Association of pro-inflammatory diet with increased risk of gallstone disease: a cross-sectional study of NHANES January 2017-March 2020.

Background and aim: Gallstone disease (GSD) is a major public health problem worldwide. The dietary inflammatory index (DII) and the energy-adjusted DII (E-DII) have been used to describe dietary inflammatory potential. The current study sought to investigate the pro-inflammatory role of diet on GSD among outpatients in the United States. Methods: Cross-sectional data from 7,334 individuals older than 20 years who participated in the National Health and Nutrition Examination Survey (NHANES) from January 2017 to March 2020 were obtained. The relationship between GSD and DII was assessed using self-reported data. An association between DII and the risk of GSD was determined using sample-weighted logistic regression and restricted cubic splines (RCS). Subgroup analyzes were conducted to assess the interaction between DII and related factors. Sensitivity analysis was further used to confirm the stability of the relationship. To control for the effect of total energy intake, E-DII was calculated and analyzed. Results: A total of 10.5% of the study participants had GSD. The DII ranged from -5.52 to 5.51, and the median DII was significantly higher for participants with GSD than those without (1.68 vs. 1.23, p < 0.001). There was a significant and stable positive relationship between DII and GSD in adjusted models (OR 1.10, 95% CI 1.00-1.20). In the fully adjusted model, subjects with DII scores in the highest tertile were more likely to have GSD than those in the lowest tertile (OR 1.52, 95% CI 1.19-1.93). An apparent dose-response association between DII and GSD was detected. The association between E-DII and GSD remained stable. Conclusion: Higher DII/E-DII scores linked to the intake of a pro-inflammatory diet were positively associated with a higher risk of GSD. These findings suggest that pro-inflammatory dietary patterns can promote the formation of gallstones.

Gypenosides Prevent and Dissolve Cholesterol Gallstones by Modulating the Homeostasis of Cholesterol and Bile Acids.

Gypenosides (GPs), obtained from Gynostemma pentaphyllum (Thunb.) Makino, have been traditionally prescribed to treat metabolic disorders in Asians. This study assessed whether GPs could prevent lithogenic diet (LD)-induced cholesterol gallstone (CG) formation and enhance CG dissolution in mice. Gallstone-susceptible C57BL/6J mice were fed an LD or normal chow, with or without GPs. Bile acids (BAs) in gallbladder bile were analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed hepatic genes were identified by RNA sequencing, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. GPs were found to prevent LD-induced CG formation and to dissolve pre-existing LD-induced CGs. GPs reduced total cholesterol levels and increased BA levels in bile, as well as reducing the BA Hydrophobicity Index, ratio of 12α-hydroxylated (12α-OH) to non-12α-OH BAs, and Cholesterol Saturation Index in gallbladder bile. GO and KEGG pathway enrichment analyses indicated that GPs-induced genes were involved in BA biosynthesis and cholesterol metabolism. GPs increased the hepatic expression of genes encoding the cytochrome P450 (Cyp) enzymes Cyp7a1, Cyp7b1, and Cyp8b1, while decreasing the hepatic expression of genes encoding the adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8. GPs may be a promising strategy for preventing and dissolving CGs.

Diagnosis and segmentation effect of the ME-NBI-based deep learning model on gastric neoplasms in patients with suspected superficial lesions - a multicenter study.

Background: Endoscopically visible gastric neoplastic lesions (GNLs), including early gastric cancer and intraepithelial neoplasia, should be accurately diagnosed and promptly treated. However, a high rate of missed diagnosis of GNLs contributes to the potential risk of the progression of gastric cancer. The aim of this study was to develop a deep learning-based computer-aided diagnosis (CAD) system for the diagnosis and segmentation of GNLs under magnifying endoscopy with narrow-band imaging (ME-NBI) in patients with suspected superficial lesions. Methods: ME-NBI images of patients with GNLs in two centers were retrospectively analysed. Two convolutional neural network (CNN) modules were developed and trained on these images. CNN1 was trained to diagnose GNLs, and CNN2 was trained for segmentation. An additional internal test set and an external test set from another center were used to evaluate the diagnosis and segmentation performance. Results: CNN1 showed a diagnostic performance with an accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 90.8%, 92.5%, 89.0%, 89.4% and 92.2%, respectively, and an area under the curve (AUC) of 0.928 in the internal test set. With CNN1 assistance, all endoscopists had a higher accuracy than for an independent diagnosis. The average intersection over union (IOU) between CNN2 and the ground truth was 0.5837, with a precision, recall and the Dice coefficient of 0.776, 0.983 and 0.867, respectively. Conclusions: This CAD system can be used as an auxiliary tool to diagnose and segment GNLs, assisting endoscopists in more accurately diagnosing GNLs and delineating their extent to improve the positive rate of lesion biopsy and ensure the integrity of endoscopic resection.

