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。

TLR10基因多态性与HBeAg阳性慢性乙型肝炎患者PEG-IFNα治疗临床转归的相关性分析

目的:探讨分析TLR10基因多态性与HBeAg阳性慢性乙型肝炎(CHB)患者聚乙二醇化干扰素α(PEG-IFNα)治疗临床归转的相关性。方法:选取2019年8月至2020年8月收治的92例HBeAg阳性CHB患者,均予以PEG-IFNα进行治疗,6个月后根据HBeAg、HBeAb情况将患者分为应答组44例和非应答组48例。提取全血基因组DNA,测定TLR10基因多态性点位(RS10004195位点和RS11096957位点),分析其不同点位基因型和等位基因分布与乙型肝炎病毒感染的关系,进而探讨TLR10基因多态性与临床转归的相关性。结果:TLR10基因RS10004195位点基因型中,应答组AA+AT型基因分布频率为77.27%显著高于非应答组的52.08%,A等位基因频率65.91%显著高于非应答组的41.67%,差异有统计学意义(P<0.05);TLR10基因RS11096957位点基因型中,应答组AC+AA型基因分布频率为70.45%,与非应答组的62.50%差异无统计学意义(P>0.05),应答组A等位基因频率为61.36%显著高于非应答组的39.58%,差异有统计学意义(P<0.05);TLR10基因RS10004195位点中,A型基因、A等位基因频率和RS11096957位点中A等位基因频率是HBeAg阳性CHB患者PEG-IFNα治疗临床转归的独立危险因素(OR>1,P<0.05)。结论:TLR10基因RS10004195位点A型基因携带、A等位基因频率,RS11096957位点A等位基因频率是HBeAg阳性CHB患者PEG-IFNα治疗临床转归的独立危险因素,对CHB患者治疗应答反应具有较好评估作用,可为临床治疗提供指导依据。

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.

HBsAg clearance by Peg-interferon addition to a long-term nucleos(t)ide analogues therapy

The ideal endpoint of hepatitis B virus(HBV)antiviral therapy is HBsAg loss,a difficult goal to obtain,especially in HBeAg negative patients.Herein,we report the results obtained by the addition of peg-interferonα-2a to a long-lasting nucleos(t)ide analogues therapy in a HBeAg negative,genotype D patient with steadily HBV-DNA negative/HBsAg positive values.In 2002,our Caucasian 44-year-old male patient received lamivudine and,4 years later,added adefovir because of a virological breakthrough.In 2011,considering his young age,liver stiffness(4.3 kPa)and HBsAg levels(3533IU/mL),we added Peg-interferonα-2a for six months(3in combination with nucleos(t)ide analogues followed by 3 mo of Peg-interferonα-2a monotherapy).A decrease of HBsAg levels was observed after 1 mo(1.21log)of Peg-interferon and 3 mo(1.88 log)after the discontinuation of all drugs.Later,a complete clearance of HBsAg was obtained with steadily undetectable HBVDNA serum levels(<9 IU/mL).HBsAg clearance by the addition of a short course of Peg-interferonα-2a represents an important result with clinical and pharmacoeconomic implications,considering that nucleos(t)ide analogues therapy in HBeAg negative chronic hepatitis B patients is considered a long-lasting/life-long treatment.

Treatment of chronic hepatitis delta virus with peg-interferon and factors that predict sustained viral response

