Association of Rs2071410 on Furin with Transient Ischemic Attack Susceptibility and Prognosis in a Chinese Population.

BACKGROUND Because genotype CG/GG of Furin rs2071410 can increase susceptibility to hypertension, this study investigated whether Furin rs2071410 is correlated with transient ischemic attack (TIA) susceptibility and prognosis. MATERIAL AND METHODS The odds ratios (ORs) and their 95% confidence intervals (95% CIs) were evaluated to assess the association of rs2071410 with TIA risk, and logistic regression was used to estimate the effects of various risk factors (e.g., diabetes, hypertension, and hyperlipidemia) on TIA. RESULTS Compared with the homozygous genotype CC of rs2071410, the frequency of CG + GG genotype in the case group was significantly higher than in the control group (OR=1.47, 95% CI: 1.05-2.05, P<0.05). The CG + GG genotype carriers were observed to have worse 90-day prognosis after TIA treatment than patients carrying CC genotype (OR=12.86, 95% CI: 7.41-22.33, P<0.05). Moreover, logistic regression analysis found that age, diabetes, hypertension, and hyperlipidemia were associated with the onset of TIA (P<0.05, all). Of note, individuals with CG + GG genotype had 49.3% increased risk of TIA compared with individuals with CC genotype (OR=1.49, 95% CI: 1.05-2.12), and patients with CG + GG genotype had worse 90-day prognosis after TIA treatment than patients with CC genotype (OR=11.39, 95% CI: 6.29-20.62). CONCLUSIONS Furin rs2071410 was significantly correlated with TIA occurrence and prognosis in the Chinese population.

New role and molecular mechanism of Gadd45a in hepatic fibrosis.

AIM: To investigate the role of Gadd45a in hepatic fibrosis and the transforming growth factor (TGF)-ß/Smad signaling pathway. METHODS: Wild-type male BALB/c mice were treated with CCl4 to induce a model of chronic liver injury. Hepatic stellate cells (HSCs) were isolated from the liver of BALB/c mice and were treated with small interfering RNAs (siRNAs) targeting Gadd45a or the pcDNA3.1-Gadd45a recombinant plasmid. Cellular α-smooth muscle actin (α-SMA), ß-actin, type I collagen, phospho-Smad2, phospho-Smad3, Smad2, Smad3, and Smad4 were detected by Western blots. The mRNA levels of α-SMA, ß-actin, and type I collagen were determined by quantitative real-time (qRT)-PCR analyses. Reactive oxygen species production was monitored by flow cytometry using 2,7-dichlorodihydrofluorescein diacetate. Gadd45a, Gadd45b, anti-Gadd45g, type I collagen, and SMA local expression in liver tissue were measured by histologic and immunohistochemical analyses. RESULTS: Significant downregulation of Gadd45a, but not Gadd45b or Gadd45g, accompanied by activation of the TGF-ß/Smad signaling pathways was detected in fibrotic liver tissues of mice and isolated HSCs with chronic liver injury induced by CCl4 treatment. Overexpression of Gadd45a reduced the expression of extracellular matrix proteins and α-SMA in HSCs, whereas transient knockdown of Gadd45a with siRNA reversed this process. Gadd45a inhibited the activity of a plasminogen activator inhibitor-1 promoter construct and (CAGA)9 MLP-Luc, an artificial Smad3/4-specific reporter, as well as reduced the phosphorylation and nuclear translocation of Smad3. Gadd45a showed protective effects by scavenging reactive oxygen species and upregulating antioxidant enzymes. CONCLUSION: Gadd45a may counteract hepatic fibrosis by regulating the activation of HSCs via the inhibition of TGF-ß/Smad signaling.

Combination lamivudine and adefovir versus entecavir for the treatment of naïve chronic hepatitis B patients: a pilot study.

