Gastroenterology Report最新文献

Background: Functional constipation includes a set of gastrointestinal symptoms unexplainable by an identifiable underlying physical cause or pathology. The prevalence of this condition is high and there is a need to develop strategies to reduce it. Probiotics, prebiotics, and synbiotics may be an alternative treatment for chronic functional constipation.

Methods: To compare the efficacy of dietary supplementation on symptoms of patients who suffer from chronic functional constipation. An exploratory, randomized, double-blind, placebo-controlled pilot clinical trial was conducted with 74 patients diagnosed with chronic functional constipation who were divided into four treatment groups-Group A: probiotics; Group B: prebiotics; Group C: synbiotics; Group D: placebo. Each patient was treated for 8 weeks. At the beginning and end of treatment, data were collected by administering questionnaires and scales, including the Bristol stool scale, on gastrointestinal symptoms, bowel movements, and sociodemographic and anthropometric characteristics.

Results: Stool frequency increased in all four study groups, and greatest difference was observed in the synbiotics group (2.8 ± 1.3 vs. 5.9 ± 2.6; P < 0.001). Stool consistency improved only in the active treatment groups. Based on the evaluation of gastrointestinal symptoms, participants treated with prebiotics, probiotics and synbiotics showed the greatest improvement in abdominal pain (8.28 ± 2.63 vs. 6.56 ± 2.62; P = 0.009), gastroesophageal reflux (4.60 ± 2.66 vs. 3.45 ± 2.42; P = 0.039) and constipation symptoms (13.00 ± 3.97 vs. 8.71 ± 3.35; P = 0.003), respectively. As for quality of life, the main changes were observed in physical health domains, with a placebo effect.

Conclusions: The present study provides evidence supporting the efficacy of dietary supplementation with probiotics, prebiotics, and synbiotics in patients with chronic functional constipation after 8 weeks of treatment.

Background: The genetic variant of tumor necrosis factor superfamily member 15 (TNFSF15) is associated with Crohn's disease (CD) and the development of intestinal fibrosis and stricturing. We aimed to investigate its predictive role in disease progression and the impact of ileal fibrosis-associated protein expression in Chinese patients with CD.

Methods: We genotyped the single nucleotide polymorphism rs6478109 within the TNFSF15 gene in 428 CD patients and 450 health controls to assess its association with CD. Genotype-phenotype correlation analyses were performed. Mucosal samples from non-diseased terminal ileum were analyzed for TL1A and fibrosis-associated protein expression using western blot and immunohistochemistry.

Results: The G allele frequency of rs6478109 was significantly higher among CD patients compared with health controls (63.3% vs. 46.7%, P < 0.001). Patients with GG genotype were more predisposed to develop the stricturing phenotype, compared with those with AA + AG genotypes with a hazard ratio of 1.426 (95% confidence interval: 1.029-1.977, P = 0.033). This trend was similarly observed in patients utilizing biological agents, with a hazard ratio of 4.396 (95% confidence interval: 1.780-10.854, P = 0.001). Furthermore, increased TL1A, pro-fibrotic proteins, and TGFβ1/Smad3 pathway activation were observed in non-diseased ileal mucosa of patients with GG genotype compared with those with AA genotype.

Conclusions: The TNFSF15 risk genotype GG could promote the expression of pro-fibrotic proteins and may serve as a predictor for stricturing CD.

Acute severe lower gastrointestinal bleeding is a rare but potentially fatal complication of Crohn's disease (CD), affecting between 0.6% and 5.5% of CD patients during their lifelong disease course. Managing bleeding episodes effectively hinges on vital resuscitation. Endoscopic evaluation and computed tomography play crucial roles in accurate identification and intervention. Fortunately, most bleeding episodes can be successfully managed through appropriate conservative treatment. Medical therapies, particularly infliximab, aim to induce and maintain mucosal healing and serve as the leading treatment approach. Minimally invasive procedures, such as endoscopic hemostasis and angio-embolization, can achieve immediate hemostasis. Surgical treatment is only considered a last resort when conservative therapies fail. Despite achieving hemostasis, the risk of rebleeding ranges from 19.0% to 50.5%. The objective of this review is to provide a comprehensive and updated overview of the clinical manifestations, diagnostic methods, therapeutic approaches, and prognostic outcomes associated with acute severe gastrointestinal bleeding in CD. Furthermore, we aimed to propose a management algorithm to assist clinicians in the effective management of this condition.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide. It usually develops due to viral hepatitis or liver cirrhosis. The molecular mechanisms involved in HCC pathogenesis are complex and incompletely understood. Gasdermin E (GSDME) is a tumor suppressor gene and is inhibited in most cancers. Recent studies have reported that, unlike those in most tumors, GSDME is highly expressed in liver cancer, and GSDME expression in HCC is negatively associated with prognosis, suggesting that GSDME may promote HCC. However, antitumor drugs can induce pyroptosis through GSDME, killing HCC cells. Therefore, GSDME may both inhibit and promote HCC development. Because functional studies of GSDME in HCC are limited, the precise molecular mechanisms of GSDME in liver cancer remain unclear. In this article, we have reviewed the role, related mechanisms, and clinical importance of GSDME at the onset and development of HCC to provide a theoretical foundation to improve the clinical diagnosis and treatment of liver cancer.

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.

Background: 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.

Methods: 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 BCL2, SNAIL, and MMP9 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.

Results: NF-κB p65 is highly expressed, while p-p65 Ser536 is not well expressed in intermediate and advanced HCC tissues. In vivo experiments demonstrated that a phosphorylation-mimetic mutant of RelA/p65 Ser536 (p65/S536D) prevents tumor progression and metastasis. In vitro 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 BCL2, SNAIL, and MMP9 promoters.

Conclusions: RelA/p65 Ser536 phosphorylation was detrimental to NF-κB p65 entry into the nucleus and inhibited HCC progression and metastasis by reducing BCL2, SNAIL, and MMP9. The phosphorylation site of RelA/p65 Ser536 has excellent potential to be a promising target for NF-κB-targeted therapy in HCC.

Background: 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.

Method: 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). β-catenin^fl/fl mice, β-catenin^Tg mice, and Dll1^{tm1 Gos} mice were used to cross with Lgr5-EGFP-IRES-creERT2 mice to generate mice of different genotypes, altering the activation of Wnt/β-catenin and Dll1-mediated Notch signaling in ISCs in vivo. 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.

Result: 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.

Conclusions: 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.

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.