Gastroenterology Report最新文献

{"title":"Advances in the management of alcohol-associated liver disease.","authors":"Ahmad Anouti, Thomas A Kerr, Mack C Mitchell, Thomas G Cotter","doi":"10.1093/gastro/goae097","DOIUrl":"10.1093/gastro/goae097","url":null,"abstract":"<p><p>Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phosphorylation of RelA/p65 Ser536 inhibits the progression and metastasis of hepatocellular carcinoma by mediating cytoplasmic retention of NF-κB p65.","authors":"Wentao Zuo, Haoyang Ma, Jianghui Bi, Tiaolan Li, Yifeng Mo, Shiyu Yu, Jia Wang, Beiqing Li, Jinfeng Huang, Yongwen Li, Li Li","doi":"10.1093/gastro/goae094","DOIUrl":"10.1093/gastro/goae094","url":null,"abstract":"<p><strong>Background: </strong>Intrahepatic and extrahepatic metastases contribute to the high recurrence rate and mortality of hepatocellular carcinoma (HCC). Constitutive activation of nuclear factor-κB (NF-κB) is a crucial feature of HCC. NF-κB p65 (p50-p65) is the most common dimeric form. Ser536 acts as an essential phosphorylation site of RelA/p65. However, the effect of RelA/p65 Ser536 phosphorylation on progression and metastases during intermediate and advanced HCC has not been reported.</p><p><strong>Methods: </strong>Phosphorylation of RelA/p65 (p-p65 Ser536) and NF-κB p65 were detected by using immunohistochemical staining in HCC tissue samples. The biological effects of RelA/p65 Ser536 phosphorylation were evaluated by using xenograft and metastasis models. NF-κB p65 nuclear translocation was detected by using Western blotting. The binding of NF-κB p65 to the <i>BCL2</i>, <i>SNAIL</i>, and <i>MMP9</i> promoters was detected by using chromatin immunoprecipitation. The biological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition were assessed by using tetrazolium-based colorimetry, colony formation, EdU incorporation, flow cytometry, cell wound healing, and transwell assay.</p><p><strong>Results: </strong>NF-κB p65 is highly expressed, while p-p65 Ser536 is not well expressed in intermediate and advanced HCC tissues. <i>In vivo</i> experiments demonstrated that a phosphorylation-mimetic mutant of RelA/p65 Ser536 (p65/S536D) prevents tumor progression and metastasis. <i>In vitro</i> experiments showed that p65/S536D inhibits proliferation, migration, and invasion. Mechanistically, RelA/p65 Ser536 phosphorylation inhibits NF-κB p65 nuclear translocation and reduces NF-κB p65 binding to the <i>BCL2</i>, <i>SNAIL</i>, and <i>MMP9</i> promoters.</p><p><strong>Conclusions: </strong>RelA/p65 Ser536 phosphorylation was detrimental to NF-κB p65 entry into the nucleus and inhibited HCC progression and metastasis by reducing <i>BCL2</i>, <i>SNAIL</i>, and <i>MMP9</i>. The phosphorylation site of RelA/p65 Ser536 has excellent potential to be a promising target for NF-κB-targeted therapy in HCC.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exclusive enteral nutrition combined with continuous succus entericus reinfusion for high-output stoma in patients with Crohn's disease: a case report.","authors":"Na Diao, Wenyou Zheng, Huiping Chen, Jian Tang","doi":"10.1093/gastro/goae100","DOIUrl":"10.1093/gastro/goae100","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cooperation of Wnt/β-catenin and Dll1-mediated Notch pathway in Lgr5-positive intestinal stem cells regulates the mucosal injury and repair in DSS-induced colitis mice model.","authors":"Weijun Ou, Weimin Xu, Yaosheng Wang, Zhebin Hua, Wenjun Ding, Long Cui, Peng Du","doi":"10.1093/gastro/goae090","DOIUrl":"https://doi.org/10.1093/gastro/goae090","url":null,"abstract":"<p><strong>Background: </strong>Lgr5-positive cells located in the basal layer of crypts have self-regenerative and proliferative differentiation potentials of intestinal stem cells (ISCs), maintaining a balance of regeneration-repair in mucosal epithelium. However, the mechanisms of mucosal repair that are regulated by ISCs in ulcerative colitis (UC) remain unclear.</p><p><strong>Method: </strong>Colon tissues from patients with UC were collected to test β-catenin and Notch1 expression by using Western blot and quantitative real-time polymerase chain reaction (PCR). <i>β-catenin^fl/fl</i> mice, <i>β-catenin^Tg</i> mice, and <i>Dll1^{tm1 Gos}</i> mice were used to cross with <i>Lgr5-EGFP-IRES-creERT2</i> mice to generate mice of different genotypes, altering the activation of Wnt/β-catenin and Dll1-mediated Notch signaling in ISCs <i>in vivo</i>. Dextran sulfate sodium (DSS) was used to induce a colitis mice model. Intestinal organoids were isolated and cultured to observe the proliferation and differentiation levels of ISCs.</p><p><strong>Result: </strong>β-catenin and Notch1 expression were significantly increased in the inflamed colon tissues from patients with UC. Wnt/β-catenin activation and Dll1-mediated Notch pathway inhibition in Lgr5-positive stem cells promoted the expressions of E-cadherin, CK20, and CHGA in colonic organoids and epithelium, implying the promotion of colonic epithelial integrity. Activation of Wnt/β-catenin and suppression of Dll1-mediated Notch pathway in Lgr5-positive ISCs alleviated the DSS-induced intestinal mucosal inflammation in mice.