Association of Antidiabetic Drug Target Genes with Inflammatory Bowel Disease: A Mendelian Randomization Study.

Background: An unmet medical need for the treatment of inflammatory bowel disease (IBD) exists. A part of antidiabetic drugs had potential effects on IBD in various observational research. Objective: To investigate the potential of antidiabetic drugs on IBD. Methods: We undertook a summary-data-based Mendelian randomization (SMR) using the expression quantitative trait loci (eQTL) expressed in the blood or colon and a two sample Mendelian randomization (TSMR) utilizing single nucleotide polymorphism (SNP) of antidiabetic drug target genes mediated by blood glucose traits. Participants encompassed patients with IBD (25,042 cases/34,915 controls), UC (12,366 cases/33,609 controls), and CD (12,194 cases/28,072 controls). Data on eQTL in the blood or the colon were from the eQTLGen consortium (31,684 individuals) or GTEx Consortium V8, respectively. SMR was performed by SMR software (20,220,322); the primary method for TSMR was inverse-variance weighted (IVW) or Wald ratio through R studio (2023.06.0+421). Sensitivity analyses were carried out. Results: A 1-SD upper expression of the KCNJ11 gene (target gene of sulfonylureas) in the blood reduced the risk of CD (OR per 1-SD = 0.728, 95% CI = 0.586-0.903, P = 0.004) according to the result of SMR. ABCC8 (target gene of sulfonylureas) expressed in the colon did not affect CD, UC, or IBD. T2D-mediated KCNJ11 has a protective effect on CD (OR = 0.475, 95% CI = 0.297-0.761, P = 0.002). Gene predicted no relationship between T2D and CD. Conclusion: Sulfonylureas (SUs) may have side effects on CD. This work provides some suggestions for the selection of antidiabetic drugs in patients with CD.

Causal Association Analysis of Periodontitis and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Periodontitis has been reported to be associated with inflammatory bowel disease (IBD), including ulcerative colitis (UC), and Crohn's disease (CD). However, the causality of these 2 diseases remains unclear. We conducted bidirectional Mendelian randomization (MR) to investigate the causal relationship between periodontitis and IBD. METHODS: We obtained the genome-wide association study (GWAS) summary data of European populations from FinnGen database (for IBD) and a published article (for periodontitis), from which independent single nucleotide polymorphisms were selected as instrumental variables. Inverse variance-weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for MR analysis. Heterogeneity or pleiotropy was detected through Cochran's Q test and MR-Egger intercept, respectively. Outlier was identified with MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) and leave-one-out analysis. All statistical analyses were performed with R 4.2.1 and the packages of TwoSampleMR version 0.5.6. RESULTS: Genetic prediction showed that periodontitis was the risk factor of UC (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01-1.26; P = .027), rather than of CD (OR, 0.92; 95% CI, 0.74-1.15; P = .456) and IBD (OR, 0.96; 95% CI, 0.81-1.13; P = .619). To the contrary, CD, not UC or IBD, resulted in exacerbating periodontitis in terms of the results of the IVW (OR, 1.09; 95% CI, 1.01-1.17; P = .021) and WM (OR, 1.10; 95% CI, 1.01-1.20; P = .030) methods. Heterogeneity or pleiotropy was acceptable. CONCLUSIONS: Our results indicated that CD was the risk factor for periodontitis; conversely, periodontitis was responsible for the exacerbation of UC, enhancing the existence of mouth-gut axis. Patients with UC should pay more attention to periodontal health, while patients with periodontitis should actively pay close heed to intestinal health.

A bidirectional Mendelian randomization study indicated that Crohn's disease was the risk factor for periodontitis; conversely, periodontitis was responsible for the exacerbation of ulcerative colitis, enhancing the existence of the mouth-gut axis and suggesting paying attention to oral health for patients of inflammatory bowel disease.

