AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. ...AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.展开更多
Objective To investigate the antiviral activity of recombinant interferonα-2b suppository(IFNα-2b)in vivo and in vitro.Methods The cytopathic-effect inhibition assay was applied in this study to investigate the anti...Objective To investigate the antiviral activity of recombinant interferonα-2b suppository(IFNα-2b)in vivo and in vitro.Methods The cytopathic-effect inhibition assay was applied in this study to investigate the antiviral activity of this drug as well as yingtelong and axiluowei as positive control.The guinea pig model of vaginitis and skin infection caused by HSV-2 infection were established,treated with IFNα-2b suppository at dosages of 60000、180000、540000 IU,using IFNα-2b injection 180000 IU·kg-1 as controls.Score the pathological changes of appearance and skin,the virus activities of vaginal secretion and tissue sections of viginae were assayed after treatment.Results The TD50 of IFN α-2b and yingtelong for Vero cells was(>100)μg·mL-1 and(>100000)IU·mL-1,respectively.The IC50 of IFN α-2b and yingtelong and axiluowei for Herpes virus type 1 was(0.29±0.08)μg·mL-1 and(185.0±28.8)IU·mL-1 and(0.19±0.03)μg·mL-1,respectively.The mean scores for vaginal and skin lesion of the treated groups were lower than those of untreated group.Among these concentrations,the IFNα-2b suppository of 540000 IU·kg-1 group.Showed highest anti-viral activity.The virus activity in vaginal secretion of treated group was lower than that of untreated group too(P<0.01 or P<0.05).Tissue sections of viginae after treatment with IFNα-2b suppository showed significantly therapeutical effects on the degrees of vaginal lesion.At the same dosage,The anti-HSV activity of IFNα-2b suppository was also compared with IFNα-2b injection,the results showed that the activity of suppository of 540000 IU·kg-1 group was similar to that of the injection.Conclusions The IFNα-2b suppository has anti-viruses function both in vivo and in vitro.展开更多
Objective:To observe the effect of interferonα-2b treatment on liver function,liver fibrosis,complement protein and oxidative stress in patients with hepatitis B.Methods:A total of 100 patients with hepatitis B in ou...Objective:To observe the effect of interferonα-2b treatment on liver function,liver fibrosis,complement protein and oxidative stress in patients with hepatitis B.Methods:A total of 100 patients with hepatitis B in our hospital were randomly divided into the control group and the observation group,with 50 cases in each group.After admission,patients in the control group were treated with entecavir,while patients in the observation group were treated with interferonα-2b combined with entecavir.The levels of serum total bilirubin(TBil),aspartate aminotransferase(AST),alanine aminotransferase(ALT),type III procollagen(PCIII),type IV collagen(CIV),complement C3 protein(C3),complement C4 protein(C4),malondialdehyde(MDA),superoxide dismutase(SOD)and nitric oxide(NO)were compared between the two groups before and after treatment.Results:After treatment,the levels of TBil,AST,ALT,PCIII,CIV,MDA and NO in serum of patients with hepatitis B in both groups were significantly lower than those before treatment,and the levels of C3,C4 and SOD were significantly higher than those before treatment(P<0.05).After treatment,the levels of TBil,AST,ALT,PC III,C IV,MDA and NO in serum of patients in the observation group were significantly lower than those in the control group,while the levels of C3,C4 and SOD in serum of patients in the observation group were significantly higher than those in the control group(P<0.05).Conclusions:The combination of interferonα-2b and entecavir has a good curative effect on hepatitis B.It can significantly improve the liver function and immune function of patients,delay the process of liver fibrosis and reduce oxidative stress injury.It is worthy of clinical promotion.展开更多
Objective To investigate a new approach of the combined use of trichosanthin (TCS) andrecombinant interferon alpha - 2b (rIFN α- 2b) against digestive system cancer cells. Methods Detect separatelythe cytotoxicity of...Objective To investigate a new approach of the combined use of trichosanthin (TCS) andrecombinant interferon alpha - 2b (rIFN α- 2b) against digestive system cancer cells. Methods Detect separatelythe cytotoxicity of TCS, rIFN α- 2b and their combination against digestive system cancer cell SGC- 7901.Results In the experiment in vitro, TCS, rIFN α- 2b both had direct, dose dependent cytotoxicity againstSGC - 7901. Their combined use demonstrated a toxicity signijicantly higher than that of the two drugs used alone,showing a signilicant synergic effect. This synergic cytotoxicity was confirmed in the animal experiment.Conclusion Combined use of TCS and rIFN α - 2b decreases the therapeutic dose of TCS and its toxic adverseellect, and this synergic effect is favorable to the clinical use of TCS protein against gastric cancer.展开更多
