SIRT1 stabilizes ß-TrCP1 to inhibit Snail1 expression in maintaining intestinal epithelial integrity to alleviate colitis.

BACKGROUND AND AIMS: Dysfunction of the intestinal epithelial barrier comprising the junctional complex of tight junctions and adherent junctions leads to increased intestinal permeability, which is a major cause of uncontrolled inflammation related to Inflammatory Bowel Disease (IBD). The NAD+-dependent deacetylase SIRT1 is implicated in inflammation and the pathological process of IBD. We aimed to elucidate the protective role and underlying mechanism of SIRT1 in cell-cell junction and intestinal epithelial integrity. METHODS: The correlation of SIRT1 expression and human IBD was analyzed by GEO or immunohistochemical analyses. BK5.mSIRT1 transgenic mice and WT mice were given dextran sodium sulfate (DSS) and the manifestation of colitis-related phenotypes were analyzed. Intestinal permeability was measured by FITC-Dextran and cytokines expression was analyzed by QPCR. The expression of the cell junction-related proteins in DSS-treated or SIRT1-knockdown Caco2 or HCT116 cells was analyzed by Western blotting. The effects of Nicotinamide mononucleotide (NMN) in DSS-induced mice colitis were investigated. Correlations of the SIRT1-ß-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway with human IBD samples were analyzed. RESULTS: Reduced SIRT1 expression is associated with human IBD specimens. SIRT1 transgenic mice exhibit much-reduced manifestations of DSS-induced colitis. the activation of SIRT1 by NMN bolsters intestinal epithelial barrier function and ameliorates DSS-induced colitis in mice. Mechanistically, DSS down-regulates SiRT1 expression, leading to destabilization of ß-TrCP1 and upregulation of Snail1, accompanied by reduced expression of E-cadherin, Occludin, and Claudin-1, consequently resulting in increased epithelial permeability and inflammation. The deregulated SIRT1-ß-TrCP1-Snail1-Occludin/Claudin-1/E-cadherin pathway correlates with human IBD. CONCLUSION: SIRT1 is pivotal in maintaining the intestinal epithelial barrier integrity via modulation of the ß-TrCP1-Snail1-E-cadhein/Occludin/Claudin-1 pathway.

The Effects of a High-Fat Diet on Inflammatory Bowel Disease.

The interactions among diet, intestinal immunity, and microbiota are complex and play contradictory roles in inflammatory bowel disease (IBD). An increasing number of studies has shed light on this field. The intestinal immune balance is disrupted by a high-fat diet (HFD) in several ways, such as impairing the intestinal barrier, influencing immune cells, and altering the gut microbiota. In contrast, a rational diet is thought to maintain intestinal immunity by regulating gut microbiota. In this review, we emphasize the crucial contributions made by an HFD to the gut immune system and microbiota.

Precision medicine in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an incurable disease characterized by remission-relapse cycles throughout its course. Both Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of IBD, exhibit tendency to develop complications and substantial heterogeneity in terms of frequency and severity of relapse, thus posing great challenges to the clinical management for IBD. Current treatment strategies are effective in different ways in induction and maintenance therapies for IBD. Recent advances in studies of genetics, pharmacogenetics, proteomics and microbiome provide a strong driving force for identifying molecular markers of prognosis and treatment response, which should help clinicians manage IBD patients more effectively, and then, improve clinical outcomes and reduce treatment costs of patients. In this review, we summarize and discuss precision medicine in IBD, focusing on predictive markers of disease course and treatment response, and monitoring indices during therapeutic drug monitoring.

A proteomic and RNA-seq transcriptomic dataset of capsaicin-aggravated mouse chronic colitis model.

An inappropriate diet is a risk factor for inflammatory bowel disease (IBD). It is established that the consumption of spicy food containing capsaicin is strongly associated with the recurrence and worsening of IBD symptoms. Moreover, capsaicin can induce neutrophil accumulation in the lamina propria, contributing to disease deterioration. To uncover the potential signaling pathway involved in capsaicin-induced relapse and the effects of capsaicin on neutrophil activation, we performed proteomic analyses of intestinal tissues from chronic colitis mice following capsaicin administration and transcriptomic analyses of dHL-60 cells after capsaicin stimulation. Collectively, these multiomic analyses identified proteins and genes that may be involved in disease flares, thereby providing new insights for future research.

