Efficacy of real-time artificial intelligence-aid endoscopic ultrasonography diagnostic system in discriminating gastrointestinal stromal tumors and leiomyomas: a multicenter diagnostic study.

Background: Gastrointestinal stromal tumors (GISTs) represent the most prevalent type of subepithelial lesions (SELs) with malignant potential. Current imaging tools struggle to differentiate GISTs from leiomyomas. This study aimed to create and assess a real-time artificial intelligence (AI) system using endoscopic ultrasonography (EUS) images to differentiate between GISTs and leiomyomas. Methods: The AI system underwent development and evaluation using EUS images from 5 endoscopic centers in China between January 2020 and August 2023. EUS images of 1101 participants with SELs were retrospectively collected for AI system development. A cohort of 241 participants with SELs was recruited for external AI system evaluation. Another cohort of 59 participants with SELs was prospectively enrolled to assess the real-time clinical application of the AI system. The AI system's performance was compared to that of endoscopists. This study is registered with Chictr.org.cn, Number ChiCT2000035787. Findings: The AI system displayed an area under the curve (AUC) of 0.948 (95% CI: 0.921-0.969) for discriminating GISTs and leiomyomas. The AI system's accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) reached 91.7% (95% CI 87.5%-94.6%), 90.3% (95% CI 83.4%-94.5%), 93.0% (95% CI 87.2%-96.3%), 91.9% (95% CI 85.3%-95.7%), and 91.5% (95% CI 85.5%-95.2%), respectively. Moreover, the AI system exhibited excellent performance in diagnosing ≤20 mm SELs (ACC 93.5%, 95% CI 0.900-0.969). In a prospective real-time clinical application trial, the AI system achieved an AUC of 0.865 (95% CI 0.764-0.966) and 0.864 (95% CI 0.762-0.966) for GISTs and leiomyomas diagnosis, respectively, markedly surpassing endoscopists [AUC 0.698 (95% CI 0.562-0.834) for GISTs and AUC 0.695 (95% CI 0.546-0.825) for leiomyomas]. Interpretation: We successfully developed a real-time AI-assisted EUS diagnostic system. The incorporation of the real-time AI system during EUS examinations can assist endoscopists in rapidly and accurately differentiating various types of SELs in clinical practice, facilitating improved diagnostic and therapeutic decision-making. Funding: Science and Technology Commission Foundation of Shanghai Municipality, Science and Technology Commission Foundation of the Xuhui District, the Interdisciplinary Program of Shanghai Jiao Tong University and the Research Funds of Shanghai Sixth people's Hospital.

Modular multimodal hospital-home chain physical activity rehabilitation programme (3M2H-PARP) in liver cancer: a protocol for a randomised controlled trial.

INTRODUCTION: Patients with liver cancer are susceptible to experiencing a decline in muscle mass and function, which can lead to physical frailty and have a negative impact on prognosis. However, there is currently a lack of physical activity interventions specifically tailored for these patients. Therefore, we have developed a modular multimodal hospital-home chain physical activity rehabilitation programme (3M2H-PARP) designed specifically for patients with liver cancer undergoing transarterial chemoembolisation (TACE). We aim to validate the effectiveness and feasibility of this programme through a randomised controlled trial (RCT). METHODS AND ANALYSIS: 3M2H-PARP RCT will compare a 12-week, modular, multimodal physical activity rehabilitation programme that includes supervised exercise in a hospital setting and self-management exercise at home. The programmes consist of aerobic, resistance, flexibility and balance exercise modules, and standard survivorship care in a cohort of liver cancer survivors who have undergone TACE. The control group will receive standard care. A total of 152 participants will be randomly assigned to either the 3M2H-PARP group or the control group. Assessments will be conducted at three time points: baseline, after completing the intervention and a 24-week follow-up visit. The following variables will be evaluated: liver frailty index, Functional Assessment of Cancer Therapy-Hepatobiliary subscale, Cancer Fatigue Scale, Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale and physical activity level. After the completion of the training programme, semi-structured interviews will be conducted with participants from the 3M2H-PARP group to investigate the programme's impact on their overall well-being. SPSS V.26.0 software will be used for statistical analyses. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Jiangnan University School of Medicine Research Ethics Committee. The findings will be disseminated through publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300076800.

ETS translocation variant 5 (ETV5) promotes CD4+ T cell-mediated intestinal inflammation and fibrosis in inflammatory bowel diseases.

