Comparison of metastasis and prognosis between early-onset and late-onset hepatocellular carcinoma: A population-based study.

Background: While hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age. Methods: Information of HCC patients was retrospectively collected from the SEER database and our hospital. Patient demographics, tumor characteristics, and survival were compared between the two groups. A 1:1 propensity score matching (PSM) was adopted to adjust confounding factors. Logistic and cox analysis were utilized to explore risk factors of DM and prognosis, respectively. Besides, the survival differences were assessed by the Kaplan-Meier curve and log-rank test. Results: In total, 19187 HCC patients obtained from the SEER database and 129 HCC patients obtained from our own center were enrolled. Among 19187 patients with HCC, 3376 were identified in the matched cohort, including 1688 early-onset patients and 1688 late-onset patients. Compared with late-onset HCC, early-onset HCC was more likely to occur in female (25.2% vs. 22.9%, P = 0.030), have large tumors (>10.0 cm, 24.1% vs. 14.6%, P = 0.000), harbor poorly differentiated/undifferentiated cancers (17.0% vs. 14.0%, P = 0.003), present advanced clinical stage (T3+T4, 33.7% vs. 28.5%; N1, 9.2% vs. 6.7%; P = 0.000), and develop DM (13.0% vs. 9.5%, P = 0.000). After adjustment for confounders by PSM, we discovered that early-onset HCC remained an independent risk factor for DM. However, combined with Kaplan-Meier curve and cox analysis, early-onset HCC was an independent favorable predictor of survival. We validated these data on an independent cohort from our hospital. Conclusion: In this population-based study, despite developing DM more frequently, early-onset HCC exhibited a superior prognosis than late-onset HCC. Nevertheless, further research is warranted to understand the underlying aetiologic basis for the disparities.

Intestinal ultrasound scan predicts corticosteroid failure and colectomy risk in patients with ulcerative colitis.

OBJECTIVE: Intestinal ultrasound (IUS) is an emerging modality for assessing disease activity, extent, and treatment response in ulcerative colitis. This study aimed to evaluate the potential of IUS in predicting severe flares, the need for rescue therapy (corticosteroid failure), and colectomy in patients with ulcerative colitis. METHODS: We conducted a retrospective review of medical records, collecting clinical and IUS data. The Milan Ultrasound Criteria (MUC) score was used to assess ulcerative colitis severity. Group comparisons were performed to identify differences in MUC scores between mild-to-moderate and severe ulcerative colitis, between steroid responders and nonresponders, and between patients who underwent colectomy and those who did not. Receiver operating characteristic (ROC) analysis was used to predict outcomes in patients with ulcerative colitis. RESULTS: This analysis included 102 patients with ulcerative colitis categorized as mild/moderate (60) or severe (42). MUC scores were significantly higher in the severe ulcerative colitis group compared with the mild/moderate group (P < 0.001). Analysis (using ROC) identified a cutoff MUC score of >8.54 to indicate severe ulcerative colitis with good sensitivity (64.29%) and excellent specificity (93.33%). Similarly, a cutoff of MUC > 10.54 showed promise in predicting corticosteroid failure, with acceptable sensitivity (50%) and high specificity (90.91%). Finally, a cutoff MUC score >12.5 demonstrated potential for predicting colectomy, exhibiting moderate sensitivity (55.56%) but excellent specificity (96.97%). CONCLUSION: IUS may be useful for differentiating severe ulcerative colitis from mild-to-moderate disease, identifying early stage failure of corticosteroid therapy, and predicting the potential need for colectomy.