Plant green pigment of chlorophyllin attenuates inflammatory bowel diseases by suppressing autophagy activation in mice.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are intestinal complications characterized by chronic inflammation, autophagy abnormality, and lysosomal stress, which are derived from genetic predisposition and environmental risk factors. It is generally precepted that dietary green vegetable is beneficial for physiological homeostasis. In this study, we found that dextran sulfate sodium (DSS)-induced colitis and altered intestinal epithelia in mice were attenuated by oral administration of chlorophyllin (CHL), a water-soluble derivate of chlorophyll. In DSS-treated mice, autophagy was persistently activated in intestinal tissues and associated with bowel disorders. Conversely, supplement of CHL in diet or gavage suppressed intestinal inflammation, downregulated autophagy flux in intestinal tissue, and relieved endoplasmic reticulum stress. In vitro studies show that CHL could activate Akt and mTOR pathways, leading to downregulation of autophagic and lysosomal flux. Thus, consumption of green vegetables and chlorophyllin may be beneficial for IBD recovery in part through alleviation of inflammation and autolysosomal flux.NEW & NOTEWORTHY Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disease, while the etiology remains poorly understood. Dietary composition and lifestyle are crucial for pathogenesis and progression of IBD. In this study, we observed that autophagy in the intestinal tissue was persistently activated in IBD mice. Chlorophyllin (CHL), a water-soluble derivate of chlorophyll, can attenuate colitis by regulating autophagy and inflammation. Thus, consumption of green vegetables and chlorophyllin may be beneficial for IBD recovery.

Enterogenous Microbiotic Markers in the Differential Diagnosis of Crohn's Disease and Intestinal Tuberculosis.

Crohn's disease (CD) is a chronic intestinal disorder characterized by refractory gastrointestinal ulcerations. Intestinal tuberculosis (ITB) is one common intestinal disease in east Asia. The two diseases share similar clinical manifestations and endoscopic characteristics. Thus, it is difficult to establish a definite diagnosis of CD, CD concomitant with ITB (CD-ITB), and ITB in practice. Some enterogeneous microbiotic markers have been applied to differentiate CD and ITB, but it remains unknown how they work for the three groups of patients. The aim of our study was to explore the diagnostic values of these enterogeneous microbiotic markers (ASCA IgG, ASCA IgA, ACCA, Anti-I2 and AMCA) among CD, CD-ITB, and ITB patients. A total of 124 individuals were retrospectively enrolled in this study, namely, 103 CD patients, 10 CD-ITB patients, 9 ITB patients, and 68 healthy controls. The demographic and clinical characteristics of these patients were collected and analyzed. The values of these individual or combined enterogeneous microbiotic markers in diagnosis and classification were assessed in CD, CD-ITB, and ITB patients. ASCA IgG, ASCA IgA, and AMCA could accurately differentiate CD patients from healthy controls with an area under curve (AUC) of 0.688, 0.601, and 0.638, respectively. ASCA IgG was significantly higher in CD patients than in CD-ITB patients (P = 0.0003). The Anti-I2 antibody was appropriate for distinguishing CD-ITB from ITB patients (P = 0.039). In CD patients, ASCA IgG was higher in severe patients than in mild (P <0.0001) and inactive patients (P <0.0001), respectively. AMCA was significantly elevated in severe and moderate patients compared to inactive patients (P = 0.001, P = 0.003, respectively). AMCA was associated with a higher risk of CD-related surgery with a significant P-value of 0.0038. In our cohort, ASCAs and AMCA could accurately distinguish CD from healthy controls with an acceptable AUC. A combination of elevated ASCA IgG and AMCA antibodies established a higher sensitivity in differentiating CD from healthy controls. Elevated ASCA IgG demonstrated a differential diagnostic value between CD and CD-ITB. Anti-I2 could also distinguish CD-ITB from ITB. The level of AMCA was associated with both disease severity and CD-related surgery. Likewise, the level of ASCA IgG was also related to disease severity.

Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs.

