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2.
Biomed Mater ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39025105

ABSTRACT

Endoscopic submucosal dissection (ESD) is the gold-standard surgical procedure for superficial esophageal cancer. A significant and challenging complication of this technique is post-ESD esophageal stricture. In this study, the feasibility of endoscopic catheter delivery of bioadhesive to esophageal lesions in a porcine model was tested. Injectable bioadhesive was composed of oxidized dextran (ODA) and chitosan hydrochloride (CS), its physicochemical properties, injectability, antibacterial activity, and cytocompatibility were investigated before in vivo test. ODA-CS bioadhesive was delivered to the wound bed of the esophageal tissue using a custom-made catheter device after ESD in a porcine model. Our results show that the ODA-CS bioadhesive is of good injectability, tissue adhesive strength, antibacterial capacity, and blood compatibility. In vivo delivery was achieved by endoscopic spraying of ODA and CS in separate catheters fixed on the endoscopic probe. ODA and CS can be mixed well to allow in situ bioadhesive formation and firmly adhere to the esophageal wound surface. After two weeks, the bioadhesive maintained structural integrity and adhered to the surface of esophageal wounds. However, histological analysis reveals that the ODA-CS bioadhesive did not show improvement in attenuating inflammatory response after ESD. This pilot study demonstrates the feasibility of ODA-CS bioadhesive for shielding esophageal wounds after ESD, whereas efforts need to improve its anti-inflammatory activity to reduce fibrosis for stricture prevention.

3.
EClinicalMedicine ; 73: 102656, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38828130

ABSTRACT

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.

4.
Mucosal Immunol ; 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38555025

ABSTRACT

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.

5.
Am J Gastroenterol ; 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38477473

ABSTRACT

INTRODUCTION: Although cytologic examination of biliary stricture brushings obtained by endoscopic retrograde cholangiopancreatography is commonly used for diagnosing malignant biliary strictures (MBSs), it has low sensitivity. Several new brushes have capabilities that are still being debated. We have developed a novel brush working from conventional back-and-forth movement to rotation in situ (RIS) that may be more efficient for MBS sampling. We aimed to compare the MBS detection sensitivity of our RIS brush with that of the conventional brush. METHODS: In this multicenter prospective study, we enrolled patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs involving biliary stricture brushings obtained using our RIS brush. The historical control group consisted of the 30-brushing arm of our previous randomized trial (patient inclusion, 2018-2020) that used the study design in the same centers and with the same endoscopists as were used in this study. The primary outcome was to compare the sensitivity and specificity of detecting MBSs by cytologic evaluation of biliary stricture brushings between the 2 groups. RESULTS: We enrolled 155 patients in the intent-to-treat analysis. Using the same number of brushing cycles, the RIS brush showed a higher sensitivity than the conventional brush (0.73 vs 0.56, P = 0.003). In per-protocol population, the sensitivity was also higher in the RIS brush group than in the conventional brush group (0.75 vs 0.57, P = 0.002). Multivariate analysis revealed that the RIS brush was the only predictive factor for MBS detection. No significant differences were observed in procedure-related complications between the 2 groups. DISCUSSION: The RIS brush was a promising tool for effective and safe MBS sampling and diagnosis. Further randomized studies are warranted to confirm our results (Chictr.org.cn, identifier: ChiCTR2100047270).

6.
BMJ ; 384: e078581, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38443074

ABSTRACT

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.


Subject(s)
Capsule Endoscopy , Esophageal and Gastric Varices , Varicose Veins , Adult , Humans , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/etiology , Liver Cirrhosis/complications , Prospective Studies
7.
Dig Liver Dis ; 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38402085

ABSTRACT

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.

8.
Chin Med ; 19(1): 16, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38268006

ABSTRACT

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.

9.
Biomed Mater ; 19(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38194703

ABSTRACT

Biomaterial scaffolds boost tissue repair and regeneration by providing physical support, delivering biological signals and/or cells, and recruiting endogenous cells to facilitate tissue-material integration and remodeling. Foreign body response (FBR), an innate immune response that occurs immediately after biomaterial implantation, is a critical factor in determining the biological outcomes of biomaterial scaffolds. Electrospinning is of great simplicity and cost-effectiveness to produce nanofiber scaffolds with well-defined physicochemical properties and has been used in a variety of regenerative medicine applications in preclinical trials and clinical practice. A deep understanding of causal factors between material properties and FBR of host tissues is beneficial to the optimal design of electrospun scaffolds with favorable immunomodulatory properties. We herein prepared and characterized three electrospun scaffolds with distinct fiber configurations and investigated their effects on FBR in terms of immune cell-material interactions and host responses. Our results show that electrospun yarn scaffold results in greater cellular immune reactions and elevated FBR inin vivoassessments. Although the yarn scaffold showed aligned fiber bundles, it failed to induce cell elongation of macrophages due to its rough surface and porous grooves between yarns. In contrast, the aligned scaffold showed reduced FBR compared to the yarn scaffold, indicating a smooth surface is also a contributor to the immunomodulatory effects of the aligned scaffold. Our study suggests that balanced porousness and smooth surface of aligned fibers or yarns should be the key design parameters of electrospun scaffolds to modulate host responsein vivo.


