目的:观察α干扰素治疗HBeAg(+)慢性乙型肝炎患者过程中病毒学及血清学动态变化情况,通过早期疗效预测终末疗效。方法:观察144例HBeAg(+)慢性乙型肝炎患者经α干扰素治疗24WK及随访24WK 过程中HBV-DNA以及HBeAg变化情况.结果:经α干扰素治疗12、24、48WK时,HBV-DNA下降到可检测值以下病例数分别为32、32、31例;同期HBeAg发生血清转换病例数分别为16、17、21例。结论:干扰素治疗12WK时患者病毒学及血清学结果可早期预测终末疗效。
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.
目的 采用干扰素和阿德福韦酯治疗慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异，比较两种治疗策略的临床疗效。 方法 选择2002年2月-年12月经100 mg拉米夫定治疗后出现YMDD变异的慢性乙型肝炎患者76例。其中，男52例，女24例；年龄18~55岁，平均年龄33岁。服用100 mg拉米夫定52～156周发生YMDD变异，HBV DNA低于治疗前水平，丙氨酸转移酶(alanine aminotransferase，ALT)lt;2×ULN/L患者分为A组(26例)，继续用100 mg拉米夫定治疗48周；服用100 mg拉米夫定52～156周发生YMDD变异，HBV DNA定量检测高于或等于治疗前水平，ALTgt;2×ULN/L，根据患者自愿分为B组(27例)和C组(23例)。B组用100 mg拉米夫定联合10 mg阿德福韦酯治疗48周；C组用干扰素治疗48周。分别观察3组ALT复常率及HBV DNA转阴率、HBeAg阳性患者血清学转换率。 结果 治疗48周时，B、C组患者ALT复常率分别是74.1%和78.3%，明显高于A组的34.6%，差异有统计学意义(Plt;0.05)；B、C组患者HBV DNA转阴率分别是77.7%和73.9%，明显高于A组的11.5%，差异有统计学意义(Plt;0.05)；3组HBeAg阳性患者血清学转换率比较，差异均无统计学意义(Pgt;0.05)。 结论 慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异，继续用拉米夫定治疗疗效不理想，改用干扰素或联合阿德福韦酯治疗更安全有效。
目的:探讨干扰素治疗水痘的效果。方法:将151例水痘患者随机分为3组, 治疗组Ⅰ给予干扰素100 万U/ 次,im,隔日1 次,连用3 次,治疗组Ⅱ同时予以干扰素局部外涂于水痘处, 2 次/ d;对照组病毒唑10 mg/ (kg·d),im, 一日2 次,连用5 天。除以上治疗外,3组均同时根据病情给予退热、止痒、抗炎等对症治疗。观察3组患者症状、体征变化。结果:治疗组患者症状、体征恢复所用时间明显优于对照组,同时还发现局部外涂干扰素于水痘处,其皮疹瘙痒、结痂恢复天数明显缩短。结论:干扰素治疗水痘可减轻症状,缩短病程,配合局部外用效果更佳。
Objective To examine the levels of interferon-gamma; (INF-gamma;), tumor necrosis factor-alpha; (TNF-alpha;) and interleukin-6(IL-6) in serum of patients with acute uveitis before and after treatment, and to explore the possible roles of those cytokines in the initiation and progression of the uveitis. Methods A series of 75 patients with acute uveitis,and 30 healthy persons from our hospital were investigated. The levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase and convalescent phase were measured by the enzymelinked immunosorbent assay. Result The serum levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase were significantly higher than that of the convalescent phase and the healthy controls (F=65.805/50.418/155.381, P=0.000). A significant negative correlation was found between the serum levels of INF-gamma;, TNF-alpha; and IL-6 in acute phase with their initial visual acuity(r=-0.656, -0.592 and -0.653, Plt;0.01). There was also a positive correlation among the serum levels of INF-gamma;, TNF-alpha; and IL-6(r=0.340, 0.467 and 0.338, Plt;0.05). Conclusions There are high serum levels of INF-gamma;, TNF-alpha; and IL-6 in patients with acute uveitis, and the cytokines levels were decreased after the treatment. The results suggested that the INF-gamma;, TNF-alpha; and IL-6 involved in initiation and progression of uveitis.