Symptom effects and central mechanism of acupuncture in patients with functional gastrointestinal disorders: a systematic review based on fMRI studies.

BACKGROUND: Functional gastrointestinal disorders (FGIDs) are closely related to disorders of brain-gut interaction. FGIDs are the dominant disease of acupuncture treatment, which can improve the symptoms and emotional state. AIM: To evaluate the results and quality of the available clinical evidence and to summarize the central mechanism and effect of acupuncture on FGIDs. METHODS: PubMed, EMBASE, Web of science, Cochrane Library, China National Knowledge Infrastructure (CNKI) were searched by computer to collect the randomized controlled trials (RCTs), which contained central mechanisms via fMRI research of acupuncture in the treatment of FGIDs patients. The search time limit was from the establishment of the database to June 22, 2022. Two researchers independently screened the literature, extracted data, and evaluated the quality. RESULTS: Ten RCTs involving fMRI data were included in this study, including 4 Functional dyspepsia (FD) studies, 3 irritable bowel syndrome (IBS) studies, and 3 functional constipation (FC) studies. The score of improvements in both gastrointestinal symptoms and psychological symptoms showed that acupuncture could significantly improve the clinical symptoms of FGIDs patients, including abdominal pain, abdominal distension, frequency of defecation, and stool characteristics, and could relieve anxiety and depression symptoms of patients. Acupuncture could regulate brain functional connections and functional activity in FGIDs patients, mainly including insula, anterior cingulate cortex, prefrontal cortex, thalamus, hippocampus, amygdala and other brain regions. CONCLUSION: Acupuncture can improve gastrointestinal symptoms and psychological status in FGIDs patients, and regulate functional connectivity and activity of brain regions such as insula, ACC, PFC, thalamus, HIPP, amygdala, etc. These changes in brain activity may related to visceral sensation, pain regulation, emotion, but further studies of high quality are still necessary.

Diagnosing and grading gastric atrophy and intestinal metaplasia using semi-supervised deep learning on pathological images: development and validation study.

OBJECTIVE: Patients with gastric atrophy and intestinal metaplasia (IM) were at risk for gastric cancer, necessitating an accurate risk assessment. We aimed to establish and validate a diagnostic approach for gastric biopsy specimens using deep learning and OLGA/OLGIM for individual gastric cancer risk classification. METHODS: In this study, we prospectively enrolled 545 patients suspected of atrophic gastritis during endoscopy from 13 tertiary hospitals between December 22, 2017, to September 25, 2020, with a total of 2725 whole-slide images (WSIs). Patients were randomly divided into a training set (n = 349), an internal validation set (n = 87), and an external validation set (n = 109). Sixty patients from the external validation set were randomly selected and divided into two groups for an observer study, one with the assistance of algorithm results and the other without. We proposed a semi-supervised deep learning algorithm to diagnose and grade IM and atrophy, and we compared it with the assessments of 10 pathologists. The model's performance was evaluated based on the area under the curve (AUC), sensitivity, specificity, and weighted kappa value. RESULTS: The algorithm, named GasMIL, was established and demonstrated encouraging performance in diagnosing IM (AUC 0.884, 95% CI 0.862-0.902) and atrophy (AUC 0.877, 95% CI 0.855-0.897) in the external test set. In the observer study, GasMIL achieved an 80% sensitivity, 85% specificity, a weighted kappa value of 0.61, and an AUC of 0.953, surpassing the performance of all ten pathologists in diagnosing atrophy. Among the 10 pathologists, GasMIL's AUC ranked second in OLGA (0.729, 95% CI 0.625-0.833) and fifth in OLGIM (0.792, 95% CI 0.688-0.896). With the assistance of GasMIL, pathologists demonstrated improved AUC (p = 0.013), sensitivity (p = 0.014), and weighted kappa (p = 0.016) in diagnosing IM, and improved specificity (p = 0.007) in diagnosing atrophy compared to pathologists working alone. CONCLUSION: GasMIL shows the best overall performance in diagnosing IM and atrophy when compared to pathologists, significantly enhancing their diagnostic capabilities.

