus supporting future tailored dietary intervention studies in this population.