Routine nasogastric tube placement in patients with small esophageal perforation after endoscopic foreign body removal may be unnecessary: a propensity score matching analysis.

Background: Nasogastric tube (NGT) placement is part of the post-operative management of upper gastrointestinal perforation, but its routine use in esophageal perforation (EP) caused by foreign bodies remains unclear. The purpose of this research was to investigate the necessity for routine NGT placement in patients with EP after endoscopic foreign body removal. Methods: A total of 323 patients diagnosed with EP caused by foreign bodies at the First Affiliated Hospital of Nanchang University between January 2012 and December 2021 were included in this retrospective study. Patients were divided into the NGT group and the non-NGT group according to whether or not NGT placement was performed. The perforation healing rate, post-operative adverse events, hospital stay, and death rate were analysed using a 1:1 propensity score matching model. Results: Before matching, there were 263 patients in the NGT group and 60 patients in the non-NGT group. There were significant differences in the time to treatment, infection, albumin, and types of endoscopy between the two groups, while the length of hospital stay in the NGT group was significantly longer than that in the non-NGT group. After 1:1 propensity score matching, 48 pairs of patients were matched between the two groups. The perforation healing rate, post-operative adverse events, length of hospital stay, and death rate did not show significant differences between the two groups. Conclusions: For patients with small EP caused by foreign bodies, routine NGT placement after endoscopic foreign body removal may be unnecessary.

Practice guidance for the use of terlipressin for liver cirrhosis-related complications.

Background: Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis-related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis-related complications. Methods: Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences. Results: Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored. Conclusion: The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis-related complications.

Incidence and risk factors for rebleeding after emergency endoscopic hemostasis for marginal ulcer bleeding.

BACKGROUND: Marginal ulcer bleeding is a cause of upper gastrointestinal bleeding, but the efficacy of emergency endoscopic hemostasis and risk factors for rebleeding have not been fully explored. The purpose of the current study was to investigate the rebleeding rate and risk factors after emergency endoscopic hemostasis for marginal ulcer bleeding. METHODS: We conducted a retrospective study of 105 patients who underwent emergency endoscopic hemostasis due to marginal ulcer bleeding from January 2015 to July 2021. Patients included in this study were divided into rebleeding and non-rebleeding groups. RESULTS: Among the 105 patients, 15.2% (16/105) patients developed rebleeding within 30 days after endoscopic hemostasis, and 87.5% of the patients had rebleeding within 7 days. The mean age of these patients was 60.3 ± 12.3 years, and 95 of them were male. In the univariate analysis, an ulcer size ≥10 mm, a PLT count <100 × 10^9/L and an AIMS65 score ≥2 were risk factors for rebleeding. According to the multivariable analysis, an ulcer size ≥10 mm (OR: 3.715; 95% CIs: 1.060-14.250; p = 0.043) and a PLT count <100 × 10^9/L (OR: 4.480; 95% CIs: 1.099-18.908; p = 0.035) were independent risk factors for rebleeding. CONCLUSION: Emergency endoscopic hemostasis is an effective treatment for marginal ulcer bleeding. An ulcer size ≥10 mm and a PLT count <100 × 10^9/L were independent risk factors for rebleeding within 30 days after endoscopic hemostasis for marginal ulcer bleeding.

Development and validation of a model to predict rebleeding within three days after endoscopic hemostasis for high-risk peptic ulcer bleeding.