O-GlcNAcylation promotes the progression of nonalcoholic fatty liver disease by upregulating the expression and function of CD36.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH), constitute a burgeoning worldwide epidemic with no FDA-approved pharmacotherapies. The multifunctional immunometabolic receptor, fatty acid translocase CD36 (CD36), plays an important role in the progression of hepatic steatosis. O-GlcNAcylation is a crucial posttranslational modification that mediates the distribution and function of CD36, but its involvement in NAFLD remains poorly understood. METHODS: O-GlcNAcylation and CD36 expression were evaluated in human liver tissues obtained from NASH patients and normal control. Mice with hepatocyte-specific CD36 knockout were administered adeno-associated viral vectors expressing wild-type CD36 (WT-CD36) or CD36 O-GlcNAcylation site mutants (S468A&T470A-CD36) and were provided with a high-fat/high-cholesterol (HFHC) diet for 3 months. RT-qPCR analysis, immunoblotting, dual-luciferase reporter assays, chromatin immunoprecipitation, and coimmunoprecipitation were performed to explore the mechanisms by which O-GlcNAcylation regulates CD36 expression. Membrane protein extraction, immunofluorescence analysis, site-directed mutagenesis, and fatty acid uptake assays were conducted to elucidate the impact of O-GlcNAcylation on CD36 function. RESULTS: O-GlcNAcylation and CD36 expression were significantly increased in patients with NASH, mouse models of NASH, and palmitic acid-stimulated hepatocytes. Mechanistically, the increase in O-GlcNAcylation facilitated the transcription of CD36 via the NF-κB signalling pathway and stabilized the CD36 protein by inhibiting its ubiquitination, thereby promoting CD36 expression. On the other hand, O-GlcNAcylation facilitated the membrane localization of CD36, fatty acid uptake, and lipid accumulation. However, site-directed mutagenesis of residues S468 and T470 of CD36 reversed these effects. Furthermore, compared with their WT-CD36 counterparts, HFHC-fed S468A&T470A-CD36 mice exhibited decreases in systemic insulin resistance, steatosis severity, inflammation and fibrosis. Pharmacological inhibition of O-GlcNAcylation and CD36 also mitigated the progression of NASH. CONCLUSIONS: O-GlcNAcylation promotes the progression of NAFLD by upregulating CD36 expression and function. Inhibition of CD36 O-GlcNAcylation protects against NASH, highlighting a potentially effective therapeutic approach for individuals with NASH.

Clinical characteristics and long-term outcomes of hospitalised patients with ischemic colitis with different degrees of haematochezia: a retrospective study.

BACKGROUND: Based on the literature, haematochezia is associated with a benign clinical course of ischaemic colitis. However, most cases in the literature presented mild haematochezia associated with ischaemic colitis. Therefore, we aimed to investigate the impact of different degrees of haematochezia on the clinical outcomes of ischaemic colitis. METHODS: Patients were divided into nonhaematochezia, mild-haematochezia, and severe-haematochezia cohorts stratified by the degree of haematochezia. The clinical characteristics and prognoses were retrospectively reviewed. RESULTS: Haematochezia cohort (n = 89) was associated with a lower rate of severe illness (25% vs. 52%, P = 0.001), lower rate of isolated right colon ischaemia (7% vs. 28%, P = 0.001), lower surgery rates (13% vs. 36%, P = 0.001), and shorter hospital stay (12 vs. 17 days, P < 0.001) compared with nonhaematochezia cohort (n = 50). Severe-haematochezia cohort (n = 11) had a higher frequency of severe illness (73% vs. 18%, P < 0.001), higher surgical intervention rate (55% vs. 6%, P < 0.001), higher nonsurgical complication rate, higher in-hospital mortality (45% vs. 0%, P < 0.001), and longer hospital stay (28 vs. 10 days, P = 0.001), compared with mild-haematochezia cohort (n = 78). Additionally, in-hospital mortality (45% vs. 6%, P = 0.003) and nonsurgical complication rate were higher in the severe-haematochezia than in the nonhaematochezia cohort. However, the three cohorts had comparable prognoses for long-term survival and recurrence. CONCLUSIONS: Mild haematochezia was related to a benign clinical course of ischaemic colitis, while lack of haematochezia or severe haematochezia was associated with worse hospitalisation outcomes.

Overexpression of pressure-responsive miRNA-5703 inhibits pressure-induced growth and metastasis of liver cancer.

