Risk of HCC decreases in HBV-related patients with cirrhosis acquired recompensation: A retrospective study based on Baveno VII criteria.

BACKGROUND: Antiviral therapy improves the clinical outcomes of patients with HBV-related cirrhosis. In this study, we aimed to evaluate the incidence rate of HCC in patients with HBV-related recompensated, compensated, or decompensated cirrhosis based on the latest Baveno VII criteria. METHODS: In this two-center retrospective study, HBV-related patients with cirrhosis were enrolled and treated with first-line nucleos(t)ide analogues therapy for at least 12 months. Participants were classified into 3 groups: (1) compensated group, (2) decompensated group, or (3) recompensated group according to Baveno VII criteria. Multivariate regression models and propensity score matching were used to identify the predictors of HCC. RESULTS: Of the 404 patients recruited, during a median follow-up of 44.5 months (interquartile range 26.8, 57.0 months), 233 (57.7%), 100 (24.8%), and 71(17.6%) patients had compensated, recompensated, and decompensated cirrhosis. In total, 38 developed HCC. The cumulative incidence of HCC development at 2, 4, and 6 years was 1.3%, 5.4%, and 20.0% in the compensated group, 1.2%, 5.2%, and 24.5% in the recompensated group, and 2.1%, 23.6%, and 41.8% in the decompensated group, respectively. In the multivariate Cox regression model, compared with the recompensated group, the decompensated group had a significant increased risk for the development of HCC (aHR 2.55; 95% CI: 1.240-5.240; p = 0.027), while the compensated group had similar HCC risk for the development of HCC (aHR 1.41; 95% CI: 0.540-3.730; p = 0.835). Propensity score-matching analysis between the recompensated and compensated groups (84 pairs) and propensity score-matching analysis between the recompensated and decompensated groups (62 pairs) showed similar results. CONCLUSIONS: Achieving recompensation reduced the risk of HCC in patients with HBV-related decompensated cirrhosis, while the risk remained comparable to that of compensated cirrhosis.

Identification of Hub Genes and Immune Infiltration in Non-alcoholic Fatty Liver Disease -Related Hepatocellular Carcinoma by Bioinformatics Analysis.

BACKGROUND: Non-alcoholic fatty liver disease has been a significant risk factor for hepatocellular carcinoma. In the study, we aimed to identify the key genes associated with the transition from non-alcoholic fatty liver disease to hepatocellular carcinoma through bioinformatics analysis. METHODS: The GSE164760 dataset was used for identifying differentially expressed genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to explore the potential function of the differentially expressed genes. Subsequently, the protein-protein interaction network was constructed to select hub genes, and the immune cell infiltration was analyzed. Finally, the receiver operating characteristic analysis was performed to assess the diagnostic ability of the crucial genes. RESULTS: A total of 156 differentially expressed genes were identified. Gene Ontology enrichment analysis indicated that differentially expressed genes were strongly associated with cellular hormone metabolic process, response to xenobiotic stimulus, collagen-containing extracellular matrix, detoxification, and regulation of growth. In the protein-protein interaction network, ESR1, CAT, CXCL8, CD4, SPP1, CYP2E1, CYP3A4, UGT2B7, GSTA1 and THBS1 were selected as the hub genes. Immune infiltration analysis demonstrated that M0 macrophages, plasma cells, CD8+T cell and M2 macrophages were significantly changed in tumor tissues. Finally, we verified the hub gene expression and selected CD4, UGT2B7, and CYP3A4 as the potential diagnostic biomarkers. CONCLUSION: CD4, UGT2B7, and CYP3A4 were selected as the potential diagnostic biomarkers of non-alcoholic fatty liver disease-hepatocellular carcinoma.

Animal naming test for the assessment of minimal hepatic encephalopathy in Asian cirrhotic populations.

