Exploring the molecular mechanisms and shared gene signatures between celiac disease and ulcerative colitis based on bulk RNA and single-cell sequencing: Experimental verification.

Many immune-mediated diseases have the common genetic basis, as an autoimmune disorder, celiac disease (CeD) primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. As for ulcerative colitis (UC), which most likely involves a complex interplay between some components of the commensal microbiota and other environmental factors in its origin. These two autoimmune diseases share a specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, ulcerative colitis and celiac disease, are not completely understood. Both are complex diseases with genetics and the environmental factors contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. This study is designed to further clarify the relationship between UC and CeD. The GEO database was used to download gene expression profiles for CeD (GSE112102) and UC (GSE75214). The GSEA KEGG pathway analysis revealed that immune-related pathways were significantly associated with both diseases. Further, we screened 187 shared differentially expressed genes (DEGs) of the two diseases. Gene Ontology (GO) and WikiPathways were carried out to perform the biological process and pathway enrichment analysis. Subsequently, based on the DEGs, the least absolute shrinkage and selection operator (LASSO) analysis was performed to screen for the diagnostic biomarkers of the diseases. Moreover, single-cell RNA-sequencing (RNA-seq) data from five colonic propria with UC showed that REG4 expression was present in Goblet cell, Enteroendocrine cell, and Epithelial. Finally, our work identified REG4 is the shared gene of UC and CeD via external data validation, cellular experiments, and immunohistochemistry. In conclusion, our study elucidated that abnormal immune response could be the common pathogenesis of UC and CeD, and REG4 might be a key potential biomarker and therapeutic target for the comorbidity of these two diseases.

Microbial metabolite deoxycholic acid-mediated ferroptosis exacerbates high-fat diet-induced colonic inflammation.

High-fat diet (HFD) has long been recognized as risk factors for the development and progression of ulcerative colitis (UC), but the exact mechanism remained elusive. Here, HFD increased intestinal deoxycholic acid (DCA) levels, and DCA further exacerbated colonic inflammation. Transcriptome analysis revealed that DCA triggered ferroptosis pathway in colitis mice. Mechanistically, DCA upregulated hypoxia-inducible factor-2α (HIF-2α) and divalent metal transporter-1 (DMT1) expression, causing the ferrous ions accumulation and ferroptosis in intestinal epithelial cells, which was reversed by ferroptosis inhibitor ferrostatin-1. DCA failed to promote colitis and ferroptosis in intestine-specific HIF-2α-null mice. Notably, byak-angelicin inhibited DCA-induced pro-inflammatory and pro-ferroptotic effects through blocking the up-regulation of HIF-2α by DCA. Moreover, fat intake was positively correlated with disease activity in UC patients consuming HFD, with ferroptosis being more pronounced. Collectively, our findings demonstrated that HFD exacerbated colonic inflammation by promoting DCA-mediated ferroptosis, providing new insights into diet-related bile acid dysregulation in UC.

Anti-angiogenesis in colorectal cancer therapy.

The morbidity of colorectal cancer (CRC) has risen to third place among malignant tumors worldwide. In addition, CRC is a common cancer in China whose incidence increases annually. Angiogenesis plays an important role in the development of tumors because it can bring the nutrients that cancer cells need and take away metabolic waste. Various mechanisms are involved in the formation of neovascularization, and vascular endothelial growth factor is a key mediator. Meanwhile, angiogenesis inhibitors and drug resistance (DR) are challenges to consider when formulating treatment strategies for patients with different conditions. Thus, this review will discuss the molecules, signaling pathways, microenvironment, treatment, and DR of angiogenesis in CRC.

Desulfovibrio vulgaris interacts with novel gut epithelial immune receptor LRRC19 and exacerbates colitis.