Objective: To study the effects of anti-HPV bioprotein dressing combined with interferon α-2b therapy on the malignant molecule expression in patients with cervical intraepithelial neoplasia (CIN) Ⅲ complicated by h...Objective: To study the effects of anti-HPV bioprotein dressing combined with interferon α-2b therapy on the malignant molecule expression in patients with cervical intraepithelial neoplasia (CIN) Ⅲ complicated by high-risk HPV positive. Methods: Patients who were diagnosed with CINⅢ and high-risk HPV positive and underwent conization in the 3201 Hospital Affiliated to Xi'an Jiaotong University between June 2014 and February 2017 were selected and randomly divided into the observation group who received preoperative anti-HPV bioprotein dressing combined with interferon α-2b therapy and the control group who received no special treatment. CIN lesion was collected to determine the expression of pro-proliferation molecules, pro-apoptosis molecules and epithelial-mesenchymal transition molecules. Results: Rsf1, Piwil2, TOPK, p38MAPK, ERK, Snail, Twist, N-cadherin and Vimentin mRNA expression in cervical intraepithelial neoplasia lesions of observation group were greatly lower than those of control group whereas LRIG3, SARI, IEX-1, FHIT and E-cadherin mRNA expression were greatly higher than those of control group. Conclusion: Anti-HPV bioprotein dressing combined with interferon α-2b therapy can inhibit the proliferation and invasive growth of tumor cells in patients with CINⅢ complicated by high-risk HPV positive.展开更多
Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and internatio...Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management guidelines.Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens.These regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently administered.Despite these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes.These include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular DNA.Moreover,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure.This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.展开更多
Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at w...Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24:HBeAg decline>2 log10 group (group A), HBeAg decline between 1 1og10-2 log10 (group B), HBeAg decline<1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α2a for 24 weeks. At week 48, the treatment efifcacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed. Results At week 48, mean reduction of serum HBV DNA:group A:5.8 log10 copies/ml, group B:3.8 log10 copies/ml, group C1:2.8 log10 copies/ml, group C2:5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P<0.01), that in group C1 was greater than group C2 (P<0.01), the difference between groups B and C1 had no statistical signiifcance (P=0.19). Mean reduction of HBeAg:group A:2.7 log10S/CO, group B:1.9 log10S/CO, group C1:0.9 log10S/CO, group C2:1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically signiifcant (P<0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4%and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P<0.01),that in group C1 was greater than group C2 (P<0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0%and 22.7%, respectively, that in group A was greater than groups B and C1 (P<0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P<0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical signiifcance. Conclusions HBeAg decline > 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline < 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.展开更多
基金Supported by National Natural Science Foundation of China, No. 30771905National Basic Research Program of China (973 Program), No. 2007CB512800+1 种基金Mega-projects of Science Research, No. 008ZX10002-008Beijing Municipal Science & Technology Commission, No. D08050700650803
文摘AIM:To investigate the effect of pegylated interferon (IFN) α-2b on specific CD8+ T lymphocytes in patients with chronic hepatitis B (CHB). METHODS:Twenty-one patients with CHB were treated with pegylated IFN α-2b. Periphery blood mononuclear cells were isolated from fresh heparinized blood by Ficoll-Hypaque density gradient centrifugation (density:1.077 g/L,Pharmingen) at weeks 0,4,8,12,and 24,respectively. Frequency of circulating hepatitis B virus (HBV) epitope-specific CD8 T cells was detected by flow cytometry. Cytokines were detected by cytometric bead assay. RESULTS:The frequency of circulating HBV core or env-specific CD8 T cells was higher (P < 0.05),the number of HBV core specific CD8 T cells was greater at week 24 (P < 0.05),the level of Th1-type cytokines [interleukin (IL)-12,tumor necrosis factor-α,and IFN-γ] was higher,while that of Th2-type cytokines (IL-4,IL-6,and IL-10) was lower in responders than in nonresponders (P < 0.05) after pegylated IFN α-2b treatment. The IL-6 level was correlated with HBV DNA (r = 0.597,P = 0.04),while the inducible protein-10 (IP-10) level was correlated with serum alanine aminotransferase (ALT) (r = 0.545,P = 0.005). The IP-10 level at week 8 after pegylated IFN α-2b treatment could predict the normalization of ALT in CHB patients (positive predict value = 56%,negative predict value = 92%). CONCLUSION:Pegylated IFN α-2b can enhance the immune response of CHB patients by increasing the frequency of HBV specific CD8+ T cells and regulating the Th1/Th2 cytokines.