AIM:To observe the efficacy of peg-interferon in the treatment of hepatitis delta virus(HDV) and to identify the factors that would be predictive of the sustained viral response(SVR).METHODS:This prospective study was conducted in Medical Unit Ⅳ of the Liaquat University of Medical and Health Sciences Hospital Jamshoro from June 2008 to September 2011.This study cohort included all patients of either sex who presented during this time with hepatitis B surface antigen positivity,hepatitis B virus DNA > 20 000 IU/mL,serum glutamic pyruvic transaminase(SGPT) > 2(upper limit of normal),HDV-RNA positivity with fibrosis stage ≥ 2.Informed consent was obtained from each of these individuals.Patients were diagnosed with hepatitis D on the basis of detectable viral antibodies and the presence of HDV-RNA in their serum.A liver biopsy was performed in all cases and fibrosis staging was performed in accordance with the METAVIR scoring system.All eligible patients were administered peg-interferon at a weekly dosage of 1.5 g/kg body weight for 48 wk.HDV-RNA was assayed at the end of this treatment period and again at 24 wk later.A biochemical response was determined by a normalization of SGPT at the end of the treatment or during follow up.The end of treatment response was defined by a HDV-RNA negative status.A sustained virological response was defined by undetectable serum HDV-RNA at six months after the end of treatment.RESULTS:Among the 277 patients enrolled in our present study,238 completed a course of peg-interferon therapy of which 180(75.6%) were male and 58(24.4%) female.Biochemical responses were achieved in 122/238(51.3%) patients.End of treatment responses were achieved in 71/238(29.8%) cases.A SVR was achieved in 70 of these patients(29.4%).A strong association was found between the SVR and the end of treatment responses(P = 0.001),biochemical responses(P = 0.001) and the degree of fibrosis(P = 0.002).CONCLUSION:Peg-interferon therapy can induce remission in nearly one third of patients harboring HDV.

Patient education improves adherence to peg-interferon and ribavirin in chronic genotype 2 or 3 hepatitis C virus infection:A prospective,real-life,observational study

AIM: To evaluate the impact of therapeutic education on adherence to antiviral treatment and sustained virological response (SVR) in a real-life setting in genotype 2/3 hepatitis C,as there are few adherence data in genotype 2/3 infection,even from randomized trials.METHODS: This prospective survey included genotype 2/3 patients who received peg-interferon alfa-2b and ribavirin.There was no intervention.Adherence was self-reported over the past 4 wk (peg-interferon) or 7 d (ribavirin).Adherence to bitherapy was defined as adherence to the two drugs for ≥ 20 wk.SVR was defined as undetectable RNA ≥ 12 wk after the end of treatment.RESULTS: 370/674 patients received education during the first 3 mo of treatment.After 6 mo,adherence to bitherapy was higher in educated patients (61% vs 47%,P = 0.01).Adherence to peg-interferon was 78% vs 69% (P = 0.06).Adherence to ribavirin was 70% vs 56% (P = 0.006).The SVR (77% vs 70%,P = 0.05) and relapse (10% vs 16%,P = 0.09) rates tended to be improved.After adjustment for baseline differences,education improved adherence [Odds ratio (OR) 1.58,P = 0.04] but not the SVR (OR 1.54,P = 0.06).CONCLUSION: In genotype 2/3 patients,therapeutic education helped maintain real-life adherence to bitherapy.

Prediction of the Response to Pegylated Interferon α-2a in Patients with HBeAg Positive Chronic Hepatitis B through Decline of Serum HBV DNA and Hepatitis B Virus Surface Antigen at Week 4

Objective To assess on-treatment serum HBsAg and HBV DNA kinetics in HBeAg-positive CHB patients to predict the efficacy of pegylated interferon(PEG-IFN) in early phase of treatment. Methods Forty-one treatment-naive HBeAg-positive patients treated with PEG-IFNα 2a at a dose of 180 μg/week for at least 24 weeks were evaluated. Their treatment response was assessed, including normalization of serum ALT, decline of serum HBV DNA and loss of HBeAg. Results We found that a decrease of HBV DNA level at the 4th week was positively correlated with the decrease of HBV DNA level at the 12th week and 24th week(r = 0.8202, P < 0.0001 and r = 0.6838, P < 0.0001, respectively). We observed that a decrease of HBsAg level at the 4th week was positively correlated with decrease of HBsAg level at the 12th week and 24th week(r = 0.4868, P = 0.0023 and r = 0.4251, P = 0.0109, respectively). A decrease of HBsAg level at the 24th week was positively correlated with the decrease of HBV DNA level at the 24th week(r = 0.5262, P = 0.0024). Serum level of IFN and IFN neutralizing antibody had no relationship with HBV DNA or HBsAg titers kinetics. Conclusions The decline of serum HBV DNA and hepatitis B surface antigen at the 4th week can be used to predict the response to PEG-IFNα 2a in patients with HBeAg positive chronic hepatitis B.