It is well established that gastrointestinal (GI) cancers are common and devastating diseases around the world. Despite the significant progress that has been made in the treatment of GI cancers, the mortality rates remain high, indicating a real need to explore the complex pathogenesis and develop more effective therapeutics for GI cancers. G protein-coupled receptors (GPCRs) are critical signaling molecules involved in various biological processes including cell growth, proliferation, and death, as well as immune responses and inflammation regulation. Substantial evidence has demonstrated crucial roles of GPCRs in the development of GI cancers, which provided an impetus for further research regarding the pathophysiological mechanisms and drug discovery of GI cancers. In this review, we mainly discuss the roles of sphingosine 1-phosphate receptors (S1PRs), angiotensin II receptors, estrogen-related GPCRs, and some other important GPCRs in the development of colorectal, gastric, and esophageal cancer, and explore the potential of GPCRs as therapeutic targets.

Sucralose enhances the susceptibility to dextran sulfate sodium (DSS) induced colitis in mice with changes in gut microbiota.

Sucralose is one of the most widely used artificial sweeteners, free of nutrients and calories. Its approval and uses correlate with many of the worldwide epidemiological changes in inflammatory bowel disease (IBD). Multiple animal studies by us and others showed that sucralose exacerbated ileitis in SAMP1/YitFc mice and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. In this study, we further investigated the effect of sucralose on dextran sulfate sodium (DSS)-induced colitis in mice and the associated mechanisms. Male C57BL/6 mice received 1.5 mg ml-1 sucralose in drinking water for 6 weeks. Then, 2.5% DSS was added to drinking water for 7 days to induce ulcerative colitis (UC). The results showed that, compared with the DSS group, administration of sucralose exacerbated the severity of colitis as indicated by the further decrease in body weight, increase in disease activity index (DAI) and the expression of pro-inflammatory cytokines, as well as the activation of the TLR5-MyD88-NF-κB signaling pathway, and the disturbances of intestinal barrier function, along with changes in the intestinal microbiota. Our findings indicate that sucralose may increase the susceptibility to DSS-induced colitis through causing dysbiosis of intestinal microbiota and damage to the intestinal barrier.

Sucralose Promotes Colitis-Associated Colorectal Cancer Risk in a Murine Model Along With Changes in Microbiota.

Sucralose is a calorie-free high-intensity artificial sweetener that is widely used in thousands of foods and beverages all over the world. Although it was initially regarded as a safe, inert food additive, its adverse effect on gut microbiota and health has drawn more and more attention as evidence accumulates. Studies by us and others revealed that sucralose exacerbated gut damage and inflammation in animal models for inflammatory bowel disease (IBD), including those for both ulcerative colitis, and Crohn's disease. Our study demonstrated that sucralose greatly aggravated dextran sulfate sodium (DSS)-induced colitis along with causing changes in gut microbiota, the gut barrier and impaired inactivation of digestive proteases mediated by deconjugated bilirubin. It is well-documented that IBD greatly increases the risk of colorectal cancer (CRC), the globally third-most-common cancer, which, like IBD, has a high rate in the developed countries. Azoxymethane (AOM)/DSS has been the most commonly used animal model for CRC. In this study, we further explored the effect of sucralose on tumorigenesis and the possible mechanism involved using the AOM/DSS mouse model. First, 1.5 mg/ml sucralose was included in the drinking water for 6 weeks to reach a relatively stable phase of impact on gut microbiota. Then, 10 mg/kg AOM was administered through intraperitoneal injection. Seven days later, 2.5% DSS was put in the drinking water for 5 days, followed by 2 weeks without DSS. The 5 days of DSS was then repeated, and the mice were sacrificed 6 weeks after AOM injection. The results showed that sucralose caused significant increases in the number and size of AOM/DSS-induced colorectal tumors along with changes in other parameters such as body and spleen weight, pathological scores, mortality, fecal ß-glucuronidase and digestive proteases, gut barrier molecules, gut microbiota, inflammatory cytokines and pathways (TNFα, IL-1ß, IL-6, IL-10, and TLR4/Myd88/NF-κB signaling), and STAT3/VEGF tumor-associated signaling pathway molecules. These results suggest that sucralose may increase tumorigenesis along with dysbiosis of gut microbiota, impaired inactivation of digestive protease, damage to the gut barrier, and exacerbated inflammation.

COVID-19 With Preexisting Hypercoagulability Digestive Disease.