Subject(s)
Foreign Bodies , Nanofibers , Humans , Tissue Scaffolds/chemistry , Biocompatible Materials/chemistry , Macrophages , Wound Healing , Tissue Engineering/methods , Nanofibers/chemistry
10.
Gastrointest Endosc ; 99(3): 387-397.e6, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37858760

ABSTRACT

BACKGROUND AND AIMS: The Zhongshan colorectal endoscopic submucosal dissection (CR-ESD) score model was proposed to grade the technical difficulty of CR-ESD. The objective of this study was to prospectively validate and update the score model. METHODS: A multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were used to validate the original model and further refine the difficulty of the prediction model. Data were randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. RESULTS: Five hundred forty-eight patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver-operating characteristic (ROC) curve for the original model was .707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), at least two-thirds circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), laterally spreading tumor-nongranular lesions (1 point), preceding biopsy sampling (1 point), and NBI International Colorectal Endoscopic type 3 (3 points). The updated model had an area under the ROC curve of .738 in the discovery cohort and of .782 in the validation cohort. Cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. CONCLUSIONS: The original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version. (Clinical trial registration number: ChiCTR2100047087.).


Subject(s)
Colorectal Neoplasms , Endoscopic Mucosal Resection , Humans , Endoscopic Mucosal Resection/adverse effects , Colorectal Neoplasms/pathology , Prospective Studies , Retrospective Studies , Cohort Studies , Treatment Outcome
11.
Plant Dis ; : PDIS07231371RE, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37814516

ABSTRACT

Fusarium wilt fungus infection of bitter gourd, a major melon vegetable crop, results in massive yield reduction. Through extensive testing, some Fusarium wilt-resistant bitter melon varieties have been produced, but the molecular mechanism of their resistance to the fungus remains unknown. Importantly, after bitter melon plants are infected with Fusarium oxysporum f. sp. momordicae (FOM), apart from altering their gene expression levels, numerous metabolites are produced because of the interaction with the fungus. In the current study, an untargeted metabolomics analysis was performed to investigate the metabolic difference between resistant and susceptible bitter gourd varieties at various timepoints postinoculation with FOM based on liquid chromatography with mass spectrometry. A total of 1,595 positive ion mode and 922 negative ion mode metabolites were identified. Between the resistant and susceptible bitter gourd varieties, 213 unique differentially abundant metabolites (DAMs) were identified, and they were mainly enriched in the alpha-linolenic acid metabolism pathway. By comparing the postinoculation with preinoculation timepoints in the resistant and susceptible bitter gourd varieties, 93 and 159 DAMs were identified, respectively. These DAMs were mainly related to beta-alanine metabolism, among others. Multiple metabolites in the biosynthesis of the phenylpropanoid pathway showed greater variability in the susceptible than the resistant varieties, which may be related to senescence and mortality in the susceptible variety. These results provide new insights into the understanding of metabolite changes after FOM infection and a theoretical foundation for the elucidation of the bitter gourd disease resistance mechanism.

12.
Dig Liver Dis ; 56(4): 641-647, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37748937

ABSTRACT

BACKGROUND: Brush cytology during endoscopic retrograde cholangiopancreatography (ERCP) is a standard approach in diagnosing biliopancreatic strictures, with yet unsatisfying sensitivity. AIMS: We brought additional simultaneous vacuum aspiration to brushing process and re-evaluate the diagnostic performance. METHODS: This multi-centered retrospective study was conducted in three tertiary centers. Consecutive patients with biliopancreatic strictures were identified. The patients were divided into two arms: the conventional arm (CA) receiving general brushing approach, and the modified arm (MA) being treated with additional vacuum aspiration when performing bushing. The 1:1 propensity-score matching was implemented to tackle the selective biases. RESULTS: A total of 555 patients were identified and 200 patient pairs (193 males, 207 females, with a mean age of 68.1 ± 13.1 years.) fell into the ultimate evaluation. A final diagnosis of malignant stricture was established in 243 patients. The diagnostic yield of the MA group was substantially better than that of the CA group, whether "suspicious malignancies" were considered malignancies or not. The rates of sensitivity, specificity and accuracy were 46.2%, 100%, 68.0% in the MA group, and 15.3%, 98.7%, and 47.0% in the CA group respectively. CONCLUSIONS: Brushing accompanied by simultaneous vacuum aspiration at ERCP improves the diagnostic yield in suspicious biliopancreatic malignancies.