BACKGROUND: The overgrowth of Desulfovibrio, an inflammation promoting flagellated bacteria, has been found in ulcerative colitis (UC) patients. However, the molecular mechanism in promoting colitis remains unestablished. METHODS: The relative abundance Desulfovibrio vulgaris (D. vulgaris) in stool samples of UC patients was detected. Mice were treated with dextran sulfate sodium to induce colitis with or without administration of D. vulgaris or D. vulgaris flagellin (DVF), and the severity of colitis and the leucine-rich repeat containing 19 (LRRC19) signaling were assessed. The interaction between DVF and LRRC19 was identified by surface plasmon resonance and intestinal organoid culture. Lrrc19-/- and Tlr5-/- mice were used to investigate the indispensable role of LRRC19. Finally, the blockade of DVF-LRRC19 interaction was selected through virtual screening and the efficacy in colitis was assessed. RESULTS: D. vulgaris was enriched in fecal samples of UC patients and was correlated with the disease severity. D. vulgaris or DVF treatment significantly exacerbated colitis in germ-free mice and conventional mice. Mechanistically, DVF could interact with LRRC19 (rather than TLR5) in colitis mice and organoids, and then induce the production of pro-inflammatory cytokines. Lrrc19 knockdown blunted the severity of colitis. Furthermore, typhaneoside, a blockade of binding interfaces, blocked DVF-LRRC19 interaction and dramatically ameliorated DVF-induced colitis. CONCLUSIONS: D. vulgaris could promote colitis through DVF-LRRC19 interaction. Targeting DVF-LRRC19 interaction might be a new therapeutic strategy for UC therapy. Video Abstract.

Prognostic value and immunological roles of GPX3 in gastric cancer.

Objective: The prognosis for gastric cancer (GC), a prevalent tumor of the digestive system, is unfavorable. The involvement of glutathione peroxidase 3 (GPX3) in tumorigenesis is significant, yet its specific role in GC remains insufficiently investigated. Thus, the aim of this study was to determine the potential impact of GPX3 on GC and elucidate the underlying mechanism. Methods: The expression and survival of GPX3 in GC were analyzed using TCGA data. Additionally, the GPX3 mRNA and protein levels in GC were also assessed using datasets from GTEx, GEPIA, and HPA. A total of 38 pairs of GC tissues, along with their adjacent normal tissues, were collected from the Tianjin Medical University General Hospital, accompanied by detailed clinical information. The expression levels of GPX3 were subsequently determined for the purpose of validation. Following expression, correlation, and survival analyses, we proceeded to investigate the upstream non-coding RNA (ncRNA) of GPX3 using starBase and miRNet. Additionally, the co-expression networks of GPX3 were examined based on LinkedOmics. Lastly, we explored the correlation between GPX3 and immune cell infiltration, as well as the biomarkers of immune cells and immune checkpoints in GC. Furthermore, the GDSC database offered valuable drug sensitivity information. Results: A lower expression of GPX3 was observed in individuals with GC, while a higher expression of GPX3 was associated with a poorer prognosis. The DUBR/hsa-miR-502-3p/GPX3 pathway was identified as the most promising upstream ncRNA pathway related to GPX3 in GC. GO and KEGG enrichment analysis revealed that GPX3 expression was linked to coagulation cascades and cell locomotion. Furthermore, GPX3 levels in GC were positively correlated with immune cell infiltration, immune cell biomarkers, and immune checkpoint expression. The group with low GPX3 expression also exhibited increased sensitivity to 5-fluorouracil, doxorubicin, and other drugs. Conclusions: Collectively, we hypothesized that the potential involvement of non-coding RNAs in the downregulation of GPX3 could contribute to the inhibition of tumor formation during the malignant transition from gastritis to GC. Nevertheless, it was plausible that GPX3 may also facilitate tumor progression to advanced stages by promoting immune cell infiltration and activating immune checkpoints.

Applications and Prospects of Artificial Intelligence-Assisted Endoscopic Ultrasound in Digestive System Diseases.

Endoscopic ultrasound (EUS) has emerged as a widely utilized tool in the diagnosis of digestive diseases. In recent years, the potential of artificial intelligence (AI) in healthcare has been gradually recognized, and its superiority in the field of EUS is becoming apparent. Machine learning (ML) and deep learning (DL) are the two main AI algorithms. This paper aims to outline the applications and prospects of artificial intelligence-assisted endoscopic ultrasound (EUS-AI) in digestive diseases over the past decade. The results demonstrated that EUS-AI has shown superiority or at least equivalence to traditional methods in the diagnosis, prognosis, and quality control of subepithelial lesions, early esophageal cancer, early gastric cancer, and pancreatic diseases including pancreatic cystic lesions, autoimmune pancreatitis, and pancreatic cancer. The implementation of EUS-AI has opened up new avenues for individualized precision medicine and has introduced novel diagnostic and treatment approaches for digestive diseases.

