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.

Development of novel-nanobody-based lateral-flow immunochromatographic strip test for rapid detection of recombinant human interferon a2b

Recombinant human interferon a2b(rhIFNa2b)is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C.The current identification test for rhIFNa2b is complex.In this study,an anti-rhIFNa2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNa2b.RhIFNa2b was used to immunize an alpaca,which established a phage nanobody library.After five steps of enrichment,the nanobody I22,which specifically bound rhIFNa2b,was isolated and inserted into the prokaryotic expression vector pET28a.After subsequent purification,the physicochemical properties of the nanobody were determined.A semiquantitative detection and rapid identification assay of rhIFNa2b was developed using this novel nanobody.To develop a rapid test,the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips.The developed rhIFNa2b detection assay had a limit of detection of 1 mg/mL.The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products.The principle of this novel assay is generally applicable for the rapid testing of other commercial products,with a great potential for routine use in detecting counterfeit recombinant protein products.

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.

The Predictive Value of Baseline HBs Ag Level and Early Response for HBs Ag Loss in Patients with HBe Ag-positive Chronic Hepatitis B during Pegylated Interferon Alpha-2a Treatment

Objective To explore the predictive value of baseline HBs Ag level and early response for HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment. Methods A total of 121 patients with HBe Ag-positive chronic hepatitis B who achieved HBs Ag loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators （HBs Ag, anti-HBs, HBe Ag, and anti-HBe） were determined before and every 3 months during treatment. Results The median treatment time for HBs Ag loss was 84 weeks （7-273 weeks）, and 74.38% （90 cases） of the patients needed extended treatment （〉 48 weeks）. The correlation between baseline HBs Ag levels and the treatment time of HBs Ag loss was significant （B = 14.465, t = 2.342, P = 0.021）. Baseline HBs Ag levels together with the decline range of HBs Ag at 24 weeks significantly correlated with the treatment time of HBs Ag loss （B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005）. Conclusion Baseline HBs Ag levels and extended therapy are critical steps toward HBs Ag loss. Baseline HBs Ag levels together with early response determined the treatment time of HBs Ag loss in patients with HBe Ag-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

Combination Therapy with Pegylated Interferon alpha-2b and Adefovir Dipivoxil in HBeAg-positive Chronic Hepatitis B versus Interferon Alone: A Prospective, Randomized Study

Currently available monotherapies of oral nucleoside/nucleotide analogs or interferon are unable to achieve a sustained and effective response in most of patients with chronic hepatitis B（CHB）. The objective of the present study was to compare the efficacy and safety of pegylated interferon（Peg-IFN） alpha-2b plus adefovir dipivoxil combination therapy versus Peg-IFN alpha-2b alone. Sixty-one HBeAg-positive chronic hepatitis B patients were randomized to receive Peg-IFN alpha-2b alone（1.5 μg/kg once weekly） or Peg-IFN alpha-2b plus adefovir（10 mg daily） for up to 52 weeks. Efficacy and safety analyses were performed on all participants who received at least one dose of study medication. The rate of HBeAg seroconversion and undetectable HBV-DNA were evaluated after 52 weeks of therapy. At the end of treatment, 11 of 30（36.7%） patients receiving combination therapy achieved HBeAg seroconversion versus 8 of 31（25.8%） in the monotherapy group（P=0.36）. In contrast, the percentage of patients with undetectable serum HBV DNA was significantly higher in the combination group than in the monotherapy group（76.7% vs. 29.0%, P〈0.001）. Thyroid dysfunction was more frequent in the combination group than in the monotherapy group（P〈0.05）. In HBeAg-positive CHB, combination of Peg-IFN alpha-2b and adefovir for 52 weeks resulted, at the end of treatment, in a higher virological response but without significant impact on the rate of HBeAg seroconversion and possibly an adverse effect on thyroid function.