BACKGROUND: Peptic ulcer bleeding remains a typical medical emergency with significant morbidity and mortality. Peptic ulcer rebleeding often occurs within three days after emergent endoscopic hemostasis. Our study aims to develop a nomogram to predict rebleeding within three days after emergent endoscopic hemostasis for high-risk peptic ulcer bleeding. METHODS: We retrospectively reviewed the data of 386 patients with bleeding ulcers and high-risk stigmata who underwent emergent endoscopic hemostasis between March 2014 and October 2018. The least absolute shrinkage and selection operator method was used to identify predictors. The model was displayed as a nomogram. Internal validation was carried out using bootstrapping. The model was evaluated using the calibration plot, decision-curve analyses, and clinical impact curve. RESULTS: Overall, 386 patients meeting the inclusion criteria were enrolled, with 48 patients developed rebleeding within three days after initial endoscopic hemostasis. Predictors contained in the nomogram included albumin, prothrombin time, shock, haematemesis/melena and Forrest classification. The model showed good discrimination and good calibration with a C-index of 0.854 (C-index: 0.830 via bootstrapping validation). Decision-curve analyses and clinical impact curve also demonstrated that it was clinically valuable. CONCLUSION: This study presents a nomogram that incorporates clinical, laboratory, and endoscopic features, effectively predicting rebleeding within three days after emergent endoscopic hemostasis and identifying high-risk rebleeding patients with peptic ulcer bleeding. Trial registration This clinical trial has been registered in the ClinicalTrials.gov (ID: NCT04895904) approved by the International Committee of Medical Journal Editors (ICMJE).

Acute kidney injury defined by cystatin C may be superior for predicting the outcomes of liver cirrhosis with acute gastrointestinal bleeding.

BACKGROUND & AIMS: Acute kidney injury (AKI) is conventionally evaluated by a dynamic change of serum creatinine (Scr). Cystatin C (CysC) seems to be a more accurate biomarker for assessing kidney function. This retrospective multicenter study aims to evaluate whether AKI re-defined by CysC can predict the in-hospital outcomes of patients with liver cirrhosis and acute gastrointestinal bleeding. METHODS: Overall, 677 cirrhotic patients with acute gastrointestinal bleeding, in whom both Scr and CysC levels were detected at admissions, were screened. eGFRScr, eGFRCysC, and eGFRScr-CysC were calculated. MELD-Na score and AKI were re-evaluated by CysC instead of Scr. Odds ratios (ORs) were calculated in the logistic regression analyses. The receiver operating characteristic (ROC) curve analyses were performed. RESULTS: Univariate logistic regression analyses demonstrated that baseline Scr and CysC levels, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, MELD-Na score re-defined by CysC, and AKI re-defined by CysC, but not conventional AKI defined by Scr, were significantly associated with in-hospital death. ROC analyses showed that baseline CysC level, eGFRScr, eGFRCysC, eGFRScr-CysC, original MELD-Na score defined by Scr, and MELD-Na score re-defined by CysC, but not baseline Scr level, could significantly predict the risk of in-hospital death. CONCLUSIONS: AKI re-defined by CysC may be superior for predicting the in-hospital mortality of cirrhotic patients with acute gastrointestinal bleeding.

Safety and Efficacy of Nonoperative Treatment in Esophageal Perforation Caused by Foreign Bodies.

INTRODUCTION: Esophageal foreign bodies are often treated by endoscopy, but the treatment of esophageal perforation caused by foreign bodies remains controversial. The purpose of this study was to investigate the safety and efficacy of nonoperative treatment of esophageal perforation caused by foreign bodies. METHODS: We retrospectively analyzed 270 patients admitted to our hospital for esophageal perforation caused by foreign bodies from January 2012 to December 2020, all of whom received nonoperative treatment. RESULTS: The mean age of the patients was 56 ± 17 years, and fish bones were the most common type of foreign body. A total of 61.2% of the perforations were in the cervical esophagus. All patients received nonoperative treatment initially, and the foreign body removal rate using endoscopy reached 97%. The perforation healing rate reached 94.8%, whereas 3 patients (1.1%) died during hospitalization. The median (range) duration of hospitalization was 4 days (3-6). Multivariable analysis showed age ≥ 66 years (odds ratio [OR]: 2.196; 95% confidence interval [CI]: 1.232-3.916; P = 0.008), men (OR: 1.934; 95% CI: 1.152-3.246; P = 0.013), and time to treatment (OR: 1.126; 95% CI: 1.027-1.233; P = 0.011) were independent risk factors for infection, whereas the risk of infection was lower when the foreign body type was fish bone (OR: 0.557; 95% CI: 0.330-0.940; P = 0.028). DISCUSSION: Nonoperative treatment is safe and effective for esophageal perforation caused by foreign bodies. Even if perforation is combined with infection, active nonoperative treatment can still achieve a good effect. Early intervention can effectively reduce the risk of infection and improve patient outcomes.