The role of the endoscopic grading of gastric intestinal metaplasia in assessing gastric cancer risk: A systematic review and meta-analysis.

Background and aim: Patients with gastric intestinal metaplasia (IM) are at increased risk of gastric cancer (GC). The endoscopic grading of gastric intestinal metaplasia (EGGIM) with high-definition endoscopes has shown the potential to facilitate GC risk stratification. However, a comprehensive review and meta-analysis of published articles are lacking. We conducted a meta-analysis to access the value of EGGIM in the assessment of histological IM. Materials: Studies were selected from PubMed, Medline, Embase, and Cochrane (last selection, Jun 2022). We extracted relevant data to calculate the accuracy of EGGIM compared with the operative link of gastric intestinal metaplasia (OLGIM) and to calculate pooled odds ratio (OR) with a 95% confidence interval (CI) assessing GC risk with different grading. Results: Four diagnostic studies and three case-control clinical trials were included in the analysis, which included 665 patients and 738 patients, respectively. Compared with OLGIM III/IV, EGGIM(5-10) had a pooled sensitivity and specificity of 0.92(95%CI 0.86-0.96) and 0.90(95%CI 0.88-0.93), and the area under the curve(AUC) was 0.9702. In assessing early GC, the pooled OR of patients with EGGIM(5-10) was 7.46(95%CI 3.41-16.31) compared with that of EGGIM(0-4). Conclusions: EGGIM is highly consistent with OLGIM, and patients with EGGIM(5-10) are at a higher risk for early GC. Some heterogeneity in the current research suggests that we need to carry out more strict control of confounding factors. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=248691], (Prospero registration number: 248691).

Chinese Herbal Medicine for Functional Dyspepsia With Psychological Disorders: A Systematic Review and Meta-Analysis.

Background and Aims: Functional dyspepsia (FD) is closely associated with gut-brain interaction disorder (DGBI), characterized by the interaction of gastrointestinal symptoms and central nervous system dysregulation. Chinese herbal medicine (CHM) has a good concurrent effect in the treatment of FD, especially for patients with concurrent psychological disorders. A meta-analysis was designed to evaluate the efficacy and safety of CHMs in the treatment of FD. Methods: The PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medical Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to collect randomized controlled trials of FD treated with CHM. The retrieval time limit is from the establishment of the database till 11 April 2022. Two researchers independently searched databases, screened documents, extracted data, and evaluated the risk of bias of included studies. RevMan 5.4 software was used for meta-analysis. Results: A total of 11 studies including 951 patients were included. The study was divided into two parts. The first part included 5 clinical trials, including 471 patients. The experimental group was treated only with CHM and the control group was only treated with placebo. The results of first part showed that the total effective rate of CHM in the treatment of FD was higher than that in the placebo group (84.5 vs. 49.4%) [relative risk (RR) = 1.76; 95% confidence interval (CI) (1.13, 2.75); P = 0.01]. In addition, CHM treatment could reduce the total symptom score [standardized mean difference (SMD) = -10.05; 95% CI (-13.50, -6.59); Z = 5.70; P < 0.0001] and depression score [SMD = -7.68; 95% CI (-14.43, -0.94); Z = 2.23; P = 0.03]. The second part included 6 clinical trials, including 480 patients. The experimental group was only treated with CHM and the control group was treated with prokinetic agents combined with flupentixol melitracen (deanxit). The results of second part showed that the total effective rate of CHM in the treatment of FD was higher than that of the control group (92.6 vs. 78.8%) [RR = 1.17; 95% CI (1.09, 1.26), P < 0.0001]. In addition, CHM treatment could reduce HAMA score [mean difference (MD) = -3.19; 95% CI (-3.79, -2.59); Z = 10.40; P < 0.00001], HAMD score [MD = -4.32; 95% CI (-6.04, -2.61); Z = 4.94; P < 0.00001], and gastric emptying rate [MD = 12.62; 95% CI (5.84, 19.40); Z = 3.65; P = 0.0003]. The results of the two parts of the meta-analysis showed no serious adverse reactions, and there was no significant difference in the adverse reactions between the experimental group and the control group [MD = 1.14; 95% CI (0.53, 2.42); Z = 0.33; P = 0.74]; [MD = 0.14; 95% CI (0.01, 2.67); Z = 1.30; P = 0.19]. Conclusion: The current evidence shows that CHM treatment has great potential and safety in alleviating the symptoms of FD and improving the psychological disorders of anxiety and depression in patients with FD. Limited by the quantity and quality of the included studies and other biases, the above conclusions need more high-quality studies to be verified. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier [CRD42022311129].