Treatment of Hepatitis C with Pegylated Interferon Alpha-2a and Ribavirin:Experience from Benin

Background: Viral hepatitis C (HCV) is common in Benin. Untreated, it can be complicated by cirrhosis and hepatocarcinoma, which are sources of death. The objectives of this work were twofold: 1) to evaluate the effectiveness and safety of treatment with classic dual interferon pegylated alpha-2a (IFN) and ribavirin therapy in Benin, and 2) to present problems related to financial accessibility to this treatment. Methods: This was a cross-sectional, descriptive and analytical study, with a retrospective collection of data from November 1, 2010 to December 31, 2015 and prospective collection from January 1, 2016 to July 31, 2016 (7 months). We included all patients treated with IFN + ribavirin for hepatitis C at CNHU/HKM. Sustained virological response (SVR) was defined as undetectable viral load C 6 months after stopping treatment. Safety was appreciated by the search for clinical and hematological adverse effects. Results: One hundred and six patients were followed for HCV, of whom 58 (54.7%) undergoing treatment (26 under standard dual therapy and 32 under direct-acting antivirals). Of the 26 patients under-conventional dual therapy, 12 (46.1%) were genotype 1, 13 (50%) genotype 2 and one (3.9%) genotype 4. In conventional dual therapy, SVR was achieved in 15 (57.7%) patients, including the genotype 4 patient, 4 out of 12 (33.3%) genotype 1 patients, and 10 out of 13 (76.9%) for genotype 2 patients. The most common side effects with this treatment were severe asthenia (23 cases), flu-like symptoms (22 cases), weight loss (21 cases) and neutropenia (22 cases), anemia and thrombocytopenia (20 of 26 cases). The overall cost of treatment per patient was 11,800,624 FCFA for genotypes 1 and 4;and 7,835,048 FCFA for genotype 2. Conclusion: The treatment of HCV with IFN + ribavirin in Benin is effective for genotype 2. But its adverse effects are manifold and its cost is high. The switch to direct-acting antivirals (more effective, better tolerated and less expensive) was therefore necessary.

重组干扰素α-2b联合CO_(2)激光气化治疗宫颈低级别上皮内病变伴HR-HPV感染患者的临床效果及对HPV转阴率的影响

目的分析重组干扰素α-2b联合CO_(2)激光气化治疗宫颈低级别上皮内病变伴高危型人乳头瘤病毒(HR-HPV)感染的临床效果。方法选取宫颈低级别上皮内病变伴HR-HPV感染患者80例,采用随机数表法分为对照组及研究组,每组40例。对照组采用重组干扰素α-2b治疗,研究组采用重组干扰素α-2b联合CO_(2)激光气化治疗。比较两组患者的治疗效果。结果研究组治疗总有效率为90.00%,高于对照组的72.50%(P<0.05)。研究组治疗3、6个月的HPV转阴率均高于对照组(P<0.05)。两组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论采用重组干扰素α-2b联合CO_(2)激光气化治疗宫颈低级别上皮内病变伴HR-HPV感染患者,可提高疗效及HPV转阴率。

Combination of "low-dose" ribavirin and interferon alfa-2a therapy followed by interferon alfa-2a monotherapy in chronic HCV-infected nonresponders and relapsers after interferon alfa-2a monotherapy

AIM To report on the efficacy, safety and tolerability of interferon alfa-2a combined with a "low dose" of ribavirin for relapsers and non responders to alpha interferon monotherapy.METHODS Thirty-four chronic hepatitis C virus-infected non-responders to interferon alfa2a monotherapy (a course of at least 3 months treatment) and 13 relapsers to interferon alfa 2a monotherapy (a dose of 3 to 6 million units three times per week for at least 20 weeks but not more than 18 months) were treated with the same dose of interferon alfa-2a used before (3 to 6 million units three times per week) and ribavirin (10 mg/ kg daily) for 6 months. In complete responders, interferon alfa-2a was administered for further 6 months at the same dose used before as monotherapy.RESULTS Seven (20.6%) of 34 non-responders stopped the combined therapy due to adverse events, including two patients with histological and clinical Child A cirrhosis. In 17/27 (63%)non-responders, the combined therapy was stopped after three months because of non-response. Ten of the 27 non-responders completed the 1;2-month treatment course. At a mean follow up of 28 months (16- 37 months)after the treatment, 4/10 (15%) previous non-responders still remained complete responders,All 13 previous relapsers completed the 12-month treatment course. At a mean follow up of 22months (9 - 36 months) after treatment, 6/13(46%) the previous relapsers were stillsustained complete responders.CONCLUSION Our treatment schedule of the combined therapy for 6 months of interferon alfa2a with a low dose of ribavirin (10 mg/kg/day)followed by 6 months of interferon alfa-2amonotherapy is able to induce a sustainedcomplete response rate in 15% of non-responders and 46% of relapsers with chronic hepatitis C virus-related liver diseases comparable to those obtained with the standarddoses of ribavirin 1000 - 1200 mg/day.Randomized prospective controlled trials using lower total amounts of ribavirin in combination with interferon should be performed.