</p><p><strong>Conclusions: </strong>Lgr5-positive ISCs are characterized by self-renewal and high dividend potential, which play an important role in the injury and repair of intestinal mucosa. More importantly, the Wnt/β-catenin signaling pathway cooperates with the Notch signaling pathway to maintain the function of the Lgr5-positive ISCs.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postpartum hepatitis flares in mothers with chronic hepatitis B infection.","authors":"Shi OuYang, Yawen Geng, Gongqin Qiu, Yueying Deng, Haitao Deng, Calvin Q Pan","doi":"10.1093/gastro/goae091","DOIUrl":"https://doi.org/10.1093/gastro/goae091","url":null,"abstract":"<p><p>Postpartum elevation of alanine aminotransferase (ALT) in mothers with chronic hepatitis B (CHB) presents a significant clinical challenge. However, the existing literature demonstrates inconsistencies regarding its incidence and predictors in mothers infected with the hepatitis B virus (HBV). Recent advancements in antiviral prophylaxis against mother-to-child transmission of HBV and postpartum cessation of antiviral therapy further complicate this issue. Our literature review, spanning PubMed, and two Chinese-language databases (CNKI and Wanfang) from 1 January 2000 to 31 December 2023 aimed to consolidate and analyse available data on the frequency and severity of postpartum ALT flares, identify risk factors, and propose a management algorithm. Data from 23 eligible studies involving 8,077 pregnant women revealed an overall incidence of postpartum ALT elevation: 25.7% for mild cases, 4.4% for moderate cases, and 1.7% for severe cases. In the subgroup of mothers who were HBeAg-positive and on antiviral prophylaxis for preventing mother-to-child transmission, postpartum intermediate and severe ALT elevations were reported with pooled rates of 5.9% and 0.8%, respectively. Importantly, none resulted in mortality or necessitated liver transplantation. Identified risk factors for postpartum ALT flares in mothers with CHB included HBV DNA levels, ALT levels during pregnancy, postpartum cessation of antiviral treatment, and HBeAg status. By leveraging this evidence and recent data on predictors of intermediate or severe postpartum ALT flares, we propose a risk-stratified algorithm for managing postpartum ALT elevation and selecting therapy in mothers with CHB, tailoring different approaches for treatment-naive vs treatment-experienced populations. These recommendations aim to provide guidance for clinical decision-making and enhance patient outcomes.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495872/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HCV elimination: is the bulk of the iceberg being missed?","authors":"Eric Kalo, Asma Baig, Alison Derrett, Scott Read, Golo Ahlenstiel","doi":"10.1093/gastro/goae093","DOIUrl":"https://doi.org/10.1093/gastro/goae093","url":null,"abstract":"","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active role of the immune system in metabolic dysfunction-associated steatotic liver disease.","authors":"Taizo Mori, Sachiyo Yoshio, Eiji Kakazu, Tatsuya Kanto","doi":"10.1093/gastro/goae089","DOIUrl":"https://doi.org/10.1093/gastro/goae089","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease, recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), is a complex multifactorial disease that progresses from steatohepatitis (MASH) to liver cirrhosis and liver cancer. Recent research has revealed that crosstalk between innate immune cells and hepatic parenchymal and non-parenchymal cells is involved in the pathogenesis of liver disease in MASLD/MASH. Of particular importance, novel inflammatory mechanisms, including macrophage diversity, neutrophil NETosis, B-cell biology, auto-reactive T cells, unconventional T cells, and dendritic cell-T cell interactions, are considered key drivers for disease progression. These mechanisms and factors are potential targets for the therapeutic intervention of MASLD/MASH. In this review, we focus on recent discoveries related to liver inflammation and discuss the role of innate immune cell subsets in MASLD/MASH.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Noninvasive tests for liver fibrosis in 2024: are there different scales for different diseases?","authors":"","doi":"10.1093/gastro/goae096","DOIUrl":"https://doi.org/10.1093/gastro/goae096","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/gastro/goae024.].</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11481166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A predictive model and rapid multi-dynamic algorithm developed based on tumor-stroma percentage in gastric cancer: a retrospective, observational study.","authors":"Yitian Xu, Yan Yang, Feichi Cheng, Zai Luo, Yuan Zhang, Pengshan Zhang, Jiahui Qiu, Zhengjun Qiu, Chen Huang","doi":"10.1093/gastro/goae083","DOIUrl":"https://doi.org/10.1093/gastro/goae083","url":null,"abstract":"<p><strong>Background: </strong>Tumor-stroma percentage (TSP) is a prognostic risk factor in numerous solid tumors. Despite this, the prognostic significance of TSP in gastric cancer (GC) remains underexplored. Through the development of a personalized predictive model and a semi-automatic identification system, our study aimed to fully unlock the predictive potential of TSP in GC.