CLIC1 knockout inhibits invasion and migration of gastric cancer by upregulating AMOT-p130 expression.

PURPOSE: To explore the regulatory relationship between Chloride intracellular channel 1 (CLIC1) and Angiomotin (AMOT)-p130, and reveal the role of AMOT-p130 in gastric cancer (GC). METHODS: Immunohistochemistry was performed to analyze the expression of CLIC1 and AMOT-p130 in GC tissues and adjacent tissues. The expression of AMOT-p130 upon CLIC1 silencing was analyzed using RT-PCR, western blot, and immunofluorescence in GC cells. Transwell and wound-healing assays were performed to detect migration and invasion in GC cells. The changes in EMT-related proteins were detected using western blot. RESULTS: Our study found that high CLIC1 expression was significantly associated with low AMOT-p130 expression in GC tissues. Silencing CLIC1 expression in MGC-803 cells (MGC-803 CLIC1 KO) and AGS cells (AGS CLIC1 KO) decreased the invasive and migratory abilities of tumor cells, which were induced by the upregulation of AMOT-p130. Subsequently, we demonstrated that AMOT-p130 inhibits the invasive and migratory abilities of GC cells by inhibiting epithelial-mesenchymal transition. CONCLUSIONS: Our study suggests that AMOT-p130 could inhibit epithelial-mesenchymal transition in GC cells. CLIC1 may participate in the metastatic progression of GC by downregulating the expression of AMOT-p130.

Nutritional State Predicts All-Cause Death Independent of Comorbidities in Geriatric Patients with Coronary Artery Disease.

OBJECTIVE: To explore whether nutritional risk is associated with poor outcomes independent of complicated clinical status in older patients with coronary artery disease (CAD). DESIGN: Cohort study. SETTING: Patients referred for coronary angiography in West China Hospital, Sichuan University, China. PARTICIPANTS: 1772 patients with angiographic documented CAD whose age was above 65 years. MEASUREMENTS: Nutritional state was appraised using geriatric nutritional risk index (GNRI). Nutritional risk was defined as the GNRI below 98. The event rate of all-cause death was observed among patients with nutritional risk and those without. RESULTS: During a median follow-up period of 27 months, 224 patients died. Multivariate Cox regression analysis showed that nutritional risk was associated with all-cause death (adjusted hazard ratio 1.99; 95% confidence interval 1.35-2.95; P=0.001). Subgroup analysis verified the association between nutritional risk and death among patients with distinct clinical features, comorbidities, and medication. There was no interaction between nutritional risk and clinical characteristics with regard to all-cause death. CONCLUSION: Nutritional state is independently associated with the risk of all-cause death in geriatric patients with CAD. Whether nutritional support in appropriate patients improves clinical outcomes deserves further investigation.

Intrahepatic hepatitis B virus replication and liver histology in subjects with occult hepatitis B infection.

We studied the intrahepatic hepatitis B virus (HBV) replicative status in 40 people with occult hepatitis B infection (OBI) and 40 patients with chronic hepatitis B (CHB). Intrahepatic HBV DNA, covalently closed circular DNA (cccDNA), and pre-genomic RNA (pgRNA) were quantified. Patients with OBI had median necroinflammation and fibrosis scores of 1 and 0, respectively. Intrahepatic total HBV DNA, cccDNA and pgRNA were detectable in 30 (77%), one (3%) and five (13%) of the participants with OBI, respectively. People with OBI had lower median intrahepatic total HBV DNA than the patients with CHB (p < 0.0001). They had nearly normal liver histology and low intrahepatic HBV replication.

Lean mass index, body fat and survival in Chinese patients with coronary artery disease.

BACKGROUND: 'Obesity paradox' was not consistently observed in Asians with coronary artery disease (CAD). AIM: The study investigated the association between body composition and outcomes in Chinese patients with CAD. DESIGN: Cohort study. METHOD: A total of 3280 patients with angiographically validated CAD were consecutively included. Body fat (BF) percentage and lean mass index (LMI) were evaluated using the Clínica Universidad de Navarra-Body Adiposity Estimator. The rate of mortality from any cause was compared across groups classified by the quartiles of LMI. RESULTS: During a median period of 24 months, 288 (8.8%) participants died. There was a close association between increasing LMI and reducing mortality rate. However, univariate analyses did not find protective effect of BF on survival. After adjusting for age, sex, diabetes, current smoking, systolic blood pressure, creatinine, white blood cell count, haemoglobin and medication, Cox regression analyses showed that the significant relation between higher quartiles (Q) of LMI and survival benefit (Q4, hazard ratio 0.58 (95% confidence interval: 0.36-0.94) vs. Q3, 0.60 (0.39-0.91) vs. Q2, 0.60 (0.41-0.88) vs. Q1, reference) remained. CONCLUSION: Low LMI but not BF predicts all-cause mortality in Chinese patients with CAD.

Increased interventricular septum wall thickness predicts all-cause death in patients with coronary artery disease.