文摘Objective To investigate the antiviral activity of recombinant interferonα-2b suppository(IFNα-2b)in vivo and in vitro.Methods The cytopathic-effect inhibition assay was applied in this study to investigate the antiviral activity of this drug as well as yingtelong and axiluowei as positive control.The guinea pig model of vaginitis and skin infection caused by HSV-2 infection were established,treated with IFNα-2b suppository at dosages of 60000、180000、540000 IU,using IFNα-2b injection 180000 IU·kg-1 as controls.Score the pathological changes of appearance and skin,the virus activities of vaginal secretion and tissue sections of viginae were assayed after treatment.Results The TD50 of IFN α-2b and yingtelong for Vero cells was(>100)μg·mL-1 and(>100000)IU·mL-1,respectively.The IC50 of IFN α-2b and yingtelong and axiluowei for Herpes virus type 1 was(0.29±0.08)μg·mL-1 and(185.0±28.8)IU·mL-1 and(0.19±0.03)μg·mL-1,respectively.The mean scores for vaginal and skin lesion of the treated groups were lower than those of untreated group.Among these concentrations,the IFNα-2b suppository of 540000 IU·kg-1 group.Showed highest anti-viral activity.The virus activity in vaginal secretion of treated group was lower than that of untreated group too(P<0.01 or P<0.05).Tissue sections of viginae after treatment with IFNα-2b suppository showed significantly therapeutical effects on the degrees of vaginal lesion.At the same dosage,The anti-HSV activity of IFNα-2b suppository was also compared with IFNα-2b injection,the results showed that the activity of suppository of 540000 IU·kg-1 group was similar to that of the injection.Conclusions The IFNα-2b suppository has anti-viruses function both in vivo and in vitro.
基金This study was supported by Nanjing Science and Technology Project(Grant No.201605033).
文摘Objective:To observe the effect of interferonα-2b treatment on liver function,liver fibrosis,complement protein and oxidative stress in patients with hepatitis B.Methods:A total of 100 patients with hepatitis B in our hospital were randomly divided into the control group and the observation group,with 50 cases in each group.After admission,patients in the control group were treated with entecavir,while patients in the observation group were treated with interferonα-2b combined with entecavir.The levels of serum total bilirubin(TBil),aspartate aminotransferase(AST),alanine aminotransferase(ALT),type III procollagen(PCIII),type IV collagen(CIV),complement C3 protein(C3),complement C4 protein(C4),malondialdehyde(MDA),superoxide dismutase(SOD)and nitric oxide(NO)were compared between the two groups before and after treatment.Results:After treatment,the levels of TBil,AST,ALT,PCIII,CIV,MDA and NO in serum of patients with hepatitis B in both groups were significantly lower than those before treatment,and the levels of C3,C4 and SOD were significantly higher than those before treatment(P<0.05).After treatment,the levels of TBil,AST,ALT,PC III,C IV,MDA and NO in serum of patients in the observation group were significantly lower than those in the control group,while the levels of C3,C4 and SOD in serum of patients in the observation group were significantly higher than those in the control group(P<0.05).Conclusions:The combination of interferonα-2b and entecavir has a good curative effect on hepatitis B.It can significantly improve the liver function and immune function of patients,delay the process of liver fibrosis and reduce oxidative stress injury.It is worthy of clinical promotion.
文摘Objective To investigate a new approach of the combined use of trichosanthin (TCS) andrecombinant interferon alpha - 2b (rIFN α- 2b) against digestive system cancer cells. Methods Detect separatelythe cytotoxicity of TCS, rIFN α- 2b and their combination against digestive system cancer cell SGC- 7901.Results In the experiment in vitro, TCS, rIFN α- 2b both had direct, dose dependent cytotoxicity againstSGC - 7901. Their combined use demonstrated a toxicity signijicantly higher than that of the two drugs used alone,showing a signilicant synergic effect. This synergic cytotoxicity was confirmed in the animal experiment.Conclusion Combined use of TCS and rIFN α - 2b decreases the therapeutic dose of TCS and its toxic adverseellect, and this synergic effect is favorable to the clinical use of TCS protein against gastric cancer.
基金Natural Science Foundation Project of Shaanxi Province No:2013CM.
