Risk factors for inadequate bowel preparation before colonoscopy: A meta-analysis.

OBJECTIVE: This meta-analysis aimed to comprehensively explore the risk factors for inadequate bowel preparation (IBP). METHODS: We searched the Embase, PubMed, Web of Science, and The Cochrane Library databases up to August 24, 2023, to identify observational studies and randomized controlled trials (RCTs) that examined risk factors for IBP. A random effects model was used to pool the adjusted odds ratios and 95% confidence intervals. RESULTS: A total of 125 studies (91 observational studies, 34 RCTs) were included. Meta-analyses of observational studies revealed that three preparation-related factors, namely, characteristics of last stool (solid or brown liquid), incomplete preparation intake, and incorrect diet restriction, were strong predictors of IBP. The other factors were moderately correlated with IBP incidence, including demographic variables (age, body mass index, male sex, Medicaid insurance, and current smoking), comorbidities (diabetes, liver cirrhosis, psychiatric disease, Parkinson's disease, previous IBP, poor mobility, inpatient, and Bristol stool form 1/2), medications (tricyclic antidepressants, opioids, antidepressants, narcotics, antipsychotics, and calcium channel blockers), and preparation-related factors (preparation-to-colonoscopy interval not within 3 to 5/6 h, nonsplit preparation, and preparation instructions not followed). No colonoscopy indications were found to be related to IBP. Meta-analyses of RCTs showed that education, constipation, stroke/dementia, and discomfort during preparation were also moderately associated with IBP. Most of the other findings were consistent with the pooled results of observational studies. However, primarily due to imprecision and inconsistency, the certainty of evidence for most factors was very low to moderate. CONCLUSIONS: We summarized five categories of risk factors for IBP. Compared to demographic variables, comorbidities, medications, and colonoscopy indications, preparation-related elements were more strongly associated with IBP. These findings may help clinicians identify high-risk individuals and provide guidance for IBP prevention.

Kuijie decoction ameliorates ulcerative colitis by affecting intestinal barrier functions, gut microbiota, metabolic pathways and Treg/Th17 balance in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Currently, the clinical treatment is limited and difficult to achieve satisfactory results for ulcerative colitis (UC). The role of traditional Chinese medicine (TCM) in the treatment of UC is very complex. Kuijie decoction (KJD) as a classic TCM, is widely used in the clinical treatment of UC, but the mechanism of its action is still unclear. AIM OF THE STUDY: This study is to investigate the protective effects of KJD on UC and the underlying mechanisms. MATERIALS AND METHODS: The experimental model of UC was induced by DSS, and KJD was introduced into the model at the same time. Clinical symptoms, including the body weight, colon length and colon histopathological, were used to measure the severity of colitis. The expression of inflammatory cytokines and tight junction proteins was quantified. The effect of KJD on intestinal flora and intestinal metabolism was determined by 16S rRNA and untargeted metabolomics analysis, respectively. The proportion of Th17 cells and Tregs in the spleen was examined by flow cytometry. RESULTS: Mice treated with KJD showed significantly alleviated clinical symptoms and histological damage, such as more body weight gain, lower disease activity index (DAI) score, and longer colon length. The administration of KJD also led to the down-regulation of inflammatory mediators, upregulation of the expression of ZO-1, occludin and decreased claudin-2, as well as altered microbiota composition against DSS challenges (especially an increase of Lachnospiraceae). KJD enhanced the percentage of Treg cells but decreased the proportion of Th17 cells to maintain intestinal homeostasis by improving gut microbiota metabolism. CONCLUSIONS: In summary, KJD maintained intestinal epithelial homeostasis by regulating epithelial barrier function, intestinal flora, and restoring Th17/Treg balance. KJD has the potential to be a Chinese medicine treatment for UC.

Role of macrophage-to-myofibroblast transition in chronic liver injury and liver fibrosis.