BACKGROUND AND AIM: To evaluate the diagnostic performance of simplified animal naming test (S-ANT1) for minimal hepatic encephalopathy (MHE) in patients with cirrhosis from a Chinese tertiary centre and to optimize the application strategy of S-ANT1 in clinical practice. METHODS: The Animal Naming Test 1 (ANT1) was performed in all included cirrhotic patients and healthy volunteers. S-ANT1 was calculated to adjust for age and education. Psychometric Hepatic Encephalopathy Score (PHES) was also performed in patients with cirrhosis. RESULTS: 88 cirrhotic patients and 34 healthy control subjects were included. Cirrhotic patients were characterized with lower S-ANT1 scores (P =  0.001). In patients with cirrhosis, score of S-ANT1 was correlated with PHES score, age, school education period, and blood ammonia (all P values <0.05). With ≤20 animals as the cut-off value, S-ANT1 could distinguish MHE and no MHE with a sensitivity of 77.5% and a specificity of 58.3%. A three-step screening strategy, with 90% as a threshold for sensitivity and specificity and two cut-off values "≤12 animals" and ">23 animals", was then formulated to rule out patients with high possibility of MHE and with high possibility of no MHE. The remaining "ruled-in" patients should be further evaluated for MHE using PHES. CONCLUSIONS: S-ANT1 is an important screening tool for MHE in cirrhotic patients. The three-step screening strategy based on S-ANT1 and PHES is conducive to the identification of MHE in clinical practice.

Psychological impact of coronavirus disease (2019) (COVID-19) epidemic on medical staff in different posts in China: A multicenter study.

OBJECTIVE: An outbreak of coronavirus disease 2019 (COVID-19) is a public health emergency of international concern and poses a big challenge to medical staff and general public. The aim is to investigate psychological impact of COVID-19 epidemic on medical staff in different working posts in China, and to explore the correlation between psychological disorder and the exposure to COVID-19. METHODS: A multicenter WeChat-based online survey was conducted among medical staff in China between 26 February and 3 March 2020. Medical staff deployed to Hubei province from other provinces and medical staffs in different posts outside Hubei were selected to represent diverse exposure intensities to the threat of COVID-19. Anxiety, depression, sleep quality, stress and resilience were evaluated using scales including GAD-7, PHQ-9, PSQI, PSS-14, and CD-RISC-10. Latent class analysis was performed to identify potential staff requiring psychological support. RESULTS: A total of 274 respondents were included, who serving at 4 posts as follows, staff backing Hubei province, isolation wards outside Hubei, fever clinic and infectious disease department, and other departments outside Hubei. The total scores of anxiety, depression, sleep quality and stress were statistically different among groups, meanwhile an increasing tendency of anxiety, depression and sleep quality scores with increasing risk of exposure to COVID-19 was found (p < 0.05). Subsequent post-hoc analysis indicated that the staff backing Hubei had higher scores of anxiety, depression, sleep quality and perceived stress (adjusted p < 0.05). The combined prevalence of anxiety, depression and insomnia of staff backing Hubei reached as high as 38%. Four-class latent class analysis showed 3 categories of population (69.4%) may need psychological support. CONCLUSIONS: High prevalence of anxiety, depression and insomnia exist in medical staff related to COVID-19. The higher the probability and intensity of exposure to COVID-19 patients, the greater the risk that medical staff will suffer from mental disorders, suggesting continuous and proper psychiatric intervention are needed.

Prognostic Value of Noninvasive Fibrosis Scores in Primary Biliary Cholangitis.

