Association between serum omentin-1 and mucosal disease activity in patients with ulcerative colitis.

PURPOSE: Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC. STUDY DESIGN: A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity. RESULTS: Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5-72.6 versus healthy controls, 103.5 interquartile range: 48.3-156.2 ng/ml; P < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC. CONCLUSIONS: These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC.

Network meta-analysis of different dosages of esomeprazole and rabeprazole for the treatment of Helicobacter pylori.

BACKGROUND: The optimal dosage of new generation proton pump inhibitors (PPIs) in increasing cure rate of Helicobacter pylori (H. pylori) infection remains unclear. This network meta-analysis aimed to comprehensively evaluate the comparative efficacy and safety of different dosages of esomeprazole and rabeprazole in treating H. pylori infection. MATERIALS AND METHODS: We searched PubMed, Cochrane Central Registry for Controlled Trials (CENTRAL), and EMBASE for randomized controlled trials (RCTs) involving esomeprazole and rabeprazole with different dosages from their inception through 31 March, 2022. After data extraction and risk of bias assessment, network meta-analyses were conducted using STATA 14.0. We calculated the surface under the cumulative ranking (SUCRA) to rank all regimens. RESULTS: Thirteen studies including 14 reports were included. Six dosages including rabeprazole 10 mg (R10bid), 20 mg (R20bid), and 40 mg (R40bid) twice daily and esomeprazole 20 mg (E20bid) and 40 mg (E40bid) twice daily as well as 40 mg once daily (E40qd) were identified. Network meta-analysis suggested that R40bid ranked highest in the cure rate (83.8%), followed by E40bid (82.6%), E20bid (54.5%), R20bid (34.2%), R10bid (22.8%), and E40qd (22.0%); however, E40qd ranked highest in adverse events (91.1%), followed by R20bid (57.8), R10bid (57.6%), E20bid (38.9%), E40bid (34.2%), and R40bid (20.4%). Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: Based on the available evidence, R40bid and E40bid might be the optimum dosage to increase the cure rate; however, E40qd was superior for adverse events. Nevertheless, future studies should validate the results from this network meta-analysis.

Clinical significance of a novel uric-acid-based biomarker in the prediction of disease activity and response to infliximab therapy in Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is an inflammatory bowel disease marked by a chronic remission-relapse cycle. Biomarkers are critical to reflect the bowel wall inflammation and detect the treatment response. Here, we investigated a new index-the ratio of neutrophil to uric acid (NUR)-as a predictor of CD activity and responses to infliximab (IFX) treatment. METHODS: Clinical and laboratory data were retrieved for CD patients and healthy control subjects from an electronic medical records database. Disease and endoscopic activity were determined using the Crohn's Disease Activity Index (CDAI) and Simple Endoscopic Score for Crohn's Disease (SES-CD), respectively. RESULTS: We found firstly that NUR was remarkably higher in CD patients (n = 162) than controls (n = 170) (0.27 ± 0.10 vs. 0.19 ± 0.04, p < .0001). NUR was positively correlated with disease activity and prior to treatment, it was lower in CD patients who responded to IFX than in those who did not (0.25 ± 0.07 vs. 0.38 ± 0.12, p = .0019). Pre-treatment NUR was effective in predicting the patients' responses to IFX (AUC = 0.8469, p = .0034). CONCLUSION: The results of this study support the utility of NUR for detecting CD activity and predicting the response to IFX treatment.

Sauchinone ameliorates intestinal inflammation and promotes Th17 cell production of IL-10 via Blimp-1.