Cloning and high-level expression of human interferon alpha-8 in E.coli

Human interferon alpha-8(IFN-α8) is an important cytokine with multiple biological functions.A genetically engineered strain, E. coli XL1-Blue/pBm, was constructed by DNA recombination technology and characterized by restriction analysis, DNA sequencing.

Chimeric oncogenic interferon regulatory factor-2 (IRF-2): Degradation products are biologically active

Interferon Regulatory Factor-2 (IRF-2) belongs to IRF family, was identified as a mammalian transcription factor involved in Interferon beta (IFNβ) gene regulation. Besides that IRF-2 is involved in immunomodulation, hematopoietic differentiation, cell cycle regulation and oncogenesis. We have done molecular sub-cloning and expression of recombinant murine IRF-2 as GST (Glutathione-S-Transferase)- IRF-2 fusion protein in E. coli/XL-1blue cells. Recombinant IRF-2 with GST moiety at N-terminus expressed as GST-IRF-2 (~66 kd) in E. coli along with different low molecular mass degradation products revealed approximately 30, 42, 60 and 62 kd by SDS-PAGE and Western blot, respectively. We further confirm that degradation takes place at C-terminus of the fusion protein not at N-terminus as anti-GST antibody was detecting all bands in the immunoblot. The recombinant IRF-2 was biologically active along with their degradation products in terms of their DNA binding activity as assessed by Electrophoretically Mobility Shift Assay (EMSA). We observed three different molecular mass DNA/protein complexes (1 - 3) with Virus Response Element (VRE) derived from human Interferon IFNβ gene and five different molecular mass complexes (1 - 5) with IRF-E motif (GAAAGT)4 in EMSA gel. GST only expressed from empty vector did not bind to these DNA elements. To confirm that the binding is specific, all complexes were competed out completely when challenged with 100-X fold molar excess of IRF-E oligo under cold competition. It means degradation products along with full-length protein are able to interact with VREβ as well as IRF-E motif. This means degradation products may regulate the target gene (s) activation/repression via interacting with VRE/IRF-E.

重组白细胞介素-2、γ-干扰素对感染血吸虫小鼠肝纤维化作用研究

目的探讨重组白细胞介素-2(IL-2)和γ-干扰素(IFN-γ)对日本血吸虫小鼠肝纤维化作用. 方法 ABC免疫组化法,VG染色及多媒体图文分析,观察不同时期感染血吸虫小鼠肝脏IL-2、IFN-γ和胶原纤维变化以及分别注射重组IL-2、IFN-γ后小鼠肝脏IL-2、IFN-γ和胶原纤维变化. 结果小鼠肝脏IL-2、IFN-γ水平随感染时间延长而缓慢下降,胶原纤维含量随感染时间延长逐渐上升;注射重组IL-2或IFN-γ组小鼠随着相应因子补充显著上升,胶原纤维含量逐渐下降,末次注射后1～6周,肝脏相应因子水平明显高于正常组和感染组P<0.01,胶原纤维含量明显低于感染组P<0.01. 结论重组IL-2和IFN-γ明显降低肝脏胶原纤维合成,延缓肝纤维化发生.

重组IL-2联合大蒜素治疗胰腺癌的作用机制

目的评价重组白细胞介素(r IL-2)联合大蒜素(allicin)治疗胰腺癌的效果并探讨其相关机制。方法构建裸鼠肿瘤异位移植模型,60只裸鼠随机分为对照组、r IL-2治疗组、allicin治疗组及联合治疗组。治疗后4周,分离获得外周血,记录肿瘤的体积、质量和生存时间并计算生存率。流式细胞术分析肿瘤细胞凋亡情况,同时检测CD4+、CD8+T淋巴细胞和自然杀伤细胞(NK细胞);使用ELISA法检测IFNγ的水平。Western Blot分析肿瘤组织蛋白Bcl-2的表达水平。计量资料组间比较采用方差分析,进一步两两比较采用SNK-q检验。结果治疗后4周发现,r IL-2组、allicin组及联合治疗组肿瘤体积与对照组比较均明显降低,且差异均有统计学意义(P值均<0.05),其中联合治疗组降低最为显著(P<0.01),其肿瘤抑制率为90.5%。联合治疗能够显著延长小鼠的生存时间(联合治疗组在55 d时仍有60%的小鼠存活)。联合治疗组的肿瘤细胞凋亡率与对照组比较显著升高[(23.3±4.3)%vs(9.0±3.7)%],差异有统计学意义(P<0.05),联合治疗组中促凋亡蛋白Bcl-2的表达水平与对照组比较明显增加。治疗组外周血中CD4+、CD8+T淋巴细胞及NK细胞的比例相比于对照组有显著升高(F值分别为23.74、26.38、19.72,P值均<0.001)。与其他组比较,联合治疗组IFNγ的水平显著升高(F=9.84,P=0.026)。结论 r IL-2和allicin联合治疗能够通过增强固有免疫和适应性免疫的效应来改善胰腺癌患者的生存状况。