Effect of Body Mass Index on the Prognosis of Liver Cirrhosis.

Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis. Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI <18.5 kg/m2), normal weight (18.5 ≤ BMI < 23.0 kg/m2), and overweight/obese (BMI ≥ 23.0 kg/m2). Results: In the first part, Kaplan-Meier curve analyses demonstrated a significantly higher cumulative survival rate in the overweight/obese group than the normal weight group (p = 0.047). Cox regression analyses demonstrated that overweight/obesity was significantly associated with decreased long-term mortality compared with the normal weight group [hazard ratio (HR) = 0.635; 95% CI: 0.405-0.998; p = 0.049] but not an independent predictor after adjusting for age, gender, and Child-Pugh score (HR = 0.758; 95%CI: 0.479-1.199; p = 0.236). In the second part, Kaplan-Meier curve analyses demonstrated no significant difference in the cumulative survival rate between the overweight/obese and the normal weight groups (p = 0.094). Cox regression analyses also demonstrated that overweight/obesity was not significantly associated with in-hospital mortality compared with normal weight group (HR = 0.349; 95%CI: 0.096-1.269; p = 0.110). In both of the two parts, the Kaplan-Meier curve analyses demonstrated no significant difference in the cumulative survival rate between underweight and normal weight groups. Conclusion: Overweight/obesity is modestly associated with long-term survival in patients with cirrhosis but not an independent prognostic predictor. There is little effect of overweight/obesity on the short-term survival of patients with cirrhosis and with AGIB.

Risk Factors for Rebleeding after Emergency Endoscopic Treatment of Dieulafoy Lesion.

Background and Objective: Dieulafoy lesion is a rare, but life-threatening, cause of gastrointestinal hemorrhage, and endoscopic therapy is the preferred first-line treatment. The present study aims to analyze the risk factors for rebleeding after endoscopic hemostasis of gastroduodenal Dieulafoy lesion. Methods. A retrospective review of patients with Dieulafoy lesion who developed acute gastrointestinal bleeding and were treated primarily with endoscopic therapy from September 2014 to April 2019 was conducted. Results. A total of 133 patients with Dieulafoy lesion were included in the present study. The mean age of these patients was 56.05 ± 16.58 years, and 115 patients were male. Among these 133 patients, 26 patients developed rebleeding within 30 days of endoscopic therapy. The 30-day rebleeding rate for pure injection therapy (epinephrine, cyanoacrylate, or lauromacrogol injection alone), nonpure injection therapy (argon plasma coagulation, band ligation, and hemoclip application alone), and combination therapy (combination of any >2 methods) was 45.2%, 12.8%, and 11%, respectively. In the univariable analysis, endoscopic treatment, prothrombin time, gender, Rockall score, and leukocyte count were the risk factors for rebleeding. In the multivariable analysis, pure injection endoscopic treatment, white blood cells (>10 × 109/L), and prothrombin time >12 seconds were the independent risk factors for rebleeding. Conclusion. Patients who undergo pure injection endoscopic treatment and have a high leukocyte count (>10 × 109/L) or elevated prothrombin time (>12 seconds) have an increased risk of rebleeding within 30 days after endoscopic treatment for gastroduodenal Dieulafoy lesion. Combined endoscopic treatment is the most effective therapy to prevent rebleeding in gastroduodenal Dieulafoy lesion.

Terlipressin May Decrease In-Hospital Mortality of Cirrhotic Patients with Acute Gastrointestinal Bleeding and Renal Dysfunction: A Retrospective Multicenter Observational Study.