OBJECTIVE: To explore the prognostic value of several widely used noninvasive fibrosis scores (NIFS) for the mortality due to liver-related events in Chinese primary biliary cholangitis (PBC) population. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Hepatology, the Second Hospital of Shandong University, Jinan, China, from August 2008 to July 2018. METHODOLOGY: Patients were diagnosed as PBC when they fulfilled at least two of the following criteria: presence of antimitochondrial antibodies (AMA), or other PBC-specific autoantibodies; and/or biochemical evidence of cholestasis; and/or histological evidence of liver biopsy. Patients were excluded if they were just started UDCA administration within last year, followed up for less than a year, diagnosed as overlap syndrome, or suffered from other coexisting hepatic diseases. Clinical data were recorded and scores of 11 generally accepted NIFS were calculated. Cox proportional hazards model was performed to explore independent predictors of liver-related mortality. RESULTS: Sixty-five PBC patients were included in the current cohort. Five patients died due to liver-related events during a median of 35-month follow-up. The 5-year cumulative survival rate was 88.4%. Non-survival patients were characterised with lower platelet count (p=0.049), lower level of albumin (p=0.018), higher fibrosis index (p<0.001) and higher Doha score (p=0.006). Multivariate Cox regression analysis identified fibrosis index (HR 17.449, 95% CI 1.410-215.989, p=0.026) and Doha score (HR 1.782, 95% CI 1.146-2.771, p=0.010) as independent predictors for liver-related mortality of PBC patients. CONCLUSION: Fibrosis index and Doha score could serve as valuable prognostic factors for liver-related mortality in Chinese PBC population.

Hepatic Steatosis in Chronic Hepatitis B as Measured by Controlled Attenuation Parameter: Frequency and Distribution.

OBJECTIVE: To determine the frequency of liver steatosis in chronic hepatitis B (CHB) patients measured by controlled attenuation parameter (CAP) and to describe the distribution of fibrosis and inflammation in different steatosis grading. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Hepatology, The Second Hospital of Shandong University, Jinan, China, from January 2017 to December 2018. METHODOLOGY: CHB patients who were evaluated with transient elastography (TE) for liver fibrosis and steatosis were included. Liver biochemical testing was performed within 3 days of TE measurements. Steatosis grading was assessed as S0 (no steatosis, CAP 0-247 dB/m), S1 (mild steatosis, CAP 248-267 dB/m), S2 (moderate steatosis, CAP 268-279 dB/m) and S3 (severe steatosis, CAP >=280 dB/m). Statistically comparisons of continuous variables or percentages were performed. RESULTS: A total of 1,621 CHB patients were included. The frequencies of liver steatosis in CHB patients were 35.4% (574 patients), of which 314 patients (19.3%) were diagnosed as severe steatosis (grading S3). Comparisons of age, gender and liver fibrosis in different steatosis grading revealed no statistical differences (p=0.109, 0.075 and 0.269, respectively). However, ALT values in patients with severe steatosis (grading S3) were higher than those patients with steatosis grading S0 (p<0.001) and S2 (p=0.047). CONCLUSION: Steatosis is common in CHB patients. Liver fibrosis seemed not discrepant in different steatosis grading. More obvious hepatic inflammation is seen in CHB patients with severe steatosis.

Entecavir and Low Genetic Barrier Antiviral Agents for Hepatocellular Carcinoma in Hepatitis B Viral Cirrhosis: Propensity Score Matching.

OBJECTIVE: To compare the reduction of hepatocellular carcinoma (HCC) risk between long-term treatment of entecavir and low genetic barrier antiviral agents in hepatitis B virus (HBV)-related cirrhotic patients. STUDY DESIGN: An observational study. PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Hepatology, the Second Hospital of Shandong University, Jinan, China, from October 2008 to October 2016. METHODOLOGY: HBV-related cirrhotic patients with antiviral treatment for at least 12 months were consecutively included. Propensity score matching analysis was performed to improve comparability of the data from both entecavir group and the control group. Log-rank test was used to compare influence of various nucleos(t)ide analogs (NAs) for incidence of HCC. Independent risk factors were estimated by multivariable Cox proportional hazards models. RESULTS: The total cohort included 207 HBV-related cirrhotic patients, of which 83 patients were treated with entecavir initially. The present study found no statistical difference for the incidence of HCC between entecavir group and the control group in the total cohort (p=0.525). However, the difference became statistically significant (p=0.014) after propensity score matching. Number needed to treat (NNT) were 8 patients, 6 patients and 3 patients at years 2, 3 and 4, respectively. Multivariable Cox regression in propensity score matching cohort revealed older age (HR: 1.066, p=0.041), NAs of low generic barrier (HR: 6.944, p=0.016), NAs resistance (HR: 3.648, p=0.041), and lower platelet counts (<80x10 9/L) (HR: 6.718, p=0.009) as independent risk factors for HCC incidence. CONCLUSION: Entecavir is more efficient in reducing the incident HCC risk for HBV-related cirrhotic patients in comparison to low genetic barrier NAs.