BACKGROUND: Chronic liver injury contributes to liver fibrosis, which is characterized by the excessive deposition of extracellular matrix (ECM) components. ECM is mainly composed of myofibroblasts. Recently, macrophage-to-myofibroblasts transition (MMT), has been identified as a novel origin for myofibroblasts. However, the potential functions of MMT in chronic liver injury and liver fibrosis remain unknown. METHODS: To clarify the transformation of fibrotic cells in hepatic fibrosis, liver specimens were collected from people at different stages in the progression of hepatic fibrosis and stained with immunofluorescence. Models of hepatic fibrosis such as the CCL4 model, HFD-induced NAFLD model, MCD-induced NAFLD model and ethanol-induced AFLD model were demonstrated and were stained with immunofluorescence. RESULTS: Here, we uncovered macrophages underwent MMT in clinical liver fibrosis tissue samples and multiple animal models of chronic liver injury. MMT cells were found in specimens from patients with liver fibrosis on the basis of co-expression of macrophage (CD68) and myofibroblast (a-SMA) markers. Moreover, macrophages could transform into myofibroblasts in CCL4-induced liver fibrosis model, high-fat diet (HFD) and methionine-choline-deficient diet (MCD)-induced nonalcoholic fatty liver diseases (NAFLD) model, and ethanol-induced alcoholic fatty liver diseases (AFLD) model. In addition, we highlighted that MMT cells mainly had a predominant M2 phenotype in both human and experimental chronic liver injury. CONCLUSIONS: Taken together, MMT acts a crucial role in chronic liver injury and liver fibrosis.

Global research trends and hotspots of Helicobacter pylori eradication based on clinical trial registration platforms: A cross-sectional analysis.

BACKGROUND: This study aimed to obtain an overview of clinical trials on Helicobacter pylori (H. pylori) eradication and analyze the global trends and hotspots in this field. METHODS: We collected the data from clinical trials focused on H. pylori eradication in the primary clinical trial registries from 2000 to 2022 in the world. Then we analyzed the research trends and hotspots in H. pylori eradication regimens in different regions at different periods. RESULTS: A total of 780 clinical trials were included, which were mainly conducted in Asia (682), followed by Europe (59), Africa (20), North America (16), South America (7), Oceania (2). The most active countries were China (343), Iran (140), South Korea (63), and Japan (73). "Bismuth-containing quadruple therapy (BQT)" was the most studied regimen (159, 20.38 %). Additionally, clinical trials focused on potassium-competitive acid blockers (P-CABs)-based therapy, probiotics, and high-dose dual therapy (HDDT) were constantly increasing. BQT received the most attention in China (26.53 %) and Iran (22.14 %), while it was tailored therapy in South Korea (23.29 %). P-CABs-based therapy was the main reseach hotspot in Japan (61.90 %). CONCLUSION: How to eradicate H. pylori infection has been a heated research topic. BQT, P-CABs-based therapy, probiotics, and HDDT attracted the most attention in recent years.

Gastric xanthelasma is a warning sign for Helicobacter pylori infection, atrophic gastritis, and intestinal metaplasia.

Background: Contradictory evidence suggested gastric xanthelasma (GX) was associated with some upper gastrointestinal (GI) diseases. Additionally, no research has been performed on the relationship between esophageal/duodenal xanthelasma and upper GI diseases. Methods: Individuals who underwent esophagogastroduodenoscopy at Tongji Hospital, Tongji Medical College, participated in this retrospective study. This study evaluated whether the risk of GX or esophageal/duodenal xanthelasma was influenced by the following gastroesophageal diseases: superficial gastritis, gastric polyp, bile reflux, peptic ulcer, reflux esophagitis, Barrett's esophagus, esophageal cancer, atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia, gastric cancer, and Helicobacter pylori (H. pylori) infection. Furthermore, subgroup analysis was conducted to establish the relationship between the number of GX and upper GI diseases. Results: Of the 69,071 subjects reviewed, 1,220 (1.77%) had GX, and 54 (0.08%) had esophageal/duodenal xanthelasma. There was no difference in the prevalence of upper GI diseases between patients with and without esophageal/duodenal xanthelasma. Nevertheless, compared with non-xanthelasma patients, GX patients had a greater proportion of AG, IM, dysplasia, gastric cancer, and H. pylori infection and a lower incidence of superficial gastritis (p < 0.05). The multivariate logistic regression analysis indicated AG (OR = 1.83, 95%CI: 1.56-2.16), IM (OR = 2.42, 95%CI: 2.41-2.85), and H. pylori infection (OR = 1.32, 95%CI: 1.17-1.50) were independent risk factors for GX. In addition, patients with multiple GXs had a higher rate of AG and IM than those with single GX. Conclusion: Esophageal/duodenal xanthelasma may not be associated with upper GI diseases, and further research is needed to support this hypothesis. Notably, GX, especially multiple GXs, may be a more easily detected warning sign of AG, IM, or H. pylori infection.