Inflammatory bowel disease (IBD) is characterized by chronic, unpredictable relapsing and inflammatory disease of the gastrointestinal tract. Daily diet patterns have long been one of the most important hotspots for IBD therapeutic strategies. Sauchinone (SAU), a key bioactive lignin isolated from the roots of the herb Saururus chinensis, has been known to play an anti-inflammatory role in several diseases. However, its effect on IBD has not yet been investigated. In the current study, we established 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice and treated them with SAU. Flow cytometric analysis was performed to determine the phenotype of T cells in the lamina propria. qRT-PCR and ELISA were performed to measure cytokine transcript and protein levels, respectively. We found that SAU ameliorated TNBS-induced mouse colitis and inflammatory responses in mucosal tissues and peripheral blood CD4+ T cells from IBD patients. SAU significantly suppressed Th17 differentiation but facilitated IL-10 production, and SAU-treated Th17 cells exhibited inhibitory functions in vitro and in vivo. Mechanistically, we demonstrated that SAU induced Blimp-1 expression (encoded by Prdm1) in Th17 cells, and SAU failed to increase IL-10 production in Prdm1-knockout Th17 cells. Our data reveal an uncharacterized mechanism through which SAU regulates intestinal inflammation and Th17 differentiation.

PPI-amoxicillin dual therapy for Helicobacter pylori infection: An update based on a systematic review and meta-analysis.

BACKGROUND AND AIMS: The efficacy of PPI-amoxicillin dual therapy (high-dose dual therapy) in the eradication of Helicobacter pylori is controversial. We aimed to investigate whether PPI-amoxicillin dual therapy is effective. METHODS: We searched several publication databases for randomized controlled trials (RCTs) that compared PPI-amoxicillin dual therapy with controls up to March 2019. Meta-analyses of eradication rates were performed using random-effects models. RESULTS: Data from twelve RCTs including 2249 patients suggested that PPI-amoxicillin dual therapy and the current mainstream guidelines-recommended therapies achieved similar efficacy (83.2% vs 85.3%, risk ratio [RR]: 1.00, 95% CI 0.97-1.03, intention-to-treat analysis), (87.5% vs 90.1%, RR: 0.98, 95% CI 0.95-1.02, per-protocol analysis), and compliance (94.3% vs 93.5%, RR: 1.11, 95% CI 0.78-1.59), but side effects were less likely in the dual therapy (12.9% vs 28.0%, RR: 0.53, 95% CI 0.37-0.76). Further subgroup analyses showed that the seven RCTs (1302 patients) that reported antimicrobial susceptibility test results also showed that PPI-amoxicillin dual therapy and the current guidelines-recommended therapies achieved similar efficacy, and PPI-amoxicillin dual therapy was as effective for rescue therapy (RR: 0.97, 95% CI 0.89-1.05) as for first-line treatment (RR: 0.97, 95% CI 0.93-1.02). CONCLUSIONS: Compared with the current mainstream guidelines-recommended therapies, PPI-amoxicillin dual therapy has the same efficacy and compliance, and generally PPI-amoxicillin dual therapy causes fewer side effects.

Ascl2 facilitates IL-10 production in Th17 cells to restrain their pathogenicity in inflammatory bowel disease.

Inflammatory bowel disease (IBD) has been well-documented as a chronic gastrointestinal autoimmune disease, but its etiology remains to be elusive. Ascl2 (achaete-scute complex homologue 2), identified as a homologue of the Drosophila achaete-scute gene, has been shown to play an essential for the pathogenesis of autoimmune diseases and cancers. However, whether it is associated with the pathogenesis of IBD remains unclear. Here, we demonstrated that Ascl2 was greatly down-regulated in human IBD and experimental colitis. Interestingly, CD4+ T cell expression of Ascl2 was regulated by intestinal microbiota. Moreover, we revealed that Ascl2 inhibited the differentiation of Th17 cells and restrained their pathogenicity through facilitating IL-10 production. We further showed that Blimp-1 might be involved in the Ascl2-inducing IL-10 expression in CD4+ T cells under Th17 differentiating condition. Notably, lentivirus-mediated overexpression of Ascl2 remarkably alleviated the severity of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis in mice, with decreased level of colonic IL-17A. Our findings demonstrated an unappreciated mechanism whereby Ascl2 negatively modulates pathogenic Th17 cell differentiation via promoting IL-10 production, and alleviates intestinal inflammation. Thus, Ascl2 may serve as a novel therapeutic target of IBD.