A vast majority of liver cancers coexist with cirrhosis and/or portal hypertension. A high-pressure tumour microenvironment may lead to malignant progression of liver cancer. Through quantitative reverse transcription-polymerase chain reaction, we found that miRNA-5703 was expressed at low levels in HepG2 and Huh-7 cells and pressure-treated MHCC97H implanted mouse cancer tissues, while its potential target gene, sarcoma gene (SRC), was highly expressed. The expression of miRNA-5703 was higher in liver cancer tissues from Barcelona Clinic Liver Cancer (BCLC) stage A1 patients than those from BCLC stage A2-D patients, whereas SRC showed the opposite expression pattern. Bioinformatics analysis, luciferase reporter assay, and western blotting were performed to verify the relationship between miRNA-5703 and its potential target SRC. Using intravital imaging and immunohistochemistry, we demonstrated that pressure promotes tumour growth in subcutaneous tumourigenesis nude mice, and overexpression of miRNA-5703 significantly downregulated Ki67 and upregulated NM23 in tumour tissues of mice, implying the blockage of tumour growth and metastasis. The activation of proliferation, migration, and invasion of HepG2 and Huh-7 cells by pressure, and inhibition by overexpressing miRNA-5703 were observed by cell counting kit-8 assay, flow cycle assay, transwell assay, and wound healing assay. After the intervention of pressure, inhibitor, and lentivirus to hepatoma cells, SRC, focal adhesion kinase (FAK), phosphatidylinositol 3-kinase (PI3K), serum/glucocorticoid regulated kinase-3 (SGK3), phosphoinositide dependent protein kinase 1 (PDK1), and paxillin were upregulated, and forkhead box O1 (FOXO1) and cyclin dependent kinase inhibitor 1B (P27Kip1) were downregulated in pressure-loaded hepatoma cells, which could be reversed by overexpression of miRNA-5703 or SRC knockdown. In conclusion, upregulation of miRNA-5703 inhibited pressure-induced growth and metastasis by suppressing the SRC-FAK-FOXO1 axis and SRC-paxillin axis. This novel perspective may be conducive to the mechano-inspired anticancer drugs of liver cancer.

New Insights into the Role of Oral Microbiota Dysbiosis in the Pathogenesis of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory disorders with a prolonged duration characterized by recurrent relapse and remission. The exact etiology of IBD remains poorly understood despite the identification of relevant risk factors, including individual genetic susceptibility, environmental triggers, and disruption of immune homeostasis. Dysbiosis of the gut microbiota is believed to exacerbate the progression of IBD. Recently, increasing evidence has also linked oral microbiota dysbiosis with the development of IBD. On the one hand, IBD patients show significantly unbalanced composition and function of the oral microbiota known as dysbiosis. On the other, overabundances of oral commensal bacteria with opportunistic pathogenicity have been found in the gut microbiota of IBD patients. Herein, we review the current information on the causative factors of IBD, especially recent evidence of IBD-associated oral microbiota dysbiosis, which has seldom been covered in the previous literature review, highlighting the pathogenic mechanisms of specific oral bacteria in the development of IBD. Ectopic colonization of several oral bacteria, including a subset of Porphyromonas gingivalis, Streptococcus mutans, Fusobacterium nucleatum, Campylobacter concisus, and Klebsiella pneumoniae, may lead to destruction of the intestinal epithelial barrier, excessive secretion of inflammatory cytokines, disruption of the host immune system, and dysbiosis of gut microbiota, consequently aggravating chronic intestinal inflammation. Studying oral microbiota dysbiosis may open future horizons for understanding IBD pathogenesis and provide novel biomarkers for IBD. This review also presents the current treatment and new perspectives for IBD treatment.

Timing of endoscopic intervention in patients with cirrhosis with acute variceal haemorrhage (TEACH trial): protocol for a randomised clinical trial (RCT).

