Objective To detect the effects of cytokines on the expression of early growth response gene-1 (Egr-1) in cultured human retinal pigment epithelial (RPE) cells. Methods Immunofluorescence staining, Western blotting and reverse transcription polymerase chain reaction (RT-PCR) were used to detect and quantitatively analyze the expression of Egr-1 protein and mRNA in cultured human RPE cells which were exposed to stimulants, including 20 mu;g/ml lipopolysaccharide (LPS), 40 ng/ml tumor necrosis factor (TNF)-alpha;, 10 U/ml interferon (IFN)gamma;, 30% supernatant of monocyte/macrophage strain (THP1 cells) and the vitreous humor from healthy human eyeballs, for 0, 10, 20, 30, 40 and 60 minutes, respectively. Results The RPE cells stimulated for 0 minute revealed faint green fluorescence of Egr-1 in the cytoplasm. With exposure to the stimulants, the expressionof Egr-1 increased obviously and b green fluorescence was found in cytoplasm in some nuclei of RPE cells. Compared with the untreated RPE cells, after stimulated by 20 mu;g/ml LPS, 40 ng/ml TNFalpha;, 10 U/ml IFNgamma;, 30% supernatant of THP-1 cells and the vitreous humor, the approximate ultimate amplitudes of Egr-1 mRNA enhanced 1.9, 1.3, 14, 1.2, and 1.4 times, respectively; the greatest amplitudes of Egr-1 protein increased 3.4, 1.2, 1.7, 32, and 1.3 times, respectively. Conclusion LPS, TNF-alpha;, IFN-gamma;, supernatant of THP-1 cells and the vitreous humor can upregulate the expression of Egr-1 mRNA and protein in cultured human RPE cells, and induce its nuclear transposition, which suggests the activation of Egr-1.
ObjectiveTo investigate the changes of plasma platelet activating factor (PAF) interleukin-8(IL-8) and interferon-γ (IFN-γ) in patients after surgery with extracorporeal circulation (ECC) and their clinical significance. MethodsSeventy-five patients undergoing surgery with ECC in the First College of Clinical Medicine,China Three Gorges University from June 2012 to June 2013 were enrolled in this study. According to the presence of postoperative acute lung injury/acute respiratory distress syndrome (ALI/ARDS) all the 75 patients were divided into 2 groups. In ALI/ARDS group, there were 28 patients including 20 male and 8 female patients with their age of 53.6±8.2 years. In the control group,there were 47 patients without postoperative ALI/ARDS,including 32 male and 15 female patients with their age of 56.9±11.8 years. Dynamic variations of plasma PAF,IL-8 and IFN-γ of these patients were examined with enzyme-linked immunosorbent assay (ELISA) and compared between the 2 groups. ResultsIn ALI/ARDS group,plasma IL-8 and IFN-γ reached peak levels at 48 hours after surgery and gradually decreased after that;plasma PAF reached the peak level at 96 hours after surgery and gradually decreased after that. Postoperative plasma PAF (96 hours after surgery:16 029.5±4 203.7 mU/ml vs. 4 520.1±312.2 mU/ml,P<0.05) IL-8 (48 hours after surgery:48 580.5±8 095.8 pg/ml vs. 5 990.5±1 179.0 pg/ml,P<0.05) and IFN-γ (48 hours after surgery:258.5±76.1 pg/ml vs. 26.1±11.5 pg/ml,P<0.05) of ALI/ARDS group were significantly higher than those of the control group at 48 hours,96 hours and 144 hours after surgery. ConclusionPlasma PAF,IL-8 and IFN-γ change significantly after surgery with ECC,which may play an important role in the pathogenesis of postoperative ALI/ARDS.
【Abstract】Objective To investigate the prevention and treatment for recurrence of hepatitis B after liver transplantation on HBV-related diseases. Methods Making a literature summarization based on published papers review.Results Acute and chronic HBV-related diseases are the main indications of liver transplantation.Recurrence rate of hepatitis B is from 80% to 100% in the untreated patients after liver transplantation,and it affects the survivals of patients seriously.It has become a focus to prevent and treat the recurrence of hepatitis B.After a series of explotation and application,there have been a lot of drugs of preventing and treating HBV reinfection, including hepatitis B immunoglobulin,interferon and nucleotide analog antivirus drugs(lamivudine, famcyclovir, adefovir),etc.The therapeutic characteristics of them are different. Their utilizations of dividing or alliance are developing rapidly.Conclusion Liver transplatation is an effective therapy for HBV-related disease. Anti-HBV treatments perioperation play an important role in the improvement of succeed of liver transplantation.