MicroRNA-425 facilitates pathogenic Th17 cell differentiation by targeting forkhead box O1 (Foxo1) and is associated with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic autoimmune disease, and its pathogenesis remains mostly unknown. MicroRNAs (miRs) has drawn much attention as a crucial regulator of autoimmune diseases. In this study, we demonstrated, for the first time, that miR-425 was significantly up-regulated in peripheral blood mononuclear cells (PBMC) and mucosa of patients with IBD. In note, T helper (Th) 17 cells were found to be the major source of miR-425 expression. Using gain-of-function approaches, we demonstrated that miR-425 could facilitate the differentiation of CD4+ T cells into Th17 lineage. In addition, forkhead box O1 (Foxo1) was identified as a novel target gene of miR-425, which was able to inhibit Th17 cell differentiation, and it was observed to be markedly decreased in PBMC and mucosa of patients with IBD. Notably, in vivo inhibition of miR-425 significantly alleviated the disease severity of TNBS-induced colitis in mice, with down-regulated levels of IL-17A. Our data reveal a novel mechanism in which the elevated miR-425 in IBD mediates pathogenic Th17 cell generation through down-regulation of Foxo1. In vivo blockade of miR-425 may serve as a novel therapeutic approach in the treatment of IBD.

Satisfaction, burnout and intention to stay of emergency nurses in Shanghai.

BACKGROUND: Stability of the nursing workforce is considered a key factor for high-quality healthcare. Satisfaction and burnout are reported to be closely related to staff turnover. This study investigates satisfaction and burnout of ED nurses in Shanghai and association of these factors with intention to stay on the job. METHODS: This is a cross-sectional descriptive survey study conducted between October and December 2015. Our own questionnaire and the Maslach Burnout Inventory were used to construct the survey. The convenience sampling method was used. The survey targeted ED nurses in 30 Shanghai hospitals. Data were analysed using descriptive, non-paired t-tests, analysis of variance and multivariable logistic regression to decipher possible causes for burnout and identify reasons for continued interest in staying on the job by ED nurses. RESULTS: Of 1137 nurses who received surveys, 976 (87%) responded. Among the respondents, 75% reported being very satisfied or satisfied with their jobs, but there was a high level of burnout, and 22.5% of the nurses expressed their intention to leave the ED within the following year (p<0.05). Nurses' satisfaction and burnout were associated with intention to leave. Salary, nurse-patient relationships, nurse staffing and work environment were areas where nurses were less satisfied, while group cohesion was associated with greater satisfaction. CONCLUSION: ED nurses in Shanghai report a high level of burnout, which is associated with an intention to leave their jobs. Interventions are needed to improve satisfaction and reduce burnout to maintain the stability of the nursing workforce.

Clinical Utility of the Neutrophil-to-Bilirubin Ratio in the Detection of Disease Activity in Ulcerative Colitis.

Background: Ulcerative colitis (UC) is a chronic relapsing remitting form of inflammatory bowel disease (IBD). Current disease monitoring includes evaluation of symptoms, fecal calprotectin, and colonoscopy. Due to limited availability of the latter two modalities in China, we sought a readily available, inexpensive, disease monitoring laboratory assessment. We recently identified a novel serological index (the neutrophil-to-bilirubin ratio, NBR) for monitoring disease activity in Crohn's disease. However, the clinical significance has not been evaluated in UC. Here, we aimed to verify the hypothesis that NBR might be useful in monitoring clinical and endoscopic activity in patients with UC. Methods: To test our hypothesis, we conducted a single-center, retrospective study including a total of 188 patients with UC and 145 non-IBD controls. NBR was calculated to determine its practical value in monitoring disease activity (including clinical and endoscopic activity). Disease activity of UC was determined by the partial Mayo score and the Mayo endoscopic score (MES) system. Results: NBR was significantly higher in patients with UC than that in controls (12.10, IQR: 9.85-16.69 versus 5.06, IQR: 3.94-6.55; p < 0.001) and showed positive correlations with clinical and endoscopic disease activity in UC. Additionally, NBR was significantly lower in patients with endoscopic mucosal healing (MH) than that in those without endoscopic MH (8.81, IQR: 6.67-11.67 versus 13.51, IQR: 11.04-18.71; p < 0.001). Serial evaluation of NBR in a subset of patients demonstrated that NBR was significantly decreased during the MH stage compared with that during the endoscopically active stage. Conclusion: Our study suggests that NBR may be a promising candidate for assessing disease activity in UC, with potential for widespread clinical use and significant clinical implications.