Combined immunotherapy for hepatocellular carcinoma: How to maximize immune checkpoint blockade synergic anti-tumor effect.

Hepatocellular carcinoma (HCC) is the most prevalent form of liver cancer and has an increasing incidence worldwide. The management of HCC still has many restrictions, despite the fact that there are now numerous treatment options, including liver transplantation/resection, locoregional treatments (LRT), and systemic medication. As a turning point in the history of cancer treatment, the discovery of the immune checkpoints and the development of their inhibitors provide new hope for HCC patients. However, limited objective response rate and insignificant overall survival improvement are still urgent problems to be solved for immune checkpoint inhibitors (ICIs). Combination therapies are considered a solution for improving the effectiveness and response rate of ICIs, and several forms of combination treatments are currently being actively researched. In this review, we summarize the mainstream combination strategies, explain their theoretical basis, introduce several important and ongoing clinical trials, and suggest some potential future paths in this area at the conclusion of the review. AVAILABILITY OF DATA AND MATERIALS: Not applicable.

Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial-mesenchymal transition.

KIAA1199, a major glycosaminoglycan component of the extracellular matrix, was reported to induce a fibrosis-like process. However, the relationship between KIAA1199 and liver fibrosis remains unclear. The liver fibrosis mouse model was established with carbon tetrachloride (CCl4). Here, we found that KIAA1199 was upregulated in CCl4-induced liver fibrosis. The expression of KIAA1199 was also increased in TGF-ß-stimulated LX-2 cells. To clarify the impact of KIAA1199 in hepatic stellate cells (HSCs), we downregulated the expression of KIAA1199 in LX-2 cells by RNA interference. Cell proliferation, apoptosis, and migration were determined by CCK-8, flow cytometry, and transwell assay. We found that KIAA1199 knockdown reduced the expression of fibrosis markers α-SMA and COL1A1. Depletion of KIAA1199 inhibited cell proliferation by downregulating cyclin B1 and cyclin D1 and promoted cell apoptosis by upregulating Bax and downregulating Bcl-2. Moreover, KIAA1199 knockdown decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression to inhibit the migration ability of LX-2 cells. Silencing KIAA1199 also suppressed the epithelial-mesenchymal transition phenomenon. Collectively, our study revealed that KIAA1199 knockdown alleviated the activation, proliferation, and migration of HSCs, while promoting apoptosis of HSCs, which suggests that KIAA1199 may be a potential regulator of liver fibrosis.

Determination of an Appropriate Endoscopic Monitoring Interval for Patients with Gastric Precancerous Conditions in China.

OBJECTIVE: Gastric precancerous conditions such as atrophic gastritis (AG) and intestinal metaplasia (IM) are considered independent risk factors for gastric cancer (GC). The suitable endoscopic monitoring interval is unclear when we attempt to prevent GC development. This study investigated the appropriate monitoring interval for AG/IM patients. METHODS: Totally, 957 AG/IM patients who satisfied the criteria for evaluation between 2010 and 2020 were included in the study. Univariate and multivariate analyses were used to determine the risk factors for progression to high-grade intraepithelial neoplasia (HGIN)/GC in AG/IM patients, and to determine an appropriate endoscopic monitoring scheme. RESULTS: During follow-up, 28 AG/IM patients developed gastric neoplasia lesions including gastric low-grade intraepithelial neoplasia (LGIN) (0.7%), HGIN (0.9%), and GC (1.3%). Multivariate analysis identified H. pylori infection (P=0.022) and extensive AG/IM lesions (P=0.002) as risk factors for HGIN/GC progression (P=0.025). CONCLUSION: In our study, HGIN/GC was present in 2.2% of AG/IM patients. In AG/IM patients with extensive lesions, a 1-2-year surveillance interval is recommended for early detection of HIGN/GC in AG/IM patients with extensive lesions.

