PEG-IFNα-2b联合替诺福韦治疗慢性乙型肝炎的疗效及对HBeAg转阴率、免疫功能的影响

目的:分析聚乙二醇干扰素α-2b(PEG-IFNα-2b)联合替诺福韦治疗慢性乙型肝炎的效果及对HBeAg转阴率、免疫功能的影响。方法:选取某院2019年3月—2022年3月收治的慢性乙型肝炎患者88例作为研究对象,依据随机抽签法分成研究组与对照组,每组44例。对照组接受替诺福韦治疗,研究组接受PEG-IFNα-2b联合替诺福韦治疗,比较2组HBeAg转阴率、HBsAg转阴率、治疗前后肝功能指标[谷氨酰转肽酶(GGT)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)]、免疫功能指标(CD3^(+)、CD4^(+)/CD8^(+)、C3、C4)及血清炎性因子[视黄酸受体相关孤核受体(RORγt)、白细胞介素-17(IL-17)、IL-4]水平。结果:研究组HBeAg转阴率、HBsAg转阴率分别为45.45%、13.64%,高于对照组的11.36%、0,差异有统计学意义(P<0.05)。治疗后,研究组GGT、AST、ALT、IL-4、IL-17、RORγt分别为(30.42±5.39)U/L、(31.08±6.64)U/L、(29.37±4.68)U/L、(1.32±0.42)pg/mL、(0.64±0.19)pg/mL、(0.80±0.30),均低于对照组的(56.93±8.75)U/L、(38.72±5.83)U/L、(49.61±6.42)U/L、(3.91±1.14)pg/ml、(3.01±0.87)pg/ml、(1.61±0.36),差异有统计学意义(P<0.05)。研究组CD3^(+)、CD4^(+)/CD8^(+)、C3、C4分别为(66.81±8.55)%、(1.53±0.16)、(1.22±0.01)g/L、(0.42±0.07)g/L,均高于对照组的(61.03±8.49)%、(1.26±0.2)、(0.73±0.09)g/L、(0.22±0.06)g/L,差异有统计学意义(P<0.05)。结论:PEG-IFNα-2b联合替诺福韦治疗慢性乙型肝炎效果明显,可提高HBeAg、HBsAg转阴率,改善肝功能,增强免疫功能,抑制炎性反应。

Pegylated interferon α-2b up-regulates specific CD8+ T cells in patients with chronic hepatitis B

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.

5-氮杂-2′-脱氧胞苷对肝癌细胞HepG2凋亡及其PEG10基因表达的影响

目的探讨去甲基化药物5-氮杂-2′-脱氧胞苷(5-Aza-CdR)对人肝癌细胞系HepG2凋亡及其PEG10基因表达调控的影响,进一步探讨肝癌的发病机制及5-Aza-CdR治疗肝癌的可行性。方法用浓度为50μmol/L的5-Aza-CdR分别处理HepG2细胞24、48、72 h,hoechst 33342/PI双染荧光显微镜检测HepG2细胞凋亡情况。RT-PCR、Western blot法分别检测PEG10 mRNA和蛋白表达水平的变化。结果与对照组相比,5-Aza-CdR作用24、48、72 h后,HepG2细胞的凋亡率明显升高,PEG10 mR-NA和蛋白表达水平显著下降,并呈现时间依赖性(P<0.05)。结论 5-Aza-CdR可促进HepG2细胞凋亡并抑制PEG10基因的表达。

PEG/SiO_2-TiO_2杂化纤维的制备与表征

以正硅酸乙酯(TEOS)和钛酸四丁酯(TBT)为无机前驱体,采用溶胶-凝胶法制备了PEG/SiO2-TiO2杂化溶胶,通过提拉法制得杂化纤维,并对其进行了简单表征。结果表明,随钛硅物质的量比的增加或有机相质量的增加,溶胶的可纺性变好;有机相与无机相之间通过化学键连接;纤维直径为40μm左右;TiO2的引入增强了其抗紫外性,杂化纤维的耐热性优于纯PEG。

溶胶-凝胶法制备复合相变PEG/SiO_2的实验研究

PEG/SiO_2是一种新型的复合相变材料,具有非常好的储热性能和化学热力学性质,而溶胶-凝胶法是一种新型的化学制备方法,可以制备出颗粒很细,性质较好的产品。通过实验采用了溶胶-凝胶法去制备复合相变PEG/SiO_2,并且对化学合成产品进行了热力学性能的分析和红外表征,从而证明了采用溶胶-凝胶法后产品具有非常良好的化学热力学性质,并指出此方法合成的该产品在混凝土掺料方面具有潜在的应用价值。

