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Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and an urgent target for clinical intervention. Notch1 signaling pathway activity was found to be related to the severity of NAFLD, but the specific mechanism is not precise. Here, we investigated the potential mechanisms of Notch1 signaling in the development of NAFLD. Firstly, we found that Notch1 signaling is activated in free fatty acids-treated HepG2 cells accompanied by lipid accumulation, apoptosis, oxidative stress, and mitochondrial damage, which could be alleviated by Notch1 inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). In the meantime, we found that administration of DAPT activated the autophagy pathway in NAFLD. Furthermore, the use of autophagy inhibitor chloroquine reversed the DAPT-mediated protective effect in NAFLD. All our results uncover a vital role of Notch1 in hepatocyte injury and metabolism of NAFLD, giving rise to a new sight for NAFLD treatment by regulation of Notch signaling and autophagy pathway.

Background: The results from previous studies on association between prostaglandin E receptor 4 (PTGER4) polymorphisms and inflammatory bowel disease (IBD) risk in Caucasian were conflict. The present study aimed to investigate the genetic association by conducting a meta-analysis. Methods: Systematic literature search was conducted through Wiley Online Library, Chinese National Knowledge Infrastructure (CNKI), and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to investigate the associations between rs4613763 T/C, 17234657T/G polymorphisms, and IBD risk in Caucasian. Results: Twenty case-control studies consisting of 18,495 Crohn disease (CD) patients and 4203 ulcerative colitis (UC) patients, as well as 26,063 controls were included in this meta-analysis. The rs4613763T/C polymorphism had obvious influence on CD, UC risk in Caucasian. However, rs17234657T/G polymorphism had obvious influence on CD but not UC in Caucasian. Conclusion: This meta-analysis suggested that both the rs4613763 T/C, rs17234657T/G polymorphisms had obvious influence on risk of CD in Caucasian. In addition, rs4613763 T/C, polymorphism had obvious influence on risk of UC in Caucasian.

COVID-19 pneumonia is a global viral disease and has been classified as a pandemic by the World Health Organization. The coronavirus that causes it can remain in the stool of some infected patients for a short period, even after recovery from COVID-19 pneumonia. Studies have increasingly reported the involvement of other organs, including the gastrointestinal system, in addition to the respiratory system. Ulcerative colitis is an inflammatory bowel disease with an unknown cause. Emerging data suggest that the gas trointestinal system may be influenced by COVID-19 via the expression of angiotensin-converting enzyme-2 (ACE-2), but data on the association between COVID-19 and inflammatory bowel diseases, including ulcerative colitis, are lacking. In this report, we describe a case of ulcerative colitis diagnosed in a 50-year-old male patient who presented with complaints of bloody diarrhea and abdominal pain following the completion of treatment for COVID-19 pneumonia. It is possible for the novel coronavirus to trigger ulcerative colitis. Hence, patients presenting with gastrointestinal com plaints should also be evaluated for COVID-19.

Objective. To investigate the association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD). Methods. Data from 2051 participants who underwent 13C urea breath test and abdominal ultrasound examinations was collected. Participants were allocated to NAFLD risk group and NAFLD nonrisk group based on definite risk factors for NAFLD. The relationship between H. pylori infection and NAFLD was analyzed. Results. No significant difference was found between rates of H. pylori infection and NAFLD using the chi-square test (P=0.30) or regression analysis (P=0.70). There was no significant difference between rates of H. pylori infection with and without NAFLD (P=0.47) in the NAFLD risk group or in the NAFLD nonrisk group (P=0.59). There was no significant difference between rates of H. pylori infection in men (P=0.69) and in women (P=0.27) or in participants aged 18–40 years (P=0.43), 41–65 years (P=0.14), and ≥66 years (P=0.66) with and without NAFLD in the NAFLD risk group or between the same sex or age groups (P=0.82, P=0.66, P=0.24, P=0.53, and P=1.00, resp.) in the NAFLD nonrisk group. Conclusions. H. pylori infection does not appear to increase the NAFLD prevalence rate or to be associated with, or a risk factor for, NAFLD.