Impact of body size on efficacy of high-dose dual therapy for Helicobacter pylori eradication.

BACKGROUND: High-dose dual therapy (HDDT) is an emerging and promising therapeutic regime for Helicobacter pylori (H. pylori) eradication. However, the pharmacokinetics of the components of HDDT, amoxicillin and proton pump inhibitor, are likely to be affected by body size. In this study, we aimed to find out the impact of body size on the efficacy of HDDT. METHODS: We collected the medical data of 385 treatment-naive patients infected with H. pylori who received HDDT (esomeprazole 20 mg and amoxicillin 750 mg four times daily) for 14 days from July 2020 to December 2021. The associations among the eradication efficacy, adverse events, and variables (sex, age, height, body weight, body mass index (BMI), body surface area (BSA), smoking, drinking, etc.) were analyzed respectively in our study. Among these factors, continuous variables were classified into categorical variables using the cut-off values which were calculated by receiver operating characteristic analysis. RESULTS: The eradication rate of HDDT was 89.9%. There were 55 (14.3%) patients who occurred adverse events during the treatment. Patients with height <170.5 cm, body weight <60.5 kg, BMI <20.55 kg/m2 , BSA <1.69 m2 had a higher eradication rate (92.1% vs. 84.0%, 93.1% vs. 86.8%, 96.0% vs. 87.8%, 93.4% vs. 84.8%, all p < .05). The multivariate analysis showed that BSA ≥1.69 m2 (OR 2.53, 95% CI: 1.28-4.99, p = .007) was the only independent predictor of eradication failure. CONCLUSION: HDDT could achieve better eradication efficacy in patients with small BSA. Clinicians should be aware of the impact of BSA on the H. pylori eradication rate and pay more attention to patients with large BSA.

Relationship between endoscopic gastric abnormalities and colorectal polyps: a cross-sectional study based on 33439 Chinese patients.

Background: No study on the relationship between common abnormalities of the upper digestive tract and colorectal polyps (CPs) has been conducted. Methods: 33439 patients were enrolled in this cross-sectional study, of which 7700 had available Helicobacter pylori (H.pylori) information. All participants underwent colonoscopy and esophagogastroduodenoscopy (EGD) simultaneously or within six months at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2015 to November 2021. The study assessed whether the risk of CPs was affected by the following gastroesophageal diseases: atrophic gastritis (AG), gastric polyps, Barrett's esophagus and reflux esophagitis, bile reflux, gastric ulcer, gastric mucosal erosion, superficial gastritis, and gastric H.pylori infection. The crude and adjusted odds ratios (ORs) of H.pylori on the occurrence of CPs were computed by logistic regression. Additionally, we also evaluated whether AG had an impact on the relationship between H.pylori infection and CPs. Results: A total of 10600 cases (31.7%) were diagnosed as CPs. Multivariate logistic analysis showed that age, male (OR, 1.80; 95% confidence interval [CI], 1.61 to 2.02), gastric polyps (OR, 1.61; 95% CI, 1.05 to 2.46 for hyperplastic polyps; OR, 1.45; 95% CI, 1.09 to 1.94 for fundic gland polyps), H.pylori infection (OR, 1.21; 95% CI, 1.07 to 1.37) and atrophic gastritis (OR, 1.38; 95% CI, 1.21 to 1.56) were independent risk factors for colorectal polyps. Moreover, the combined effect of H.pylori infection and AG was slightly greater than the sum of their individual effects on the risk of CPs, but there was no additive interaction between them. Conclusions: Gastric conditions including gastric polyps, H.pylori infection, and AG increased the risk of CPs. However, Barrett's esophagus and reflux esophagitis, bile reflux, erosive gastritis, gastric ulcer, and superficial gastritis might not have relationship with CPs occurrence.

Development and validation of a three-dimensional deep learning-based system for assessing bowel preparation on colonoscopy video.