INTRODUCTION: Acute variceal haemorrhage (AVH) in patients with cirrhosis remains a topic of great interest. Although several guidelines recommend endoscopy within 24 hours after AVH, there is no consensus on the most appropriate time to perform this intervention. The purpose of this study is to identify whether urgent endoscopy (within 6 hours after gastroenterological consultation) is superior to non-urgent endoscopy (between 6 hours and 24 hours after gastroenterological consultation) in reducing the rebleeding rate of these patients. METHODS AND ANALYSIS: This is a single-centred, prospective, randomised clinical trial. Between March 2021 and December 2023, an estimated 400 patients will be randomised in a 1:1 ratio to receive endoscopic intervention either within 6 hours or between 6 and 24 hours after gastroenterological consultation. Randomisation will be conducted by permuted block randomisation, with stratification by age, systolic blood pressure and pulse rate. The primary efficacy endpoint is rebleeding within 42 days after control of AVH. The secondary efficacy endpoints mainly include all-cause mortality within 42 days after randomisation, persistent bleeding, length of hospitalisation, etc. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethical Committees of Jinling Hospital (authorised ethics no. DZQH-KYLL-21-01). This trial will provide valuable insights into the timing of endoscopic intervention for AVH in patients with cirrhosis. Furthermore, the trial results and conclusions could provide high-quality evidence to guide clinical research and treatment. TRIAL REGISTRATION NUMBER: NCT04786743.

Prediction of overall survival in patients with Stage I esophageal cancer: A novel web-based calculator.

BACKGROUND AND AIMS: In this study, we aimed to develop a convenient web-based calculator to predict the overall survival (OS) of patients with Stage I esophageal cancer (EC). METHODS: Data of 1664 patients, between 2004 and 2015, were extracted from the Surveillance, Epidemiology, and End Results database. Least absolute shrinkage and selection operator regression was employed to sift variables; subsequently, Cox proportional hazards regression model was built. We applied the enhanced bootstrap validation to appraise the discrimination and calibration of the model. Clinical benefit was measured using decision curve analysis (DCA). Thereafter, a web-based calculator based on the model, which could be used to predict the 1-, 3-, and 5-year OS rates, was developed. RESULTS: Race, age, histologic type, grade, N stage, and therapeutic methods were selected. C-indices of the prediction model in the training and validation groups were 0.726 (95% confidence interval [CI], 0.679-0.773) and 0.724 (95% CI, 0.679-0.769), respectively. Calibration curves showed good agreement between the groups. The DCA demonstrated that the prediction model is clinically useful. CONCLUSIONS: The prediction model we developed showed a good performance in calculating the OS rates in patients with Stage I EC. The web-based calculator is available at https://championship.shinyapps.io/dynnomapp/.

Serum metabolomic profiling reveals an increase in homocitrulline in Chinese patients with nonalcoholic fatty liver disease: a retrospective study.

BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) has multiple causes, is triggered by individual genetic susceptibility, environmental factors, and metabolic disturbances, and may be triggered by acquired metabolic stress. The metabolic profiles of NAFLD show significant ethnic differences, and the metabolic characteristics of NAFLD in Chinese individuals are unclear. Our study aimed to identify the metabolites and pathways associated with NAFLD in a Chinese cohort. METHODS: One hundred participants, including 50 NAFLD patients and 50 healthy controls, were enrolled in this retrospective observational study at Jinling Hospital in Nanjing; serum samples were collected from the patients and healthy subjects. The metabolome was determined in all samples by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). Univariate and multivariate statistical analyses were used to compare the metabolic profiles between the two groups. RESULTS: The comparison indicated that the levels of 89 metabolites were different between the two groups. The glycerophospholipid family of metabolites was the most abundant family of metabolites that demonstrated significant differences. L-acetylcarnitine, L-homocitrulline, and glutamic acid were the top three metabolites ranked by VIP score and had favorable effective functions for diagnosis. Moreover, pathway enrichment analysis suggested 14 potentially different metabolic pathways between NAFLD patients and healthy controls based on their impact value. Biological modules involved in the lipid and carbohydrate metabolism had the highest relevance to the conditions of NAFLD. Glycerophospholipid metabolism had the strongest associations with the conditions of NAFLD. CONCLUSIONS: Our data suggest that the serum metabolic profiles of NAFLD patients and healthy controls are different. L-Homocitrulline was remarkably increased in NAFLD patients.

NLRP3 protects mice from radiation-induced colon and skin damage via attenuating cGAS-STING signaling.

