Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression

AIM To investigate the therapeutic effect of hydrogen-rich water(HRW) on inflammatory bowel disease(IBD) and to explore the potential mechanisms involved.METHODS Male mice were randomly divided into the following four groups: control group, in which the mice received equivalent volumes of normal saline(NS) intraperitoneally(ip); dextran sulfate sodium(DSS) group, in which the mice received NS ip(5 m L/kg body weight, twice per day at 8 am and 5 pm) for 7 consecutive days after IBD modeling; DSS + HRW group, in which the mice received HRW(in the same volume as the NS treatment) for 7 consecutive days after IBD modeling; and DSS + HRW + Zn PP group, in which the mice received HRW(in the same volume as the NS treatment) and ZnP P [a heme oxygenase-1(HO-1) inhibitor, 25 mg/kg] for 7 consecutive days after IBD modeling. IBD was induced by feeding DSS to the mice, and blood and colon tissues were collected on the 7th d after IBD modeling to determine clinical symptoms, colonic inflammation and the potential mechanisms involved.RESULTS The DSS + HRW group exhibited significantly attenuated weight loss and a lower extent of disease activity index compared with the DSS group on the 7th d(P < 0.05). HRW exerted protective effects against colon shortening and colonic wall thickening in contrast to the DSS group(P < 0.05). The histological study demonstrated milder inflammation in the DSS + HRW group, which was similar to normal inflammatory levels, and the macroscopic and microcosmic damage scores were lower in this group than in the DSS group(P < 0.05). The oxidative stress parameters, including MDA and MPO in the colon, were significantly decreased in the DSS + HRW group compared with the DSS group(P < 0.05). Simultaneously, the protective indicators, superoxide dismutase and glutathione, were markedly increased with the use of HRW. Inflammatory factors were assessed, and the results showed that the DSS + HRW group exhibited significantly reduced levels of TNF-α, IL-6 and IL-1β compared with the DSS group(P < 0.05). In addition, the pivotal proteins involved in endoplasmic reticulum(ER) stress, including p-e IF2α, ATF4, XBP1 s and CHOP, were dramatically reduced after HRW treatment in contrast to the control group(P < 0.05). Furthermore, HRW treatment markedly up-regulated HO-1 expression, and the use of Zn PP obviously reversed the protective role of HRW. In the DSS + HRW + ZnP P group, colon shortening and colonic wall thickening were significantly aggravated, and the macroscopic damage scores were similar to those of the DSS + HRW group(P < 0.05). The histological study also showed more serious colonic damage that was similar to the DSS group.CONCLUSION HRW has a significant therapeutic potential in IBD by inhibiting inflammatory factors, oxidative stress and ER stress and by up-regulating HO-1 expression.

Neutrophil-to-lymphocyte ratio predicts acute kidney injury occurrence after gastrointestinal and hepatobiliary surgery

BACKGROUND Postoperative acute kidney injury(AKI) is a complex pathological process involved intrarenal and systemic inflammation caused by renal hypoperfusion, nephrotoxic drugs and urinary obstruction. Neutrophil-to-lymphocyte ratio(NLR) is a marker of inflammation reflecting the progress of many diseases. However, whether NLR at admission can predict the occurrence of AKI after surgery in the intensive care unit(ICU) remains unknown.AIM To clarify the relationship between NLR and the occurrence of AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU.METHODS A retrospective analysis of 282 patients receiving surgical ICU care after gastrointestinal and hepatobiliary surgery in our hospital from December 2014 to December 2018 was performed.RESULTS Postoperative AKI occurred in 84 patients(29.79%) in this cohort. NLR by the multivariate analysis was an independent risk factor for occurrence of postoperative AKI in patients with gastrointestinal and hepatobiliary surgery in the ICU. In this cohort, receiver operating characteristic curves of AKI occurrence showed that the optimal cut-off value of NLR was 8.380. NLR was found to be significantly correlated with the white blood cell count, neutrophil count, lymphocyte count, arterial lactate and dialysis(P < 0.05). Additionally, NLR value at admission was higher in AKI patients compared with the non-AKI patients and increased with the severity of AKI. Patients with NLR ≥ 8.380 exhibited significantly higher incidences of postoperative AKI and severe AKI than patients with NLR < 8.380(AKI: 38.12% vs 14.85%, P < 0.001;severe AKI: 14.36% vs 1.98%, P = 0.001).CONCLUSION NLR at admission is a predictor of AKI occurrence in patients with gastrointestinal and hepatobiliary surgery in ICU. NLR should be included in the routine assessment of AKI occurrence.

Irisin attenuates intestinal injury,oxidative and endoplasmic reticulum stress in mice with L-arginine-induced acute pancreatitis

BACKGROUND Acute pancreatitis(AP)is often associated with intestinal injury,which in turn exaggerates the progression of AP.Our recent study has shown that a low level of serum irisin,a novel exercise-induced hormone,is associated with poor outcomes in patients with AP and irisin administration protects against experimental AP.However,the role of irisin in intestinal injury in AP has not been evaluated.AIM To investigate the effect of irisin administration on intestinal injury in experimental AP.METHODS AP was induced in male adult mice by two hourly intraperitoneal injections of Larginine.At 2 h after the last injection of L-arginine,irisin(50 or 250μg/kg body weight)or 1 mL normal saline(vehicle)was administered through intraperitoneal injection.The animals were sacrificed at 72 h after the induction of AP.Intestinal injury,apoptosis,oxidative and endoplasmic reticulum(ER)stress were evaluated.RESULTS Administration of irisin significantly mitigated intestinal damage,reduced apoptosis,and attenuated oxidative and ER stress in AP mice.In addition,irisin treatment also effectively downregulated serum tumor necrosis factor-alpha and interleukin-6 levels and alleviated injury in the pancreas,liver and lung of AP mice.CONCLUSION Irisin-mediated multiple physiological events attenuate intestinal injury following an episode of AP.Irisin has a great potential to be further developed as an effective treatment for patients with AP.

Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma

AIM:To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio(PLR) in patients with gallbladder carcinoma(GBC).METHODS:Clinical data of 316 surgical GBC patients were analyzed retrospectively,and preoperative serum platelet and lymphocyte counts were used to calculate the PLR.The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic(ROC) curve.The primary outcome was overall survival,which was estimated by the Kaplan-Meier method.The log-rank test was used to compare the differences in survival.Then,we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients.RESULTS:For the PLR,the area under the ROC curve was 0.620(95%CI:0.542-0.698,P = 0.040) in detecting death.The cut-off value for the PLR was determined to be 117.7,with 73.6% sensitivity and 53.2% specificity.The PLR was found to be significantlypositively correlated with CA125 serum level,tumornode-metastasis(TNM) stage,and tumor differentiation.Univariate analysis identified carcinoembryonic antigen(CEA),CA125 and CA199 levels,PLR,TNM stage,and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data.Multivariate analysis showed that CA125 > 35 U/mL,CA199 > 39 U/mL,PLR ≥ 117.7,and TNM stage Ⅳ were independently associated with poor survival in GBC.When expressed as a continuous variable,the PLR was still an independent predictor for survival,with a hazard ratio of 1.018(95%CI:1.001-1.037 per 10-unit increase,P = 0.043).CONCLUSION:The PLR could be used as a simple,inexpensive,and valuable tool for predicting the prognosis of GBC patients.

Effect of low-dose aspirin administration on long-term survival of cirrhotic patients after splenectomy: A retrospective single-center study

BACKGROUND Cirrhosis is a major risk factor for the development of hepatocellular carcinoma (HCC). Portal vein thrombosis is not uncommon after splenectomy in cirrhotic patients, and many such patients take oral anticoagulants including aspirin. However, the long-term impact of postoperative aspirin on cirrhotic patients after splenectomy remains unknown. AIM The main purpose of this study was to investigate the effect of postoperative long-term low-dose aspirin administration on the development of HCC and longterm survival of cirrhotic patients after splenectomy. METHODS The clinical data of 264 adult patients with viral hepatitis-related cirrhosis who underwent splenectomy at the First Affiliated Hospital of Xi’an Jiaotong University from January 2000 to December 2014 were analyzed retrospectively. Among these patients, 59 who started taking 100 mg/d aspirin within seven days were enrolled in the aspirin group. The incidence of HCC and overall survival were analyzed.RESULTS During follow-up, 41 (15.53%) patients developed HCC and 37 (14.02%) died due to end-stage liver diseases or other serious complications. Postoperative longterm low-dose aspirin therapy reduced the incidence of HCC from 19.02% to 3.40% after splenectomy (log-rank test, P=0.028). Univariate and multivariate analyses showed that not undertaking postoperative long-term low-dose aspirin therapy [odds ratio (OR)=6.211, 95% confidence interval (CI): 1.142-27.324, P=0.016] was the only independent risk factor for the development of HCC. Similarly, patients in the aspirin group survived longer than those in the control group (log-rank test, P=0.041). Univariate and multivariate analyses showed that the only factor that independently associated with improved overall survival was postoperative long-term low-dose aspirin therapy [OR = 0.218, 95%CI: 0.049- 0.960, P=0.044]. CONCLUSION In patients with viral hepatitis-related cirrhosis, long-term post-splenectomy administration of low-dose aspirin reduces the incidence of HCC and improves the long-term overall survival.

Thrombocytopenia for prediction of hepatocellular carcinoma recurrence: Systematic review and meta-analysis

AIM: To investigate the association between thrombocytopenia and relapse after treatment for hepatocellular carcinoma(HCC).METHODS: We searched the Pub Med, EMBASE, and Web of Science databases to obtain eligible studies. The hazard ratios(HRs) values and 95% confidence intervals(CIs) were pooled by random effects model. Subsequently, we estimated the heterogeneity, performed a sensitivity analysis, determined the publication bias, and performed subgroup and meta-regression analyses. Study quality was assessed by using the Oxford Center for Evidence Based Medicine tool.RESULTS: We identified 18 eligible studies by retrieval(published during 2000-2014). Out of the 4163 patients with HCC who were recruited, 2746(66.0%) experienced recurrence. In general, our meta-analysis suggested that low platelet count(PLT) before therapy significantly increased the probability of postoperative recurrence(HR = 1.53, 95%CI: 1.29-1.81). PLT was also valuable in the prediction of intrahepatic distant recurrence(HR = 1.49, 95%CI: 1.25-1.77). Subgroupand meta-regression analyses identified various therapeutic modalities as the source of a high degree of heterogeneity. The pooled HR values showed no obvious change when a single study was removed, but otherwise, an opposite-effects model was used. In addition, no significant publication bias was detected.CONCLUSION: Thrombocytopenia before treatment might be an inexpensive and useful predictor of postoperative recurrence in patients with HCC.

Ureteral Ewing’s sarcoma in an elderly woman: A case report

BACKGROUND Ewing’s sarcoma(ES)is regarded as a skeletal tumor,with few instances of extraskeletal ES.A primary ES in the ureter is extremely rare.CASE SUMMARY We report the case of a 69-year-old woman who presented with intermittent flank pain and hematuria and was found to have a mass in the left ureter.Pathology of the excised mass indicated ES.The clinical treatment and pathologic characteristics in this case,and a review of the literature describing ES in the urinary system,are presented.CONCLUSION Due to the rarity and malignancy of ES in ureter,early diagnosis and prompt surgical treatment are critical.