Efficacy and safety of berberine in preventing recurrence of colorectal adenomas: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Berberine(BBR) is a kind of isoquinoline alkaloids extracted from the rhizomes of Coptis chinensis Franch., which was the main active ingredient. Accumulating evidence has shown that it has potential pharmacological effects in preventing the recurrence of colorectal adenomas. AIM OF THE STUDY: The roles of BBR in the overall recurrence of colorectal adenoma have still not been assessed because of the limitations of the available data and the restriction of a single study. Therefore, we evaluated the effectiveness and safety of BBR in preventing the recurrence of colorectal adenomas through a systematic review and meta-analysis of available data. MATERIALS AND METHODS: We searched four English databases (PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials (CENTRAL), Embase and Web of Science) and four Chinese language databases (Chinese Biomedicine (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP) and the WanFang Database) from their inception through October 2020. Meta-analysis was performed with RevMan5.3 software after data extraction and the quality of studies assessment. RESULTS: Three randomized controlled clinical trials were included with 1076 patients. Our results illustrated that 1-year and 2-year supplementation with BBR was associated with lower recurrence rate of colorectal adenoma (RR 0.69, 95% CI 0.57 to 0.84, p=0.0001; RR 0.75, 95% CI 0.64 to 0.88, p=0.0004). The relative risk of oral BBR for 1 year and 2 years is not comparable, for 2-year efficacy outcomes were assessed in all participants who had at least one colonoscopy with pathological evaluation after baseline (lots of participants completed the first colonoscopy but discontinued during the second follow-up interval.). Moreover, the results also suggest that BBR had more adverse events than placebo (RR 2.91, 95% CI 1.24 to 6.85, p=0.01). Through the full-text reading, no serious adverse events were observed, and constipation was the most common event which disappears once the drug is discontinued. CONCLUSION: Generally, the present study indicated that BBR has a comparable therapeutic effect on the prevention of colorectal adenomas recurrence. Adverse reactions are worthy of attention which requires additional studies to obtain a precise conclusion. PROSPERO REGISTRATION NO: CRD42020209135.

Gastric Cancer Risk of Intestinal Metaplasia Subtypes: A Systematic Review and Meta-Analysis of Cohort Studies.

INTRODUCTION: Intestinal metaplasia (IM) is an independent risk factor for gastric cancer (GC). However, the subtypes of IM as a risk factor for GC remain controversial. We performed a systematic review and meta-analysis to evaluate the relationship between IM subtypes and GC risk. METHODS: Systematic searches were conducted in PubMed, EMBASE, and the Cochrane Library for published cohort studies of patients with complete IM (type I) or incomplete IM (type II or type III) from inception to May 15, 2021. We extracted relevant data and calculated pooled risk ratios (RRs) and 95% confidence intervals (CIs) comparing the GC risk with IM subtypes. RESULTS: Twelve cohort studies comprising 6,498 individuals were included in the study. Compared with complete IM, the pooled relative risk of GC risk of patients with incomplete IM was 5.16 (95% CI, 3.28-8.12), and the GC risk of type III IM was the highest, with a pooled relative risk of 2.88 (95% CI, 1.37-6.04) compared with that of type II. Compared with complete IM, the pooled relative risk of dysplasia risk in patients with incomplete IM was 3.72 (95% CI, 1.42-9.72), and the dysplasia risk of type III IM was 11.73 (95% CI, 2.08-66.08) compared with that of type I. DISCUSSION: Patients with incomplete IM, especially type III, were at a higher risk of GC and dysplasia than those with complete IM. The current evidence indicates a potential correlation between IM subtypes and GC risk, which may support the use of IM subtypes in GC surveillance.