Clinical significance of the C-reactive protein-to-bilirubin ratio in patients with ulcerative colitis.

Background: Ulcerative colitis (UC) is a chronic relapsing remitting disease of the colon. Appropriate monitoring of the disease status is necessary for patients to adopt optimal therapy and obtain a better prognosis. Finding an ideal non-invasive biomarker, which is suitable for long-term monitoring in clinical settings will bring a significant benefit to the individualized management of patients with UC. The aim of this study is to determine the clinical significance of a novel optimizing serological biomarker by integrating C-reactive protein (CRP) and bilirubin levels in monitoring disease activity. Methods: A total of 182 patients with UC were retrospectively enrolled. Clinical characteristics and laboratory parameters of the subjects were retrieved from the electronic medical record database of our hospital. The CRP-to-bilirubin ratio (CBR) was computed for clinical activity of UC defined by the partial Mayo score and endoscopic activity by the Mayo endoscopic score (MES). Results: CBR was significantly elevated in patients with UC than that in healthy controls. Patients with clinically or endoscopically active UC showed evidently higher CBR levels compared to those with inactive disease, even in a subset of patients with normal CRP levels. Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CBR was higher than that of CRP or bilirubin alone for determining clinical remission and endoscopic mucosal improvement. Furthermore, CBR levels were significantly decreased when patients achieved mucosal improvement compared with when they had active endoscopic inflammation. Conclusion: CBR could be useful to reflect disease activity in patients with UC.

Gut-licensed ß7+ CD4+ T cells contribute to progressive retinal ganglion cell damage in glaucoma.

Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4+ T cells expressing a gut-homing integrin ß7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, ß7+ CD4+ T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced ß7+ CD4+ T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing ß7+ CD4+ T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing ß7+ CD4+ T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed ß7+ CD4+ T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma.

A Novel Neutrophil-Based Biomarker to Monitor Disease Activity and Predict Response to Infliximab Therapy in Patients With Ulcerative Colitis.

Background: Ulcerative colitis (UC) is characterized by refractory and recurrent mucosal inflammation, leading to a substantial healthcare burden. Diagnostic biomarkers predicting disease activity and treatment response remain elusive. To evaluate the application value of a novel neutrophil-based index (the neutrophil-to-albumin ratio, NAR) as a novel diagnostic biomarker in patients with UC and a predictive marker for disease activity and response to infliximab (IFX) therapy. Methods: Clinical characteristics and laboratory parameters of enrolled subjects (patients with UC and healthy controls) were retrieved from the electronic medical record database of our hospital. Serum cytokine and fecal calprotectin levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosal expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR). Results: We found that NAR, which had not yet been explored in UC, was significantly increased in patients with UC (n = 146) compared to that in controls (n = 133) (1.95 ± 0.41 vs. 1.41 ± 0.23, p < 0.0001). NAR showed a positive association with the disease activity and inflammatory load in patients with UC. Pre-treatment NAR was significantly lower in IFX responders than that in non-responders (2.18 ± 0.29 vs. 2.44 ± 0.21, p = 0.0118), showing a significant ability to discriminate initial responders from primary non-responders to IFX induction therapy (AUC = 0.7866, p = 0.0076). Moreover, pre-treatment NAR predicted postinduction serum IFX trough level. Conclusion: Our study provides evidences to utilize NAR in the diagnosis, activity monitoring, and IFX response prediction in patients with UC.