文摘Objective: To study the effects of anti-HPV bioprotein dressing combined with interferon α-2b therapy on the malignant molecule expression in patients with cervical intraepithelial neoplasia (CIN) Ⅲ complicated by high-risk HPV positive. Methods: Patients who were diagnosed with CINⅢ and high-risk HPV positive and underwent conization in the 3201 Hospital Affiliated to Xi'an Jiaotong University between June 2014 and February 2017 were selected and randomly divided into the observation group who received preoperative anti-HPV bioprotein dressing combined with interferon α-2b therapy and the control group who received no special treatment. CIN lesion was collected to determine the expression of pro-proliferation molecules, pro-apoptosis molecules and epithelial-mesenchymal transition molecules. Results: Rsf1, Piwil2, TOPK, p38MAPK, ERK, Snail, Twist, N-cadherin and Vimentin mRNA expression in cervical intraepithelial neoplasia lesions of observation group were greatly lower than those of control group whereas LRIG3, SARI, IEX-1, FHIT and E-cadherin mRNA expression were greatly higher than those of control group. Conclusion: Anti-HPV bioprotein dressing combined with interferon α-2b therapy can inhibit the proliferation and invasive growth of tumor cells in patients with CINⅢ complicated by high-risk HPV positive.
基金Supported by National Key Research and Development Program of China 2023,No:2023YFC2308100.
文摘Achievement of a‘clinical cure’in chronic hepatitis B(CHB)implies sustained virological suppression and immunological control over the infection,which is the ideal treatment goal according to domestic and international CHB management guidelines.Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens.These regimens incorporate either nucleos(t)ide analogs,immunomodulatory agents such as pegylated interferonα,or a strategic combination of both,sequentially or concurrently administered.Despite these advancements in the clinical handling of hepatitis B,achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes.These include,but are not limited to,the emergence of antiviral resistance,incomplete immune recovery,and the persistence of covalently closed circular DNA.Moreover,the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure.This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.
文摘Objective To investigate the quantitation of hepatitis B e antigen (HBeAg) at week 24 in predicting the efifcacy of pegylated-interferon alfa-2a (Peg-IFN-α2a) in HBeAg-positive chronic hepatitis B (CHB) patients at week 48 and to find a useful predictor for treatment efficacy and investigate individualized treatment of antiviral therapy. Methods Ninety-six HBeAg-positive CHB patients with detectable HBeAg who were treated with Peg-IFN-α2a were enrolled in this trial. They were categorized into 3 groups according to the changes of HBeAg in week 24:HBeAg decline>2 log10 group (group A), HBeAg decline between 1 1og10-2 log10 (group B), HBeAg decline<1 log10 group (group C), and group C was randomly distributed into C1 and C2. The patients in group A, group B, and group C1 continued the original therapy and the patients in group C2 were given lamivudine plus Peg-IFN-α2a for 24 weeks. At week 48, the treatment efifcacy and hepatitis B virus covalently closed circular DNA (HBV cccDNA) in liver biopsies were analyzed. Results At week 48, mean reduction of serum HBV DNA:group A:5.8 log10 copies/ml, group B:3.8 log10 copies/ml, group C1:2.8 log10 copies/ml, group C2:5.7 log10 copies/ml, the reduction of HBV DNA in group A was greater than groups B and C1 (P<0.01), that in group C1 was greater than group C2 (P<0.01), the difference between groups B and C1 had no statistical signiifcance (P=0.19). Mean reduction of HBeAg:group A:2.7 log10S/CO, group B:1.9 log10S/CO, group C1:0.9 log10S/CO, group C2:1.5 log10S/CO, the difference among groups A, B and C1 and between groups C1 and C2 were statistically signiifcant (P<0.01). At week 48, HBV DNA undetectable rate in group A, group B, group C1 and group C2 were 87.5%, 34.5%, 17.4%and 81.9%, respectively, the rate in group A was greater than groups B and C1 (P<0.01),that in group C1 was greater than group C2 (P<0.01). HBeAg seroconversion rate were 75.0%, 24.1%, 13.0%and 22.7%, respectively, that in group A was greater than groups B and C1 (P<0.01). Group A had lower cccDNA in liver tissue than group B and group C1 (P<0.01). The difference of HBV cccDNA between groups B and C1 and that between groups C1 and C2 had no statistical signiifcance. Conclusions HBeAg decline > 2 log10 at week 24 in Peg-IFN-α 2a-treated hepatitis B patients suggested a better efficacy at week 48; HBeAg decline < 2 log10 at week 24 suggests a worse efficacy at week 48, the combined therapy of Peg-IFN-α and lamivudine could improve the clinical responses. The change of quantitative of HBeAg at week 24 may be used as a predictor of treatment effects at week 48.