BACKGROUND: Acute gastrointestinal bleeding (GIB) rapidly reduces effective blood volume, thereby precipitating acute kidney injury (AKI). Terlipressin, which can induce splanchnic vasoconstriction and increase renal perfusion, has been recommended for acute GIB and hepatorenal syndrome in liver cirrhosis. Thus, we hypothesized that terlipressin might be beneficial for cirrhotic patients with acute GIB and renal impairment. METHODS: In this Chinese multi-center study, 1644 cirrhotic patients with acute GIB were retrospectively enrolled. AKI was defined according to the International Club of Ascites (ICA) criteria. Renal dysfunction was defined as serum creatinine (sCr) > 133 µmol/L at admission and/or any time point during hospitalization. Incidence of renal impairment and in-hospital mortality were the primary end-points. RESULTS: The incidence of any stage ICA-AKI, ICA-AKI stages 1B, 2, and 3, and renal dysfunction in cirrhotic patients with acute GIB was 7.1%, 1.8%, and 5.0%, respectively. The in-hospital mortality was significantly increased by renal dysfunction (14.5% vs. 2.2%, P < 0.001) and ICA-AKI stages 1B, 2, and 3 (11.1% vs. 2.8%, P = 0.011), but not any stage ICA-AKI (5.7% vs. 2.7%, P = 0.083). The in-hospital mortality was significantly decreased by terlipressin in patients with renal dysfunction (3.6% vs. 20.0%, P = 0.044), but not in those with any stage ICA-AKI (4.5% vs. 6.0%, P = 0.799) or ICA-AKI stages 1B, 2, and 3 (0.0% vs. 14.3%, P = 0.326). CONCLUSION: Renal dysfunction increased the in-hospital mortality of cirrhotic patients with acute GIB. Terlipressin might decrease the in-hospital mortality of cirrhotic patients with acute GIB and renal dysfunction. TRIAL REGISTRATION: NCT03846180 ( https://clinicaltrials.gov ).

Development of hyponatremia after terlipressin in cirrhotic patients with acute gastrointestinal bleeding: a retrospective multicenter observational study.

Background: Terlipressin can effectively control acute gastrointestinal bleeding (GIB) in cirrhotic patients by acting on the V1 receptors, but may lead to the development of dilutional hyponatremia by acting on the V2 receptors.Research design and methods: This retrospective multicenter study enrolled 674 cirrhotic patients with acute GIB in whom serum sodium concentrations were tested before and during the use of terlipressin. ΔSodium reduction ≥5 mmol/L, hyponatremia (sodium <130 mmol/L), and severe hyponatremia (sodium <125 mmol/L) during the use of terlipressin were evaluated. Logistic regression analyses were employed to identify the risk factors.Results: The incidence of Δsodium reduction ≥5 mmol/L, hyponatremia, and severe hyponatremia was 37.1%, 26.3%, and 13.0%, respectively. All of them were not significantly associated with in-hospital mortality (p = 0.973; p = 0.789; p = 0.887). In multivariate logistic regression analyses, the independent risk factors of Δsodium reduction ≥5 mmol/L were higher baseline sodium concentration, lower serum creatinine and prothrombin time, and larger dosage of terlipressin; those of hyponatremia were lower baseline sodium concentration and longer duration of terlipressin; those of severe hyponatremia were lower baseline sodium concentration and prothrombin time and longer duration of terlipressin.Conclusions: Hyponatremia was common in cirrhotic patients with acute GIB treated with terlipressin, but might not significantly increase the in-hospital mortality.

Cap-Assisted Endoscopic Sclerotherapy vs Ligation in the Long-Term Management of Medium Esophageal Varices: A Randomized Trial.