Carnosol Maintains Intestinal Barrier Function and Mucosal Immune Homeostasis in DSS-Induced Colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease, characterized by recurrent flares of mucosal inflammation, which is limited in the colon and rectum. Compromised epithelial barrier functions have been indicated in the initiation of UC. Carnosol (CA), a natural active ortho-diphenol diterpene compound, is one of the active ingredients in plants such as rosemary and sage. The anti-inflammatory and anti-oxidative effects of CA have been reported in several animal models, but its effect on mucosal inflammation remains elusive. We established a mouse experimental colitis model characterized by epithelial barrier destruction using dextran sulfate sodium (DSS). CA was intraperitoneally administrated. Flow cytometry was performed to determine phenotypes of intraepithelial lymphocytes and lamina propria cells. qRT-PCR was used for gene expression. ER stress in the colon was determined by immunofluorescence staining and qRT-PCR. Thapsigargin was used to induce ER stress in HCT-116 cells in vitro. We found CA significantly alleviated DSS-induced colitis in mice marked by relieved clinical symptoms and colonic pathological damage. Inflammatory cell infiltration and cytokine expression in the colon were suppressed by CA during colitis. Furthermore, CA restored epithelial barrier functions and intestinal intraepithelial lymphocyte (IEL) homeostasis in mice with DSS insults. Mechanistically, we induced endoplasmic reticulum (ER) stress in HCT-116 cells (an intestinal epithelial cell line) with thapsigargin, and CA reversed this effect. In addition, we collected inflamed mucosal biopsies from 23 patients with UC, and cultured overnight with or without CA, showing CA significantly reduced expression of ER stress signaling molecule and pro-inflammatory agents. Our data demonstrate that CA acts as an effective drug for experimental colitis and maintains proper epithelial barrier functions via suppressing epithelial ER stress, providing new evidence that CA might be a promising therapeutic candidate for UC.

Clinical Significance of Novel Neutrophil-Based Biomarkers in the Diagnosis and Prediction of Response to Infliximab Therapy in Crohn's Disease.

With the increasing incidence and prevalence, Crohn's disease (CD) has become one of the most challenging diseases in both diagnosis and treatment of gastroenterology. Evaluation of the disease activity and mucosal healing guides clinical decisions regarding subsequent therapy for CD. In this study, we enrolled a total of 144 patients with CD and 239 healthy controls were enrolled. Clinical characteristics and laboratory parameters of enrolled subjects were retrieved from the electronic medical record database of our hospital. Serum cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). Mucosa expression levels of inflammatory agents were measured by quantitative RT-PCR (qRT-PCR). We identified two neutrophil-based indexes, the neutrophil-to-albumin ratio (NAR) and neutrophil-to-bilirubin ratio (NBR), both of which had not yet been explored in CD or UC. NAR and NBR were significantly increased in patients with CD compared to those in healthy controls, and both indexes showed significantly positive correlations with CD activity and inflammatory load. In note, NAR and NBR showed better performance than blood neutrophil percentage, serum albumin, or bilirubin alone in these scenarios. More importantly, both NAR and NBR discriminated CD patients who completely or partially responded to infliximab (IFX) induction therapy from those with primary non-response. Our observations suggest that NAR and NBR may serve as promising biomarkers in the diagnosis and prediction of response to IFX therapy in CD.

CO2 Is Beneficial to Gut Microbiota Homeostasis during Colonoscopy: Randomized Controlled Trial.

BACKGROUND: Many studies have reported minor complications and disturbance of the gut microbiota after colonoscopy. Compared with air, carbon dioxide (CO2) insufflation could decrease minor complications, but its impact on gut microbiota remains unknown. METHODS: Thirty-eight healthy subjects were assessed and twenty were randomized to receive either CO2 or air insufflation during colonoscopy. Neither the participants nor the staff involved in the follow-up knew which gas was used. Minor complications were assessed using symptom scores. Fecal samples were collected at eight time-points for microbiome analysis by full-length 16S rRNA gene amplicon analysis. RESULTS: Baseline characteristics were similar in both groups. The recovery of minor complications after colonoscopy was faster in the CO2 group (the day of the colonoscopy) than in the air group (the day after the colonoscopy). There was no significant reduction in alpha diversity (species richness) of the first stool after colonoscopy in the CO2 group (115.0 ± 32.81 vs. 97.4 ± 42.31, p = 0.28) compared with the air group (123.8 ± 37.25 vs. 84.8 ± 31.67, p = 0.04). However, there were no differences in beta diversity between the groups. Linear discriminant analysis effect size (LEfSe) analysis indicated that anaerobic probiotics such as Bacteroides caccae, Bacteroides finegoldii and Bacteroides thetaiotaomicron were more abundant in the CO2 group than in the air group within 14 days after colonoscopy. On the contrary, the content of Escherichiacoli, Ruminococcus torques and Ruminococcus guavus was higher in the air group. CONCLUSIONS: CO2 is beneficial to gut microbiota homeostasis during colonoscopy in healthy subjects. The effects in patients with different diseases need to be further studied.