BACKGROUND: The aim of this study was to compare the effect of combination lamivudine (LAM) and adefovir dipivoxil (ADV) versus entecavir (ETV) monotherapy for naïve HBeAg-positive chronic hepatitis B (CHB) patients. MATERIAL/METHODS: Fifty enrolled patients with CHB were evenly divided into 2 groups: a group treated with of lamivudine (LAM) (100 mg/day) plus adefovir (ADV) (10 mg/day) combination, and a group treated with entecavir (ETV) (0.5 mg/day). Serum levels of ALT, AST, creatinine, bilirubin, HBsAg, HBeAg and HBV viral load, and genotypic resistance were analyzed at 0, 12, 24, 52, and 104 weeks. HBV DNA levels were determined by real-time PCR and HBsAg and HBeAg by chemiluminescence. Serum levels of ALT, AST, creatinine, and bilirubin were measured by an automatic biochemical analyzer. Data analysis was performed with SPSS 12.0 software. RESULTS: There were no significant differences in the virological response (VR) rates between LAM+ADV and ETV cohorts at 24, 52, and 104 weeks (P>0.05). The HBeAg seroconversion rates were 28% and 20%, and the biochemical response (BR) rates were 88% and 84% at week 104 in the LAM+ADV and ETV groups, respectively. The rates of undetectable HBV DNA, HBeAg seroconversion, and ALT normalization rates were similar in both cohorts. No virological breakthrough or serious adverse effects were noted for any patient during the study period. CONCLUSIONS: Both LAM+ADV combination therapy and ETV monotherapy were effective and safe in the treatment of -naïve HBeAg-positive CHB patients. However, further studies are needed to obtain long-term results.

[Analyse related factors of impact and prognosis of 73 cases of severe hepatitis].

OBJECTIVE: A retrospective study was conducted to investigate the clinical features and prognostic factors of 73 cases of severe hepatitis. METHODS: To summarize clinical features of 73 cases of severe hepatitis, grouping by etiology and pathogenesis. A retrospective analysis was performed to evaluate the relationship between biochemical characteristics (liver function, renal function, electrolytes, PTA, etc) and complications (hepatic encephalopathy, upper gastrointestinal bleeding, hepatorenal syndrome, ascites, abdominal infections, etc) and prognosis. RESULTS: (1) HBV infection alone accounted for 65.75%. Alcoholic liver disease, drug-induced liver injury, hepatitis E, autoimmune hepatitis, overlapping causes and other factors were five cases (6.85%), six cases (8.22%), two cases (2.74%), two cases (2.74%), seven cases (9.59%) and three cases (4.11%) respectively. According to the incidence rate, severity and underlying liver condition, subacute hepatitis, cases based on chronic hepatitis and on cirrhosis were 12 cases (16.43%), 11 cases (15.07%), 50 cases (68.49%) respectively. Clinical manifestations with or without hepatic encephalopathy accounted for 58.90% or 41.10%. (2) The highest mortality of severe hepatitis was alcoholic liver disease and patients on the basis of overlapping factors (66.67%), followed by autoimmune liver disease (50%). The mortality of HBV-related hepatitis was 18.75%. Overall mortality of 73 cases of severe hepatitis was 28.77%, of which cirrhosis group was higher than non-cirrhotic group (40% vs 4.3%, P = 0.002). The difference was statistically significant. Patients without hepatic encephalopathy had lower mortality than with hepatic encephalopathy (3.33% vs 46.51%). The mortality of patients with hepatic encephalopathy Stage III and IV was 72.73%. (3) Independent samples t test filtered nine factors associated with death, namely cirrhosis, upper gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, serum creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), albumin (ALB) and serum sodium. The results of multivariate conditional logistic regression analysis indicated that hepatic encephalopathy, serum creatinine levels were risk factors for death, whereas ALB as a protective factor. CONCLUSION: Hepatic encephalopathy, serum creatinine levels were risk factors for severe hepatitis death, But ALB was protective factor. Nucleotide analogs using was the main reason why the mortality of hepatitis B was as low as 18.75%.