BACKGROUND: There is debate regarding the predictive value of interventricular septum (IVS) wall thickness for adverse events. AIMS: The study investigated the association between the severity of thickened IVS and all-cause death in Chinese patients with coronary artery disease (CAD). METHODS: A total of 2297 CAD patients verified by angiography was consecutively included. Patients were grouped according to the severity of thickened IVS. Cox regression analysis was conducted to determine the independent prognostic value of thickened IVS for all-cause death. RESULTS: During a median follow up of 25 months, 149 patients died. A gradient increase in the risk of death was observed across thickened IVS groups. Compared to patients with normal IVS thickness, the adjusted hazard ratio (HR) was 1.49 (95% confidence interval (CI) 1.00-2.23, P = 0.05) and 2.13 (95% CI 1.29-3.54, P = 0.003) for all-cause death in those with mildly and moderately/severely thickened IVS respectively. For one unit increase in IVS thickness, the risk of all-cause death was elevated by 14% (adjusted HR 1.14, 95% CI 1.05-1.24, P = 0.003). In patients with normal indexed left ventricular mass, thickened IVS was also demonstrated as an independent risk factor for all-cause death. CONCLUSION: Thickened IVS can be served as a reliable marker for predicting all-cause death in Chinese patients with CAD, even in those with normal left ventricular mass.

Linearized hepatitis B surface antigen and hepatitis B core-related antigen in the natural history of chronic hepatitis B.

Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n=52), immune clearance (IC group, n=105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n=97), HBeAg-negative quiescent group (ENQ group, n=95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n=55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r=0.874, p<0.001). Correlation of HQ-HBsAg with HBV DNA was less prominent and weakest in the ENH group (r=0.268, p 0.008). HBcrAg correlated best with HBV DNA in the ENQ group (r=0.537, p<0.001). In the ENQ group, 42.1% of patients had undetectable HBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, p<0.001) and HBsAg (5.05/5.96 log mIU/mL, p<0.001) levels. Forty per cent of the SC group patients had detectable HQ-HBsAg and/or HBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability.

Ficolin-A Enhances Inhibition of the C-Terminal 19 kDa Region of Merozoite Surface Protein-1 of Plasmodium berghei Using Test In Vivo.

BACKGROUND: Malaria remains a serious public health problem with significant morbidity and mortality. This study was conducted to identify whether ficolin-A could play an active role of against malaria infection. METHODS: The function of ficolin-A was analyzed in mouse model. The open reading frame of ficolin-A was cloned from the liver of new born C57BL/6 mice by RT-PCR and then inserted into the expression vector of eukaryon to construct pVAX1-ficolin-A plasmid. Meanwhile, the open reading frame of the 19-kDa fragment of merozoite surface protein-1 of Plasmodium berghei (MSP119) was cloned and then the expression vector of eukaryon, pVAX1- MSP119 was constructed. Both recombinant vectors were used in the mouse model of infection by Plasmodium berghei. RESULTS: pVAX1-ficolin-A alone could not significantly suppress parasite density and prolong survival time of infection mice; however, when injected pVAX1-ficolin-A and pVAX1-MSP119 together, the percent of invasion by Plasmodium was decreased (from 43.78% to 22.23% at 10 day after infection, compared to vector) and the survival time was prolonged significantly in the infection mouse model (P=0.01). CONCLUSION: Ficolin-A can enhance the immunoprotection of MSP119, it implies ficolin-A may be used as immunoenhancer in the study of vaccine defending malaria.

Taiwan's traffic control bundle and the elimination of nosocomial severe acute respiratory syndrome among healthcare workers.

The traffic control bundle consists of procedures designed to help prevent epidemic nosocomial infection. We retrospectively studied the serial infection control measures to determine factors most effective in preventing nosocomial infections of healthcare workers (HCWs) during the 2003 Taiwanese severe acute respiratory syndrome (SARS) epidemic. Fever screening stations, triage of fever patients, separating SARS patients from other patients, separation of entrances and passageways between patients and HCWs, and increasing hand-washing facilities all demonstrated a protective effect for HCWs (univariate analysis; P<0.05). By multiple logistic regression: (i) checkpoint alcohol dispensers for glove-on hand rubbing between zones of risk, and (ii) fever screening at the fever screen station outside the emergency department, were the significant methods effectively minimising nosocomial SARS infection of HCWs (P<0.05). The traffic control bundle should be implemented in future epidemics as a tool to achieve strict infection control measures.

A plasmid DNA vaccine encoding the extracellular domain of porcine endoglin induces anti-tumour immune response against self-endoglin-related angiogenesis in two liver cancer models.