INTRODUCTION: Compared with endoscopic variceal ligation (EVL), cap-assisted endoscopic sclerotherapy (CAES) improves efficacy in the treatment of small esophageal varices (EVs) but has not been evaluated in the management of medium EVs. The aim of this study was to compare CAES with EVL in the long-term management of patients exhibiting cirrhosis with medium EVs and a history of esophageal variceal bleeding (EVB), with respect to variceal eradication and recurrence, adverse events, rebleeding, and survival. METHODS: Cirrhotic patients with medium EVs and a history of EVB were divided randomly into EVL and CAES groups. EVL or CAES was repeated each month until variceal eradication. Lauromacrogol was used as a sclerosant. Patients were followed up until 1 year after eradication. RESULTS: In total, 240 patients (age: 51.1 ± 10.0 years; men: 70.8%) were included and randomized to the EVL and CAES groups. The recurrence rate of EVs was much lower in the CAES group than in the EVL group (13.0% vs 30.7%, P = 0.001). The predictors for variceal recurrence were eradication by EVL (hazard ratio [HR]: 2.37, P = 0.04), achievement of complete eradication (HR: 0.27, P < 0.001), and nonselective ß-blocker response (HR: 0.32, P = 0.003). There was no significant difference in the rates of eradication, rebleeding, requirement for alternative therapy, and mortality or the incidence of complications between groups. DISCUSSION: CAES reduces the recurrence rate of EVs with comparable safety to that of EVL in the long-term management of patients presenting cirrhosis with medium EVs and a history of EVB.

Development and Validation of CAGIB Score for Evaluating the Prognosis of Cirrhosis with Acute Gastrointestinal Bleeding: A Retrospective Multicenter Study.

INTRODUCTION: Acute gastrointestinal bleeding (GIB) is a major cause of death in liver cirrhosis. This multicenter study aims to develop and validate a novel and easy-to-access model for predicting the prognosis of patients with cirrhosis and acute GIB. METHODS: Patients with cirrhosis and acute GIB were enrolled and randomly divided into the training (n = 865) and validation (n = 817) cohorts. In the training cohort, the independent predictors for in-hospital death were identified by logistic regression analyses, and then a new prognostic model (i.e., CAGIB score) was established. Area under curve (AUC) of CAGIB score was calculated by receiver operating characteristic curve analysis and compared with Child-Pugh, model for end-stage liver disease (MELD), MELD-Na, and neutrophil-lymphocyte ratio (NLR) scores. RESULTS: In the training cohort, hepatocellular carcinoma (HCC), diabetes, total bilirubin (TBIL), albumin (ALB), alanine aminotransferase (ALT), and serum creatinine (Scr) were independent predictors of in-hospital death. CAGIB score = diabetes (yes = 1, no = 0) × 1.040 + HCC (yes = 1, no = 0) × 0.974 + TBIL (µmol/L) × 0.005 - ALB (g/L) × 0.091 + ALT (U/L) × 0.001 + Scr (µmol/L) × 0.012 - 3.964. In the training cohort, the AUC of CAGIB score for predicting in-hospital death was 0.829 (95% CI 0.801-0.854, P < 0.0001), which was higher than that of Child-Pugh (0.762, 95% CI 0.732-0.791), MELD (0.778, 95% CI 0.748-0.806), MELD-Na (0.765, 95% CI 0.735-0.793), and NLR (0.587, 95% CI 0.553-0.620) scores. In the validation cohort, the AUC of CAGIB score (0.714, 95% CI 0.682-0.746, P = 0.0006) remained higher than that of Child-Pugh (0.693, 95% CI 0.659-0.725), MELD (0.662, 95% CI 0.627-0.695), MELD-Na (0.660, 95% CI 0.626-0.694), and NLR (0.538, 95% CI 0.503-0.574) scores. CONCLUSION: CAGIB score has a good predictive performance for prognosis of patients with cirrhosis and acute GIB.

Protective Effect of Ursolic Acid on the Intestinal Mucosal Barrier in a Rat Model of Liver Fibrosis.