Efficacy and safety of sofosbuvir and daclatasvir in treatment of kidney transplantation recipients with hepatitis C virus infection.

AIM: To assess the efficacy and safety of sofosbuvir and daclatasvir regimens for kidney transplantation (KT) patients with hepatitis C virus (HCV) infection. METHODS: This study enrolled a prospective cohort of consecutive Chinese KT patients with HCV infection. They were given sofosbuvir combined with daclatasvir, with or without ribavirin. They were monitored regularly during and after the treatment. RESULTS: Six patients were recruited in our prospective study cohort. All patients were male and naive to direct-acting antiviral treatment. The treatment duration was 12 wk. Most patients (4/6) were infected with HCV genotype 1b. HCV RNA was undetectable at week 4 after treatment and at the end of treatment in all patients. Sustained virological response rate at 12 wk was 100% (6/6). Two patients had to accept a half dose of sofosbuvir due to serum creatinine elevation during treatment. Kidney function in the remaining patients was stable. No serious adverse events (AEs) were observed. No patient discontinued antiviral therapy due to side effects. CONCLUSION: Sofosbuvir and daclatasvir for treatment of KT recipients with HCV infection are highly efficient and safe. Patients tolerated the medications well, and no serious AEs were observed. Larger prospective cohort studies are needed to validate these results.

Efficacy and safety of direct-acting antivirals-based antiviral therapies for hepatitis C virus patients with stage 4-5 chronic kidney disease: a meta-analysis.

BACKGROUND & AIMS: The aim of this study was to assess the efficacy and safety of direct-acting antivirals (DAA)-based antiviral therapies for HCV patients with stage 4-5 chronic kidney disease. METHODS: We conducted a systematic literature search in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time and language limitations. The search strategy used was "(End stage renal disease OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR dialysis) AND (sofosbuvir OR simeprevir OR grazoprevir OR elbasvir OR ombitasvir OR paritaprevir OR ritonavir OR dasabuvir OR daclatasvir OR asuparevir OR direct-acting antiviral OR DAA)". Sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs) and/or serious adverse events (SAEs) with 95% confidence intervals (CI) were pooled. RESULTS: Eleven studies, comprising a total of 264 patients were included for our meta-analysis. The pooled SVR12 rate were 93.2% (95% CI 89.9%-95.9%, I2 =0.0%), 89.4% (95% CI 82.0%-95.0%, I2 =0.0%) and 94.7% (95% CI 91.0%-97.5%, I2 =0.0%) in total population, patients with sofosbuvir-based therapies and patients with non-sofosbuvir-based therapies respectively. For HCV genotype 1 patients, the pooled SVR12 rate was 93.1% (95% CI 88.3%-96.7%, I2 =20.0%). The pooled incidence of SAEs was 12.1% (95% CI 6.2%-19.7%, I2 =55.0%). The pooled discontinuation rate because of AEs or SAEs in our meta-analysis was 2.2% (95% CI 0.8%-4.4%, I2 =0.0%). CONCLUSIONS: DAA-based antiviral therapies are effective and well-tolerated for HCV patients with stage 4-5 chronic kidney disease.

Efficacy and safety of sofosbuvir-based interferon-free therapies for hepatitis C in liver transplant recipients.