E26 transformation-specific translocation variant 5 (ETV5) has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the exact roles of ETV5 in regulating CD4+ T cell-mediated intestinal inflammation and fibrosis formation remain unclear. Here, we reveal that ETV5 overexpression induced interleukin (IL)-9 and its transcription factor IRF4 expression in IBD CD4+ T cells under T helper type 9 (Th9) cells-polarizing conditions. The silencing of IRF4 inhibited ETV5-induced IL-9 expression. CD4+ T cell-specific ETV5 deletion ameliorated intestinal inflammation and fibrosis in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis and CD4+ T cell-transferred recombination-activating gene-1 knockout (Rag1-/-) colitis mice, characterized by less CD4+ T cell infiltration and lower fibroblast activation and collagen deposition in the colonic tissues. Furthermore, IL-9 treatment aggressive TNBS-induced intestinal fibrosis in CD4+ T cell-specific ETV5 deletion and wild-type control mice. In vitro, human intestinal fibroblasts cocultured with ETV5 overexpressed-Th9 cells expressed higher levels of collagen I and III, whereas an inclusion of anti-IL-9 antibody could reverse this effect. Ribonucleic acid sequencing analysis demonstrated that IL-9 upregulated TAF1 expression in human intestinal fibroblasts. Clinical data showed that number of α-smooth muscle actin+TAF1+ fibroblasts are higher in inflamed mucosa of patients with IBD. Importantly, TAF1 small interfering ribonucleic acid treatment suppressed IL-9-mediated profibrotic effect in vitro. These findings reveal that CD4+ T cell-derived ETV5 promotes intestinal inflammation and fibrosis through upregulating IL-9-mediated intestinal inflammatory and fibrotic response in IBD. Thus, the ETV5/IL-9 signal pathway in T cells might represent a novel therapeutic target for intestinal inflammation and fibrosis in IBD.

A deep learning model based on magnifying endoscopy with narrow-band imaging to evaluate intestinal metaplasia grading and OLGIM staging: A multicenter study.

BACKGROUND AND PURPOSE: Patients with stage III or IV of operative link for gastric intestinal metaplasia assessment (OLGIM) are at a higher risk of gastric cancer (GC). We aimed to construct a deep learning (DL) model based on magnifying endoscopy with narrow-band imaging (ME-NBI) to evaluate OLGIM staging. METHODS: This study included 4473 ME-NBI images obtained from 803 patients at three endoscopy centres. The endoscopic expert marked intestinal metaplasia (IM) regions on endoscopic images of the target biopsy sites. Faster Region-Convolutional Neural Network model was used to grade IM lesions and predict OLGIM staging. RESULTS: The diagnostic performance of the model for IM grading in internal and external validation sets, as measured by the area under the curve (AUC), was 0.872 and 0.803, respectively. The accuracy of this model in predicting the high-risk stage of OLGIM was 84.0%, which was not statistically different from that of three junior (71.3%, p = 0.148) and three senior endoscopists (75.3%, p = 0.317) specially trained in endoscopic images corresponding to pathological IM grade, but higher than that of three untrained junior endoscopists (64.0%, p = 0.023). CONCLUSION: This DL model can assist endoscopists in predicting OLGIM staging using ME-NBI without biopsy, thereby facilitating screening high-risk patients for GC.

Ganoderma lucidum polysaccharide ameliorates cholesterol gallstone formation by modulating cholesterol and bile acid metabolism in an FXR-dependent manner.

BACKGROUND: Cholesterol gallstone (CG) disease is a worldwide common disease characterized by cholesterol supersaturation in gallbladder bile. Ganoderma lucidum polysaccharide (GLP) has been shown to possess various beneficial effects against metabolic disorders. However, the role and underlying mechanism of GLP in CG formation are still unknown. This study aimed to determine the role of GLP in ameliorating lithogenic diet (LD)-induced CG formation. METHODS: Mice were fed either a normal chow diet, a LD, or LD supplemented with GLP. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression of genes involved in cholesterol and bile acid (BA) metabolism. The BA concentrations in the ileum were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The microbiota in cecal contents were characterized using 16S ribosomal RNA (16S rRNA) gene sequencing. RESULTS: GLP effectively alleviated CG formation induced by LD. Specifically, GLP reduced the total cholesterol (TC) levels, increased the total BA levels, and decreased the cholesterol saturation index (CSI) in gallbladder bile. The protective effect of GLP was attributed to the inhibition of farnesoid X receptor (FXR) signaling, increased hepatic BA synthesis and decreased hepatic cholesterol synthesis and secretion. GLP also altered the BA composition in the ileum, reducing FXR-agonistic BAs and increasing FXR-antagonistic BAs, which may contribute to the inhibition of intestinal FXR signaling. Additionally, GLP improved dysbiosis of the intestinal flora and reduced the serum levels of hydrogen sulfide (H2S), a bacterial metabolite that can induce hepatic FXR, thereby inhibiting hepatic FXR signaling. Moreover, the protective effect of GLP against CG formation could be reversed by both the global and gut-restricted FXR agonists. CONCLUSIONS: Taken together, GLP ameliorates CG formation by regulating cholesterol and BA metabolism in an FXR-dependent manner. Our study demonstrates that GLP may be a potential strategy for the prevention against CG disease.