The prospective multiple-centre randomized controlled clinical study of high-dose amoxicillin-proton pump inhibitor dual therapy for H. pylori infection in Sichuan areas.

OBJECTIVES: To evaluate the safety and efficacy of high-dose amoxicillin-proton pump inhibitor dual therapy, and to provide a new eradication regimen as a first-line option for patients with H. pylori infection. METHODS: A total of 971 H. pylori positive patients who received initial treatment were recruited from March to August 2020, and randomly divided into treatment group and control group. The treatment group received of 20 mg esomeprazole four times daily and 750 mg amoxicillin four times daily for 14 days. Control group received of 220 mg bismuth potassium citrate twice daily, 20 mg esomeprazole twice daily, 1000 mg amoxicillin twice daily and 250 mg clarithromycin capsule twice daily for 14 days. Four weeks after the end of treatment, the urea breath test was reviewed to detect whether H. pylori was eradicated. RESULTS: There were no statistical differences in age, gender, the total clinical symptom scores before and after initial treatment, the compliance, and the degree of remission of symptoms before and after initial treatment between the two groups. The eradication rates of H. pylori between dual therapy and quadruple therapy were 88.31% and 85.26% (p=.158) by intention-to-treat (ITT) analysis, 88.66% and 85.44% (p=.186) by modified intention-to-treat (mITT) analysis, and 91.63% and 90.60% (p=.116) by PP analysis, respectively. Adverse events in dual therapy group were significantly lower than quadruple therapy group (13.3% vs. 28.2% (p<.01)). CONCLUSIONS: For the initial treatment of H. pylori infection, the high-dose dual therapy regimen has the same efficacy as the bismuth-containing quadruple therapy regimen, good compliance, less adverse reactions and high safety, so it can be recommended as the empirical first-line treatment regimen for the eradication of H. pylori (KY2019173).

The Serum Citrulline and D-Lactate are Associated with Gastrointestinal Dysfunction and Failure in Critically Ill Patients.

OBJECTIVE: This study attempted to screen and combine effective biomarkers to analyse the association between these biomarkers and gastrointestinal failure (GIF) in critically ill patients. METHODS: A total of 110 critically ill patients with acute gastrointestinal injury (AGI) admitted to ICU were enrolled. The AGI grade was determined by the AGI classification proposed by ESICM. There were 67 patients in gastrointestinal dysfunction (GID) group (AGI grade II), 43 patients in GIF group (AGI grade III-IV), and 41 healthy adults in healthy control (HC) group. APACHE II and SOFA score were used to evaluate the disease severity. Peripheral blood samples of patients were collected within 24 hours of admission to the ICU (prior-treatment) and after the conventional medication therapy for 7 consecutive days (post-treatment). Citrulline serum level was detected by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and D-lactate and lipopolysaccharide (LPS) serum levels were measured by ELISA. Pearson correlation, logistic regression, and ROC curve analysis were used. RESULTS: Patients with GID or GIF had lower serum level of citrulline, while higher levels of D-lactate and LPS than HC. Compared with GID patients, serum level of citrulline was reduced, while D-lactate and LPS were elevated in GIF patients. Correlation analysis displayed that serum levels of citrulline, D-lactate, and LPS were associated with the APACHE II and SOFA score in patients with GID or GIF. Logistics regression analysis showed that citrulline and D-lactate were risk for both GID and GIF. ROC curve analysis exhibited that combination of citrulline and D-lactate had relatively high value to distinguish GID from HC, GIF from GID, and GIF from HC. CONCLUSION: Serum citrulline and D-lactate were associated with severity of GIF, combination of citrulline and D-lactate improved the diagnostic efficacy to identify GIF in critically ill patients.

[Reduced expression of miR-218 and its significance in gastric cancer].