Pegα-2α-IFN联合利巴韦林治疗慢性丙型肝炎30例疗效观察

目的观察pegα-2α-IFN联合利巴韦林治疗慢性丙型肝炎的疗效及不良反应。方法将60例慢性丙型肝炎病人随机分为两组,治疗组和对照组各30例。治疗组给予pegα-2α-IFN135μg皮下注射,每周1次,联合利巴韦林1000-1200mg/d治疗;对照组给予α-2b干扰素300MIU,每周3次,利巴韦林使用量同治疗组,疗程24周。治疗期间1、2、4、6、8、12周,之后每4周随访1次,停药后继续观察24周,治疗及随访期间观察肝功能的生化指标,血常规,肾功,HCVRNA及用药期间的不良反应。结果治疗期间两组血清生理指标复常率,治疗终点应答率,不良反应无显著性差异,持续治疗的应答率分别为36.7%和63.3%有显著差异。结论Pegα-2α-IFN联合利巴韦林治疗慢性丙型肝炎能够提高持续治疗应答率,完全性好,可提高慢性丙型肝炎疗效。

Study on pharmacodynamics of recombinant interferon α-2b suppository

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.

Effects of interferon α-2b on liver function, complement level and oxidative stress in patients with hepatitis B

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.

SYNERGIC CYTOTOXICITY TO GASTRIC CANCER CELLS BY COMBINED USE OF TRICHOSANTHIN ANDRECOMBINANT INTERFERON α-2B

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.

PEG IFN-α-2α胜过丙型肝炎传统治疗

意大利和美国的研究人员报告，PEG干扰素(IFN)-α-2α与利巴韦林(ribavirin)联合治疗(Ⅰ)成人慢性丙型肝炎比传统的IFN-α-2b加利巴韦林治疗(Ⅱ)价效比更好。

Effects of anti-HPV bioprotein dressing combined with interferon α-2b therapy on the malignant molecule expression in patients with CINⅢ complicated by high-risk HPV positive

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.

治疗丙型肝炎首选利巴韦林联合Peg干扰素α-2a

《胃肠病学》杂志刊登意大利2项研究，表明在慢性丙型肝炎病毒（HCV）感染联合治疗中，利巴韦林联合Peg干扰素α-2a优于联合Peg干扰素α-2b。米兰大学的Colombo和那不勒斯的Ascione分别发现，对于初治的慢性丙型肝炎患者，

聚乙二醇干扰素α-2a联合阿德福韦酯治疗慢性乙型肝炎的Meta分析

慢性乙型肝炎由乙型肝炎病毒感染所致,首选干扰素(IFN)或核苷(酸)类似物(NUC)单药抗病毒治疗,但IFN单药治疗往往应答率低,NUC长期用药易发生病毒变异,产生耐药,影响疗效,因此提倡联合治疗。目前,联合治疗分为初始联合及治疗中联合,联合药物有NUC联合NUC,或IFN联合NUC。临床试验发现,聚乙二醇干扰素α-2a(Peg-IFNα-2a)联合拉米夫定短期疗效不佳,联合替比夫定可能出现周围神经病变,因此,寻找新的联合治疗方案十分必要。笔者查阅Peg-IFNα-2a联合阿德福韦酯(ADV)治疗CHB的临床试验发现,其疗效和安全性各方评价不一。本文就Peg-IFNα-2a联合ADV治疗CHB有效性和安全性的随机对照试验进行Meta分析,以期为临床用药提供参考。

聚乙二醇干扰素α-2a联合利巴韦林治疗慢性丙型肝炎的疗效评价

目的:评估聚乙二醇干扰素α-2a联合利巴韦林抗病毒治疗前后慢性丙型肝炎肝脏的病理变化。方法:选取我院2014年10月至2015年10月收治的40例慢性丙肝患者为研究对象,随机将患者分为观察组与对照组,每组20例。观察组采用聚乙二醇干扰素α-2a联合利巴韦林(PR方案)抗病毒治疗,对照组采用一般保肝降酶治疗,比较两组患者治疗前后谷丙转氨酶(ALT)、丙型肝炎病毒(HCV)RNA水平及肝脏病理组织的变化。结果:治疗后,观察组ALT复常率80%,与对照组比较无统计学差异(P>0.05);观察组HCVRNA转阴率为90.0%,与对照组比较显著升高(P<0.05);观察组肝组织炎症活动度、纤维化程度较治疗前明显降低,且显著低于对照组(P<0.05)。结论:抗病毒治疗能明显降低肝脏炎症活动度及纤维化程度;从病理的角度评估抗病毒治疗的效果有着重要的意义。

