Digestive Diseases and Sciences最新文献

Background: Proline-rich tyrosine kinase 2 (PYK2) is involved in the occurrence, proliferation, migration, and invasion of various tumors. However, few studies have reported the role of PYK2 in colorectal cancer (CRC).

Aim: To explore the effects of PYK2 on CRC metastasis and elucidate the detailed molecular mechanisms involved.

Methods: The expression and prognosis value of PYK2 in CRC prognosis were analyzed using data from The Cancer Genome Atlas (TCGA). PYK2 was knocked down or overexpressed in human CRC cell line, HCT116. Cell proliferation, migration, invasion, and cycle changes were analyzed using CCK-8, Transwell, and flow cytometry assays. Western blotting and quantitative real-time PCR were performed to detect the mRNA and protein levels of cell proliferation and epithelial-mesenchymal transition (EMT) indicators. Fluorescence staining was performed to examine the cytoskeleton.

Results: Lower expression of PYK2 was observed in CRC tissues and associated with poor prognosis and metastasis in patients with CRC in TCGA database. PYK2 knockdown significantly induced the migration and invasion of CRC cells but did not affect cell proliferation or cycle. Immunofluorescence staining of phalloidin showed that the downregulation of PYK2 increased the cytoskeleton in CRC cells. Moreover, low expression of PYK2 induced the downregulation of E-cadherin and upregulation of snail and vimentin by activating Wnt/β-catenin signaling, thus promoting EMT in CRC cells.

Conclusions: Low PYK2 expression was found in tumor tissues, especially metastases, and significantly correlated with patient prognosis. Moreover, decreased PYK2 induces EMT by activating Wnt/β-catenin signaling, which is the potential mechanism of CRC metastasis. Regulating the expression of PYK2 to suppress tumor cell metastasis may represent a promising therapeutic strategy for metastatic CRC.

Background: Common gastrointestinal disease irritable bowel syndrome (IBS) is marked by symptoms like changed bowel habits, bloating, and stomach ache. A low-FODMAP combined gluten-free diet (LF-GFD) has been suggested as a possible therapy for IBS symptoms management.

Objective: This study sought to investigate whether a LF-GFD would help patients with IBS.

Methods: Strict inclusion and exclusion criteria from internet databases helped to identify clinical studies evaluating the intervention of LF-GFD in the treatment of IBS patients. Using measurements including the visual analog scale (VAS) for bloating and pain, the IBS symptom severity scale (IBS-SSS), and IBS quality of life (IBS-QoL), the main results evaluated were the efficacy of LF-GFD in reducing IBS symptoms. Furthermore assessed were the psychological impacts of LF-GFD utilizing the self- rating depression scale (SDS) and self- rating anxiety scale (SAS).

Results: A total of 437 patients (221 on LF-GFD diet and 216 on GFD) were involved in 4 randomized controlled trials and 4 cohort studies. The combined results indicated that LF-GFD reduced the VAS bloating ratings (RR = - 0.58, 95%CI - 0.92-0.23, P = 0.0010, I2 = 83%) and the VAS pain scores (RR = - 0.42, 95%CI - 0.66-0.19, P = 0.005, I2 = 58%). In addition, LF-GFD indicated a substantial enhancement in IBS-SSS scores (MD = - 1.42, 95%CI - 2.74-0.10, P = 0.03, I2 = 24%) and IBS-QoL ratings (MD = 3.75, 95%CI 0.98-6.53, P = 0.008, I2 = 33%). Moreover, the LF-GFD group showed a substantial drop in SDS (MD = - 2.56, 95%CI - 3.38-1.74, P < 0.00001, I2 = 65%) and SAS (MD = - 4.30, 95%CI - 6.53-2.24, P < 0.0001, I2 = 0%) scores compared to the GFD group.

Conclusion: LF-GFD therapy significantly enhances clinical symptoms and reduces anxiety and depression in individuals diagnosed with irritable bowel syndrome.

Background and aims: Data regarding histologic recurrence of EoE on PPI maintenance therapy are lacking.

Methods: Retrospective review of 101 patients with histologic PPI-responsive EoE.

Results: 52/101 (51%) patients underwent follow-up EGD with biopsies. Of the 52 patients, 29 (56%) maintained histologic remission and 23 (44%) had histologic recurrence. 21 (40%) patients maintained BID PPI, 20 (39%) tapered to QD, and 11 (21%) had discontinued PPI. Of the 21 patients on BID PPI, 7 (33%) had histologic recurrence, of which 6 (86%) were asymptomatic.

Conclusions: Patients on PPI therapy for EoE benefit from serial clinical, endoscopic, and histologic surveillance.

Background and aims: Physicians are required to spend a significant amount of reading time of magnetically controlled capsule endoscopy. However, current deep learning models are limited to completing a single recognition task and cannot replicate the diagnostic process of a physician. This study aims to construct a multi-task model that can simultaneously recognize gastric anatomical sites and gastric lesions.

Methods: A multi-task recognition model named Mul-Recog-Model was established. The capsule endoscopy image data from 886 patients were selected to construct a training set and a test set for training and testing the model. Based on the same test set, the model in this study was compared with the current single-task recognition model with good performance.