Astragalus Polysaccharides Ameliorate Diet-Induced Gallstone Formation by Modulating Synthesis of Bile Acids and the Gut Microbiota.

Cholesterol gallstone (CG) disease has relationships with several metabolic abnormalities. Astragalus polysaccharides (APS) have been shown to have multiple benefits against metabolic disorders. We attempted to uncover the effect and mechanism of action of APS on diet-induced CG formation in mice. Animals were fed a chow diet or lithogenic diet (LD) with or without APS supplementation. The effect of APS on CG formation was evaluated. The level of individual bile acids (BAs) in gallbladder bile and ileum were measured by liquid chromatography-tandem mass spectrometry. Real-time reverse transcription-quantitative polymerase chain reaction and western blotting were used to assess expression of the genes involved in BA metabolism and the enterohepatic circulation. Cecal contents were collected to characterize microbiota profiles. APS ameliorated LD-induced CG formation in mice. APS reduced the level of total cholesterol, bile acid hydrophobicity index and cholesterol saturation index in gallbladder bile. The protective effect of APS might result from reduced absorption of cholic acid in the intestine and increased hepatic BA synthesis. APS relieved the LD-induced activation of the intestinal farnesoid X receptor and decreased ileal expression of fibroblast growth factor 15. In the liver, expression of cytochrome P450 (Cyp) enzyme Cyp7a1 and Cyp7b1 was increased, whereas expression of adenosine triphosphate-binding cassette (Abc) transporters Abcg5 and Abcg8 was decreased by APS. APS improved the diversity of the gut microbiota and increased the relative abundance of the Bacteroidetes phylum. APS had demonstratable benefits against CG disease, which might be associated with enhanced BA synthesis and improved gut microbiota. Our results suggest that APS may be a potential strategy for the prevention of CG disease.

Deoxycholic acid-stimulated macrophage-derived exosomes promote intestinal metaplasia and suppress proliferation in human gastric epithelial cells.

The crosstalk between macrophages and gastric epithelial cells has emerged as a player in chronic inflammation during intestinal metaplasia. However, the role of bile acid on this modulation remains to be studied. We hypothesized that deoxycholic acid-induced macrophages secreted exosomes to mediate intercellular communication and promoted intestinal metaplasia in human gastric epithelial cells (GES-1 cells). Macrophage-derived exosomes (M-Exos) and deoxycholic acid-induced macrophage-derived exosomes (D-Exos) were isolated by ultracentrifugation. EdU staining and CCK-8 assay were utilized to evaluate the effects of exosomes on the proliferation of GES-1 cells. Intestinal metaplasia was assessed by the expression of caudal-related homeobox transcription factor 2 (CDX2) at both mRNA and protein level. MicroRNA sequencing revealed the microRNA (miRNA) expression profiles of M-Exos and D-Exos. The role of a specific miRNA and mRNA was analyzed by using miRNA mimics, miRNA inhibitors and siRNAs. D-Exos promoted the expression of CDX2 and suppressed the proliferation of GES-1 cells, compared to M-Exos. The miRNA profiles and quantitative real-time PCR examination showed D-Exos enriched a higher level of hsa-miR-30a-5p than M-Exos. Overexpressed has-miR-30a-5p increased CDX2 expression and inhibited the proliferation in GES-1 cells via targeted Forkhead Box D1 (FOXD1), a potential regulatory factor in the process of intestinal metaplasia. D-Exos may promote intestinal metaplasia and suppress proliferation of GES-1 cells via hsa-miR-30a-5p targeting FOXD1, which may be involved in the action mechanism of bile acid on gastric mucosa.

A new exploration of white globe appearance (WGA) in ulcerative lesions.