Background/Objectives Atopic dermatitis (AD) is a common condition affecting up to 20% of the paediatric population in Singapore. It is often associated with significant psychosocial morbidity and can affect patients' quality of life (QOL) tremendously. This study investigated the varying lifestyle impacts, and psychosocial domains most affected by AD in adolescent children in Singapore. Methods A prospective study evaluating the impact of AD on the QOL of adolescents was conducted over a 6-month period from July to December 2014. Adolescents aged 11–16 years with varying eczema severity were recruited. Eczema severity was determined by using the eczema area and severity index (EASI) scores. Lifestyle impact of AD was evaluated using patient-reported children's dermatology life quality index (CDLQI) scores. Statistical analysis was performed using an analysis of one-way variance and Student's t-test. Results A total of 50 patients were enrolled and divided into three groups: mild ( 20.9) eczema based on EASI scores. Patients with mild and moderate eczema had lower CDLQI scores. Adolescents were most affected by the disruption that their symptoms had on their leisure and physical activities and sleep as a result of itch and scratching, respectively. Conclusion Chronic sufferers of severe eczema experience poorer QOL than those with mild or moderate eczema. They also experience significant psychosocial impact as a consequence of their condition.

Background: An outbreak and worldwide spread of COVID-19 was derived from Wuhan, China where over half of the confirmed COVID-19 cases were reported Protection

© 2019 by the AGA Institute, Background & aims: Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. Methods: We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. Results: Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). Conclusions: In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide., This study was funded by the National Institute of Alcohol Abuse and Alcoholism grants U01AA021908 and U01AA020821, a scholarship grant from the Spanish Association for the Study of the Liver (M.V.-C.), and a grants NSFC 81570530 and 81370550 from the National Natural Science Foundation of China (L.Y.).

The value of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy in the gastric linitis plastica (GLP) with negative malignant endoscopy biopsies was investigated. Forty-six patients with linitis plastica who had undergone EUS-FNA were retrospectively studied, and their clinicopathological data were examined. Among the 46 eligible patients, 38 cases were diagnosed clearly by EUS-FNA. There were 24 cases with lymph node metastasis in the 38 patients. Both the lymph nodes and gastric lesions were punctured by EUS-FNA in the 24 cases. We compared the diagnostic accuracy in different sites, and the results showed that the diagnostic accuracy in lymph nodes was significantly higher than that in gastric lesions (P

Background Tumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC. Methods Publications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study. Results Final 19 papers were identified in this meta-analysis, including 1068 patients with UC and 130 normal tissue samples. Immunohistochemical p53 expression was significantly higher in UC without dysplasia and carcinoma (UC group) compared to normal tissue samples (OR = 3.14, P = 0.001), higher in UC with dysplasia than in UC group (OR = 10.76, P

The aim of this study was to determine the clinical and endoscopic manifestations, and pathological characteristics of intestinal schistosomiasis in China, in order to raise awareness of intestinal schistosomiasis and prevent misdiagnosis and missed diagnosis. The retrospective analysis of clinical and endoscopic manifestations, and histopathological characteristics, were conducted for 96 patients with intestinal schistosomiasis. Among these patients, 21 lived in areas that were not infected with Schistosoma and 25 (26%) had no history of schistosome infection or contact with infected water. These patients were mainly hospitalized due to symptoms of diarrhea, mucus and bloody purulent stool. Sixteen cases were of the acute enteritis type, and colonoscopy results determined hyperaemic edema and dispersed small mucosal ulcers. The acute infection in patients was pathologically characterized by the deposition of intact ova with a large quantity of eosinocyte infiltration. Forty‑one cases were of the chronic enteritis type which predominantly manifested with yellow nodules and disorder of the vascular surfaces in the intestines. Thirty‑nine cases were diagnosed with mixed type enteritis, which demonstrated acute and chronic histopathological appearances. In addition, six cases of complicated colorectal cancer were observed. Of the 24 misdiagnosed patients, eight were misdiagnosed with ulcerative colitis, five with colorectal cancer, five with colorectal tuberculosis, four with chronic bacillary dysentery and two with irritable bowel syndrome. Intestinal schistosomiasis demonstrated no specific clinical or endoscopic manifestations and it was determined that patients with abdominal pain, diarrhea and mucous stool may be infected with intestinal schistosomiasis. Epidemiological investigations and colonoscopy combined with multi‑block and multi‑site biopsies may improve the diagnosis of intestinal schistosomiasis. In addition, it is necessary for intestinal schistosomiasis to be followed up by colonoscopy, due to its possible correlation with colorectal tumors.