Global, regional, and national burden of inflammatory bowel disease and its associated anemia, 1990 to 2019 and predictions to 2050: An analysis of the global burden of disease study 2019.

AIM: Inflammatory bowel disease (IBD) exhibited a global increase in incidence over the past decade. Understanding global burden of IBD can offer valuable insights for shaping future management strategies. We aimed to provide a comprehensive assessment of global burden of IBD from 1990 to 2019 and predictions to 2050. METHODS: Data on prevalence, incidence, Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLDs) and IBD-attributable impairment factor (anemia) were extracted from the Global Burden of Diseases (GBD) 2019. Subgroup analyses were performed based on gender, geographical regions, and the Socio-Demographic Index (SDI). Joinpoint model, Bayesian age-period-cohort model and decomposition methodology were utilized to evaluate the temporal trends from 1990 to 2019, forecast the disease burden up to 2050 and decompose incidence, prevalence, YLDs and DALYs of IBD by population age structure, population growth and epidemiologic changes. RESULTS: From 1990 to 2019, number of prevalence, DALYs, YLDs for IBD and number of prevalence for IBD-related-anemia increased significantly. Age-standardized rates of incidence, prevalence, DALYs, and YLDs showed declining trends, with this decline anticipated to continue until 2050 for both genders. The IBD burden remained high in countries with high and high-middle SDI. Besides, countries with low, low-middle, and middle SDI were experiencing an increasing burden. Number and ASR of prevalence and YLDs of IBD related anemia increased with SDI Decomposition analysis indicated that population growth was the primary contributing factor, followed by population aging. CONCLUSION: Due to population growth and aging, the burden of IBD is projected to continue rising until 2050, which emphasizes the urgency of addressing the evolving public health challenge posed by IBD.

Hyodeoxycholic acid attenuates cholesterol gallstone formation via modulation of bile acid metabolism and gut microbiota.

BACKGROUND & AIMS: Hyodeoxycholic acid (HDCA), a hydrophilic bile acid (BA), may prevent and suppress the formation of cholesterol gallstones (CGs). However, the mechanism by which HDCA prevents CGs formation remains unclear. This study aimed to investigate the underlying mechanism of HDCA in preventing CG formation. METHODS: C57BL/6J mice were fed either a lithogenic diet (LD), a chow diet, or LD combined with HDCA. The concentration of BAs in the liver and ileum were determined using liquid chromatography-mass spectrometry (LC-MS/MS). Genes involved in cholesterol and BAs metabolism were detected using polymerase chain reaction (PCR). The gut microbiota in the faeces was determined using 16S rRNA. RESULTS: HDCA supplementation effectively prevented LD-induced CG formation. HDCA increased the gene expression of BA synthesis enzymes, including Cyp7a1, Cyp7b1, and Cyp8b1, and decreased the expression of the cholesterol transporter Abcg5/g8 gene in the liver. HDCA inhibited LD-induced Nuclear farnesoid X receptor (Fxr) activation and reduced the gene expression of Fgf15 and Shp in the ileum. These data indicate that HDCA could prevent CGs formation partly by promoting BA synthesis in the liver and reduced the cholesterol efflux. In addition, HDCA administration reversed the LD-induced decrease in the abundance of norank_f_Muribaculaceae, which was inversely proportional to cholesterol levels. CONCLUSIONS: HDCA attenuated CG formation by modulating BA synthesis and gut microbiota. This study provides new insights into the mechanism by which HDCA prevents CG formation. LAY SUMMARY: In this study, we found that HDCA supplementation suppressed LD-induced CGs in mice by inhibiting Fxr in the ileum, enhancing BA synthesis, and increasing the abundance of norank_f_Muribaculaceae in the gut microbiota. HDCA can also downregulate the level of total cholesterol in the serum, liver, and bile.