Differentiating Gastrointestinal Stromal Tumors From Leiomyomas of Upper Digestive Tract Using Convolutional Neural Network Model by Endoscopic Ultrasonography.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) and leiomyomas are the most common submucosal tumors of the upper digestive tract, and the diagnosis of the tumors is essential for their treatment and prognosis. However, the ability of endoscopic ultrasonography (EUS) which could correctly identify the tumor types is limited and closely related to the knowledge, operational level, and experience of the endoscopists. Therefore, the convolutional neural network (CNN) is used to assist endoscopists in determining GISTs or leiomyomas with EUS. MATERIALS AND METHODS: A model based on CNN was constructed according to GoogLeNet architecture to distinguish GISTs or leiomyomas. All EUS images collected from this study were randomly sampled and divided into training set (n=411) and testing set (n=103) in a ratio of 4:1. The CNN model was trained by EUS images from the training set, and the testing set was utilized to evaluate the performance of the CNN model. In addition, there were some comparisons between endoscopists and CNN models. RESULTS: It was shown that the sensitivity and specificity in identifying leiomyoma were 95.92%, 94.44%, sensitivity and specificity in identifying GIST were 94.44%, 95.92%, and accuracy in total was 95.15% of the CNN model. It indicates that the diagnostic accuracy of the CNN model is equivalent to skilled endoscopists, or even higher than them. CONCLUSION: While identifying GIST or leiomyoma, the performance of CNN model was robust, which is highlighting its promising role in supporting less-experienced endoscopists and reducing interobserver agreement.

Efficacy of endoscopic ultrasound and endoscopic resection for esophageal schwannoma.

BACKGROUND: Esophageal schwannoma (ES) is a rare submucosal tumor, and its complete and safe resection is a topic that deserves special attention. AIM: This study aimed to investigate the clinical value of endoscopic ultrasound (EUS) in the diagnosis of ES and the clinical efficacy of endoscopic resection for ES. METHODS: The clinical data, endoscopic characteristics, endoscopic treatment, postoperative complications, immunohistochemical results, and follow-up records of patients with ES admitted to the Tianjin Medical University General Hospital from January 2012 to January 2022 were retrospectively analyzed. RESULTS: Under white-light endoscopy, 81.8% (9/11) of lesions were submucosal elevations, covering the normal esophageal epithelium. Two of the lesions with redness and erosive surface. Eight lesions (72.7%) appear on EUS originating from the muscularis propria were homogeneous or inhomogeneous hypoechoic signals. Two lesions were inhomogeneous hyperechoic originating from the submucosa or muscularis propria, respectively. One lesion was homogeneous hypoechoic originating from the submucosa. All lesions had no blood flow signals, cystic changes, or calcification, and were completely removed by submucosal tunnel endoscopic resection (STER) or endoscopic submucosal dissection (ESD). All patients did not experience serious adverse events as well as recurrence, metastasis, or cicatricial esophageal stenosis during the follow-up period. CONCLUSION: ES is a rare submucosal lesion, which endoscopic characteristics are difficult to distinguish from other esophageal submucosal tumors. Endoscopic resection can provide a minimally invasive and alternative treatment for ES.

Design, Synthesis and Biological Evaluation of Conjugates of 3-O-Descladinose-azithromycin and Nucleobases against rRNA A2058G- or A2059G-Mutated Strains.

Structurally unrelated antibiotics MLSB (macrolide-lincosamide-streptogramin B) compromised with clinically resistant pathogens because of the cross-resistance resulting from the structural modification of rRNA A2058. The structure-activity relationships of a novel 3-O-descladinose azithromycin chemotype conjugating with nucleobases were fully explored with the aid of engineered E. coli SQ110DTC and SQ110LPTD. The conjugates of macrolides with nucleobases, especially adenine, displayed antibacterial superiority over telithromycin, azithromycin and clindamycin against rRNA A2058/2059-mutated engineered E. coli strains at the cost of lowering permeability and increasing vulnerability to efflux proteins against clinical isolates.