外源5-氨基乙酰丙酸和PEG处理下栀子幼苗光合及抗氧化特性变化

采用溶液培养方式,研究不同浓度(0、25、50、100 mg·L^(-1)和200mg·L^(-1))5-氨基乙酰丙酸(ALA)对PEG胁迫条件下栀子幼苗有机渗透调节物质含量、光合生理及抗氧化系统等生理生化指标。结果表明,栀子幼苗PEG胁迫14 d,地上和地下部分干重、苗高、根长、相对含水量、光合色素含量、净光合速率(Pn)、蒸腾速率(Tr)、气孔导度(Gs)和水分利用率(WUE)下降;脯氨酸、丙二醛(MDA)、过氧化氢(H_2O_2)含量和相对电导率显著上升,而抗氧化酶(SOD、POD、CAT)活性明显下降,一定浓度ALA处理降低了PEG引起栀子幼苗生理上的压力,50 mg·L^(-1)的外源ALA处理可以显著缓解PEG诱导生长抑制,与单独PEG胁迫处理相比,叶绿素a和叶绿素b含量、净光合速率、SOD、POD、CAT活性、相对含水量和脯氨酸的积累分别提高了25.35%、31.85%、228.68%、41.92%、27.26%、41.50%、170.26%、31.01%,MDA含量、H_2O_2含量和相对电导率分别降低39.00%、31.18%、45.56%。相反,200 mg·L^(-1)ALA处理则可能加剧干旱胁迫伤害。

PEG-柠檬酸盐双水相体系纯化α-淀粉酶及模型构建

探索了采用PEG 柠檬酸盐双水相体系纯化α 淀粉酶的可行性和工艺条件 ,实验考察了PEG分子量 ,结线长度、pH、上清加入量和NaCl浓度对α 淀粉酶的分配的不同影响。双水相分离体系复杂 ,影响因素多 ,为进行分析、预测和优化 ,采用了响应面方法 ,以PEG 335 0浓度、柠檬酸盐浓度和NaCl浓度为自变量进行了α 淀粉酶分配系数、总蛋白分配系数、纯化因子和α 淀粉酶收率的优化 ,确定了特定的系统组成区域 ,通过实验验证了该区域内纯化因子大于 2 ,收率约 90 % 。

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。

PEG6000修饰物混合吐温80-硫酸铵盐的液-固萃取体系分离纯化血红蛋白

采用聚乙二醇 6 0 0 0 (PEG6 0 0 0 )修饰物混合吐温 80 硫酸铵盐的液 -固萃取体系对血红蛋白分离纯化进行研究 ,考察了修饰物、盐、吐温 80浓度以及体系酸度、温度等因素对血红蛋白分离纯化的影响 ,用该体系直接从三种血液中分离纯化血红蛋白 ,操作简便快速 ,萃取容量大 ,一次萃取固相收得率 99%以上 ,一次反萃取率达 75 % ,一步纯化倍数达 2 0倍 ,用多种手段验证了所获猪血红蛋白 ,纯度达 99% .

高铁试剂作萃取剂的PEG2000液-液萃取的研究

在PEG2000-(NH_4)_2SO_4—H_2O体系中,用高铁试剂作萃取剂,研究了Fe(Ⅲ)、U(Ⅵ)、V(Ⅴ)等金属离子络合物在两相的分配,借控制酸度和加入掩蔽剂的方法,实现了Fe(Ⅲ)—U(Ⅵ),V(Ⅴ)—U(Ⅵ),Fe(Ⅲ)—V(Ⅴ)的定量萃取分离。利用加入表面活性剂的方法,探讨了PEG相的萃取机理。