Overexpression of RAB31 in gastric cancer is associated with released exosomes and increased tumor cell invasion and metastasis.

BACKGROUND: Gastric cancer (GC) is one of most common cancers worldwide. Several studies have suggested that Rab31 functions as a membrane vesicle transport regulator; however, the mechanism by which RAB31 regulates exosome secretion and promotes metastasis remains to be clarified. METHODS: We examined the expression of RAB31 protein and mRNA in GC tissue samples via immunohistochemistry and reverse transcription-polymerase chain reaction assays, respectively. We elucidated the function of RAB31 in GC cells by constructing a cell model and a pulmonary metastatic model of GC with overexpression of RAB31. Protein mass spectrometry was used to identify the exosomal protein. RESULTS: RAB31 expression increased at both the protein and mRNA levels with the development of GC. Cells overexpressing RAB31 showed an enhanced ability to migrate in both the in vitro cell model and the pulmonary metastatic model of GC. Exosome nanoparticle tracking analysis and electron microscopy revealed that the both the number and size of the exosomes secreted by GC cells were reduced when RAB31 expression was depleted. Injection of exosomes derived from RAB31 overexpressing cells promoted pulmonary metastasis in vivo. Analysis of the exosomal proteins revealed that PSMA1 was overexpressed in GC tissue in accordance with RAB31 expression. PSMA1 overexpression was highly associated with poor prognosis of GC patients. CONCLUSION: Our findings revealed a key role for RAB31 in GC metastasis through regulation of exosome secretion.

The features of gastric epithelial reactive hyperplastic lesions under magnifying endoscopy combined with narrow-band imaging.

BACKGROUND AND PURPOSE: Gastric reactive hyperplasia (RH) is a common benign lesion of the gastric mucosa that can be resolved by conservative treatment without endoscopic intervention. Some RH lesions are indistinguishable from low-grade intraepithelial neoplasia (LGIN) lesions of gastric mucosa under endoscopy. The aim of this study was to investigate the morphological features of RH lesions under magnifying endoscopy combined with narrow-band imaging (ME-NBI). METHODS: A retrospective study of 653 patients with superficial suspicious lesions of gastric mucosa was performed. According to the pathological results of biopsies, the final included lesions were divided into the RH group (n = 88) and LGIN group (n = 138). We analysed the microvascular and microsurface patterns of these lesions under ME-NBI, extracted the most significant combination of endoscopic features of RH lesions, and evaluated their diagnostic performance. RESULTS: ME-NBI characteristics that could distinguish RH lesions from LGIN lesions after univariate analysis were included in multivariate logistic regression. The results showed that ten characteristics, including intervening part (IP) length homogeneity, type III gastric pit pattern and homogeneity of marginal crypt epithelium (MCE), were statistically significant. Receiver operating characteristic (ROC) analysis showed that the triad of these features was the best combination for diagnosing RH lesions with an AUC of 0.886 (95% confidence interval; 0.842-0.929), the sensitivity of 85.5% and specificity of 79.5%. CONCLUSIONS: The triad of IP length homogeneity, type III pit pattern and MCE homogeneity under ME-NBI helps endoscopists to identify gastric RH lesions, thereby avoiding unnecessary biopsy and repeat endoscopy due to misjudgment of neoplastic lesions.

FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by Lactobacillus Strains.