BACKGROUND AND AIM: The aim of this study is to assess the efficacy and safety of sofosbuvir-based interferon-free therapies in liver transplantation recipients with hepatitis C virus infection recurrence. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time or language limitation. The search strategy used was "sofosbuvir AND transplantation." Sustained virologic response at 12 weeks after the end of treatment (SVR12) rate, incidence of serious adverse events (SAEs) and/or adverse events, discontinuation rate with 95% confidence intervals (CI) were pooled with random-effects model. RESULTS: Twenty-two studies (1730 patients) were included for our meta-analysis. The pooled SVR12 rate was 90.1% (95% CI 86.4-93.4%, I2 = 81.6%). SVR12 rate was higher in patients with mild fibrosis than in patients with advanced fibrosis and cirrhosis (RR = 1.072, 95% CI 1.031-1.115, I2 = 3.6%). For patients with hepatitis C virus genotype 1, the pooled SVR12 rate was 91.9% (95% CI 89.2-94.2%, I2 = 53.3%). The pooled SAEs incidence was 8.3% (95% CI 5.6-11.5%, I2 = 78.4%). The pooled discontinuation rate because of adverse events or SAEs was 3.3% (95% CI 1.8-5.2%). CONCLUSIONS: Sofosbuvir-based interferon-free therapy is an effective and well-tolerated treatment strategy for patients with hepatitis C virus infection recurrence after liver transplantation.

A Beginning or the End? A Meta-analysis to Assess the Diagnostic Accuracy of Transient Elastography for the Prediction of Esophageal Varices.

BACKGROUND/AIMS: To assess the accuracy of transient elastography (TE) in the prediction of esophageal varices (EV). MATERIALS AND METHODS: The literature search was conducted by using PubMed, EMBASE, Web of Science, and CENTRAL on The Cochrane Library without time or language restrictions. Terms used were "FibroScan," "transient elastography," "stiffness," and "esophageal varices." The pooled sensitivity, specificity, and other parameters were obtained using a bivariate mixed-effects regression model. RESULT: Twenty studies (2530 patients) were identified for inclusion. The pooled sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio were 0.84 (95% confidence interval [CI], 0.79-0.87), 0.68 (95% CI, 0.61-0.73), 2.58 (95% CI, 2.15-3.10), 0.24 (95% CI, 0.19-0.32), and 10.60 (95%CI, 7.20-15.62), respectively. The summary area under receiver operating characteristics (AUROC) curves was 0.82 (95% CI, 0.79-0.86). Especially, for hepatitis C patients, the diagnostic performance of TE for detecting the presence of EV was similar to all other patients with a sensitivity of 0.83 and a specificity of 0.63, but without heterogeneity (I2 = 0.00). For the prediction of large esophageal varices in patients with viral liver cirrhosis, the pooled sensitivity and specificity of TE were 0.82 (95% CI 0.74-0.89) and 0.77 (95% CI 0.65-0.85), respectively, without significant heterogeneity (I2 = 0.00). CONCLUSION: Transient elastography has good sensitivity and moderate specificity. TE can be used as an effective noninvasive screening tool for the prediction of esophageal varices, especially in hepatitis C patients, and for the prediction of large esophageal varices in patients with viral liver cirrhosis.

Evaluation of large esophageal varices in cirrhotic patients by transient elastography: a meta-analysis