Background: The performance of existing image-based training models in evaluating bowel preparation on colonoscopy videos was relatively low, and only a few models used external data to prove their generalization. Therefore, this study attempted to develop a more precise and stable AI system for assessing bowel preparation of colonoscopy video. Methods: We proposed a system named ViENDO to assess the bowel preparation quality, including two CNNs. First, Information-Net was used to identify and filter out colonoscopy video frames unsuitable for Boston bowel preparation scale (BBPS) scoring. Second, BBPS-Net was trained and tested with 5,566 suitable short video clips through three-dimensional (3D) convolutional neural network (CNN) technology to detect BBPS-based insufficient bowel preparation. Then, ViENDO was applied to complete withdrawal colonoscopy videos from multiple centers to predict BBPS segment scores in clinical settings. We also conducted a human-machine contest to compare its performance with endoscopists. Results: In video clips, BBPS-Net for determining inadequate bowel preparation generated an area under the curve of up to 0.98 and accuracy of 95.2%. When applied to full-length withdrawal colonoscopy videos, ViENDO assessed bowel cleanliness with an accuracy of 93.8% in the internal test set and 91.7% in the external dataset. The human-machine contest demonstrated that the accuracy of ViENDO was slightly superior compared to most endoscopists, though no statistical significance was found. Conclusion: The 3D-CNN-based AI model showed good performance in evaluating full-length bowel preparation on colonoscopy video. It has the potential as a substitute for endoscopists to provide BBPS-based assessments during daily clinical practice.

Hypertriglyceridemia may contribute to stroke and pancreatitis: A case report and review of the literature.

Hypertriglyceridemia (HTG) is one of the most common clinical dyslipidemia. Nevertheless, stroke and acute pancreatitis co-occurrence due to hypertriglyceridemia are extremely rare. We present a case of hypertriglyceridemia-associated stroke and pancreatitis in a 39-year-old woman. The patient's laboratory tests reported high triglyceride concentrations beyond the instrument's detection range, and radiological examination showed typical signs of cerebral infarction and acute pancreatitis. The patient received combined blood purification therapy, intravenous thrombolysis with urokinase, and conservative treatment of pancreatitis. We discuss the clinical features, pathogenesis, diagnosis, and treatment of hypertriglyceridemic stroke and pancreatitis combined with the relevant literature. We reviewed the mechanisms by which triglycerides contribute to atherosclerosis and acute pancreatitis. We point out the superiority of combined blood purification therapy and caution physicians about the effects of prescribed drugs on blood lipids.

Hepatic HRC induces hepatocyte pyroptosis and HSCs activation via NLRP3/caspase-1 pathway.

The histidine-rich calcium-binding protein (HRC) is a regulator of Ca2 + homeostasis and it plays a significant role in liver fibrosis. Pyroptosis, a specific inflammatory cell death, can lead to hepatic stellate cells (HSCs) activation and liver fibrosis. However, the role of HRC in pyroptosis has not been explored. In this study, we demonstrated that HRC, mainly located in the hepatocyte, was over expressed in fibrotic liver tissues. We further found that enforced expression of HRC in hepatocytes induced pyroptosis and HMGB1 release, and subsequently led to HSCs activation by NLRP3/caspase-1 pathway. In addition, the proliferation and migration of HSCs were also enhanced by HRC overexpression in hepatocytes. Furthermore, NLRP3 inhibitor MCC950 and caspase-1 inhibitor VX-765 alleviated hepatic HRC-mediated hepatocytes pyroptosis and HSCs activation. This study demonstrated that hepatic HRC promoted HSCs activation by inducing hepatocyte pyroptosis, which suggests that HRC may be a promising therapeutic target to prevent liver fibrosis.

Improving the quality of bowel preparation by smartphone education platform prior to colonoscopy: a randomized trail.