OBJECTIVE: To investigate the expression and function of miR-218 in gastric cancer. METHODS: miR-218 levels were evaluated in 20 non-cardia gastric cancer tissues using TaqMan stem-loop real-time PCR analysis. Pre-miR-218 and anti-miR-218 inhibitor were used to change the miR-218 expression level and examine its effects on cell proliferation, apoptosis, cell cycle and cell invasion. RESULTS: Comparing with the corresponding normal tissues, miR-218 expression was significantly reduced in the gastric cancer tissue (P < 0.01). Forced expression of miR-218 increased apoptosis in AGS cells. The proportion of apoptosis cells induced by transfection of pre-miR-218 was greater than that induced by control (21.6% vs. 10.4%, P = 0.032). Pre-miR-218 resulted in a significantly decreased cell growth activity (P < 0.01) and cell invasion (P < 0.05) of AGS cells compared with that of the control. CONCLUSION: miR-218 expression is reduced in gastric cancer. miR-218 may function as a tumor suppressor in gastric carcinoma.

High dose dual therapy versus bismuth quadruple therapy for Helicobacter pylori eradication treatment: A systematic review and meta-analysis.

AIM: The aim of this study was to perform a systematic review and meta-analysis on high-dose dual therapy (HDDT) versus bismuth quadruple therapy (BQT) for Helicobacter pylori infection. METHODS: Comparing HDDT to BQT were identified from PubMed, EMBASE, Cochrane library, CNKI, and Wanfang databases in Chinese up to March 2018. Statistical analyses were conducted using Review Manager 5.3 to compare the efficacy and side effects of these 2 therapies for H pylori infection. Dichotomous data were pooled to score the relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Four randomized clinical trials (RCTs) including 829 patients with a diagnosis of H pylori infection were assessed. Overall the meta-analysis showed that both HDDT and BQT achieved similar efficacy of intention-to-treat (ITT) eradication rate, 85.5% versus 87.2%, RR 1.01 (95% CI: 0.96-1.06), P = .63, and of per-protocol (PP) eradication rate, 88.4% versus 91.5%, RR 1.00 (95% CI: 0.96-1.04), P = .99, and adherence 97.8% versus 95.0%, RR 1.01 (95% CI: 0.99-1.04), P = .32, but side effects were more likely in BQT (14.4% vs 40.4%, RR 0.42 (95% CI: 0.32-0.54), P <.00001). CONCLUSION: Both HDDT and BQT can achieve similar eradication rate for H pylori infection and adherence, and generally HDDT causes fewer side effects.

miR-21 plays a pivotal role in gastric cancer pathogenesis and progression.

Gastric cancer causes nearly one million deaths worldwide per year. Although Helicobacter pylori infection is the main risk factor, in about 80% or more of gastric cancers, the molecular pathway underlying H. pylori infection leading to the development of gastric cancers remains unclear. Recently accumulating evidence suggests that microRNAs (miRNAs) may regulate diverse biological processes and may be important in tumorigenesis. miR-21 has been frequently observed to be aberrantly overexpressed in various tumors. Using TaqMan quantitative real-time PCR, we confirmed that miR-21 was significantly overexpressed in human gastric cancer tissues and cell lines. Remarkably, miR-21 was also significantly overexpressed in H. pylori-infected gastric mucosa, implying that overexpression of miR-21 in gastric cancer may be due in part to H. pylori infection. More importantly, we showed that forced expression of miR-21 significantly enhanced cell proliferation and invasion in AGS cells, a human gastric cancer cell line, whereas knockdown of miR-21 by inhibitor caused a significant reduction in cell proliferation and a significant increase in apoptosis. Furthermore, we demonstrated that knockdown of miR-21 significantly decreased cell invasion and migration of AGS cells. Finally, we showed that RECK, a known tumor suppressor in gastric cancer, is a bona fide target of miR-21. Taken together, miR-21 may be important in the initiation and progression of gastric cancers as an oncomiR, likely through regulating RECK. Our findings suggest a potential regulatory pathway in which H. pylori infection upregulates expression of miR-21, which in turn downregulates RECK, and then leads to the development of gastric cancer.