The prognostic role of a combined fibrinogen and inflammation-based index in patients with metastatic breast cancer.

BACKGROUND: The activation of inflammation and coagulation cascades plays an essential role in the development of various malignancies, including metastatic breast cancer (MBC). This retrospective study aimed to investigate the prognostic role of the combination of fibrinogen and the inflammation-based index in patients with MBC. METHODS: A total of 176 patients with MBC were retrospectively reviewed. The clinical and pathological data of included patients were followed-up and analyzed. The plasma fibrinogen concentration (FIB), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were measured. Dynamic variations in the FIB, NLR, and PLR values were collected from 56 MBC patients before and after first-line therapy. Receiver operating characteristic (ROC) curves were constructed to assess the optimal cut-off values. Correlations between FIB and NLR or PLR were evaluated using Spearman correlation analysis. The Kaplan-Meier method, two-tailed log-rank test, and Cox proportional hazard model were used for statistical analysis. RESULTS: Baseline FIB was positively correlated with NLR and PLR values in MBC patients (P<0.05). Additionally, multivariable analysis proved that the ERBB2 + subtype (P=0.023), basal-like subtype (P=0.032), targeted therapy (P=0.033), other regimens (P=0.005), and baseline FIB level (P=0.004) were independent prognostic variables for progression-free survival (PFS) in MBC patients. Furthermore, ERBB2+, basal-like subtypes, and baseline hyperfibrinogenemia were independent factors for poor prognosis in MBC patients [hazard ratio (HR): 3.717, 95% confidence interval (CI): 1.561-8.851, P=0.003; HR: 3.245, 95% CI: 1.368-7.698, P=0.008; HR: 2.069, 95% CI: 1.352-3.167, P=0.001, respectively]. Most importantly, the FIB level increased significantly after first-line therapy in patients with disease progression (3.73±0.63 vs. 5.32±0.52 g/L, P=0.042) and also decreased markedly in stable disease (3.42±1.05 vs. 3.03±0.73 g/L, P=0.036). However, PFS and overall survival (OS) were not significantly correlated with the dynamic changes of FIB and the inflammation-based index. CONCLUSIONS: The present study provided evidence that baseline FIB combined with NLR and PLR could serve as prognostic predictors for MBC patients. Dynamic change of FIB before and after first-line therapy could also be used as a potential predictor of therapeutic response in MBC patients.

Using neural networks to estimate the losses of ascorbic acid, total phenols, flavonoid, and antioxidant activity in asparagus during thermal treatments.

Artificial neural networks (ANNs) with back-propagation algorithm were developed to predict the percentage loss of ascorbic acid, total phenols, flavonoid, and antioxidant activity in different segments of asparagus during water blanching at temperatures ranging from 65 to 95 degrees C as a function of blanching time and temperature. In this study, the one-hidden-layer ANNs are used, and the number of neurons in the hidden layer were chosen by trial and error. Optimized ANN models were developed for predicting nutrient losses in bud, upper, middle, and butt segments of asparagus. ANN models were then tested against an independent data set. Our results showed that the predicted values of the correlation coefficients between experimental and ANNs ranged from 0.8166 to 0.9868. Therefore, ANNs could be potential tools for the prediction of nutrient losses in vegetables during thermal treatments.