Subject(s)
Bile Duct Neoplasms , Cytology , Male , Female , Humans , Middle Aged , Aged , Aged, 80 and over , Constriction, Pathologic/pathology , Retrospective Studies , Propensity Score , Vacuum Curettage , Sensitivity and Specificity , Cholangiopancreatography, Endoscopic Retrograde , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/pathology
13.
Autoimmun Rev ; 23(3): 103498, 2023 Dec 03.
Article in English | MEDLINE | ID: mdl-38052263

ABSTRACT

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.

15.
Eur J Pharmacol ; 955: 175891, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37429516

ABSTRACT

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.


Subject(s)
Gallstones , Gastrointestinal Microbiome , Animals , Mice , Gallstones/etiology , Gallstones/prevention & control , Gallstones/metabolism , RNA, Ribosomal, 16S/genetics , Chromatography, Liquid , Mice, Inbred C57BL , Tandem Mass Spectrometry , Cholesterol/metabolism , Liver , Bile Acids and Salts/metabolism , Cholesterol 7-alpha-Hydroxylase/genetics
16.
Cancer Med ; 12(12): 13497-13510, 2023 06.
Article in English | MEDLINE | ID: mdl-37222416

ABSTRACT

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.


Subject(s)
Exosomes , MicroRNAs , Stomach Neoplasms , Humans , Exosomes/metabolism , Stomach Neoplasms/pathology , RNA, Messenger/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , MicroRNAs/genetics , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , rab GTP-Binding Proteins/genetics , rab GTP-Binding Proteins/metabolism
18.
Diagn Interv Radiol ; 29(1): 91-102, 2023 01 31.
Article in English | MEDLINE | ID: mdl-36960545

ABSTRACT

PURPOSE: Early monitoring and intervention for patients with novel coronavirus disease-2019 (COVID-19) will benefit both patients and the medical system. Chest computed tomography (CT) radiomics provide more information regarding the prognosis of COVID-19. METHODS: A total of 833 quantitative features of 157 COVID-19 patients in the hospital were extracted. By filtering unstable features using the least absolute shrinkage and selection operator algorithm, a radiomic signature was built to predict the prognosis of COVID-19 pneumonia. The main outcomes were the area under the curve (AUC) of the prediction models for death, clinical stage, and complications. Internal validation was performed using the bootstrapping validation technique. RESULTS: The AUC of each model demonstrated good predictive accuracy [death, 0.846; stage, 0.918; complication, 0.919; acute respiratory distress syndrome (ARDS), 0.852]. After finding the optimal cut-off for each outcome, the respective accuracy, sensitivity, and specificity were 0.854, 0.700, and 0.864 for the prediction of the death of COVID-19 patients; 0.814, 0.949, and 0.732 for the prediction of a higher stage of COVID-19; 0.846, 0.920, and 0.832 for the prediction of complications of COVID-19 patients; and 0.814, 0.818, and 0.814 for ARDS of COVID-19 patients. The AUCs after bootstrapping were 0.846 [95% confidence interval (CI): 0.844-0.848] for the death prediction model, 0.919 (95% CI: 0.917-0.922) for the stage prediction model, 0.919 (95% CI: 0.916-0.921) for the complication prediction model, and 0.853 (95% CI: 0.852-0.0.855) for the ARDS prediction model in the internal validation. Based on the decision curve analysis, the radiomics nomogram was clinically significant and useful. CONCLUSION: The radiomic signature from the chest CT was significantly associated with the prognosis of COVID-19. A radiomic signature model achieved maximum accuracy in the prognosis prediction. Although our results provide vital insights into the prognosis of COVID-19, they need to be verified by large samples in multiple centers.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , COVID-19/diagnostic imaging , Tomography, X-Ray Computed , Algorithms , Nomograms , Respiratory Distress Syndrome/diagnostic imaging , Retrospective Studies
19.
Scand J Gastroenterol ; 58(8): 953-962, 2023.
Article in English | MEDLINE | ID: mdl-36843535

ABSTRACT

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.


Subject(s)
Carcinoma in Situ , Stomach Neoplasms , Humans , Hyperplasia/diagnostic imaging , Retrospective Studies , Stomach Neoplasms/diagnostic imaging , Endoscopy, Gastrointestinal , Carcinoma in Situ/pathology , Narrow Band Imaging , Gastroscopy/methods
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