重组鸡α干扰素/白细胞介素-2融合蛋白对鸡外周血T淋巴细胞亚群的影响研究

为了研究重组鸡α干扰素/白细胞介素-2融合蛋白（rChIFN-α-Linker-ChIL-2,重组融合蛋白）对SPF鸡外周血T淋巴细胞亚群含量影响,本研究采用流式细胞术对重组融合蛋白（第2组）和rChIFN-α蛋白（第3组）注射14日龄SPF鸡后不同时间对各试验组鸡外周血T淋巴细胞（PBLC）中CD3^＋CD4^＋、CD3^＋CD8^＋百分含量以及CD4^＋/CD8^＋比值进行检测。结果表明,与对照组相比,重组融合蛋白和rChIFN-α蛋白在鸡体内接种后3～14d均可明显提高鸡外周血T淋巴细胞中CD3^＋CD4^＋细胞百分含量,降低CD3^＋CD8^＋细胞的百分含量,提高CD4^＋/CD8^＋比值;接种后3～7d期间,第2组鸡的CD3^＋CD4^＋、CD3^＋CD8^＋细胞含量及CD4^＋/CD8^＋比值与PBS对照组（第1组）相比差异均极显著（P〈0.01）,第3组与第1组相比差异均显著（P〈0.05）。以上结果表明,重组融合蛋白和rChIFN-α蛋白接种鸡体后均可显著影响鸡PBLC中淋巴细胞亚群百分含量,提高CD4^＋/CD8^＋比值,增强机体的细胞免疫功能;重组融合蛋白对鸡淋巴细胞亚群百分含量、CD4^＋/CD8^＋比值影响程度和细胞免疫功能的增强作用优于rChIFN-α蛋白;重组融合蛋白在体内发挥了鸡α干扰素和白细胞介素-2对细胞免疫功能的协同增强作用。

重组鸡α干扰素/白细胞介素-2融合蛋白体外活性评价方法研究

为建立稳定、便捷的重组鸡α干扰素/白细胞介素-2融合蛋白(rChIFN-α-Linker-ChIL-2蛋白,重组融合蛋白)体外活性评价方法,本研究分别采用ChIFN-α和ChIL-2ELISA方法检测重组融合蛋白与抗ChIFN-α单抗和抗ChIL-2单抗发生特异性免疫反应的活性;采用细胞病变抑制法检测重组融合蛋白在DF1细胞上抑制水疱性口炎病毒(VSV)和传染性法氏囊病病毒(IBDV)增殖活性;采用MTS法分别测定重组融合蛋白促鸡外周血T淋巴细胞(PBLC)和脾淋巴细胞增殖活性。结果表明,重组融合蛋白可以与抗ChIFN-α单抗和抗ChIL-2单抗发生特异性免疫反应;重组融合蛋白在DF1细胞上具有明显抗病毒活性,其抗VSV活性高于抗IBDV活性,且均明显高于rChIFN-α蛋白对照;不同浓度的重组融合蛋白均具有明显的促鸡PBLC和脾淋巴细胞增殖活性,且其促增殖活性明显高于rChIFN-α蛋白对照。本研究成功建立了重组融合蛋白体外活性检测评价方法,为进一步探究重组融合蛋白在鸡体内协同作用奠定基础。