In the present study, the effects of NLRP3 on radiation-induced tissue damage, including colon and skin damage in mice, and the possible mechanisms were explored in vivo and in vitro. The mice were subjected to whole abdomen radiation by timed exposure to X-ray at a cumulative dose of 14 Gy. The survival rate showed that NLRP3 deficiency increased the mortality rate in mice. Furthermore, colon damage, evaluated by H&E staining and barrier function analysis, were significantly aggravated by NLRP3 deficiency. Enhanced phosphorylation of p-TBK1 and p-IRF3 in colonic tissue as well as elevated IFN-ß levels in the serum indicated hyperactivation of cGAS-STING signaling. Moreover, radiation-induced expression of p-TBK1, p-IRF3, and IFN-ß in BMDMs increased in vitro after NLRP3 knockout. Thus, our study outcomes suggest that NLRP3 may protect mice from radiation-induced tissue damage via attenuating cGAS-STING signaling.

Correlation of liver-to-spleen ratio on computed tomography with colorectal polyps.

Aim of the study: To explore the correlation of the liver-to-spleen (L/S) ratio on computed tomography (CT) with colorectal polyps. Material and methods: Consecutive participants from Jinling Hospital Affiliated to Nanjing University who underwent routine biochemical tests, colonoscopies, and CT between January 2018 and December 2019 were selected. The L/S ratio on CT was used to measure the liver fat content. Colonoscopy findings were applied to create the polyp-free group and colorectal polyp group. All included subjects were also classified in the non-alcoholic fatty liver disease (NAFLD) group or the non-NAFLD group according to the CT (L/S) ratio to identify risk factors for colorectal polyps. All data were analysed with SPSS 25 software. Results: Among 481 participants, 27.8% (79/284) of the patients were diagnosed with NAFLD in the colorectal group, which was higher than the corresponding proportion of the polyp-free group [9.1% (18/197)]. In NAFLD patients, most adenomatous polyps were found in the transverse colon, and hyperplastic polyps were largely located in the rectum. Linear regression suggested that the CT (L/S) ratio correlated with the number of colorectal polyps and with the number of adenomatous polyps. After adjusting for confounding factors, multivariate analysis indicated that NAFLD was an independent risk factor for adenomatous polyps and hyperplastic polyps. Conclusions: A lower CT (L/S) ratio (higher liver fat content) was significantly correlated with a higher risk of colorectal polyps. This finding suggested that NAFLD patients with a reduced CT (L/S) ratio need to undergo colonoscopy examinations to detect high-risk colorectal polyps in a timely manner.

High-throughput sequencing provides insights into oral microbiota dysbiosis in association with inflammatory bowel disease.

Although the prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, the etiology remains elusive. Investigating oral microbiota dysbiosis is essential to understanding IBD pathogenesis. Our study evaluated variations in salivary microbiota and identified potential associations with IBD. The saliva microbiota of 22 IBD patients and 8 healthy controls (HCs) was determined using 16S ribosomal RNA (rRNA) gene sequencing and analyzed using QIIME2. A distinct saliva microbiota dysbiosis in IBD, characterized by alterations in microbiota biodiversity and composition, was identified. Saccharibacteria (TM7), Absconditabacteria (SR1), Leptotrichia, Prevotella, Bulleidia, and Atopobium, some of which are oral biofilm-forming bacteria, were significantly increased. Moreover, levels of inflammatory cytokines associated with IBD were elevated and positively correlated with TM7 and SR1. Functional variations include down-regulation of genetic information processing, while up-regulation of carbohydrate metabolism and protein processing in the endoplasmic reticulum in IBD. Our data implicate salivary microbiota dysbiosis involving in IBD pathogenesis.

Clinical Features and Prognosis of Crohn's Disease with Upper Gastrointestinal Tract Phenotype in Chinese Patients.