PEG-胆固醇双重修饰PBCA纳米粒脑靶向机制

目的中枢神经系统疾病目前存在的主要问题是血脑屏障(BBB)通透性的问题,本实验期望通过制备PEG-胆固醇双重修饰PBCA纳米粒,提高难透过BBB的中枢神经系统疾病的治疗及早期诊断药物的治疗作用,并对其经过BBB进入脑组织的机制进行探讨。方法采用乳化聚合法制备双重修饰PBCA纳米粒并对其理化特性进行评价。(1)双重修饰PBCA纳米粒体内药动学及脑组织分布研究:实验前12小时大鼠进行颈静脉插管手术。实验时于插管处给予原药溶液,胆固醇单修饰及PEG-胆固醇双重修饰PBCA纳米粒。给药后不同时间点取血200μL,化学/发光分析仪测定血液中香豆素-6的含量。大鼠尾静脉分别给予原药溶液、胆固醇单修饰及PEG-胆固醇双重修饰PBCA纳米粒。给药后不同时间点处死大鼠,取脑组织测定香豆素-6的含量。(2)双重修饰PBCA纳米粒体外细胞摄取及转运机制研究:采用b End.3细胞模型(永生化小鼠脑内皮细胞株)评价了载体及纳米粒的体外细胞毒性,同时选用了巨胞饮介导的内吞作用(细胞松弛素D),网格蛋白介导的内吞作用(氯丙嗪),小窝蛋白介导的内吞作用(染料木素),胆固醇耗竭(MβCD和制霉菌素),高尔基体抑制剂(布雷菲德菌素A)和耗能(叠氮钠)等七种细胞摄取抑制剂来研究载药纳米粒的细胞摄取及转运机制。结果 (1)制备的纳米粒粒径为(191.1±1.22)nm、载药量约为1.97%,包封率大于98%。同时双重修饰PBCA纳米粒在体外具有更明显的缓释效果。(2)双重修饰PBCA纳米粒在体内具有更高的血药浓度及缓释效果,能持续释放12 h,而胆固醇单修饰纳米粒仅释放8 h,原药溶液仅4 h内能检测到药物。脑组织分布研究结果表明,双重修饰PBCA纳米粒静脉给药后脑组织中药物含量显著增高且成缓慢释放的过程,说明具有成为脑靶向制剂的研究潜力。(3)载体及载药纳米粒细胞安全性良好,纳米粒在实验范围内没有明显的细胞毒性,具有较好的安全性。选择不同类型的摄取和转运抑制剂研究了载药纳米粒的细胞摄取及转运机制。结果表明,参与细胞转运和摄取的机制可以是不同的,而胆固醇-PEG双修饰PBCA纳米粒在b End.3细胞中的转运机制,是一个包括巨胞饮介导、耗能、同时需要胆固醇参与等多种机制介导的复杂过程。结论本实验制备的PEG20000-胆固醇双重修饰PBCA纳米粒,可解决中枢神经系统疾病的治疗及诊断药物体内BBB通透率低、安全性差、缓释性差等瓶颈问题,具有重要应用前景。

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。

PEG功能化1,3-二唑盐的合成及在水相Heck反应中的研究

以商品化的聚乙二醇单甲醚为起始原料,通过三步反应制备了4种PEG功能化的1,3-二唑季铵盐(L1~L4),产物的收率都在90%以上.随后将上述4种产物作为水溶性卡宾前体分别和Na_2PdCl_4反应在线生成卡宾钯络合物并用于催化均相的水相Heck反应.优化实验结果表明:L1的催化性能最优,在纯水相中模型反应的TON值大于8 900.建立的催化体系对底物的适用性较好,可用于制备许多二苯乙烯类化合物,收率为51%~98%.该方法具有产物分离简便、收率高、催化剂用量少和环境友好等优点.

不同相对分子质量PEG-CHMC修饰乳剂对二次注射PE2000诱导产生ABC现象的研究

目的研究比较不同相对分子质量PEG-CHMC修饰乳剂(PEG-CHMC coating emulsion,CHMCE)在大鼠体内的药动学行为及其对二次注射PEG2000-DSPE修饰乳剂(PEG2000-DSPE coating emulsion,PE2000)诱导的ABC现象,探究PEG相对分子质量对乳剂药动学行为及ABC现象的影响。方法以摩尔分数10%PEG修饰密度制备载药乳剂CHMCE和PE,以磷脂剂量5μmol·kg^(-1)进行大鼠尾静脉注射,分别于不同时间点进行静脉取血,处死大鼠后分离肝、脾组织,血浆和组织样品经处理后通过HPLC分析药物含量。结果通过比较药动学参数AUC(0-240 min)、tMRT(0-240 min)可知,高相对分子质量CHMCE(1 000、2 000、5 000)的循环时间较低相对分子质量CHMCE(400、600、800)有所延长,但延长程度不高;CHMCE诱导PE2000产生ABC现象的结果显示,低相对分子质量CHMCE无ABC现象,而高相对分子质量CHMCE诱导了一定强度的ABC现象(CHMCE1000、CHMCE2000和CHMCE5000的ABC index(0-60 min)分别为0.64、0.59和0.53)。结论 PEG相对分子质量在CHMCE的药动学行为及ABC现象的产生中具有重要影响,研究结果对PEG相对分子质量在ABC现象中的影响规律进行了补充,为PEG化制剂相对分子质量的选择提供了一定借鉴。