Oxidative stress mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) plays an important role in intestinal mucosal barrier damage in various disease states. Recent evidence suggests that intestinal mucosal barrier damage and intestinal dysbiosis occur in mice with hepatic fibrosis induced by CCl4 or bile duct ligation. Another study showed that ursolic acid (UA) attenuates experimental colitis via its anti-inflammatory and antioxidant activities. The goal of this study was to investigate the effects of UA on the intestinal mucosal barrier in CCl4-induced hepatic fibrosis in rats and identify its associated mechanisms. Male Sprague-Dawley rats were randomly divided into the following 3 groups (n = 10/group): the control, CCl4 model and UA treatment groups. Rats were sacrificed at 72 h after the hepatic fibrosis model was established and assessed for liver fibrosis, intestinal injury, enterocyte apoptosis, bacterial translocation, system inflammation, intestinal oxidative stress, and tight junction protein and NOX protein expression. The results demonstrated that UA attenuated the following: (i) liver and intestinal pathological injury; (ii) cleaved caspase-3 expression in the ileal epithelial cells; (iii) serum lipopolysaccharide and procalcitonin levels; (iv) intestinal malondialdehyde levels; and (v) the expression of the NOX protein components NOX2 and P67phox in ileal tissues. Furthermore, our results suggested that UA improved intestinal dysbiosis and the expression of the tight junction proteins Claudin 1 and Occludin in the ileum of rats. These results indicate that UA has protective effects on the intestinal mucosal barrier in rats with CCl4-induced liver fibrosis by inhibiting intestinal NOX-mediated oxidative stress. Our findings may provide a basis for further clinical studies of UA as a novel and adjuvant treatment to cure liver fibrosis.

Interaction Mechanisms Between the NOX4/ROS and RhoA/ROCK1 Signaling Pathways as New Anti- fibrosis Targets of Ursolic Acid in Hepatic Stellate Cells.

BACKGROUND: Studies have shown that both NOX4 and RhoA play essential roles in fibrosis and that they regulate each other. In lung fibrosis, NOX4/ROS is located upstream of the RhoA/ROCK1 signaling pathway, and the two molecules are oppositely located in renal fibrosis. Currently, no reports have indicated whether the above mechanisms or other regulatory mechanisms exist in liver fibrosis. OBJECTIVES: To investigate the effects of the NOX4/ROS and RhoA/ROCK1 signaling pathways on hepatic stellate cell (HSC)-T6 cells, the interaction mechanisms of the two pathways, and the impact of UA on the two pathways to elucidate the role of UA in the reduction of hepatic fibrosis and potential mechanisms of HSC-T6 cell proliferation, migration, and activation. METHODS: Stable cell lines were constructed using the lentiviral transduction technique. Cell proliferation, apoptosis, migration, and invasion were examined using the MTS, TdT-mediated dUTP nick-end labeling, cell scratch, and Transwell invasion assays, respectively. The DCFH-DA method was used to investigate the ROS levels in each group. RT-qPCR and western blotting techniques were utilized to assess the mRNA and protein expression in each group. CoIP and the Biacore protein interaction analysis systems were used to evaluate protein interactions. RESULTS: The NOX4/ROS and RhoA/ROCK1 signaling pathways promoted the proliferation, migration, and activation of HSCs. UA inhibited cell proliferation, migration, and activation by inhibiting the activation of the two signaling pathways, but the mechanism of apoptosis was independent of these two pathways. The NOX4/ROS pathway was upstream of and positively regulated the RhoA/ROCK1 pathway in HSCs. No direct interaction between the NOX4 and RhoA proteins was detected. CONCLUSION: The NOX4/ROS and RhoA/ROCK1 signaling pathways are two critical signaling pathways in a series of behavioral processes in HSCs, and NOX4/ROS regulates RhoA/ROCK1 through an indirect pathway to control the activation of HSCs. Additionally, NOX4/ROS and RhoA/ROCK1 constitute a new target for UA antifibrosis treatment.

IL-25 protects against high-fat diet-induced hepatic steatosis in mice by inducing IL-25 and M2a macrophage production.