BACKGROUND: The epidemiology of upper gastrointestinal (L4) Crohn's disease in China remains poorly characterized. AIMS: We aimed to identify the clinical characteristics of L4 disease and clarify the relationship between disease characteristics at diagnosis and early outcomes. METHODS: We retrospectively enrolled 246 patients diagnosed between 2013 and 2017 and followed up for > 1 year post-diagnosis. Primary outcomes included the 1-year rates of hospitalization and abdominal surgery according to disease location and behavior. RESULTS: Of 80 patients with L4 disease (61, 25, and 18 with esophagogastroduodenal, jejunal, and proximal ileal involvement, respectively), none had granuloma, whereas 66.7%, 50%, 46.9%, 75%, and 70% had disease-specific endoscopic lesions in the esophagus, stomach, duodenum, jejunum, and proximal ileum, respectively. Compared to non-L4 disease, L4 disease was associated with higher rates of abdominal surgery (41.3% vs. 11.4%, P < 0.001) but similar rates of hospitalization within 1 year post-diagnosis. In L4 disease, jejunal and proximal ileal involvement was associated with stricturing behavior (P = 0.034, P < 0.001) and higher abdominal surgery rate (both: P < 0.001). Risk factors for abdominal surgery within 1 year post-diagnosis included age ≥ 40 years (OR 1.920; 95% CI 1.095-3.367), L4 phenotype (OR 6.335; 95% CI 3.862-10.390), stricturing disease (OR 3.162; 95% CI 1.103-9.866), and penetrating disease (OR 11.504; 95% CI 3.409-38.825), whereas the protective factor was female sex (OR 0.214; 95% CI 0.123-0.373). CONCLUSIONS: Early outcomes are worse for L4 than for non-L4 disease. Jejunoileum involvement predicts stricturing disease and early surgery. More aggressive initial therapy is needed to improve L4-disease prognosis.

Serum Procalcitonin as a Potential Early Predictor of Short-Term Outcomes in Acute Severe Ulcerative Colitis.

BACKGROUND: Delayed colectomy can be life-threatening for patients with acute severe ulcerative colitis (ASUC). However, few biomarkers can predict the outcomes of ASUC patients before treatment. Serum procalcitonin (PCT) has been observed to be increased in ASUC patients. AIM: The aim of this study was to estimate the association between serum PCT and short-term outcomes in patients with ASUC. METHODS: A single-center observational study was conducted at a referral hospital from January 2012 to January 2018. Hospitalized ASUC patients, who were administered intravenous corticosteroids (IVCS), were enrolled and followed up for 6 months. The primary outcome was IVCS failure; the secondary outcome was colectomy. Relationships between indicators and clinical outcomes were assessed. RESULTS: Of 152 ASUC patients enrolled in this study, 81 responded to IVCS and 71 failed (62 required short-term colectomy and 9 responded to second-line rescue therapy). Serum PCT on admission was significantly higher in IVCS-failure cases and surgical cases than in medical responders. Serum PCT ≥ 0.10 µg/L (OR = 4.134, p = 0.001) predicted IVCS failure with specificity of 0.741, and the combined measurement with fecal calprotectin (FC) ≥ 1500 µg/g improved the sensitivity. Serum PCT correlated significantly with the Ulcerative Colitis Endoscopic Index of Severity (r = 0.416, p < 0.001) and FC (r = 0.384, p < 0.001). CONCLUSION: Serum PCT on admission could be a potential early non-invasive predictive biomarker for IVCS failure in ASUC patients, and a combination of PCT and FC could improve the predictive value.

Comparison of the short-term and long-term outcomes of surgical treatment versus endoscopic treatment for early esophageal squamous cell neoplasia larger than 2 cm: a retrospective study.