Objective To evaluate the efficacy and safety of anti-vascular endothelial growth factor (VEGF) agents for advanced renal cell carcinoma. Methods We searched MEDLINE, EMbase, The Cochrane Library, CBMdisc and China Academic Periodical database from the establishment of each database to April 2009. We included randomized controlled trials (RCTs) that evaluated anti-VEGF agents (sunitinib, sorafenib and bevacizumab). The quality of the included trials was evaluated by two reviewers independently. Meta-analyses were conducted by the Cochrane Collaboration’s RevMan 4.2 software. Results Four RCTs involving 2 320 patients were identified. According to the different interventions for advanced renal cell carcinoma, we divided the patients into two groups: anti-VEGF agents monotherapy and anti-VEGF agents plus interferon combination treatment. Our meta-analyses showed: monotherapy was superior to interferon on inhibition of tumor progression [OR=0.38, 95%CI (0.29, 0.51), Plt;0.01] and control of tumor [OR=2.53, 95%CI (1.87, 3.43), Plt;0.01], but was not significantly different from interferon on the overall effective rate [OR=1.97, 95%CI (0.20, 19.57), P=0.56] and serious side effects [OR=1.98, 95%CI (0.90, 4.34), P=0.09]. There were significant differences between anti-VEGF agents plus interferon and interferon alone on inhibition of tumor progression [OR=0.67, 95%CI (0.53, 0.84), P=0.000 5], overall effective rate [OR=2.65, 95%CI (1.94, 3.61), Plt;0.01], control of tumor [OR=2.14, 95%CI (1.65, 2.78), Plt;0.01] and serious side effects [OR=2.63, 95%CI (2.09, 3.31), Plt;0.01]. Conclusion Compared with interferon, anti-VEGF agents could inhibit tumor progression more effectively. Moreover, the combination therapy with interferon could offer a more favorable overall effective rate for advanced renal cell carcinoma, but then followed by more serious side effects. We need to weigh the merits and demerits of drugs before making a clinical decision for advanced renal cell carcinoma.
Objective To explore the immunopathologic mechanism underlying the inflammatory response after severe acute respiratory syndrome（SARS） invasion.Methods Pathway focused cDNA microarrays were employed for comparision of the gene expression patterns in 16HBEs treated with interferon-γ(IFN-γ) or the S protein of SARS-CoV.The S proteins were administered to BALB/c mice and the pathological changes of lung and spleen were observed.Results S protein activated JAK/STAT signal pathway in the 16HBEs with inducible protein 10（IP-10） gene expression，and the specific inhibitors of the JAK/STAT signal pathway were able to downregulate the induction of IP-10.The mice instilled intracheally with S proteins revealed obvious acute diffuse damage and increased IP-10 expression and CD68+ macrophages infiltration in both lung and spleen tissues.In contrast，the treatment with JAK3 inhibitors attenuated lung and spleen injury in the mice.Conclusion Our findings support that the activation of JAK/STAT pathway induced by SARS-CoV S protein plays a key role in promotion of an IFN -γ inducible chemokine cascade，which can help in the development of novel drug and therapeutics for prevention and treatment of SARS.
【Abstract】ObjectiveTo inquire into the regulative effect of interferon (IFN) on human leucocyte antigen-DR(HLADR) expression in human colonic cancer cells. MethodsThe expression of HLA-DR in 4 colonic cancer cell lines HCT-8，lovo，SW-480 and Ls-174-T was detected with immunohistochemical SP and ELISA method before and after being stimulated by different doses of α-IFN or γ-IFN. ResultsAll cell lines except lovo cell were HLA-DR positive before stimulation with α-IFN or γ-IFN. HLA-DR expression was enhanced on all of the 4 cell lines after stimulation, and it was correlated with γ-IFN and the dose of γ-IFN. The effect of γ-IFN was more obvious than that of α-IFN. ConclusionIFN can enhance HLA-DR expression in human colonci cancer cells and clinical therapy of IFN for colon cancer has a certain applying prospect.
Objective To investigate the expression of aquaporin-1( AQP-1) in pulmonary tissues of asthma mice and the effects of acetazolamide( AZ) on AQP-1 expression. Methods Forty C57BL/6 mice were randomly divided into five groups. Group A was treated with phosphate buffer as a non-asthmatic group.The mice in group B, C, D, and E were sensitized with ovalbumin( OVA) and challenged with aerosol OVA to establish asthma model. The mice in group B, C, and D were interperitoneally injected with AZ at doses of 300, 200, 100 mg/kg, respectively during the challenge period. Results ①Wet/dry weight ratio of lung tissues in group E was significantly higher than that in group A( P lt;0. 05) , while it was lower in B, C and D groups than group E. ②The total number of cells, the number of eosinophils, and interleukin-5( IL-5) inBALF of group E were higher than those in group A( P lt;0. 05) , and interferon-γ( IFN-γ) level was lower in group E than in group A ( P lt; 0. 05) . After AZ treatment, the total number of cells, the number of eosinophils, neutrophils and lymphocytes were significantly decreased( P lt; 0. 05) , which were positively correlated with the dose of AZ. ③AQP-1 were expressed in tracheal epithelium, microvascular endothelial cell and bronchial peripheral vascular bed, and the expression in group E was significantly higher than that in group A( P lt;0. 01) . AQP-1 expression was significantly decreased after the intervention of AZ ( P lt;0. 05) .The decrease was positively correlated with the dose of AZ. The expression of AQP-1 mRNA showed no significant difference among these groups( P gt;0. 05) . Conclusions AQP-1 was over-expressed in the lung tissue of mice with asthma. AZ can inhibit the expression of AQP-1 and relieve lung inflammatory cells infiltrationin a dose-dependent manner. It is the protein expression of AQP-1 not the AQP-1 mRNA which were significantly different in different groups, suggesting that AZ affected AQP-1 in the post-transcriptional stage.