The outbreak of coronavirus disease of 2019 (COVID-19) has become a global public health and economic crisis. The advent of hypercoagulability and thrombotic complications can substantially influence the prognosis of COVID-19 patients. In this review, we elaborate on the clinical findings, potential underlying pathogenesis, and therapeutic strategy of hypercoagulability and thromboembolism in COVID-19, particularly focusing on the COVID-19 patients with preexisting digestive hypercoagulability disease.

The Functional Role of Fecal Microbiota Transplantation on Dextran Sulfate Sodium-Induced Colitis in Mice.

Increasingly studies revealed that dysbiosis of gut microbiota plays a pivotal role in the pathogenesis of ulcerative colitis (UC). Fecal microbiota transplantation (FMT) has drawn more and more attention and become an important therapeutic approach. This study aims to examine the facts about the effective components and look into potential mechanisms of FMT. Colitis was induced by 3% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days. Colitis mice were administered by oral gavage with fecal suspension, fecal supernatant, fecal bacteria, or boiling-killed fecal bacteria from healthy controls and the disease activity index was monitored daily. On the seventh day, mice were euthanized. The length, histological score, parameters related to inflammation, gut barrier functions of the colon, activities of digestive protease and ß-glucuronidase in feces were measured. All of the four fecal components showed certain degree of efficacy in DSS-induced colitis, while transplantation of fecal suspension showed the most potent effect as demonstrated by less body weight loss, lower disease activity scores, more expression of tight junction proteins and TRAF6 and IκBα, less expression of TNF-α, IL-1ß, IL-10, TLR-4, and MyD88 in gut tissue, as well as restoration of fecal ß-glucuronidase and decreases in fecal digestive proteases. These results provide a novel insight into the possible mechanism of FMT and may help to improve and optimize clinical use of FMT.

The transjugular approach is a safe and effective alternative for performing portal vein embolization.

To evaluate the safety and efficacy of the novel technique, transjugular portal vein embolization (TPVE).A single-center retrospective review of 18 patients (12 males and 6 females; mean age, 62 years) who underwent TPVE between January 2012 and January 2013 was conducted. The technical success rate, future liver remnant (FLR) volume, total liver volume (TLV) and FLR/TLV ratio after PVE were analyzed. Liver function, including total bilirubin (TB), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and International Normalized Ratio (INR), was assessed before and after PVE. Any complications of TPVE and liver resection after TPVE were recorded.TPVE was performed on 18 patients before right hepatic resection for both primary and secondary hepatic malignancies (10 hepatocellular carcinomas, 4 cases of colorectal liver metastasis, and 4 cholangiocarcinomas). Technical success was achieved in 100% of patients (18 of 18). The mean FRL significantly increased to 580 ±â€Š155 mL (P < .001) after PVE. The mean FLR/TLV ratio (%) significantly increased to 34 ±â€Š4 (P < .001) after PVE. One patient suffered septicemia after TPVE. A small number patients experienced mild to moderate abdominal pain during TPVE. No other major complications occurred after TPVE in our study. The patient who developed septicemia died 3 days after the surgery as a result of this complication and subsequent multiple organ dysfunction syndrome (MODS).Transjugular portal vein embolization is a safe, efficacious, and promising novel technique to induce hypertrophy of the FLR.

Unconjugated bilirubin alleviates experimental ulcerative colitis by regulating intestinal barrier function and immune inflammation.