Assessment of colonic motor dysfunction is rarely done because of inadequate methodology and lack of knowledge about normal motor patterns. Here we report on elucidation of intraluminal pressure patterns using High Resolution Colonic Manometry during a baseline period and in response to a meal, in 15 patients with constipation, chronically dependent on laxatives, 5 healthy volunteers and 9 patients with minor, transient, IBS-like symptoms but no sign of constipation. Simultaneous pressure waves (SPWs) were the most prominent propulsive motor pattern, associated with gas expulsion and anal sphincter relaxation, inferred to be associated with fast propagating contractions. Isolated pressure transients occurred in most sensors, ranging in amplitude from 5–230 mmHg. Rhythmic haustral boundary pressure transients occurred at sensors about 4–5 cm apart. Synchronized haustral pressure waves, covering 3–5 cm of the colon occurred to create a characteristic intrahaustral cyclic motor pattern at 3–6 cycles/min, propagating in mixed direction. This activity abruptly alternated with erratic patterns resembling the segmentation motor pattern of the small intestine. High amplitude propagating pressure waves (HAPWs) were too rare to contribute to function assessment in most subjects. Most patients, dependent on laxatives for defecation, were able to generate normal motor patterns in response to a meal.

Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis which is autoimmune mediated. The international consensus diagnostic criteria (ICDC) 2011 proposed two types of AIP: type I is associated with histological pattern of lymphoplasmacytic sclerosing pancreatitis (LPSP), characterized by serum IgG4 elevation, whereas type 2 is named idiopathic duct-centric pancreatitis (IDCP), with granulocytic epithelial lesion (GEL) and immunoglobulin G4 (IgG4) negative. The pathogenic mechanism is unclear now; based on genetic factors, disease specific or related antigens, innate and adaptive immunity may be involved. The most common clinical manifestations of AIP are obstructive jaundice and upper abdominal pain. The diagnosis can be made by a combination of parenchymal and ductal imaging, serum IgG4 concentrations, pancreatic histology, extrapancreatic disease, and glucocorticoid responsiveness according to ICDC 2011. Because of the clinical and imaging similarities with pancreatic cancer, general work-up should be done carefully to exclude pancreatic malignant tumor before empirical trial of glucocorticoid treatment. Glucocorticoid is the most common drug for AIP to induce remission, while there still exists controversy on steroid maintenance and treatment for relapse. Further studies should be done to identify more specific serum biomarkers for AIP, the pathogenic mechanisms, and the treatment for relapse.

Background/Aims Neurotensin is a gut-brain peptide with both inhibitory and excitatory actions on the colonic musculature; our objective was to understand the implications of this for motor patterns occurring in the intact colon of the rat. Methods The effects of neurotensin with concentrations ranging from 0.1–100 nM were studied in the intact rat colon in vitro, by investigating spatio-temporal maps created from video recordings of colonic motility before and after neurotensin. Results Low concentration of neurotensin (0.1–1 nM) inhibited propagating long distance contractions and rhythmic propagating motor complexes; in its place a slow propagating rhythmic segmental motor pattern developed. The neurotensin receptor 1 antagonist SR-48692 prevented the development of the segmental motor pattern. Higher concentrations of neurotensin (10 nM and 100 nM) were capable of restoring long distance contraction activity and inhibiting the segmental activity. The slow propagating segmental contraction showed a rhythmic contraction—relaxation cycle at the slow wave frequency originating from the interstitial cells of Cajal associated with the myenteric plexus pacemaker. High concentrations given without prior additions of low concentrations did not evoke the segmental motor pattern. These actions occurred when neurotensin was given in the bath solution or intraluminally. The segmental motor pattern evoked by neurotensin was inhibited by the neural conduction blocker lidocaine. Conclusions Neurotensin (0.1–1 nM) inhibits the dominant propulsive motor patterns of the colon and a distinct motor pattern of rhythmic slow propagating segmental contractions develops. This motor pattern has the hallmarks of haustral boundary contractions.