AIM: White globe appearance (WGA), a small white lesion with a globular shape that can be clearly visualized by magnifying endoscopy with narrow-band imaging (ME-NBI), was reported to be a reliable marker of early gastric cancer (EGC). However, we found that this endoscopic presentation could also be seen in non-cancerous tissues, especially in ulcerative lesions. This study aimed to further investigate the diagnostic value of WGA in differentiating non-cancerous lesions from EGC in ulcer-type cases. MATERIALS AND METHODS: We retrospectively reviewed 54 cases of EGC and 155 cases of non-cancerous lesions in this study, all of which had endoscopic imaging data of ME-NBI scanning and pathological data of biopsy or resected specimens. The correlation of the prevalence of WGA and ulcerative lesions, as well as the characteristics of WGA between the 2 groups were analyzed in this study. RESULTS: WGA was more common in ulcerative lesions (27.6 %, 21/76) than in non-ulcerative lesions (3.8 %, 5/133) (p < 0.001) in our study. In the ulcerative cases, no significant difference in prevalence of WGA was observed between EGC and non-cancerous lesions (p = 0.532). Compared with WGA in EGC, WGA in non-cancerous lesions tended to show the characteristic of tree-branch-like vessels on globular shape (p < 0.001). CONCLUSIONS: WGA is more likely to occur in ulcerative lesions, and the presence of WGA alone cannot distinguish EGC from non-cancerous lesions in ulcer-type cases. In WGA-positive tissue, tree-branch-like vessels of globular shape may provide a certain clinical value in diagnosis of non-cancerous lesions or EGC.

Endoscopic acanthosis nigricans appearance: A novel specific marker for diagnosis of low-grade intraepithelial neoplasia.

BACKGROUND AND AIM: At present, there is no recognized diagnostic criteria for gastric low-grade intraepithelial neoplasia (LGIN). The purpose of this study was to determine whether an "endoscopic acanthosis nigricans appearance (EANA)" could be a useful endoscopic marker for distinguishing LGIN lesions from peripheral non-neoplastic tissues. METHODS: A retrospective study was conducted on 638 cases of suspected superficial lesions with endoscopic images from white light endoscopy and magnifying endoscopy combined with narrow band imaging. According to the pathological results of accurate biopsies, those lesions were divided into three groups: a control group, an LGIN group, and an early gastric cancer (EGC) group. RESULTS: According to the presence of EANAs, the sensitivity, specificity, positive predictive value, and negative predictive value for differentiating between the LGIN and control groups were 24.8%, 97.3%, 78.3%, and 76.6%, respectively. The sensitivity (84.1%) and negative predictive value (92.4%) were significantly improved by combining EANA with types IV-VI pit pattern. The intervening part and mean gray value of glands, representing microsurface features and microvascular variation, were significantly larger or higher in EANA lesions than in the surrounding non-neoplastic mucosa. LGIN with EANA was more likely to be present in lesions of type 0-IIa. In addition, the prevalence of EANAs in EGC was 16.7%. CONCLUSION: An EANA could be used as an auxiliary indicator for a diagnosis of LGIN in suspected lesions. It could also play a potential assistive role in the diagnosis of EGC lesions.

Deoxycholic acid-stimulated macrophage-derived exosomes promote spasmolytic polypeptide-expressing metaplasia in the stomach.

RATIONALE: Spasmolytic polypeptide-expressing metaplasia (SPEM) is an important risk factor for the occurrence of gastric cancer. It may be driven by a chronic inflammatory environment in which macrophage is involved. Studies have shown that intestinal metaplasia may originate from SPEM, and bile acid-induced chronic inflammation plays an important role in the process of intestinal metaplasia. However, whether bile acids are involved in the development of SPEM and the specific mechanism are unclear. Meanwhile, macrophages are known to be involved in inflammation regulation by releasing various factors, including exosomes. In this study, we hypothesized that the exosomes released from macrophages stimulated by deoxycholic acid participated in the development of SPME. METHODS: In vivo, mice were gavaged with deoxycholic acid for 4 weeks, and gastric tissues were harvested. In vitro, deoxycholic acid-induced macrophage-derived exosomes were isolated by ultracentrifugation and cocultured with the gastric organoids of mice. Immunofluorescence staining and quantitative real-time PCR were used to analyze markers of macrophages and SPEM. RESULTS: In vivo, after 4 weeks of deoxycholic acid intragastric administration, macrophage markers (F4/80) and SPEM markers (TFF2 and GSII lectin) were increased in from treated mice compared with those from normal control mice. In vitro, macrophage-derived exosomes labeled with PKH67 were internalized by gastric organoids. Deoxycholic acid-induced macrophage-derived exosomes increased the expression of SPEM markers (TFF2 and GSII lectin) in gastric organoids compared to exosomes derived from macrophages without deoxycholic acid stimulation. CONCLUSION: Macrophage-derived exosomes may be a novel mechanism by which deoxycholic acid promotes SPEM.