LEEP术联合干扰素及重组人白介素－2对宫颈上皮内瘤变伴高危型HPV的疗效

目的：观察并探讨宫颈环形电切术（ LEEP）联合干扰素及重组人IL－2对宫颈上皮内瘤变Ⅱ（ CINⅡ）伴高危型HPV疗效的影响。方法选取2012年2月—2013年2月160例行LEEP术的CINⅡ患者并随机分为四组（每组40例）：对照组仅采用LEEP术治疗；A组采用LEEP术联合干扰素治疗；B组采用LEEP术联合重组人IL－2治疗；C组采用LEEP术联合干扰素及重组人IL－2治疗。治疗3个月、6个月后复查TCT、阴道镜及HPV，并对患者的疗效、并发症、HPV－DNA转阴率情况进行比较。结果6个月后C组治愈率及HPV－DNA转阴率分别为92．5％、95％，高于其他三组（P＜0．05）；与其他三组相比，C组创面愈合时间、阴道出血时间与阴道排液持续时间更短（P＜0．05）。结论 LEEP联合干扰素及白介素对CINⅡ级伴高危型HPV的治疗效果明显优于单纯采用LEEP术及LEEP术单用干扰素或白介素，且愈合时间短，并发症较少，值得在临床上推广应用。

Lys-2-rhTNFα单用或联合其它细胞因子抗肿瘤作用的研究

研究了 L ys- 2 - rh TNFα(1)单用或联合 1 2 5Ser- rh IL - 2 (2 )和 /或 rh INFα- 2 a(3)的体内外抗肿瘤作用。实验结果表明 1对人结肠癌细胞株 (M76 0 9)、小鼠黑色素瘤细胞株 (B16 )、小鼠白血病细胞株 (Yac- 1)均有抑制细胞增殖的作用。 1合用 2及 3较它们各自单用及任意两者合用的细胞毒作用明显增强 (P<0 .0 1)。 1与 2、3联合用药组较它们各自单独用药对小鼠结肠癌 Colon2 6细胞移植性肿瘤的抑瘤作用明显提高 (P<0 .0 5 )。

重组人干扰素α-2b阴道泡腾胶囊治疗宫颈人乳头瘤病毒亚临床感染的疗效

目的探讨重组人干扰素α-2b阴道泡腾胶囊治疗宫颈人乳头瘤病毒(HPV)亚临床感染患者的疗效。方法将127例宫颈HPV亚临床感染的患者按随机数字表法分为2组。研究组68例,使用重组人干扰素α-2b阴道泡腾胶囊于月经干净第3天起每晚1颗阴道塞入,10 d为1个疗程,而后停药至下次月经干净第3天开始下一个疗程,共3个疗程。对照组59例暂不治疗。于治疗前,疗程结束后3、9个月对2组患者进行二代杂交捕获技术(HC2)检测,了解HPV病毒负荷量。结果研究组使用重组人干扰素α-2b阴道泡腾胶囊3个疗程结束后3、9个月HC2较治疗前分别下降36.64%、70.63%;对照组6、12个月HC2较第1个月前分别下降3.80%、10.84%,2组比较均差异有统计学意义(P<0.05或P<0.01)。结论重组人干扰素α-2b阴道泡腾胶囊治疗宫颈HPV病毒亚临床感染,疗效肯定,用药方便,无明显的不良反应。

人重组干扰素-α-2b治疗子宫内膜异位症的临床分析

目的观察分析人重组干扰素-α-2b治疗子宫内膜异位症的临床疗效。方法选取2010年6月-2012年6月子宫内膜异位症的患者56例,按照随机数字法分成观察组和对照组,各28例,观察组使用人重组干扰素-α-2b治疗,对照组使用戈舍瑞林治疗,观察对比两组治疗效果。结果两组术后血清CA125、EMAb水平术后1、2、3个月与术前对比存在明显差异(P<0.05),具有统计学意义;两组治疗期间药物不良反应发生率进行比较存在一定差异(P<0.05),具有统计学意义。结论人重组干扰素-α-2b治疗子宫内膜异位症的临床疗效显著,与常规使用戈舍瑞林治疗作用类似,药物不良反应表现在使用早期较多,但持续时间短,停药后皆能自行消失,安全性较高。

重组人干扰素α-2b凝胶联合微波治疗慢性宫颈炎临床体会

目的探讨重组人干扰素α-2 b凝胶联合微波治疗慢性宫颈炎的疗效。方法按照数字随机表法将我院妇科门诊收治的282例慢性宫颈炎患者分为微波治疗组(对照组)和重组人干扰素α-2 b凝胶联合微波治疗组(观察组),每组各141例,比较两组患者的临床疗效。结果观察组患者治疗总有效率为94.3%高于对照组患者的85.1%,对比两组患者在治疗总有效率,P<0.05,差异具有统计学意义。结论重组人干扰素α-2 b凝胶联合微波治疗慢性宫颈炎的疗效较为理想,是一种理想的治疗方案。