Interleukin (IL)-25 is a cytokine that has previously been shown to have a protective role against nonalcoholic fatty liver disease (NAFLD), which is associated with the induction of M2 macrophage differentiation. However, the direct relationships between IL-25 expression regulation, M2 induction and NAFLD remain unknown. In this study, we demonstrate that IL-25 promotes hepatic macrophage differentiation into M2a macrophages both in vivo and in vitro via the IL-13/STAT6 pathway. M2 macrophages that were differentiated in vitro were able to ameliorate high-fat diet HFD-induced hepatic steatosis. Furthermore, we found that IL-25 treatment, both in vitro and in vivo, promotes direct binding of STAT6 to the IL-25 gene promoter region. This binding of STAT6 in response to IL-25 treatment also resulted in the increase of IL-25 expression in hepatocytes. Together, these findings identify IL-25 as a protective factor against HFD-induced hepatic steatosis by inducing an increase of IL-25 expression in hepatocytes and through promotion of M2a macrophage production.

External validation of Liaoning score for predicting esophageal varices in liver cirrhosis: a Chinese multicenter cross-sectional study.

BACKGROUND: Our previous study developed Liaoning score as a non-invasive approach for predicting esophageal varices (EVs) in liver cirrhosis. This nationwide multicenter cross-sectional study aimed to externally validate the diagnostic accuracy of Liaoning score and further evaluate its performance for predicting high-risk EVs. METHODS: Cirrhotic patients with acute gastrointestinal bleeding (GIB) without history of endoscopic variceal therapy who underwent endoscopic examinations at their admissions were included. Liaoning score and several non-invasive liver fibrosis scores, including aspartate aminotransferase (AST) to platelet ratio index (APRI), AST to alanine aminotransferase ratio (AAR), fibrosis 4 index (FIB-4), King, and Lok scores, were evaluated. Area under curves (AUCs), cut-off value, sensitivity, and specificity were calculated. RESULTS: Overall, 612 patients were included. The prevalence of EVs and high-risk EVs was 96.2% and 95.6%, respectively. In overall patients, the AUCs of Liaoning score for predicting EVs and high-risk EVs were higher than non-invasive liver fibrosis scores (0.737 versus 0.626-0.721; 0.734 versus 0.611-0.719). The cut-off value of Liaoning score for high-risk EVs was 0.477 with a sensitivity of 81.96% and a specificity of 65.22%. In patients with hematemesis, Liaoning score could significantly predict EVs and high-risk EVs (AUCs =0.708 and 0.702, respectively), but not non-invasive liver fibrosis scores. The cut-off value of Liaoning score for high-risk EVs was 0.437 with a sensitivity of 83.16% and a specificity of 60%. CONCLUSIONS: Liaoning score should be a non-invasive alternative for predicting EVs and high-risk EVs in cirrhotic patients with acute GIB.

N-Acetylcysteine Reduces ROS-Mediated Oxidative DNA Damage and PI3K/Akt Pathway Activation Induced by Helicobacter pylori Infection.

BACKGROUND: H. pylori infection induces reactive oxygen species- (ROS-) related DNA damage and activates the PI3K/Akt pathway in gastric epithelial cells. N-Acetylcysteine (NAC) is known as an inhibitor of ROS; the role of NAC in H. pylori-related diseases is unclear. AIM: The aim of this study was to evaluate the role of ROS and the protective role of NAC in the pathogenesis of H. pylori-related diseases. METHOD: An in vitro coculture system and an in vivo Balb/c mouse model of H. pylori-infected gastric epithelial cells were established. The effects of H. pylori infection on DNA damage and ROS were assessed by the comet assay and fluorescent dichlorofluorescein assay. The level of PI3K/Akt pathway-related proteins was evaluated by Western blotting. The protective role of N-acetylcysteine (NAC) was also evaluated with in vitro and in vivo H. pylori infection models. RESULTS: The results revealed that, in vitro and in vivo, H. pylori infection increased the ROS level and induced DNA damage in gastric epithelial cells. NAC treatment effectively reduced the ROS level and inhibited DNA damage in GES-1 cells and the gastric mucosa of Balb/c mice. H. pylori infection induced ROS-mediated PI3K/Akt pathway activation, and NAC treatment inhibited this effect. However, the gastric mucosa pathological score of the NAC-treated group was not significantly different from that of the untreated group. Furthermore, chronic H. pylori infection decreased APE-1 expression in the gastric mucosa of Balb/c mice. CONCLUSIONS: An increased ROS level is a critical mechanism in H. pylori pathogenesis, and NAC may be beneficial for the treatment of H. pylori-related gastric diseases linked to oxidative DNA damage.