</p><p><strong>Methods: </strong>We screened GC patients from Shanghai General Hospital (SGH) between 2012 and 2019 to develop and validate a nomogram. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic factors influencing the prognosis for GC patients. The nomogram was further validated externally by using a cohort from Bengbu Medical College (BMC). All patients underwent radical gastrectomy, with those diagnosed with locally advanced GC receiving adjuvant chemotherapy. The primary outcome measured was overall survival (OS). The semi-automatic identification of the TSP was achieved through a computer-aided detection (CAD) system, denoted as TSP-cad, while TSP identified by pathologists was labeled as TSP-visual.</p><p><strong>Results: </strong>A total of 813 GC patients from SGH and 59 from BMC were enrolled in our study. TSP-visual was identified as an adverse prognostic factor for OS in GC and was found to be associated with pathological Tumor Node Metastasis staging system (pTNM) stage, T stage, N stage, perineural invasion (PNI), lymphovascular invasion (LVI), TSP-visual, tumor size, and other factors. Multivariate Cox regression using the training cohort revealed that TSP-visual (hazard ratio [HR], 2.042; 95% confidential interval [CI], 1.485-2.806; <i>P </i><<i> </i>0.001), N stage (HR, 2.136; 95% CI, 1.343-3.397; <i>P </i>=<i> </i>0.010), PNI (HR , 1.791; 95% CI, 1.270-2.526; <i>P </i>=<i> </i>0.001), and LVI (HR, 1.482; 95% CI, 1.021-2.152; <i>P </i>=<i> </i>0.039) were independent predictors. These factors were incorporated into a novel nomogram, which exhibited strong predictive accuracy for 5-year OS in the training, internal validation, and external validation cohorts (area under the curve = 0.744, 0.759, and 0.854, respectively). The decision curve analysis of the nomogram and concordance indexes across the three cohorts outperformed the traditional pTNM (<i>P </i><<i> </i>0.05). Additionally, TSP-cad assessment using a rapid multi-dynamic algorithm demonstrated good agreement with TSP-visual.</p><p><strong>Conclusions: </strong>The novel nomogram based on TSP could effectively identify individuals at risk of a poor prognosis among patients with GC. TSP-cad is anticipated to enhance the evaluation process of TSP.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of actionable gene fusions in a large cohort of Chinese patients with colorectal cancer.","authors":"Fu-Rong Kou, Jian Li, Zheng-Hang Wang, Ting Xu, Juan-Juan Qian, En-Li Zhang, Li-Jun Zhang, Lin Shen, Xi-Cheng Wang","doi":"10.1093/gastro/goae092","DOIUrl":"10.1093/gastro/goae092","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer (CRC). Published data on gene fusions are limited by relatively small sample sizes, with a primary focus on Western populations. This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population.</p><p><strong>Methods: </strong>This study included 5,534 consecutive CRC patients from the Genecast database. Genomic profiling was performed using a panel of 769 cancer-related genes. Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq.</p><p><strong>Results: </strong>Among 5,534 CRC patients, 54 (0.98%) had actionable gene fusions, with <i>NTRK1/2/3</i> being the most common fusion (0.38%), accounting for 38.9% (21/54) of those with fusions. Actionable gene fusion enrichment was higher in patients with microsatellite instability-high (MSI-H) (6.7% vs. 0.5%, <i>P </i><<i> </i>0.001), <i>RAS/BRAF</i> wildtype (2.0% vs. 0.2%, <i>P </i><<i> </i>0.001) and <i>RNF43</i> mutation (7.7% vs. 0.4%, <i>P </i><<i> </i>0.001) than in patients with microsatellite stability/MSI-low, <i>RAS/BRAF</i> mutation and <i>RNF43</i> wildtype, respectively. When these markers were combined, the fusion detection rate increased. Among patients with <i>RAS/BRAF</i> wildtype and MSI-H, fusions were detected in 20.3% of patients. The fusion detection rate further increased to 37.5% when <i>RNF43</i> mutation was added. The fusion detection rate was also higher in colon cancer than in rectal cancer. No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast, cBioPortal, and ChimerSeq databases.</p><p><strong>Conclusions: </strong>Approximately 1% of the unselected Chinese CRC population carries actionable gene fusions, mostly involving <i>NTRK</i>. Actionable gene fusions are more prevalent in MSI-H, <i>RAS/BRAF</i> wildtype, or <i>RNF43</i>-mutated CRC, as well as in colon cancer. Mapping of these molecular markers can markedly increase the fusion detection rate, which can help clinicians select candidates for fusion testing and targeted therapy.</p>","PeriodicalId":54275,"journal":{"name":"Gastroenterology Report","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}