Results: The sensitivity and specificity of the model for recognizing gastric anatomical sites were 99.8% (95% confidence intervals: 99.7-99.8) and 98.5% (95% confidence intervals: 98.3-98.7), and for gastric lesions were 98.8% (95% confidence intervals: 98.3-99.2) and 99.4% (95% confidence intervals: 99.1-99.7). Moreover, the positive predictive value, negative predictive value, and accuracy of the model were more than 95% in recognizing gastric anatomical sites and gastric lesions. Compared with the current single-task recognition model, our model showed comparable sensitivity, specificity, positive predictive value, negative predictive value, and accuracy (p < 0.01, except for the negative predictive value of ResNet, p > 0.05). The Areas Under Curve of our model were 0.985 and 0.989 in recognizing gastric anatomical sites and gastric lesions. Furthermore, the model had 49.1 M parameters and 38.1G Float calculations. The model took 15.5 ms to recognize an image, which was less than the superposition of multiple single models (p < 0.01).

Conclusions: The Mul-Recog-Model exhibited high sensitivity, specificity, PPV, NPV, and accuracy. The model demonstrated excellent performance in terms of parameters quantity, Float computation, and computing time. The utilization of the model for recognizing gastric images can improve the efficiency of physicians' reports and meet complex diagnostic requirements.

Background: In patients with metabolic dysfunction-associated steatotic liver disease (MASLD), there are limited data on how changes in FIB4 and liver stiffness measurement (LSM) correlate in non-biopsy cohorts.

Aims: Our objective was to evaluate associations between changes in FIB4 and LSM in MASLD patients.

Methods: We included MASLD patients with serial VCTE from 2015-2022. The primary predictors were change in FIB4 and presence of diabetes, obesity, and high alanine aminotransferase (ALT). The primary outcome, applied only to patients with LSM1 < 8 kPa, was incident significant fibrosis (SF) defined as a ≥ 20% increase in LSM2 vs. LSM1 and LSM2 ≥ 8 kPa. A secondary outcome was LSM progression with a similar definition but applied to all participants, not only those with LSM1 < 8 kPa.

Results: Of 285 included patients, 216 had LSM1 < 8 kPa and were included in the primary analysis; of these, 34 (16%) had incident SF. Changes in FIB4 correlated with changes in LSM (R = 0.16, p = 0.016). Independent predictors of incident SF included comorbid diabetes mellitus (OR 2.43, 95% CI 1.04-6.56), obesity (OR 3.88, 95% CI 1.63-9.25), and baseline ALT ≥ 30 (OR 8.55, 95% CI 1.10-66.29). A model including ALT, diabetes, and obesity outperformed a model with FIB4 change alone.

Conclusion: Among patients with MASLD, changes in FIB4 correlated with changes in LSM but more significant correlates of incident significant fibrosis included diabetes mellitus, obesity, and high baseline ALT.

Background: Digital health interventions (DHIs) could be a valuable self-management tool for patients with irritable bowel syndrome (IBS), but little research exists on IBS-focused DHIs and their effectiveness. This review aimed to identify DHIs for IBS and evaluate their characteristics, effectiveness, and feasibility.

Methods: Our study team, including patient partners, conducted a systematic review using Medline, PsycINFO, Embase, Web of Science, and CINAHL from database inception to May 2024. Experimental and observational studies evaluating DHIs designed for use by IBS patients were included. Data extraction and assessment included study and DHI characteristics, effectiveness outcomes (symptom severity, quality of life, psychological indices, patient empowerment), and feasibility measures (adherence, usability, user satisfaction). Study quality and bias were assessed using a modified checklist of Downs and Black.

Results: Of the 929 identified, 13 studies of DHIs were included and deemed good quality on average (21,510 total participants) with six primary areas of focus: education, diet, brain-gut behavior skills, physiological support, health monitoring, and community engagement. Most DHIs were self-directed and reported statistically significant improvements in most effectiveness outcomes. Evidence suggests that DHIs focusing on brain-gut behavior skills or health monitoring may be most effective compared to other types of DHIs. However, their feasibility remains unclear, and the generalization of their impacts is limited.

Conclusion: This review underscores the potential of DHIs in supporting IBS patients and improving their outcomes. However, additional research is warranted for continued intervention use in this population, including assessments on feasibility, safety, cost-effectiveness, and patient empowerment and experiences.

Background: Psychological state, self-reported gut symptoms, and somatic complaints are recognized relationships that can impact health assessment and subsequent treatment.

Aim: To investigate the impact of psychological state and personality on symptom self-reporting and somatization.

Methods: Sixty-two (62) participants from the Hunter region of NSW (Australia) undertook a survey of health and lifestyle along with an MMPI-2-RF assessment of personality, psychopathology, and test-taking attitude. Participants also completed the Rome Criteria to assess functional gastrointestinal disorders (FGIDs). To assist the interpretation of MMPI-2-RF results, clustering was applied to identify similar responses and sub-cohort profiles of reporting.

Results: Cluster analysis revealed four sub-cohorts, stratified by psychopathology, gut-related symptoms, and the validity of self-reported somatic complaints. Sample clustering identified one sub-cohort defined by high rates of negative affectivity and suicidal ideation. Apart from these differences, clusters were uniform for age, sex, smoking, mental health diagnoses, as well as for gut-related conditions.

Conclusion: Results provide further evidence of the interaction of the gut-brain axis and its relationship to serious mental health conditions. It also points to the need to assess the veracity of self-reported symptomatology that may be both pathognomonic for psychopathology but might also be a consequence of gut dysbiosis. Clustering assisted these investigations by defining distinct sub-cohorts based on participant MMPI-2-RF responses.