The effect of virulence genotypes of Helicobacter pylori on eradication therapy in children.

Background/Aim: It is important to eradicate Helicobacter pylori at an early stage in patients during childhood to potentially prevent the development of H. pylori-related diseases. Studies have demonstrated that the virulence genotype of H. pylori influences the efficacy of eradication therapy. The efficacy of triple therapy has decreased significantly, which has seriously affected the clinical outcome of children with H. pylori infection. In this study we aimed to investigate the influence of virulence genotypes of H. pylori on triple eradication therapy in children. Patients and Methods: H. pylori strains were isolated from the gastric antrum mucosa in children with upper gastrointestinal symptoms. Polymerase chain reaction (PCR) was conducted to determine the H. pylori cagA, vacA, and iceA genotypes. All patients with H. pylori infection were administered 14-day triple therapy. After drug withdrawal for at least 4 weeks, the 13C-urea breath test (13C-UBT) was used to observe the therapeutic effect of H. pylori eradication. The eradication rates were evaluated by intention-to-treat (ITT) and per-protocol (PP) analyses. Results: A total of 107 patients were enrolled in this study. Nine patients were lost to follow-up, and 98 patients were administered eradication therapy. Based on ITT and PP analyses, the H. pylori eradication rate was 64.5% (69/107) and 70.4% (69/98), respectively. Among the successful eradication groups, the cagA-positive, vacA s1a, vacA s1c, vacA m1, vacA m2, iceA 1, and iceA 2 genes were identified in 72.8%, 68.1%, 76.9%, 60.0%, 74.6%, 71.8%, and 75.0% of strains, respectively. Of the unsuccessful eradication groups, the cagA-positive, vacA s1a, vacA s1c, vacA m1, vacA m2, iceA 1, and iceA 2 genes were identified in 27.2%, 31.9%, 23.1%, 40.0%, 25.4%, 28.2%, and 25.0% of strains, respectively. No statistically significant differences were noted in the detection rate of the H. pylori genotypes between the H. pylori successful and unsuccessful eradication groups (P > 0.05). Conclusions: The cagA, vacA, and iceA genotypes of H. pylori are not associated with the efficacy of omeprazole-based triple therapy on the eradication of H. pylori infection in children.

Ursolic acid ameliorates CCl4-induced liver fibrosis through the NOXs/ROS pathway.

Liver fibrosis is a reversible wound-healing response that occurs after liver injury. NADPH oxidases (NOXs) and reactive oxygen species (ROS) which are expressed in hepatocytes (HCs), hepatic stellate cells (HSCs), and Kupffer cells (KCs) play an important role in the development of hepatic fibrosis. In in vitro studies, we had shown that ursolic acid (UA) could reverse liver fibrosis by inhibiting the activation of NOX-mediated fibrotic signaling networks in HSCs. In this study, we verified that UA could alleviate CCl4-induced liver fibrosis by reducing the expression of NOXs/ROS in HCs, HSCs, KCs. Meanwhile, the phagocytic index α and clearance index K which represent phagocytosis of KCs were unchanged. Together, all our data demonstrated that UA induced the proliferation of HCs, promoted apoptosis in HSCs, and prevented activation of KCs in vivo by reducing the expression of NOXs/ROS in HCs, HSCs, KCs. Besides, UA had no effect on the host defense function.