Background and purpose: Transient elastography (TE) has been shown to be a valuable tool for the prediction of large esophageal varices. However, the conclusions have not been always consistent throughout the different studies. Therefore, we performed a further meta-analysis in order to evaluate the diagnostic accuracy of transient elastography for the prediction of large esophageal varices. Methods: We performed a systematic literature search in PubMed, EMBASE, Web of Science, and CENTRAL in The Cochrane Library without time restriction. The strategy we used was "(fibroscan OR transient elastography OR stiffness) AND esophageal varices". Accuracy measures such as pooled sensitivity, specificity, among others, were calculated using Meta-DiSc statistical software. Results: Twenty studies (2,994 patients) were included in our meta-analysis. The values of pooled sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio were as follows: 0.81 (95% CI, 0.79-0.84), 0.71 (95% CI, 0.69-0.73), 2.63 (95% CI, 2.15-3.23), 0.27 (95% CI, 0.22-0.34) and 10.30 (95% CI, 7.33-14.47). The area under the receiver operating characteristics curve was 0.83. The Spearman correlation coefficient was 0.246 ith a p-value of 0.296, indicating the absence of any significant threshold effects. In our subgroup analysis, the heterogeneity could partially explained by the geographical origin of the study or etiology; or it could be partially explained blindingly, through the appropriate interval and cut-off value of the liver stiffness (LS). Conclusions: Transient elastography could be used as a valuable non-invasive screening tool for the prediction of large esophageal varices. However, since LS cut-off values vary throughout the different studies and significant heterogeneity also exists among them, we need more reasonable approaches or flow diagram in order to improve the operability of this technology (AU)

No disponible

Evaluation of large esophageal varices in cirrhotic patients by transient elastography: a meta-analysis.

BACKGROUND AND PURPOSE: Transient elastography (TE) has been shown to be a valuable tool for the prediction of large esophageal varices. However, the conclusions have not been always consistent throughout the different studies. Therefore, we performed a further meta-analysis in order to evaluate the diagnostic accuracy of transient elastography for the prediction of large esophageal varices. METHODS: We performed a systematic literature search in PubMed, EMBASE, Web of Science, and CENTRAL in The Cochrane Library without time restriction. The strategy we used was "(fibroscan OR transient elastography OR stiffness) AND esophageal varices". Accuracy measures such as pooled sensitivity, specificity, among others, were calculated using Meta-DiSc statistical software. RESULTS: Twenty studies (2,994 patients) were included in our meta-analysis. The values of pooled sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratio were as follows: 0.81 (95% CI, 0.79-0.84), 0.71 (95% CI, 0.69-0.73), 2.63 (95% CI, 2.15-3.23), 0.27 (95% CI, 0.22-0.34) and 10.30 (95% CI, 7.33-14.47). The area under the receiver operating characteristics curve was 0.83. The Spearman correlation coefficient was 0.246 with a p-value of 0.296, indicating the absence of any significant threshold effects. In our subgroup analysis, the heterogeneity could be partially explained by the geographical origin of the study or etiology; or it could be partially explained blindingly, through the appropriate interval and cut-off value of the liver stiffness (LS). CONCLUSIONS: Transient elastography could be used as a valuable non-invasive screening tool for the prediction of large esophageal varices. However, since LS cut-off values vary throughout the different studies and significant heterogeneity also exists among them, we need more reasonable approaches or flow diagram in order to improve the operability of this technology.

Efficacy and safety of simeprevir for chronic hepatitis virus C genotype 1 infection: A meta-analysis.

BACKGROUND AND OBJECTIVE: To gain a profile of the efficacy and safety of simeprevir-based triple therapy in chronic hepatitis virus C (HCV) genotype 1 infected patients. METHODS: We searched in Medline, Embase, Cochrane database of systematic reviews and CINAHL for randomized controlled trials (RCTs) without year or language restriction. Eligible studies should evaluate simeprevir plus peginterferon and ribavirin combination therapy for chronic hepatitis C genotype 1 patients, while the standard peginterferon and ribavirin therapy as control group. Results must include the data of achieving sustained virological response (SVR), rapid virological response (RVR), incidence of discontinuation and severe adverse events (SAE). RESULTS: Six RCTs (2209 patients) were included. The proportion of achieving SVR at 12 weeks after planned end of treatment (SVR12) was significantly higher in the simeprevir group than in the control group (RR=1.69, 95%CI: 1.37-2.08, P<0.001). The results also showed that the RVR rate was significantly higher in the simeprevir group (RR=9.57, 95%CI: 5.82-15.73, P<0.001). The addition of simeprevir was not accompanied with the increased risks of SAE (RR=0.67, 95%CI: 0.47-0.94, P=0.023). The incidence of discontinuation due to adverse events seems a little higher in simeprevir group than in the control group (3.0% vs. 1.1%), though there was no statistical difference (RR=1.26, 95%CI: 0.58-2.74, P=0.566). CONCLUSION: Simeprevir-based triple therapy significantly increase the SVR12 rate and RVR rate without increasing the incidences of SAE and treatment discontinuation due to adverse events. However, further inquiries on the long-term safety of simeprevir are required in future.