OBJECTIVE: Adequate bowel preparation is an essential factor in colonoscopy. Enhanced education on the procedure of bowel preparation is very necessary for patients before colonoscopy. We analysed the influence of a novel education platform on bowel preparation quality before colonoscopy. PATIENTS AND METHODS: The study enrolled outpatients who underwent colonoscopy in the digestive endoscopy centre of Wuhan Tongji Hospital. They were divided into the control group and the intervention group according to different educational ways. The control group patients were provided with the regular colonoscopy preparation leaflet. The intervention group patients were asked to add the education platform. The primary outcome was the rate of adequate bowel preparation. The study was registered at Chinese ClinicalTrials.gov (ChiCTR2100053547, 24/11/2021). RESULTS: A total of 378 patients who underwent colonoscopy were enrolled, including 189 patients in the control group and 189 patients in the intervention group. The Boston bowel preparation score (BBPS) was significantly higher in the intervention group than that in the control group (p < .05). The adequate rate of bowel preparation in the intervention group was significantly improved than that in the control group (p = .000). Compared with the control group, the polyp detection rate (PDR) was significantly higher in the intervention group (p = .006), especially in the left colonic (p = .006). Among constipation patients, the adequate rate of bowel preparation (p = .000) and the PDR (p = .004) were significantly improved than that in the control group. CONCLUSIONS: The smartphone education platform may effectively improve bowel preparation quality, PDR, and patients' compliance.Key messagesThe quality of bowel preparation mainly relies on the patients' compliance with the bowel preparation instructions.The study reveals that the superiority of the smartphone education platform by Mini Program in improving bowel preparation and colorectal polyp detection rate.The smartphone education platform may provide a more effective, convenient, and labour-saving way to provide further improvements to patients prior to colonoscopy.

Short-chain fatty acids affect the development of inflammatory bowel disease through intestinal barrier, immunology, and microbiota: A promising therapy?

Intestinal metabolites are attracting increasing interest, especially more and more studies have found they are closely related to diseases. Microbial fermentation of indigestible dietary fibers in the gut produces short chain fatty acids (SCFAs) as the main product. SCFAs can exert influences on the integrity of the intestinal epithelial and mucosal barrier, immune reactions, and the diversity of microbiota in humans. Thus, alteration in SCFAs may affect inflammatory bowel disease (IBD). In IBD, SCFAs are involved in the main pathogenic process and play an important role in the development of intestinal inflammation. Although many studies have proved that pretreatment with SCFAs can effectively ameliorate inflammation in the gut, the mechanisms are not fully understood. In this review, we describe the relationship between SCFAs and IBD from the aspects of defense barrier, immune effects, and microbial alterations. We also summarize the effects of SCFAs on comorbidities in IBD via the gut-brain, gut-liver, and gut-lung axis, and we give an overview of the prospects of their clinical application. A better understanding of the relevance of SCFAs in IBD may reveal novel targets for future study.

Epstein-Barr Virus is Associated with Gastric Cancer Precursor: Atrophic Gastritis.

Background: About 10% of gastric cancer (GC) has been described to be Epstein-Barr virus (EBV) positive. Previous researches have described the association between EBV and GC. However, the association of EBV with atrophic gastritis (AG) is underrecognized. Our study aimed to investigate the relationship between EBV and AG and assess the influence of EBV on gastric function. Methods: A total of 468 pathologically-confirmed chronic gastritis patients underwent circulating EBV DNA test, include 271 non-atrophic gastritis (NAG) and 197 AG patients. Results: In this study, H. pylori infection rate was 33.3%, EBV infection rate was 40%, and co-infection rate was 15%. The EBV DNA-positive was significantly associated with AG (P=0.031, OR= 1.509, 95% CI 1.037-2.194), especially in H. pylori-negative subjects (P=0.044, OR=1.619, 95% CI 1.012-2.589). EBV DNA-positive patients had a lower pepsinogen I (PG I) / pepsinogen II (PG II) ratio (PGR) than EBV DNA-negative patients (P=0.0026), especially in the AG subgroup (P=0.0062). There was no significant association between EBV and H. pylori co-infection with increased risk of AG (P>0.05). Conclusion: EBV infection significantly increased the risk of AG, especially in H. pylori-negative patients. The circulating EBV DNA had a potential in predicting the risk of atrophic gastritis.

NSAID-Associated Small Intestinal Injury: An Overview From Animal Model Development to Pathogenesis, Treatment, and Prevention.

With the wide application of non-steroidal anti-inflammatory drugs (NSAIDs), their gastrointestinal side effects are an urgent health burden. There are currently sound preventive measures for upper gastrointestinal injury, however, there is a lack of effective defense against lower gastrointestinal damage. According to a large number of previous animal experiments, a variety of NSAIDs have been demonstrated to induce small intestinal mucosal injury in vivo. This article reviews the descriptive data on the administration dose, administration method, mucosal injury site, and morphological characteristics of inflammatory sites of various NSAIDs. The cells, cytokines, receptors and ligands, pathways, enzyme inhibition, bacteria, enterohepatic circulation, oxidative stress, and other potential pathogenic factors involved in NSAID-associated enteropathy are also reviewed. We point out the limitations of drug modeling at this stage and are also pleased to discover the application prospects of chemically modified NSAIDs, dietary therapy, and many natural products against intestinal mucosal injury.