Cholesterol gallstone (CGS) disease is characterized by an imbalance in bile acid (BA) metabolism and is closely associated with gut microbiota disorders. However, the role and mechanism by which probiotics targeting the gut microbiota attenuate cholesterol gallstones are still unknown. In this study, Limosilactobacillus reuteri strain CGMCC 17942 and Lactiplantibacillus plantarum strain CGMCC 14407 were individually administered to lithogenic-diet (LD)-fed mice for 8 weeks. Both Lactobacillus strains significantly reduced LD-induced gallstones, hepatic steatosis, and hyperlipidemia. These strains modulated BA profiles in the serum and liver, which may be responsible for the activation of farnesoid X receptor (FXR). At the molecular level, L. reuteri and L. plantarum increased ileal fibroblast growth factor 15 (FGF15) and hepatic fibroblast growth factor receptor 4 (FGFR4) and small heterodimer partner (SHP). Subsequently, hepatic cholesterol 7α-hydroxylase (CYP7A1) and oxysterol 7α-hydroxylase (CYP7B1) were inhibited. Moreover, the two strains enhanced BA transport by increasing the levels of hepatic multidrug resistance-associated protein homologs 3 and 4 (Mrp3/4), hepatic multidrug resistance protein 2 (Mdr2), and the bile salt export pump (BSEP). In addition, both L. reuteri and L. plantarum reduced LD-associated gut microbiota dysbiosis. L. reuteri increased the relative abundance of Muribaculaceae, while L. plantarum increased that of Akkermansia. The changed gut microbiota was significantly negatively correlated with the incidence of cholesterol gallstones and the FXR-antagonistic BAs in the liver and serum and with the FXR signaling pathways. Furthermore, the protective effects of the two strains were abolished by both global and intestine-specific FXR antagonists. These findings suggest that Lactobacillus might relieve CGS through the FXR signaling pathways. IMPORTANCE Cholesterol gallstone (CGS) disease is prevalent worldwide. None of the medical options for prevention and treatment of CGS disease are recommended, and surgical management has a high rate of recurrence. It has been reported that the factors involved in metabolic syndrome are highly connected with CGS formation. While remodeling of dysbiosis of the gut microbiome during improvement of metabolic syndrome has been well studied, less is known about prevention of CGS formation after regulating the gut microbiome. We used the lithogenic diet (LD) to induce an experimental CGS model in C57BL/6J mice to investigate protection against CGS formation by Limosilactobacillus reuteri strain CGMCC 17942 and Lactiplantibacillus plantarum strain CGMCC 14407. We found that these L. reuteri and L. plantarum strains altered the bile acid composition in mice and improved the dysbiosis of the gut microbiome. These two Lactobacillus strains prevented CGS formation by fully activating the hepatic and ileal FXR signaling pathways. They could be a promising therapeutic strategy for treating CGS or preventing its recurrence.

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.

Sodium butyrate alleviates cholesterol gallstones by regulating bile acid metabolism.

Cholesterol overloading and bile acid metabolic disorders play an important role in the onset of cholesterol gallstone (CGS). Short-chain fatty acids (SCFAs) can regulate bile acid metabolism by modulating the gut microbiota. However, the role and mechanism by which sodium butyrate (NaB) targets bile acids to attenuate CGS are still unknown. In this study, continuous administration of 12 mg/day for 8 weeks was decreased the incidence of gallstones induced by lithogenic diet (LD) from 100% to 25%. NaB modulated SCFAs and improved the gut microbiota. The remodeling of the gut microbiota changed the bile acid compositions and decreased cecal tauro-α-muricholic acid (T-α-MCA) and tauro-ß-muricholic acid (T-ß-MCA) which are effective farnesoid X receptor (FXR) antagonists. The quantitative real-time PCR examination showed that NaB significantly increased levels of ileal Fxr, fibroblast growth factor-15 (Fgf-15) and small heterodimer partner (Shp) mRNA and subsequently inhibited bile acid synthesis. In addition, NaB enhanced bile acid excretion by increasing the levels of hepatic multidrug resistance protein 2 (Mdr2) and bile salt export pump (Bsep) mRNA, and it enhanced bile acid reabsorption in the intestine by increasing the levels of ileal bile acid transporter (Ibat) mRNA. In addition, NaB reduced the absorption of cholesterol in the intestine and inhibited the excretion of cholesterol in the liver, which reduced the cholesterol concentration in serum and bile. Furthermore, the protective effects of NaB administration were abolished by FXR antagonists. Taken together, our results suggest that NaB mitigates CGS by modulating the gut microbiota to regulate the FXR-FGF-15/SHP signaling pathway.

Impacts of psychological resilience on self-efficacy and quality of life in patients with diabetic foot ulcers: a prospective cross-sectional study.

BACKGROUND: Patients with diabetic foot ulcer (DFU) usually have a poor quality of life (QoL) and self-efficacy, which is affected by many risk factors. However, the role of psychological resilience in QoL and self-efficacy in DFU patients has remained unclear. METHODS: This prospective cross-sectional study was performed in a single center from January 2018 to February 2020. A total of 98 DFU patients were enrolled in this study. Some demographic and clinical data were prospectively collected from participants. The psychological resilience of participants was assessed by Connor-Davidson resilience scale (CD-RISC). Self-efficacy was also assessed using the diabetes management self-efficacy scale (DMSES) and QoL was assessed by the 36-item short-form (SF-36) health survey. Univariable and multivariable linear regression were used to analyze the risk factors of self-efficacy and QoL. Then, logistic regression was used to analyze the predictors of psychological resilience among the participants. RESULTS: A CD-RISC score of more than 85 points was defined as high psychological resilience in this study; there were 28 participants diagnosed with high psychological resilience and 70 patients with low psychological resilience. Those with high psychological resilience had significantly higher self-efficacy, general health, vitality, social functioning, role emotional, and mental health than those with low psychological resilience. According to multivariable linear regression, low psychological resilience and older age were identified as risk factors of self-efficacy. On the contrary, low psychological resilience, older age, lower perceived social support and higher level of glycated hemoglobin were identified as risk factors of QoL. Finally, males had lower psychological resilience than females and those receiving more social support had higher psychological resilience than participants receiving less social support. CONCLUSIONS: Some risk factors of QoL and self-efficacy were identified in this study and these results may provide some evidence for the improvement of QoL and self-efficacy in DFU patients. Being female and receiving higher social support were shown to have potential for improving psychological resilience in DFU patients.