The different expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and possible roles in gastric carcinomas.

The purpose of this study was to investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its effects on promoting angiogenesis in gastric adenocarcinomas. Paraffin wax sections of 222 patients with gastric adenocarcinomas having undergone surgery between 2001 and 2006 were classified into three histotypes: intestinal, diffuse, and mixed carcinomas following the Laurén classification. Immunohistochemistry (IHC) was used to study the distribution of CEACAM1, and double-labeling immunohistochemistry was used to observe the relationship between CEACAM1 expression and neovascularization in carcinoma areas. No CEACAM1 expression was found in normal non-metaplastic mucosa adjacent to the tumors; but in metaplastic mucosa, CEACAM1 was expressed on the apical surface. However, all of the collected gastric carcinomas expressed CEACAM1 with cytoplasmic or membranous staining. CEACAM1 was expressed mainly with a membranous pattern in the intestinal carcinomas, and with a cytoplasmic pattern in the diffuse carcinomas. There was a significant difference between the expression patterns and the histotypes (P<0.0001). CEACAM1 expression was classified as high (> or =66% positive cells) and low (<66% positive cells), and high CEACAM1 expression was associated with lymph nodes metastasis (P<0.05). High microvessel density (MVD) was observed more frequently in the tumors with membranous expression, and low MVD in the tumors with cytoplasmic staining (P<0.0001). The transformation of CEACAM1 distribution from membrane to cytoplasm is an important incident for the reverse effects on the tumorous angiogenesis, and high expression of CEACAM1 facilitates the metastasis of carcinoma cells to lymph nodes. Moreover, the different distribution of CEACAM1 in the intestinal and diffuse carcinomas indicates a different tumorigenic pathway.

Inhibitory effects of short hairpin RNA against caspase-8 on apoptosis of murine hepatoma Hepa1-6 cells.

Caspase-8 plays an important role in death-receptor-mediated apoptosis of hepatocytes. We constructed short hairpin RNAs (shRNAs) against caspase-8 and investigated the effects of caspase-8 targeting shRNAs on apoptosis of Hepa1-6 cells induced by TNF-alpha. Oligonucleotides coding for four shRNAs against caspase-8 were cloned into mammalian expression vector Pgenesil-1 containing U6 promoter, which were then introduced into Hepa1-6 cells using liposome-mediated transfection. Effects of caspase-8-shRNAs on apoptosis of Hepa1-6 cells induced by TNF-alpha were detected by PI apoptosis detection kit. Effects of caspase-8-shRNAs on caspase-8 mRNA expression in apoptosis Hepa1-6 cells induced by TNF-alpha were detected by real-time fluorescent RT-PCR. Of the four caspase-8-shRNAs, Pgenesil-caspase-8-1 and Pgenesil-caspase-8-2 were successfully constructed. The apoptosis of Hepa1-6 cells induced by TNF-alpha was significantly inhibited by either Pgenesil-caspase-8-1 or Pgenesil-caspase-8-2 (p < 0.05). Caspase-8 mRNA expression levels in apoptosis Hepa1-6 cells induced by TNF-alpha were significantly decreased by either Pgenesil-caspase-8-1 or Pgenesil-caspase-8-2 (p < 0.05). This study suggested that shRNAs against caspase-8 could effectively inhibit apoptosis of Hepa1-6 cells induced by TNF-alpha by suppressing caspase-8 mRNA expression.