注射用重组人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在健康受试者的耐受性研究

目的评价重组(酵母分泌型)人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在健康受试者的耐受性和安全性。方法将26例健康受试者(男女各半)按先后顺序入组,进行4个剂量组试验(150,300,500,650μg·kg^-1),每组分别入组4,6,8,8例。根据体重计算给药剂量,受试者于给药当天上臂三角肌部位皮下注射给药1次。用药后观察药物不良事件(AE),定时进行实验室检查、心电图检查。结果共25例受试者发生AE,共145例次。150,300,500及650μg·kg^-1剂量组的AE分别为13,11,56和65例次。其中134例次考虑与研究药物相关。常见的AE有骨痛、单核细胞计数升高、血碱性磷酸酶升高、头痛、高尿酸血症、血乳酸脱氢酶升高、脾肿大、肌肉疲劳。研究中未出现AE导致的用药暂停、受试者退出或试验提前中止。未发生严重不良事件(SAE)。未发生剂量限制性毒性。结论注射用重组(酵母分泌型)人血清白蛋白-人粒细胞集落刺激因子(Ⅰ)融合蛋白在中国健康受试者中单次给药150,650μg·kg^-1剂量范围内有较好的安全性,本临床试验未探索到健康人群的最大耐受剂量。     

粒细胞巨噬细胞刺激因子联合全肺灌洗对特发性肺泡蛋白沉积症的疗效和安全性

目的 观察粒细胞巨噬细胞刺激因子（GM-CSF）联合全肺灌洗治疗特发性肺泡蛋白沉积症（IPAP）的疗效和安全性。方法 选取2015年8月至2017年3月在第二军医大学附属长海医院就诊的2例IPAP患者,经全肺灌洗后,分别予皮下注射和雾化吸入GM-CSF治疗,观察其疗效和安全性。结果 2例患者经GM-CSF联合全肺灌洗治疗,病情缓解。结论 GM-CSF联合全肺灌洗治疗对IPAP患者治疗有效、用药安全。     

Delivery of radix ophiopogonis polysaccharide via sucrose acetate isobutyrate-based in situ forming systems alone or combined with its mono-PEGylation

This work aimed to achieve long-lasting delivery of radix ophiopogonis polysaccharide (ROP) by sucrose acetate isobutyrate (SAIB)-based in situ forming systems (ISFSs) alone or combined with mono-PEGylation of ROP. When the ‘90%SAIB/10% solvent’ system was used, the mean residence time (MRT) of ROP was prolonged by 4.3 5?～?7.00 times and the initial release rate was reduced significantly. However, this system was only suitable for days-long sustained release of ROP in short-term therapy. As to the ‘SAIB/additives/solvent’ system containing mono-PEGylated ROP, the results indicated that SAIB/poly(d,l-lactide-co-glycolide) (PLGA)/N-methyl-2-pyrrolidone (NMP) was superior to SAIB/polylactic acid (PLA)/NMP and SAIB/PLA/ethanol in controlled release. Moreover, weeks- to months-long (16–60 d) smooth release of ROP could be achieved by varying the concentration (10–30%) and molecular weight (MW) of PLGA (10–50?kDa) or by employing a moderate MW of PEGylated ROP (～20 or ～30?kDa). With further increasing the conjugate MW to ～40?kDa, the contribution of drug elimination to its plasma retention seemed to surpass that of the SAIB-based system, resulting in that the system no longer had an obvious influence on the in vivo behavior of the conjugate. Besides, the results of host response confirmed that with less solvent being used, the SAIB-based systems showed a higher biocompatibility than the PLGA-based systems, suggesting that they could be freely chosen in the prevention and/or cure of chronic diseases.     