利巴韦林联合聚乙二醇干扰素α-2a治疗慢性丙型肝炎临床效果分析

目的分析利巴韦林联合聚乙二醇干扰素α-2a治疗慢性丙型肝炎的临床效果。方法将本院收治的96例慢性丙型肝炎患者按照随机数表法分为对照组与观察组。对照组患者行常规治疗,并加用利巴韦林治疗;观察组患者采用利巴韦林联合聚乙二醇干扰素α-2a治疗。两组患者均连续治疗24周,分别于治疗开始后第12、24、48周测定两组患者血清中丙型肝炎病毒(HCV)抗体与HCV RNA水平,比较两组患者肝功能、疗效及不良反应发生情况。结果观察组患者随访至48周治疗结束时病毒学应答(ETVR)、持续病毒学应答(SVR)比例均明显高于对照组(P<0.05)。治疗后,两组患者丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平均较治疗前降低,观察组患者上述指标水平均低于对照组(P<0.05),且两组患者透明质酸酶(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(CⅣ)、层粘连蛋白(LN)水平均低于治疗前,观察组患者上述指标水平均明显低于对照组(P<0.05)。两组患者各不良反应发生率比较差异均无显著性(P>0.05)。结论利巴韦林联合聚乙二醇干扰素α-2a可有效治疗慢性丙型肝炎,降低患者HCV-RNA水平,安全性高,具有重要临床价值。

聚乙二醇修饰重组人干扰素α-2b修饰产物的初步分析研究

目的 对聚乙二醇(PEG)修饰重组人干扰素α-2b(rhIFNa-2b)的修饰产物进行了初步分析研究。方法以单甲氧基聚乙二醇甲酸琥珀酰亚胺酯对rhIFNα-2b进行修饰,修饰产物以Superdex 75 Highload制备型凝胶色谱柱进行分离、纯化,SDS-PAGE鉴定各组分,采用Mariner电喷雾飞行时间质谱对单修饰IFNα-2b(Inono-PEG-IFNα-2b)进行分析。结果 分别获得了纯化的mono-PEG-IFNα-2b和多修饰IFNα-2b(poly-PEG-IFNα-2b)。ESI-TOF质谱也证明mono-PEG-IFNα-2b分子量比rhIFNα-2b多5 000左右;紫外光谱分析表明,PEG修饰产物的结构没有发生改变。结论获得了纯化的PEG修饰产物。

PEG1000用量对多孔TiO_2薄膜结构及光催化性能的影响

以钛酸四丁酯为钛源,PEG1000为模板剂,乙酰丙酮为稳定剂,制备了TiO2溶胶,通过浸渍-提拉法在载玻片上制备了多孔TiO2薄膜。采用X射线衍射、扫描电镜、紫外-可见透射光谱、X射线光电子能谱、N2吸附-脱附等对TiO2薄膜的晶相结构、表面形貌、化学组成及TiO2粉体的BET比表面积和孔径分布进行了表征。考察了TiO2薄膜对甲基橙的光催化降解活性。实验结果表明,TiO2薄膜催化剂的晶型为锐钛矿型,Ti以Ti4+形式存在。随着PEG1000添加量的增加,薄膜表面形貌变得粗糙,孔数量先增加而后下降;多孔TiO2薄膜在紫外区域内的吸收边沿向短波方向移动,薄膜透射率也发生波动,但薄膜的厚度基本不变。当PEG1000添加量为2.0g时,薄膜中存在大量的介孔,薄膜的比表面积最大,光催化性能最佳。

白细胞介素－2的PEG化

用自制的氨基ＰＥＧ化试剂ｒＩＬ－２进行化学修饰，研究了试剂浓度，溶液ｐＨ，反应时间等与ＰＥｃａ－ｒＩＬ－２产率及ＩＬ－２活性保持之间的关系，建立了一套获得稳定修饰度的ＰＥＧ－ｒＩＬ－２的方法。研究发现，反应时间跟修饰度关系不大；溶液ｐＨ对修饰度有一定的影响，中性ｐＨ以上反应都可进行；而试剂浓度直接决定修饰度的高低，过量越多，修饰度越高，而生物活性保留也越低；但低度修饰，对活性几乎没有影响，可保留活性在９５％左右。