Query2: Query over queries for improving gastrointestinal stromal tumour detection in an endoscopic ultrasound.

Gastrointestinal stromal tumour (GIST) lesions are mesenchymal neoplasms commonly found in the upper gastrointestinal tract, but non-invasive GIST detection during an endoscopy remains challenging because their ultrasonic images resemble several benign lesions. Techniques for automatic GIST detection and other lesions from endoscopic ultrasound (EUS) images offer great potential to advance the precision and automation of traditional endoscopy and treatment procedures. However, GIST recognition faces several intrinsic challenges, including the input restriction of a single image modality and the mismatch between tasks and models. To address these challenges, we propose a novel Query2 (Query over Queries) framework to identify GISTs from ultrasound images. The proposed Query2 framework applies an anatomical location embedding layer to break the single image modality. A cross-attention module is then applied to query the queries generated from the basic detection head. Moreover, a single-object restricted detection head is applied to infer the lesion categories. Meanwhile, to drive this network, we present GIST514-DB, a GIST dataset that will be made publicly available, which includes the ultrasound images, bounding boxes, categories and anatomical locations from 514 cases. Extensive experiments on the GIST514-DB demonstrate that the proposed Query2 outperforms most of the state-of-the-art methods.

Bibliometric analysis of the 100 most-cited papers about the role of gut microbiota in irritable bowel syndrome from 2000 to 2021.

AIM: Over the last few decades, gut microbiota research has been the focus of intense research and this field has become particularly important. This research aimed to provide a quantitative evaluation of the 100 most-cited articles on gut microbiota and IBS and highlight the most important advances in this field. METHODS: The database Web of Science Core Collection was used to download the bibliometric information the top 100 most-cited papers. Microsoft Excel 2021, CiteSpace, VOSviewer, R software, and an online analytical platform ( https://bibliometric.com/ ) were was applied to perform bibliometric analysis of these papers. RESULTS: The total citation frequency in the top 100 article ranged from 274 to 2324, with an average citation of 556.57. A total of 24 countries/regions made contributions to the top 100 cited papers, and USA, Ireland, and China were the most top three productive countries. Cryan JF was the most frequently nominated author, and of the top 100 articles, 20 listed his name. Top-cited papers mainly came from the Gastroenterology (n = 13, citations = 6373) and Gut (n = 9, citations = 3903). There was a significant citation path, indicating publications in molecular/biology/immunology primarily cited journals in molecular/biology/genetics fields. Keywords analysis suggested that the main topics on gut microbiota and IBS were mechanisms of microbiome in brain-gut axis." Behavior" was the keyword with the strongest burst strength (2.36), followed by "anxiety like behavior" (2.24), "intestinal microbiota" (2.19), and "chain fatty acid" (1.99), and "maternal separation" (1.95). CONCLUSION: This study identified and provided the bibliometric information of the top 100 cited publications related to gut microbiota and IBS. The results provided a general overview of this topic and might help researchers to better understand the evolution, Influential findings and hotspots in researching gut microbiota and IBS, thus providing new perspectives and novel research ideas in this specific area.

Development and validation of a nomogram based on neutrophil-to-lymphocyte ratio and fibrinogen-to-lymphocyte ratio for predicting recurrence of colorectal adenoma.

Background: There are many risk factors for the recurrence of colorectal adenoma (CRA). The purpose of this study was to explore the predictive performance of fibrinogen-to-lymphocyte ratio (FLR) and neutrophil-to-lymphocyte ratio (NLR) on the recurrence of CRA and to construct a predictive model. Methods: This study analyzed the clinicopathological features of 421 CRA patients who underwent colonoscopy and adenectomy, and evaluated the recurrence of polyps under colonoscopy. Among them, 301 were training cohort and 120 were validation cohort. Multivariate logistic regression was used to identify independent risk factors associated with CRA recurrence. Established a nomogram model to predict the risk of recurrence in CRA patients using independent risk factors. The receiver operating characteristic (ROC) curves were used to verify the nomogram model discrimination. Calibration curves were used to verify the model calibration degree. The decision curve analysis (DCA) curves were used to verify the clinical efficacy of the nomogram model. Results: Totally, six independent predictors, including smoking, diabetes, adenoma number, adenoma size, NLR, and FLR, were enrolled in the nomogram. In the training cohort and validation cohort, the area under the curve (AUC) of the nomogram for predicting the risk of CRA recurrence was 0.846 and 0.841, respectively. The calibration curves displayed a good agreement. DCA curves showed that this model had a high net clinical benefit. Conclusions: Smoking, diabetes, adenoma number, adenoma size, NLR, and FLR were influencing factors for CRA recurrence.