BACKGROUND: NCCN Guidelines of esophageal cancer recommend that endoscopic therapy is considered "preferred" for patients with limited early-stage disease less than or equal to 2 cm. However, there is currently no definite evidence to support either endoscopic therapy or esophagectomy for early esophageal cancer larger than 2 cm. We aimed to explore the optimal treatment for this condition. METHODS: From January 2010 to June 2016, 116 patients with early esophageal neoplasia [high-grade dysplasia (HGD), lamina propria and muscularis mucosae (T1a) cancer, selected superficial submucosa (T1b) cancer without lymph node metastases] larger than 2 cm and treated either surgically or endoscopically were included. RESULTS: Endoscopic therapy was performed in 69 patients and esophagectomy in 47 patients, respectively. The median follow-up time was 43.8 months in the endoscopic cohort and 49.4 months in the surgical cohort. The overall survival was similar between the two cohorts (97.1% vs. 91.5%, P = 0.18). Survival without readmission for treatment-related complicates was also similar. Minor and severe procedure-related complications occurred more often in the surgical cohort than in the endoscopic cohort (63.8% vs. 43.5% and 8.5% vs. 0 respectively, P < 0.05 for both). Four patients in the endoscopic cohort had to undergo additional esophagectomy and were alive during follow-up. There were no procedure-related deaths in the endoscopic cohort, whereas two deaths occurred in the surgical cohort. Recurrence occurred in nine patients in the endoscopic group (13%): six with local recurrence, one with residual neoplasia and two with metachronous neoplasia. None of them died after repeated endoscopic treatments. CONCLUSIONS: Efficacy was similar between endoscopic therapy and esophagectomy in the treatment of early esophageal squamous cell neoplasia larger than 2 cm and endoscopic therapy was associated with fewer and manageable complications. We recommend endoscopic treatment should be preferred selected for early esophageal neoplasia larger than 2 cm.

Helicobacter pylori infection and inflammatory bowel disease in Asians: a meta-analysis.

AIM: To investigate the relationship between Helicobacter pylori infection and inflammatory bowel disease (IBD) in an Asian population. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched for observational studies published up until June 2014, without language restrictions. Additional references were obtained from reviewed articles. RESULTS: Ten studies involving 1299 IBD patients and 1817 controls were included in the meta-analysis (24.9% of IBD patients had H. pylori infection vs 48.3% of the controls). The pooled risk ratio for H. pylori infection in IBD patients compared with controls was 0.48 (95%CI: 0.43-0.54; P < 0.001). There was no significant heterogeneity in the included studies (I (2) = 21%). Egger's linear regression indicated that there was no significant publication bias (P = 0.203). CONCLUSION: The H. pylori infection rate in Asian IBD patients is significantly lower than in non-IBD patients, indicating that infection protects against the development of IBD.

Unfavorable outcome of antiviral therapy in cytomegalovirus-positive ulcerative colitis may be due to inappropriate study inclusion in meta-analysis.

Some previous articles reported that antiviral treatment was effective to reduce the colectomy rate in ulcerative colitis (UC) patients with cytomegalovirus (CMV) infection. Kopylov et al recently carried out a systematic review and meta-analysis to evaluate the impact of antiviral therapy on CMV-positive UC. The results showed that patients who received antiviral treatment had a higher risk of 30-d colectomy. We found that in this meta-analysis, some studies were inappropriately included, leading to an unfavorable outcome of anti-CMV therapy in UC patients.

Confusing untypical intestinal Behcet's disease: Skip ulcers with severe lower gastrointestinal hemorrhage.

Behcet's disease (BD) is a rare and life-long disorder characterized by inflammation of blood vessels throughout the body. BD was originally described in 1937 as a syndrome involving oral and genital ulceration in addition to ocular inflammation. Intestinal BD refers to colonic ulcerative lesions documented by objective measures in patients with BD. Many studies have shown that over 40% of BD patients have gastrointestinal complaints. Symptoms include abdominal pain, diarrhea, nausea, anorexia and abdominal distension. Although gastrointestinal symptoms are common, the demonstration of gastrointestinal ulcers is rare. This so-called intestinal BD accounts for approximately 1% of cases. There is no specific test for BD, and the diagnosis is based on clinical criteria. The manifestations of intestinal BD are similar to those of other colitis conditions such as Crohn's disease or intestinal tuberculosis, thus, it is challenging for gastroenterologists to accurately diagnose intestinal BD in patients with ileo-colonic ulcers. However, giant ulcers distributed in the esophagus and ileocecal junction with gastrointestinal hemorrhage are rare in intestinal BD. Here, we present a case of untypical intestinal BD. The patient had recurrent aphthous ulceration of the oral mucosa, and esophageal and ileo-colonic ulceration, but no typical extra-intestinal symptoms. During examination, the patient had massive acute lower gastrointestinal bleeding. The patient underwent ileostomy after an emergency right hemicolectomy and partial ileectomy, and was subsequently diagnosed with incomplete-type intestinal BD by pathology. The literature on the evaluation and management of this condition is reviewed.