Peg-IFNα序贯联合NUCs治疗高病毒载量e抗原阳性乙型肝炎疗效观察

目的：探讨应答指导治疗（RGT）策略下聚乙二醇干扰素α与核苷类药物序贯联合治疗较单用聚乙二醇干扰素a治疗高病毒载量e抗原（HBeAg）阳性的慢性乙型肝炎患者的临床疗效与安全性。方法47例HBeAg阳性、乙型肝炎病毒（HBV）DNA〉1×107IU/ml的慢性乙型肝炎患者应用聚乙二醇干扰素α抗病毒治疗12周后，根据患者HBV DNA下降是否〉2lg IU/ml分为联合组和单药组：联合组加用一种核苷类药物，单药组为继续单用聚乙二醇干扰素α，两组均治疗至48周。观察两组治疗24周、48周的丙氨酸氨基转移酶（ALT）复常率、HBV DNA转阴率、血清HBeAg及HBsAg转阴/转换率。结果联合组24周及48周的HBV DNA不可检测率均高于单药组，但两组间差异均无统计学意义（P〉0.05）；24周及48周联合组HBeAg和表面抗原（HBsAg）定量的下降幅度大于单药组。结论 RGT策略下聚乙二醇干扰素α应答不佳的高病毒载量HBeAg阳性慢性乙型肝炎患者序贯联合核苷（酸）类似物（NUCs）可以提高应答，但长期效果仍有待于进一步研究。

PEG 600反应介质中合成14-芳基-1,6,7,14-四氢二苯并[a,i]吖啶-1,6-二酮(英文)

在室温条件下以PEG 600为反应介质,三组分一锅法高效地合成了14-芳基-1,6,7,14-四氢二苯并[a,i]吖啶-1,6-二酮.该方法具有反应时间短、产率高、污染小、操作简单等优点.作为反应介质的PEG可以回收使用.

Hepatitis C virus core protein-induced miR-93-5p upregulation inhibits interferon signaling pathway by targeting IFNAR1

AIM To investigate the mechanism by which hepatitis C virus(HCV) core protein-induced mi R-93-5 p up-regulation regulates the interferon(IFN) signaling pathway.METHODS HCV-1 b core protein was exogenously expressed in Huh7 cells using pc DNA3.1(+) vector. The expression of mi R-93-5 p and interferon receptor 1(IFNAR1) was measured using quantitative reverse transcriptionpolymerase chain reaction and Western blot. The protein expression and phosphorylation level of STAT1 were evaluated by Western blot. The overexpression and silencing of mi R-93-5 p and IFNAR1 were performed using mi R-93-5 p agomir and antagomir, and pc DNA3.1-IFNAR1 and IFNAR1 si RNA, respectively. Luciferase assay was used to identify whether IFNAR1 is a target of mi R-93-5 p. Cellular experiments were also conducted.RESULTS Serum mi R-93-5 p level was increased in patients with HCV-1 b infection and decreased to normal level after HCV-1 b clearance, but persistently increased in those with pegylated interferon-α resistance, compared with healthy subjects. Serum mi R-93-5 p expression had an AUC value of 0.8359 in distinguishing patients with pegylated interferon-α resistance from those with pegylated interferon-α sensitivity. HCV-1 b core protein increased mi R-93-5 p expression and induced inactivation of the IFN signaling pathway in Huh7 cells. Furthermore, IFNAR1 was identified as a direct target of mi R-93-5 p, and IFNAR1 restore could rescue mi R-93-5 p-reduced STAT1 phosphorylation, suggesting that the mi R-93-5 p-IFNAR1 axis regulates the IFN signaling pathway.CONCLUSION HCV-1 b core protein-induced mi R-93-5 p up-regulation inhibits the IFN signaling pathway by directly targeting IFNAR1, and the mi R-93-5 p-IFNAR1 axis regulates STAT1 phosphorylation. This axis may be a potential therapeutic target for HCV-1 b infection.