Endoscopic resection in the treatment of intramural esophageal bronchogenic cysts: A retrospective analysis of 17 cases.

BACKGROUND: Intramural esophageal bronchogenic cysts (EBCs) are rare congenital malformations. Differences in reports on the clinical features of intramural EBCs and some controversies about the treatment strategy for intramural EBCs exist. OBJECTIVES: To investigate the clinical characteristics of intramural EBCs and evaluate the safety and efficacy of endoscopic resection. METHODS: The clinical and endoscopic features, endoscopic resection treatment, postoperative adverse events, and follow-up results of 17 patients with intramural EBCs were retrospectively studied. RESULTS: Intramural EBCs exhibited male predominance with a male/female ratio of 58.8% (10/7) and were predominantly found in the distal esophagus. Approximately 94.1% of patients presented with gastrointestinal symptoms. All lesions were protruding masses covered by intact mucosal epithelium. The morphologies of intramural EBCs were diverse under white light endoscopy. On endoscopic ultrasonography, intramural EBCs presented as homogeneous or inhomogeneous hypoechoic or anechoic lesions. Eleven lesions originated from the muscularis propria, which underwent submucosal tunnel endoscopic resection (STER), and six lesions were from the submucosa, which underwent endoscopic submucosal dissection (ESD). Approximately 88.2% of patients underwent complete endoscopic resection. No serious pneumothorax, bleeding, pleural effusion, esophagotracheal fistula, or other adverse events occurred in all patients after endoscopic resection, and no cyst recurrence, metastasis, or esophageal scar stenosis was observed during the follow-up period. CONCLUSIONS: Intramural EBCs can be treated by digestive endoscopic surgery. STER and ESD are safe, effective, and minimally invasive resection methods.

Fecal biomarkers: Non-invasive diagnosis of colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer in the world in terms of morbidity and mortality, which brings great health hazards and economic burdens to patients and society. A fecal examination is an effective method for clinical examination and the most commonly used method for the census. It is simple, non-invasive, and suitable for large-scale population screening. With the development of molecular biology, lots of efforts have been made to discover new fecal biomarkers for the early screening of colorectal cancer. In this review, we summarize and discuss the recent advances of fecal biomarkers for CRC screening or diagnosis, including DNA biomarkers, RNA biomarkers, protein biomarkers, gut microbes and volatile organic compounds focusing on their diagnostic evaluation for CRC, which can provide a basis for the further development of new and effective CRC fecal screening and early diagnosis techniques.

Role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors.

BACKGROUND AND AIM: Diagnosis and complete resection of esophageal granular cell tumors (GCTs) is an area of concern. However, articles on endoscopic ultrasound (EUS) and endoscopic resection of esophageal granular cell tumors are few. To evaluate the role of endoscopic ultrasound and endoscopic resection in the diagnosis and treatment of esophageal granular cell tumors. METHODS: A retrospective analysis of 15 patients with esophageal granular cell tumors who underwent endoscopic ultrasound examination and endoscopic resection in our hospital was conducted. The clinical data, endoscopic ultrasound images, endoscopic treatment, pathological characteristics, postoperative complications and follow-up status of all patients were evaluated. Ten board-certified endoscopists independently evaluated the white light endoscopic images of the 15 patients (Test 1) and the endoscopic ultrasound images together with white light endoscopic images of the same patient set (Test 2). RESULT: Female patients accounted for 53.4% of the participants. The average age at the time of diagnosis was 49.13 ± 9.31 years old. Ten lesions (66.67%) showed hypoechoic signal, four lesions (26.67%) showed hyperechoic signal and one lesion showed medium signal. The diagnostic accuracy was significantly higher with Test 2(65.3% vs. 92.0%, p < .001). Complete endoscopic resection was performed in all the patients. No complications occurred in any of the patients. No esophageal stenosis, recurrence, or metastases was found in all patients during the follow-up period. CONCLUSION: The endoscopic ultrasound images of esophageal granular cell tumors have certain characteristics that help diagnose esophageal granular cell tumors. Endoscopic resection of esophageal granular cell tumors is an effective, safe and feasible treatment method.