BACKGROUND: Anti-angiogenesis therapy has showed a promising future in tumour treatment. More and more evidence suggest that endoglin is a powerful marker of angiogenesis in solid malignancies, including liver cancer. AIM: To explore whether a plasmid DNA encoding the porcine endoglin has the ability of breaking immune tolerance against endoglin-related tumour angiogenesis in mice. METHODS: A eukaryotic plasmid encoding the extracellular domain of porcine endoglin was constructed, and then used it as a xenogeneic DNA vaccine. Hepa1-6 and H22 hepatoma models were established to observe the anti-tumour activities. Western blot, enzyme-linked immunoadsorbent assay and enzyme-linked immunospot assay were used to determine the antibody characters. Immunohistochemistry and alginate-encapsulated tumour cell assay were used to observe the anti-angiogenesis effects. RESULTS: Immunotherapy with recombinant plasmid encoding extracellular domain of porcine endoglin was effective at both protective and therapeutic anti-tumour immunity in two hepatoma models. Autoantibodies against murine endoglin were identified. IgG1 and IgG2b were the major subclasses in response to recombinant plasmid encoding extracellular domain of porcine endoglin vaccination. Anti-endoglin antibody-producing B cells were significantly increased in the spleens of mice immunised with recombinant plasmid encoding extracellular domain of porcine endoglin. In addition, mouse self-immunoglobulins were found deposited on the blood vessels of recombinant plasmid encoding extracellular domain of porcine endoglin-immunised tumour tissues. The similar anti-tumour activity was induced by the adoptive transfer of the purified immunoglobulins from the sera of mice immunised with recombinant plasmid encoding extracellular domain of porcine endoglin. Furthermore, angiogenesis was apparently inhibited within the tumour tissues from the recombinant plasmid encoding extracellular domain of porcine endoglin-immunised mice, and the vascularisation of alginate balls was also reduced in recombinant plasmid encoding extracellular domain of porcine endoglin-immunised mice. Most importantly, recombinant plasmid encoding extracellular domain of porcine endoglin could really induce cytotoxic T lymphocyte-mediated cytotoxicity and inhibit cell proliferation against endothelial cells. In addition, both CD4+ and CD8+ T lymphocytes took part in the function of inhibiting tumour growth and were synergistically responsible for induction of the anti-tumour activities. CONCLUSIONS: This approach may provide an alternative strategy for liver cancer immunotherapy.

Using an integrated infection control strategy during outbreak control to minimize nosocomial infection of severe acute respiratory syndrome among healthcare workers.

Healthcare workers (HCWs) are at risk of acquiring severe acute respiratory syndrome (SARS) while caring for SARS patients. Personal protective equipment and negative pressure isolation rooms (NPIRs) have not been completely successful in protecting HCWs. We introduced an innovative, integrated infection control strategy involving triaging patients using barriers, zones of risk, and extensive installation of alcohol dispensers for glove-on hand rubbing. This integrated infection control approach was implemented at a SARS designated hospital ('study hospital') where NPIRs were not available. The number of HCWs who contracted SARS in the study hospital was compared with the number of HCWs who contracted SARS in 86 Taiwan hospitals that did not use the integrated infection control strategy. Two HCWs contracted SARS in the study hospital (0.03 cases/bed) compared with 93 HCWs in the other hospitals (0.13 cases/bed) during the same three-week period. Our strategy appeared to be effective in reducing the incidence of HCWs contracting SARS. The advantages included rapid implementation without NPIRs, flexibility to transfer patients, and re-inforcement for HCWs to comply with infection control procedures, especially handwashing. The efficacy and low cost are major advantages, especially in countries with large populations at risk and fewer economic resources.

Nosocomial and community-acquired Enterobacter cloacae bloodstream infection: risk factors for and prevalence of SHV-12 in multiresistant isolates in a medical centre.

In a medical centre in northern Taiwan, 60 patients had bloodstream infection caused by Enterobacter cloacae from 1 January 2002 to 30 April 2003. Forty (66.7%) were nosocomial and 26 were caused by multiresistant isolates. Twenty patients died due to the infection. Central venous catheterization and mechanical ventilation were relative risks for nosocomial E. cloacae infection. Age and mechanical ventilation were risk factors for multiresistant E. cloacae infection. Mortality was associated with multiresistant isolates and polymicrobial infection. Pulsed-field gel electrophoresis (PFGE) analysis showed, the 26 multiresistant isolates comprised 12 different types, with type A predominating (12 isolates). Excluding the patients infected with PFGE type A, central venous catheterization was a relative risk for infection, and polymicrobial infection was a risk factor for mortality. All but one of the 26 multiresistant isolates had the extended-spectrum beta-lactamase SHV-12. TEM-1 and ampC beta-lactamase genes were also detected in 25 of the 26 multiresistant isolates. Southern blotting indicated that the SHV-12 gene was located on plasmids. Eleven of the 26 multiresistant isolates had minimum inhibitory concentrations (MIC) > or =16 mg/L for cefepime, which was reduced by the addition of sulbactam for most isolates, resulting in susceptibility. The combination of cefepime and sulbactam may be effective in the treatment of multiresistant E. cloacae bloodstream infection.

Theory of strain relaxation for epitaxial layers grown on substrate of a finite dimension

We present an equilibrium theory for strain relaxation in epitaxial layers grown on substrates of a finite dimension. The conventional dislocation model is refined to take account of the multiple reflection of image dislocations. The effect of strain transfer and dilution due to finite vertical and lateral dimensions of the substrate is also considered. The critical thickness has been obtained based on an energy balance approach. Detailed numerical analysis with primary experiments for the SiGe alloy system is also provided.