Facile Synthesis of Highly Dispersed and Well-Alloyed Bimetallic Nanoparticles on Oxide Support.

Supported alloy catalysts play a pivotal role in many heterogeneous catalytic processes of socioeconomic and environmental importance. But the controlled synthesis of supported alloy nanoparticles with consistent composition and tight size distribution remains a challenging issue. Herein, a simple yet effective method for preparation of highly dispersed, homogeneously alloyed bimetallic nanoparticles on oxide supports is reported. This method is based on solid solution of metal cations in parent oxide and strong electrostatic adsorption of a secondary metal species onto the oxide surface. In the reductive annealing process, hydrogen spillover occurs from the surface metal with a higher reduction potential to the solute metal in solid solution, leading to metal exsolution and homogenous alloying of the metals on the oxide surface. The ceria-supported Ni-Pt alloy is chosen as a model catalyst and hydrazine monohydrate decomposition is chosen as a probe reaction to demonstrate this method, and particularly its advantages over the conventional impregnation and galvanic replacement methods. A systematic application of this method using different oxides and base-noble metal pairs further elucidates its applicability and generality.

HRC promotes anoikis resistance and metastasis by suppressing endoplasmic reticulum stress in hepatocellular carcinoma.

Histidine-rich calcium binding protein (HRC) is markedly overexpressed in hepatocellular carcinoma (HCC) and is significantly correlated with metastasis. Anoikis resistance and endoplasmic reticulum (ER) stress may have a critical effect on survival before metastasis. However, the potential functions of HRC in anoikis resistance in HCC remain unknown. Here, we uncovered the clinical value of HRC and its functional significance on anoikis in HCC. The positive expression of HRC was observably correlated with tumor size, tumor encapsulation, and tumor-node-metastasis (TNM) stage. The expression of HRC increased in HCC cells cultured in suspension. HRC enhanced the anoikis resistance of HCC, and promoted the HCC metastasis in vivo. Mechanistically, the anoikis resistance was probably dependent on endoplasmic reticulum stress. Modulating HRC level changed the ERS to affect anoikis resistance by acting protein kinase RNA-like ER kinase (PERK)-eIF2a-ATF4-CHOP signaling axis. In conclusion, we define HRC as a novel candidate oncogene involved in anoikis resistance and HCC metastasis, and provide a new potential therapeutic target for HCC.

SLC7A2 deficiency promotes hepatocellular carcinoma progression by enhancing recruitment of myeloid-derived suppressors cells.

The main reason for poor prognosis in hepatocellular carcinoma (HCC) patients is high metastasis and recurrence. Cancer progression depends on a tumor-supportive microenvironment. Therefore, illustrating the mechanisms of tumor immunity in underlying HCC metastasis is essential. Here, we report a novel role of solute carrier family 7 member 2 (SLC7A2), a member of the solute carrier family, in HCC metastasis. The reduction of SLC7A2 was an independent and significant risk factor for the survival of HCC patients. Upregulation of SLC7A2 decreased HCC invasion and metastasis, whereas downregulation of SLC7A2 promoted HCC invasion and metastasis. We further found that deficient SLC7A2 medicated the upregulation of CXCL1 through PI3K/Akt/NF-kκB pathway to recruit myeloid-derived suppressor cells (MDSCs), exerting tumor immunosuppressive effect. Moreover, we found that G9a-mediated di-methylation of H3K9 (H3K9me2) silenced the expression of SLC7A2 to suppress HCC metastasis and immune escape. In conclusion, G9a-mediated silencing of SLC7A2 exerts unexpected functions in cancer metastasis by fostering a tumor-supportive microenvironment through CXCL1 secretion and MDSCs recruitment. Thus, SLC7A2 may provide new mechanistic insight into the cancer-promoting property of MDSCs.