Analysis of the effect of a root cause analysis in elderly patients with acute pancreatitis: a randomized trial.

BACKGROUND: A root cause analysis (RCA) is a structured method used to address problems. It seeks to identify the root causes of problems, and proposes solutions to achieve an ultimate goal. This study sought to investigate the effects of an RCA in treating elderly patients with acute pancreatitis (AP). METHODS: 94 patients with AP, who had been admitted to our hospital from January 2019 to January 2020, were enrolled in the study. The patients were divided into two groups using the random number table method. Each group comprised 47 patients. The control group received routine care, while the observation group underwent RCA care. The clinical efficacy, patients' negative emotions before and after the intervention, the incidence of complications, and patients' levels of satisfaction with the nursing they received were compared between the two groups. RESULTS: The total clinical effective rate of the observation group was higher than that of the control group (P<0.05). The Hamilton Anxiety Scale and Hamilton Depression Scale scores of the observation group were lower than those of the control group after the 2-week intervention (P<0.05). The incidence of total complications in the observation group was lower than that in the control group (P<0.05). The observation group's level of satisfaction with the nursing they received was higher than that of the control group (P<0.05). CONCLUSIONS: The RCA method can improve clinical efficacy, relieve negative emotion, reduce the incidence of complications, and improve the level of satisfaction with nursing of elderly patients with AP. It is worthy of promotion. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045908.

Adiponectin Inhibits NLRP3 Inflammasome Activation in Nonalcoholic Steatohepatitis via AMPK-JNK/ErK1/2-NFκB/ROS Signaling Pathways.

Adiponectin, an adipose-derived adipokine, possesses a hepatoprotective role in various liver disorders. It has been reported that hypoadiponectinemia can affect with the progression of non-alcoholic fatty liver diseases (NAFLD). Inflammasome activation has been recognized to play a major role during the progression of NAFLD. This research aimed to explore the effect of adiponectin on palmitate (PA)-mediated NLRP3 inflammasome activation and its potential molecular mechanisms. Male adiponectin-knockout (adiponectin-KO) mice and C57BL/6 (wild-type) mice were fed a high-fat-diet (HFD) for 12 weeks as an in vivo model of non-alcoholic steatohepatitis (NASH). Serum biochemical markers, liver histology and inflammasome-related gene and protein expression were determined. In addition, the hepatocytes isolated from wide type mice were exposed to PA in the absence or presence of adiponectin and/or AMPK inhibitor. The activation of NLRP3 inflammasome was assessed by mRNA and protein expression. Furthermore, ROS production and related signaling pathways were also evaluated. In the in vivo experiments, excessive hepatic steatosis with increased NLRP3 inflammasome and its complex expression were found in adiponectin-KO mice compared to wild-type mice. Moreover, the expression levels of NLRP3 inflammasome pathway molecules (NFκB and ROS) were upregulated, while the phosphorylation levels of AMPK, JNK, and Erk1/2 were downregulated in adiponectin-KO mice compared with wild-type mice. In the in vitro study, PA increased lipid droplet deposition, NF-kB signaling and ROS production. Additionally, PA significantly promoted NLRP3 inflammasome activation and complex gene and protein expression in hepatocytes. Adiponectin could abolish PA-mediated inflammasome activation and decrease ROS production, which was reversed by AMPK inhibitor (compound C). Furthermore, the results showed that the inhibitory effect of adiponectin on PA-mediated inflammasome activation was regulated by AMPK-JNK/ErK1/2-NFκB/ROS signaling pathway. Adiponectin inhibited PA-mediated NLRP3 inflammasome activation in hepatocytes. Adiponectin analogs or AMPK agonists could serve as a potential novel agent for preventing or delaying the progression of NASH and NAFLD.