The prognostic value of high-density lipoprotein cholesterol in patients with decompensated cirrhosis: a propensity score matching analysis.

BACKGROUND: Emerging evidence has implicated that high-density lipoprotein cholesterol (HDL-C) as a prognostic surrogate in the context of cirrhosis. However, an exact cutoff has not been fully elucidated. OBJECTIVE: We aimed to clarify optimal cutoff of HDL-C for short-term mortality based on time-to-event analysis and validated this association by performing propensity score matching (PSM) analysis. METHOD: A total of 238 patients with decompensated cirrhosis were enrolled. The optimal cutoff of HDL-C was initially determined by X-tile program. Independent risk factors for 180-day mortality were identified by multiple Cox regression. The Kaplan-Meier method was implemented to generate survival curves. A 1:2 ratio PSM was performed to diminish selection bias and potential confounders. RESULTS: The X-tile implied that the difference in survival was most significant for HDL <0.4mmol/L (<16mg/dL). Circulating HDL <0.4mmol/L exhibited an independent risk factor both in the entire cohort and PSM subset (HR 2.696, 95% CI 1.082-6.791, P = 0.033; HR 2.735, 95% CI 1.027-7.734, P = 0.048). Furthermore, HDL-C combined with conventional scoring systems had higher AUCs associated with poor prognosis than Child-Pugh classification or model for end-stage liver disease (MELD) in isolation (0.78 vs 0.66; 0.74 vs 0.54, P < 0.05 for both). CONCLUSION: HDL-C <0.4 mmol/L may serve as a readily available and robust cutoff for stratifying cirrhotic patients at high 180-day mortality risk. The incorporation of HDL-C to Child-Pugh classification or MELD has the potentials to provide substantially clinical relevance without extra economic cost.

20-Year Trends in Detection Rates of Cardia Cancer via Endoscopic Surveillance in Tianjin, China: A Hospital-Based Study.

Background: To analyze the time trends in cardia cancer detection rates using endoscopic surveillance from 1999 to 2019 in a high-volume Chinese hospital. Methods: In this retrospective, single-center study, data were collected from the Endoscopy Center of the Department of Gastroenterology, Tianjin Medical University General Hospital, from 1999 to 2019. Cases of cardia cancer (n = 1567) were extracted from a database of patients who underwent endoscopy. Clinical and epidemiological characteristics of patients with cardia cancer were analyzed, including sex, age, and proportion of early gastric cancer and degree of tumor differentiation. The joinpoint regression method was used to identify change points in incidence trends. Annual percent change (APC) values, with 95% confidence intervals (CI), were calculated for time periods before and after change points. Results: Of the 343942 patients who underwent endoscopy during 1999-2009, 1567 (4.6%) were identified with cardia cancer. The overall cardia adenocarcinoma detection rate decreased significantly from 1999 to 2004 (APC = -37.3, 95% CI: -20.9, -6.4), followed by a relatively slower decline rate from 2004 to 2019 (APC = -7.7, 95% CI: -4.4, -7.6). The crude rate of detection of early cardia cancer could not be determined by joinpoint analysis. Rates of detection reduced significantly in patients aged 60-69 and 70-79 years (APC = -8.3, 95% CI: -9.8, -6.8 and APC = -7.3, 95% CI: -8.8, -5.8, respectively). The detection rate in males decreased rapidly from 1999 to 2004 (APC = -35.9, 95% CI: -18.2, 5.6, P < 0.05), while the decline rate was relatively slow from 2005 to 2019 (APC = -6.9, 95% CI: -3.4, -6.1, P < 0.05). Among females, the detection rates also decreased from 1999 to 2004 (APC = -21.2, 95% CI: -28.1, -13.7), but remained stable from 2007 to 2019 (APC = -3.8, 95% CI: -7.9, -0.5). Detection of poorly differentiated cardia cancer also declined from 2009 to 2019 (APC = -12.8, 95% CI: -15.3, -10.0). Conclusions: The detection rate of cardia cancer among gastric cancers has been stable from 2008 to 2019. The trend of detection rate of early cardia cancer showed no significant statistical meaning; hence, it remains necessary to carefully observe the cardia area during endoscopy examination.