BACKGROUND: Unconjugated bilirubin (UCB) is generally considered toxic but has gained recent prominence for its anti-inflammatory properties. However, the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved. AIM: To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis. METHODS: Acute colitis was induced by 3% (w/v) dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d. Concurrently, mice with colitis were administered 0.2 mL UCB (400 µmol/L) by intra-gastric gavage for 7 d. Disease activity index (DAI) was monitored daily. Mice were sacrificed at the end of the experiment. The length of the colon and weight of the spleen were recorded. Serum level of D-lactate, intestinal digestive proteases activity, and changes to the gut flora were analyzed. In addition, colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins. RESULTS: Mice treated with UCB had significantly relieved severity of colitis, including lower DAI, longer colon length, and lower spleen weight (colon length: 4.92 ± 0.09 cm vs 3.9 ± 0.15 cm; spleen weight: 0.33 ± 0.04 vs 0.74 ± 0.04, P < 0.001). UCB administration inactivated digestive proteases (chymotrypsin: 18.70 ± 0.69 U/g vs 44.81 ± 8.60 U/g; trypsin: 1.52 ± 0.23 U/g vs 9.05 ± 1.77 U/g, P < 0.01), increased expression of tight junction (0.99 ± 0.05 vs 0.57 ± 0.03, P < 0.001), decreased serum level of D-lactate (31.76 ± 3.37 µmol/L vs 54.25 ± 1.45 µmol/L, P < 0.001), and lowered histopathological score (4 ± 0.57 vs 7 ± 0.57, P < 0.001) and activity of myeloperoxidase (46.79 ± 2.57 U/g vs 110.32 ± 19.19 U/g, P < 0.001). UCB also regulated the intestinal microbiota, inhibited expression of tumor necrosis factor (TNF) α and interleukin 1ß (TNF-α: 52.61 ± 7.81 pg/mg vs 105.04 ± 11.92 pg/mg, interleukin 1ß: 13.43 ± 1.68 vs 32.41 ± 4.62 pg/mg, P < 0.001), decreased expression of Toll-like receptor 4 (0.61 ± 0.09 vs 1.07 ± 0.03, P < 0.001) and myeloid differentiation primary response gene 88 (0.73 ± 0.08 vs 1.01 ± 0.07, P < 0.05), and increased expression of TNF-receptor-associated factor 6 (0.79 ± 0.02 vs 0.43 ± 0.09 P < 0.05) and inhibitor of kappa B α (0.93 ± 0.07 vs 0.72 ± 0.07, P < 0.05) in the colon. CONCLUSION: UCB can protect intestinal barrier function, regulate normal intestinal homeostasis, and suppress inflammation via the Toll-like receptor 4/ nuclear factor-κB signaling pathway.

Bacterial ß-glucuronidase alleviates dextran sulfate sodium-induced colitis in mice: A possible crucial new diagnostic and therapeutic target for inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are devastating diseases of the gut. At present, all the treatments are mainly targeting symptoms like inflammation. The disease remains regarded as incurable, largely due to lacking of knowledge on its etiology. Our previous studies suggested that impaired inactivation of digestive proteases by deconjugated bilirubin in experimental colitis, thus bacterial ß-glucuronidase for catalyzing the reaction, may have played critical role in the pathogenesis of IBD. METHODS: We first analyzed ß-glucuronidase activity in gut tissue and feces of mice by a colitis model. Then the effect of ß-glucuronidase on experimental colitis was investigated in detail by administration of ß-glucuronidase (from E. coli) and fecal material transplantation to mice with 3% DSS in drinking water for 7 days. RESULTS: Mice with colitis showed unchanged activity of ß-glucuronidase in colon tissue but decreased activity in feces. Treatment with bacterial ß-glucuronidase at 100 U or above alleviated DSS-induced colitis as demonstrated by the less body weight loss, less disease activity score, increased expression of tight junction proteins and decreased gut permeability, decreases in MPO, TNF-α, IL-1ß, TLR-4 and MyD88, and increase in IL-10 and IκBα in gut, restored fecal ß-glucuronidase and gut microbiota along with decreases in fecal digestive proteases. Transplantation of fecal material from control to colitis mice showed similar effects as treatment with ß-glucuronidase. CONCLUSIONS: Bacterial ß-glucuronidase showed strong inhibition on colitis along with the reduction in fecal digestive proteases, which may be a crucial diagnostic and therapeutic target for IBD.

Long-term patency and clinical outcome of the transjugular intrahepatic portosystemic shunt using the expanded polytetrafluoroethylene stent-graft.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) creation is an established treatment option to management the complications of portal hypertension. Recent data on the long-term outcomes of TIPS are scarce. MATERIALS AND METHODS: In this single-institution retrospective study, 495 patients underwent TIPS with the Fluency stent-grafts between December 2011 and June 2015 were evaluated. The cumulative rates of TIPS dysfunction, hepatic encephalopathy (HE), survival, and variceal rebleeding were determined using the Kaplan-Meier method. Cox regression analysis was used to assess the parameters on TIPS patency, occurrence of HE and all-cause mortality. RESULTS: Technical success was 98.2%. TIPS-related complications occurred in 67 patients (13.5%) during the index hospital stay. TIPS creation resulted in an immediate decrease in mean portosystemic pressure gradient from 23.4 ± 7.1 mmHg to 7.6 ± 3.5 mmHg. The median follow-up period was 649 days. Primary TIPS patency rates were 93%, and 75.9% at 1 and 3 years, respectively. Previous splenectomy was associated with a higher risk of TPS dysfunction. The cumulative survival rates were 93.4% and 77.2% at 1 and 3 years, respectively. The 1- and 3-year probability of remaining free of variceal bleeding rates were 94.2% and 71.4%, respectively. CONCLUSIONS: This retrospective single-center experience with TIPS using the Fluency stent-grafts demonstrates good long-term patency and favorable good clinical results. Previous splenectomy strongly predicts shunt dysfunction.