PEGylating is an effective way for prolonging the half-time period and decreasing the immunogenicity of protein drugs. With experiments of single factor, it was proved that the optimal processes for PEGylating the fused protein of LL-37 and interferon (IFN)-α2a were:PEG molecular weight was 5 000, fused protein concentration was 0.6 mg/mL, the mole ratio of protein to mPEG5000-SS was 1:10, the reaction temperature was 4℃, and the pH was 9.0, respectively. With orthogonal experiments, we proved that the influential order of 3 main factors is:the fused protein concentration > the mole ratio of protein and mPEG5000-SS > pH and the optimal conditions were the fused protein concentration as 0.6 mg/mL, the mole ratio of protein and mPEG5000-SS as 1:10, pH as 8.8. Under these optimal conditions, the average rate of PEGylated protein with 3 times parallel experiments was 86.98%. After PEGylated, the interferon activity and antimicrobial activity of fused protein could be remained higher than 58% and 97%, respectively.
目的 评价国内干扰素（INF）治疗多发性骨髓瘤（MM）的疗效与安全性。 方法 计算机检索中国期刊全文数据库（1989年－2011年）、中国生物医学文献数据库（1989年-2011年）和中文科技期刊全文数据库（1989年－2011年），并手工检索所有纳入文献的参考文献，纳入INF治疗MM的随机对照试验（RCT）。评价纳入研究的方法学质量并进行资料提取后，采用RevMan 5.0软件进行Meta分析。 结果 共纳入10个RCT，包括366例患者。Meta分析显示，INF联合美法仑+泼尼松（MP） 方案与单用MP方案比较，其总有效率差异有统计学意义[OR=4.52，95% CI（1.84，11.10），P=0.001]；INF联合长春新碱+多柔比星+地塞米松/泼尼松[VAD（P）]与单用VAD（P）方案比较，其总有效率[OR=4.13，95% CI（1.53，11.14），P=0.005]和完全缓解率[OR=3.88，95% CI （1.49，10.16），P=0.006]差异也均有统计学意义；INF+其他化疗方案与单用化疗方案比较，其总有效率[OR=2.57，95%CI（1.11，5.96），P=0.03]和完全缓解率[OR=3.17，95% CI（1.21，8.27），P=0.02]，差异均有统计学意义。 结论 目前国内研究结果表明，INF与化疗联合运用能增加MM治疗的总有效率和缓解率，但由于纳入研究样本量小且质量较低，上述结论尚需要高质量、大样本的随机与双盲对照试验加以分析。
This study aims to clarify host factors of IFN treatment in the treatment of chronic hepatitis B (CHB) patients by screening the differentially expressed genes of IFN pathway CHB patients with different response to interferon (IFN) therapy. Three cases were randomly selected in IFN-responding CHB patients (Rs), non-responding CHB patients (NRs) and healthy participants, respectively. The human type I IFN response RT2 profiler PCR array was used to detect the expression levels of IFN-related genes in peripheral blood monocytes (PBMCs) from healthy participants and CHB patients before and after Peg-IFN-α 2a treatment. The results showed that more differentially expressed genes appeared in Rs group than NRs group after IFN treatment. Comparing with healthy participants, IFNG, IL7R, IRF1, and IRF8 were downregulated in both Rs and NRs group before IFN treatment; CXCL10, IFIT1, and IFITM1 were upregulated in the Rs; IL13RA1 and IFI35 were upregulated in the NRs, while IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1, and ADAR were downregulated. The expression of IL15, IFI35 and IFI44 was downregulated by 4.09 (t = 10.58, P < 0.001), 5.59 (t = 3.37, P = 0.028) and 10.83 (t = 2.8, P = 0.049) fold in the Rs group compared with the NRs group, respectively. In conclusion, IFN-response-related gene array is able to evaluate IFN treatment response by detecting IFN-related genes levels in PBMC. High expression of CXCL10, IFIT1 and IFITM1 before treatment may suggest satisfied IFN efficacy, while high expression of IL13RA1, IL15, IFI35 and IFI44 molecules and low expression of IFRD2, IL11RA, IL4R, IRF3, IRF4, PYHIN1 and ADAR molecules may be associated with poor IFN efficacy.
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.