Genomic Epidemiology Insights on NDM-Producing Pathogens Revealed the Pivotal Role of Plasmids on blaNDM Transmission.

Incidences of nosocomial infections mediated by New Delhi metallo-ß-lactamase (NDM) enzyme-producing Enterobacterales are increasing globally, resulting in a great burden to public health. The carbapenem-resistant Enterobacterales (CRE) were collected from Henan, China during 2013-2016. The blaNDM-positive strains were characterized using PCR, antimicrobial susceptibility testing, conjugation assay, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot, whole-genome sequencing (WGS), and bioinformatics analysis. Eighty-one NDM-producing strains were identified among 391 nonduplicate CRE strains. Among them, four strains cocarried mcr and blaNDM genes, and two carried blaIMP-4 and blaNDM genes. The coexistence of blaNDM-5 and mcr-9 in Enterobacter hormaechei was found for the first time. In total, four blaNDM subtypes were identified. Among them, blaNDM-1 and blaNDM-5 were predominant. There was an obvious increasing trend in blaNDM-5 from 2013 to 2016. Thirteen different bacterial species were found among the 81 strains, and Escherichia coli was the dominant strain. blaNDM genes were located on nine different Inc-type plasmids, most of them on the IncX3 plasmids, except for the Pr-15-2-50 strain, which was located on the chromosome. We characterized two novel plasmids: the IncHI5-like plasmid carrying blaNDM-9 found in K. pneumonia, and the IncI1 blaNDM-5-positive plasmid. These findings provide the genomic basis for the widespread transmission of blaNDM and pave the way for the formulation of more effective monitoring and control methods. IMPORTANCE To control the emergence and transmission of CRE, it is important to perform retrospective genomic investigations. It is important to evaluate the plasmid diversity, genetic environment, and evolutionary relationships of the blaNDM-positive clinical strains in the early transmission stages. This study conducted an in-depth analysis of blaNDM-positive pathogens during a 4-year period using different methods for observing the high prevalence and active transmission of blaNDM-positive CRE. Moreover, we also explored the coexistence of the blaNDM and mcr, a clinically important mobile colistin resistance gene. This study shows that the prevalence of blaNDM-positive pathogens in Henan is high and the isolation rates increase each year. Moreover, plasmid-mediated horizontal transfer plays an important role in blaNDM dissemination. The co-occurrence of multiple resistance genes highlighted a long-lasting evolutionary pathway. Therefore, we have suggested the long-term continuous surveillance of clinical pathogens carrying blaNDM to learn the future transmission trend and curb the public health risk caused by CRE.

Therapeutic potential of Saccharomyces boulardii in liver diseases: from passive bystander to protective performer?

Saccharomyces boulardii (S. boulardii) is a probiotic yeast that has been elucidated to be efficacious in fighting various gastrointestinal diseases in preclinical as well as clinical studies. Its general mechanisms of probiotic action in the treatment of gastrointestinal conditions cover multifaceted aspects, including immune regulation, production of antimicrobial substances, pathogen competitive elimination, gut barrier integrity maintenance, intestinal trophic effect and antioxidant potency. In this review, basic knowledge with regard to the gut-liver axis, available probiotics remedies and mechanistic insights of S. boulardii as probiotics will be elucidated. In addition, we summarize the therapeutic potential of S. boulardii in several liver diseases evident from both bench and bedside information, such as acute liver injury/failure, fibrosis, hepatic damages due to metabolic disturbance or infection and obstructive jaundice. Future prospects in relation to medicinal effects of S. boulardii are also exploited and discussed on the basis of novel and attractive therapeutic concept in the latest scientific literature.

Prenatal Maternal Stress Exacerbates Experimental Colitis of Offspring in Adulthood.

The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.