Effect of Transjugular Intrahepatic Portosystemic Shunt Creation on Pulmonary Gas Exchange in Patients with Hepatopulmonary Syndrome: A Prospective Study.

PURPOSE: To evaluate effect of transjugular intrahepatic portosystemic shunt (TIPS) creation on pulmonary gas exchange in patients with hepatopulmonary syndrome (HPS). MATERIALS AND METHODS: All patients with cirrhosis or Budd-Chiari syndrome undergoing elective TIPS creation at a single institution between June 2014 and June 2015 were eligible for inclusion. Twenty-three patients with HPS (age 55.0 y ± 14.4; 11 men; Model for End-Stage Liver Disease score 10.2 ± 2.7) who achieved technical success were included in the analysis. Diagnosis of HPS was established by contrast-enhanced echocardiography demonstrating intrapulmonary vascular dilatation and arterial blood gas analysis demonstrating arterial oxygenation defects. RESULTS: Mean portosystemic gradient was reduced from 21.7 mm Hg ± 8.3 before TIPS creation to 10.8 mm Hg ± 5.1 after TIPS creation. Among the 5 (21.7%) patients who experienced dyspnea, 4 (80.0%) reported improvement after TIPS creation. This improvement was not maintained at 3 months after TIPS creation in 2 (50.0%) patients. Compared with before TIPS creation, mean change in alveolar-arterial oxygen gradient for patients with HPS was statistically significant at 1 month (-9.2 mm Hg ± 8.0; P < .001) after TIPS creation, but not at 2-3 days (-0.9 mm Hg ± 10.5; P = .678) or 3 months (-3.4 mm Hg ± 11.8; P = .179) after TIPS creation. CONCLUSIONS: TIPS creation can transiently improve pulmonary gas exchange in patients with HPS.

Comparison of transjugular intrahepatic portosystemic shunt (TIPS) alone and combined with embolisation for the management of cardiofundal varices: a retrospective study.

OBJECTIVES: To assess the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) with and without adjunctive embolisation in managing cardiofundal varices bleeding. METHODS: The retrospective study comprised 82 patients (54 men; mean age 53.9 years; mean Model of End-stage Liver Disease score 9.3) with cardiofundal varices bleeding who underwent TIPS creation from 2011 to 2015. Variceal rebleeding, the outflow tracts of varices, overt hepatic encephalopathy (HE) and post-procedure varices patency were assessed. RESULTS: Gastrorenal shunt was present in 92.7% of patients (n = 76). Embolisation was performed in 67.1% of patients (n = 55). The 1- and 2-year variceal rebleeding rates in the TIPS combined with embolisation group were significantly lower than those in the TIPS alone group (3.8% and 13.4% vs 13.0% and 28.0%, respectively; p = 0.041). No significant differences between the two groups were found in the cardiofundal varices patency, overt HE or survival (p > 0.05). CONCLUSIONS: The results suggest that TIPS combined with embolisation can reduce the risk of variceal rebleeding for patients with cardiofundal varices. KEY POINTS: • TIPS combined with embolisation reduces the risk of rebleeding in treating cardiofundal varices. • TIPS combined with embolisation could not completely occlude cardiofundal varices. • TIPS combined with embolisation could not prevent the development of hepatic encephalopathy.

Changes in arterial oxygenation after portal decompression in Budd-Chiari syndrome patients with hepatopulmonary syndrome.