Ping Zhang, He-Sheng Luo, Ming Li, Shi-yun Tan Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’sRepublic of China Abstract: Artesunate, a derivative of artemisinin isolated from Artemisia annua L., has been traditionally used to treat malaria, and artesunate has demonstrated cytotoxic effects against a variety of cancer cells. However, there is little available information about the antitumor effects of artesunate on human gastric cancer cells. In the present study, we investigated the antitumor effect of artesunate on human gastric cancer cells and whether its antitumor effect is associated with reduction in COX-2 expression. The effects of artesunate on the growth and apoptosis of gastric cancer cells were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis of annexin V–fluorescein isothiocyanate/propidium iodide staining, rhodamine 123 staining, and Western blot analysis. Results indicate that artesunate exhibits antiproliferative effects and apoptosis-inducing activities. Artesunate markedly inhibited gastric cancer cell proliferation in a time- and dose-dependent manner and induced apoptosis in gastric cancer cells a dose-dependent manner, which was associated with a reduction in COX-2 expression. Treatment with the selective COX-2 inhibitor celecoxib, or transient transfection of gastric cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Furthermore, the treatment with artesunate promoted the expression of proapoptotic factor Bax and suppressed the expression of antiapoptotic factor Bcl-2. In addition, caspase-3 and caspase-9 were activated, and artesunate induced loss of mitochondrial membrane potential, suggesting that the apoptosis is mediated by mitochondrial pathways. These results demonstrate that artesunate has an effect on anti-gastric cancer cells. One of the antitumor mechanisms of artesunate may be that its inhibition of COX-2 led to reduced proliferation and induction of apoptosis, connected with mitochondrial dysfunction. Artesunate might be a potential therapeutic agent for gastric cancer. Keywords: artesunate, gastric cancer cells, COX-2, apoptosis

AIM: To systematically evaluate the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer. METHODS: A comprehensive electronic search was conducted for articles published up until January 27, 2014 in Medline (PubMed), Excerpta Medica Database (Embase), the Cochrane Library and Google Scholar. Only case-control studies published in English that evaluated the association between the miR-146a rs2910164 polymorphism and susceptibility to gastric cancer were included. Furthermore, only studies with sufficient data allowing for calculation of odds ratio (OR) and corresponding 95% confidence interval (CI) were included. These values were used in the quantitative synthesis to assess the strength of the association between the miR-146a rs2910164 polymorphism and risk of gastric cancer. RESULTS: The database search identified 1002 eligible studies, of which seven (comprising 4112 cases and 5811 controls) were included for the meta-analysis. The results indicate that miR-146a rs2910164 polymorphism is more likely to be associated with gastric cancer risk. In the overall analysis, a significantly increased cancer risk was found in the heterozygote (GG vs GC) comparison (OR = 1.14, 95%CI: 1.03-1.27; P = 0.01 for pooled OR). In the ethnicity subgroup analysis, a similar result was found among Caucasians (OR = 1.36, 95%CI: 1.01-1.85; P = 0.04 for pooled OR). In the stratified analysis by quality of studies, a significantly increased cancer risk was found in the heterozygote comparison among high quality studies (OR = 1.12, 95%CI: 1.01-1.26; P = 0.04 for pooled OR). When stratified on the basis of sample size, a significantly increased cancer risk was found among small sample size subgroups for the allelic (G vs C: OR = 1.16, 95%CI: 1.03-1.30; P = 0.01), homozygote (GG vs CC: OR = 1.33, 95%CI: 1.03-1.73; P = 0.03) and recessive model (GG vs GC + CC: OR = 0.05, 95%CI: 0.00-0.10; P = 0.03) comparisons. CONCLUSION: The miR-146a rs2910164 polymorphism is associated with increased gastric cancer risk, particularly evident in high quality studies with small sample sized Caucasian populations.