ObjectiveTo evaluate the effect of autoantibody on the efficacy and safety of pegylated interferonα-2a (Peg-IFNα-2a) and ribavirin on chronic hepatitis C (HCV). MethodsWe enrolled 106 chronic HCV infected patients, who were divided into autoantibody-positive group and negative group based on the baseline autoantibody detection. The patients were treated for 48 weeks. The anti-viral response and adverse effects were observed. Data analyses were reported using the SPSS 20.0 statistical package. ResultsThe prevalence of any autoantibody in chronic hepatitis C patients amounted to 31.1%, and serum anti-nuclear antibody was positive in 24 patients. Difference in age, sex, serum alanine transaminase level, aspartate transaminase level, total bilirubin level, thyroid function and HCV RNA level between autoantibody-positive group and negative group was not significant (P > 0.05). The level of hemoglobin in autoantibody-positive group was significantly lower than the negative group (P=0.018). Of the 106 patients, 82 patients achieved sustained virological response (SVR), 56 achieved rapid virological response (RVR), 98 achieved ealy virological response (EVR) and 8 were non-responders. There were no significant differences between RVR, EVR and SVR in autoantibody-positive group and negative group (P > 0.05). The most common adverse effects in this study were fatigue, weight loss, hair loss and fever, and no significant differences in adverse effects were observed between the two groups (P > 0.05). ConclusionAutoantibody positivity may not affect the treatment response and is safe in chronic HCV infected patients with combination therapy of pegylated interferonα-2a plus ribavirin.
Objective To evaluate the cost-effectiveness of three LTBI screening strategies: the tuberculin skin test (TST), the T-SPOT.TB and the combination of TST and T-SPOT (TST+T.SPOT), to provide economic evidence for T.SPOT application in China. Methods A decision analysis model evaluated three strategies among a cohort of 1000 tuberculosis (TB) close contacts, using incremental cost-effectiveness of prevention a active TB patient (1 year post contact). Meta analyses were conducted to calculate the key parameters of T.SPOT and TST. The official data or literature was searched and the unaccessible data was to specify other parameters, such as cost, LTBI prevalence, etc. The one-way sensitivity analysis was performed, varying key parameters over a wide range of reasonable values to evaluate the impact of data uncertainties and to determine the robustness of our overall conclusion. Results a) As for the total cost, the TST+T.SPOT strategy (?212 213.81 per 1 000 contacts) cost the least, while the single T.SPOT strategy cost the most; b) Subsequently, the TST+T.SPOT strategy required less contacts to be treated to prevent an active case of TB (8.31) than the single TST strategy (25.67); c) the TST+T.SPOT strategy shared the most cost-effectiveness (?3 063.50 per active TB case prevented) than the single TST or T.SPOT strategy; and d) The results of one-way sensitivity analyses showed that cost-effectiveness values were sensitive to changes in LTBI prevalence (gt;60%), Sen and Spn of TST test (gt;70%), with the single TST being superior to the single T.SPOT. Conclusion The Single T.SPOT strategy enjoys the most cases prevented from active TB, while the TST+S.SPOT strategy is the most cost-effective. The conclusion is sensitive to a few parameters, such as LTBI prevalence, but the TST+T.SPOT strategy is always the best.
Objectives To evaluate the efficacy of interferon (IFN) maintenance therapy in patients with small cell lung cancer (SCLC). Methods We searched MEDLINE (1966-Jan.2006), EMbase (1984-Jan.2006), The Cochrane Library(Issue 1, 2006)and the Chinese Biomedical Database (1980-Jan.2006). We checked the references in the reports of related studies and handsearched the education books of ASCO and ESMO meetings. The quality of the included trials was evaluated. Data were extracted by two reviewers independently into a specially designed extraction form. The Cochrane Collaboration’s RevMan 4.2.7 software was used for data analysis. Results Five randomized controlled trials involving 587 patients were included. The pooled result of the 5 studies showed that IFN plus chemotherapy induction treatment did not have a significant effect on 1-year (RR 1.19, 95%CI 0.88-1.6) or 2-year survival rate (RR 1.44, 95% CI 0.99-2.10). However, IFN maintenance therapy significantly increased 2-year (RR 2.08, 95%CI 1.16-3.72) and 1-year survival (RR 2.99, 95%CI 1.13-7.93). Conclusion IFN maintenance therapy may increase 2-year and 1-year survival rates after patients have achieved complete or partial response to chemotherapy. Further randomized, double-blind multi-center trials are needed to investigate this further.