OBJECTIVES: To evaluate the changes in arterial oxygenation after portal decompression in Budd-Chiari syndrome (BCS) patients with hepatopulmonary syndrome (HPS). METHODS: From June 2014 to June 2015, all patients with BCS who underwent balloon angioplasty or transjugular intrahepatic portosystemic shunt (TIPS) creation at our institution were eligible for inclusion in this study. Arterial blood gas analysis was performed with the patient in an upright position and breathing room air at 2-3 days and 1 and 3 months after the procedure. RESULTS: Eleven patients with HPS and 14 patients without HPS were included in this study. The procedure was technically successful in 24 patients. One patient with HPS had technically unsuccessful TIPS creation. Reobstruction or TIPS dysfunction was not detected in any patient within 3 months after the procedure. For patients with HPS, the alveolar-arterial oxygen gradient (A-aO2) remained comparable to baseline 2-3 days after the procedure (-3.2 ± 11.9 mmHg; p = .412), significantly improved 1 month after the procedure (-11.7 ± 6.4 mmHg; p < .001), and then returned to baseline 3 months after the procedure (-1.3 ± 12.5 mmHg; p = .757). For patients without HPS, the A-aO2 remained comparable to baseline at all three time points after the procedure (+1.4 ± 8.3 mmHg, +3.5 ± 8.1 mmHg, and +1.3 ± 8.2 mmHg; p = .543, p = .137, and p = .565). CONCLUSIONS: Arterial oxygenation transiently improves after portal decompression in BCS patients with HPS. KEY POINTS: • Intrapulmonary vascular dilation and hepatopulmonary syndrome are common in patients with Budd-Chiari syndrome. • Arterial oxygenation transiently improves after portal decompression in Budd-Chiari syndrome patients with hepatopulmonary syndrome.

Unconjugated bilirubin ameliorates the inflammation and digestive protease increase in TNBS-induced colitis.

The authors previously demonstrated that unconjugated bilirubin (UCB) may inhibit the activities of various digestive proteases, including trypsin and chymotrypsin. The digestive proteases in the lower gut are important in the pathogenesis of inflammatory bowel diseases. The effects of UCB on the inflammation and levels of digestive proteases in feces of rats with colitis have not yet been revealed. The present study investigated the effect of UCB on the inflammatory status and levels of trypsin and chymotrypsin in the feces of rats with trinitrobenzenesulfonic acid (TNBS)­induced colitis. The data indicated that treatment with TNBS resulted in a marked reduction in weight gain, which was significantly alleviated in UCB­treated rats. Furthermore, UCB treatment alleviated the inflammation induced by TNBS, detected via macroscopic damage and microscopic inflammation scores, and pro­inflammatory markers including myeloperoxidase (MPO), tumor necrosis factor (TNF)­α and interleukin (IL)­1ß. Furthermore, rats with colitis demonstrated significant increases in fecal trypsin and chymotrypsin levels, whereas UCB treatment significantly alleviated these increases. A significant positive correlation was additionally revealed among the pro­inflammatory markers (MPO, TNF­α and IL­1ß) and fecal digestive proteases (trypsin and chymotrypsin) in colitis. The results of the present study demonstrated that UCB ameliorated the inflammation and digestive protease increase in TNBS-induced colitis.

Sucralose Increases Antimicrobial Resistance and Stimulates Recovery of Escherichia coli Mutants.

Because of heavy use of antimicrobials, antimicrobial resistance in bacteria has become of great concern. The effect of some widely used food additives such as sucralose on bacteria in the gut and the environment has also drawn increasing attention. In this study, we investigated the interaction between antimicrobials and sucralose impacting antimicrobial resistance and mutation of Escherichia coli (E. coli). To examine antimicrobial resistance and mutation frequency, different subinhibitory concentrations of sucralose were added to cultures of E.coli BW25113 that were then treated with antimicrobials, oxolinic acid, or moxifloxacin. Then the E.coli were assayed for bacterial survival and recovery of mutants resistant to an unrelated antimicrobial, rifampicin. Pre-treatment of E.coli BW25113 with 1/2 minimal inhibitory concentration (MIC) of sucralose increased the survival rate in oxolinic acid or moxifloxacin. A 1/3 MIC of sucralose increased rifampicin-resistant mutation rate of E.coli BW25113 after 72 h, while rifampicin-resistant mutation rate was increased when co-treated with 1/8 MIC, 1/4 MIC, 1/3 MIC sucralose, and oxolinic acid after 24 h. Sucralose can increase the antimicrobial resistance and mutation frequency of E.coli to some antimicrobials.