Objective: We report a rare but serious case of upper gastrointestinal hemorrhage from hepatic artery pseudoaneurysm. Clinical Presentation and Intervention: An 11-year-old child with a history of hepatic trauma 6 months before was admitted for hematemesis and melena. Repeat ultrasound examination showed a 3.6 × 2.8 cm anechoic area with clear border in the right hepatic lobe. Selective angiography confirmed the presence of a pseudoaneurysm of the right hepatic artery. Transcatheter arterial embolization was used to successfully treat the pseudoaneurysm. Conclusion: This report shows that hepatic artery pseudoaneurysm should be considered as a possible cause of upper gastrointestinal hemorrhagefollowing known hepatic injury. A high index of suspicion, repeated Doppler ultrasound and timely selective angiography are required for diagnosis. Embolotherapy is the treatment of choice.

To investigate the relationship between the staging by endoscopic ultrasonography (EUS) and the expression of carcinoma metastasis associated gene in the patients with gastric carcinoma.Sixty-three patients with gastric cancer were diagnosed by electric gastroscopy and EUS. The preoperative staging of gastric cancer was measured by EUS and compared with pathologic staging and MMP-9 expression. Peripheral serum level of MMP-9 was measured with enzyme-linked immunosorbent assay (ELISA), while the expression of MMP-9 protein was tested with immunohistochemistry and hybridization in situ in the gastric carcinoma tissues.The total accuracy of EUS in estimating invasive depth of gastric cancer was 80.95%, while that in estimating lymphatic metastasis was 73.02%. Serum MMP-9 levels were consistent with the expression of MMP-9 protein and MMP-9 mRNA in tissue, a result closely correlated with invasive degree, staging with EUS and lymphatic metastasis in gastric cancer (P0.05). The total accuracy of estimating invasive depth in gastric cancer was 95.22% using both EUS and MMP-9.The MMP-9 level of preoperative serum presents the reference value for preoperative staging by EUS in the patients with gastric cancer. When serum MMP-9 level in gastric cancer is significantly high, physicians should pay closer attention to the metastasis which reaches the serosa or beyond. Combining EUS and MMP-9 improves the accuracy in deciding the invasion and metastasis in the patients with gastric carcinoma.

To determine whether the mast cell (MCs) and tumor-associated macrophage (TAMs) counts have any correlation with clinical outcome in colorectal cancer, and to investigate whether MCs undergo phenotypic changes in colorectal cancer.The MC and TAM counts were determined immunohistochemically in 60 patients with colorectal cancer and the depth of invasion, lymph node metastasis rate, distant metastasis rates, and survival rates were compared between patients with low (less than the mean number of positive cells) and high (more than the mean number of positive cells) cell counts.Both patients with a low MC count and patients with a low TAM count had significantly deeper depth of invasion than those with a high MC count and those with a high TAM count (P0.01 and P0.01 respectively). Patients with a high MC count and patients with a high TAM count were significantly higher showing significantly lower rates of lymph node metastasis, distant metastasis than those with a low MC count and those with a low TAM count. There were significant positive correlation between MC counts and TAM counts (r = 0.852, P0.01). In both cancerous tissue and normal colorectal tissue, the predominant MC phenotype was MC(TC). The 5-year survival rate estimated was significantly lower in both patients with a low MC count and patients with a low TAM count than in those with a high MC count and those with a high TAM count (P0.05 and P0.01 respectively).There appears to be a direct relationship between the number of MCs and clinical outcome in patients with colorectal cancer, even though MCs exhibited no significant phenotypic changes. TAM count is of value to predict the clinical outcome or prognosis. It is more beneficial for estimating biological character of colorectal carcinoma to combine MC and TAM counts.