Involvement of 90-kuD ribosomal S6 kinase in collagen type I expression in rat hepatic fibrosis.

AIM: To investigate the relationship between 90-kuD ribosomal S6 kinase (p90RSK) and collagen type I expression during the development of hepatic fibrosis in vivo and in vitro. METHODS: Rat hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine. The protein expression and cell location of p90RSK and their relationship with collagen type I were determined by co-immunofluoresence and confocal microscopy. Subsequently, RNAi strategy was employed to silence p90RSK mRNA expression in HSC-T6, an activated hepatic stellate cell (HSC) line. The expression of collagen type I in HSC-T6 cells was assessed by Western blotting and real-time polymerase chain reaction. Furthermore, HSCs were transfected with expression vectors or RNAi constructs of p90RSK to increase or decrease the p90RSK expression, then collagen type I promoter activity in the transfected HSCs was examined by reporter assay. Lastly HSC-T6 cells transfected with p90RSK siRNA was treated with or without platelet-derived growth factor (PDGF)-BB at a final concentration of 20 microg/L and the cell growth was determined by MTS conversion. RESULTS: In fibrotic liver tissues, p90RSK was over-expressed in activated HSCs and had a significant positive correlation with collagen type I levels. In HSC-T6 cells transfected with RNAi targeted to p90RSK, the expression of collagen type I was down-regulated (61.8% in mRNA, P < 0.01, 89.1% in protein, P < 0.01). However, collagen type I promoter activity was not increased with over-expression of p90RSK and not decreased with low expression either, compared with controls in the same cell line (P = 0.076). Furthermore, p90RSK siRNA exerted the inhibition of HSC proliferation, and also abolished the effect of PDGF on the HSC proliferation. CONCLUSION: p90RSK is over-expressed in activated HSCs and involved in regulating the abnormal expression of collagen type I through initiating the proliferation of HSCs.

Differential expression genes analyzed by cDNA array in the regulation of rat hepatic fibrogenesis.

PURPOSE: To analyze the gene expression pattern in rat hepatic fibrogenesis and further assess the role of some key genes during the pathological process. METHODS: Hepatic fibrosis was induced by intraperitoneal injection of dimethylnitrosamine or carbon tetrachloride (CCl(4)) injection subcutaneously in rats, and identification of the hepatic fibrosis related genes with cDNA microarray was performed. After some key genes up-regulated during the development of hepatic fibrosis were screened and confirmed, their effects on the function of the activated rat hepatic stellate cells (HSC) were assessed using the small interfering RNA (siRNA) technique. RESULTS: Using an Atlas rat cDNA array, a number of differentially expressed genes in fibrotic liver tissues were identified compared with non-diseased control. A total of 15 genes predominantly associated with the mitogen-activated protein kinase (MAPK) signal transduction pathway were upregulated in the fibrotic liver. Immunohistochemical study revealed that the expressions of both extracellular signal-regulated kinases (ERK) and ribosomal protein S6 kinase (RSK), two of the key genes in the MAPK pathway, were remarkably induced, which was closely correlated to that of collagen types I and III during the development of hepatic fibrosis. Transfection of siRNA targeting ERK1 mRNA (siERK1) into HSC led to a 66% and 72% reduction of ERK1 mRNA and protein expression, respectively. Furthermore, siERK1 exerted the inhibition of the proliferation of HSC, accompanied by the induction of HSC apoptosis and reduction of collagen types I and III. In addition, siERK1 abolished the effect of platelet-derived growth factor-BB on the proliferation of HSC. CONCLUSIONS: The present study provided strong evidence for the participation of the MAPK pathway in the pathogenesis of hepatic fibrosis. Selective targeting of ERK1 inhibitors to HSC might present as a novel strategy for the treatment of hepatic fibrosis.