Analysis of relationships between polymorphisms in the genes encoding the pentameric complex and neutralization of clinical cytomegalovirus isolates

IntroductionAs congenital cytomegalovirus (CMV) infection is one of the major causes of birth defects and developmental abnormalities, it is essential to develop vaccines and therapeutic antibodies against CMV. Clinical trials demonstrated that the subunit vaccine based on glycoprotein B, which had been believed to be the major target for neutralization, did not induce sufficient protective immunity. On the other hand, it has been reported that the immunization of animals with the Pentamer, the pentameric complex of gH/gL/UL128/UL130/UL131A, induced strong neutralizing antibodies. Here, we sought to clarify whether any polymorphic alterations present in the Pentamer of clinical isolates affect neutralization by anti-Pentamer antibodies.MethodsSequences of the genes encoding the Pentamer components of 25 Japanese clinical isolates were determined. Neutralization of infection by two seropositive sera and by anti-Pentamer serum was measured using a CMV reporter cell line based on ARPE-19.ResultsPolymorphisms of the amino acid sequence of UL128, UL130, and UL131A ORFs were limited and clustered into two major groups. The identified alterations, except UL128 I140T, were mapped outside of the reported regions recognized by neutralizing antibodies. Anti-Pentamer serum neutralized infection with all isolates to a similar degree and had no correlation with the polymorphic groups.ConclusionsOur findings indicate that Pentamer antigens prepared from Merlin Fix strain induce antibodies that neutralize infection with all isolates to a similar level and that anti-Pentamer antibodies neutralize CMV infection better than do human sera, suggesting that vaccines and therapeutic antibodies based on Pentamer as an antigen have some promise.     

人类疱疹病毒6型对血液病患者巨噬细胞集落刺激因子表达的 …

探讨人类疱疹病毒６型与血液病患者巨噬细胞集落刺激因子异常表达的关系。方法：以卵白素－和物素复合物免疫酶２标和逆转录－聚合酶链反应方法检测３０例血液病患者骨髓单个核细胞体外感染ＨＨＶ－６后Ｍ－ＣＳＦｍＲＮＡ的表达。     

眼用即型凝胶的现状与研究进展简

眼用即型凝胶避免了传统眼用制剂滞留时间短、消除速度快、生物利用度低等缺点,可以增强眼用制剂的药效,近年来倍受研究者的关注.本文介绍了眼用即型凝胶的分类及其不同成胶机制,综述了其在国内外的研究进展和上市产品.作为一种新型制剂,虽然眼用即型凝胶在国内的研究尚处于起步阶段,但其具有广阔的临床应用前景,值得进一步研究开发.     

Granulocyte colony‐stimulating factor improves neuron survival in experimental spinal cord injury by regulating nucleophosmin‐1 expression

Granulocyte colony‐stimulating factor (G‐CSF) and its related mechanisms were investigated to assess the potential for this factor to exert neuroprotective effects against spinal cord injury in mice. Recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) was injected into mice spinal cord hemisection models. Locomotor activity was assessed by using the Basso‐Bettie‐Bresnahan scale. Neurons isolated from spinal cords were cultured in vitro and used in a neuronal mechanical injury model. Three treatment groups were compared with this model, 1) G‐CSF, 2) G‐CSF + NSC348884 (a nucleophosmin 1‐specific inhibitor), and 3) NSC348884. Immunofluorescence staining and Western blotting were performed to analyze the expression of G‐CSF and nucleophosmin 1 (Npm1). TUNEL staining was performed to analyze apoptosis after G‐CSF treatment. We found that the G‐CSF receptor (G‐CSFR) and Npm1 were expressed in neurons and that Npm1 expression was induced after G‐CSF treatment. G‐CSF inhibited neuronal apoptosis. NSC348884 induced p53‐dependent cell apoptosis and partially blocked the neuroprotective activity of G‐CSF on neurons in vitro. G‐CSF promoted locomotor recovery and demonstrated neuroprotective effects in an acute spinal cord injury model. The mechanism of G‐CSF's neuroprotection may be related in part to attenuating neuronal apoptosis by NPM1. © 2014 Wiley Periodicals, Inc.     

Approaches and considerations for the assessment of immunotoxicity for environmental chemicals: A workshop summary

As experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential. Additionally, discussions on study design, critical windows, and new guideline approaches and experiences identified important factors to consider before initiating DIT evaluations including assay choice and timing and the impact of existing adult data. Participants agreed that integrating endpoints into standard repeat-dose studies should be considered for fulfilling any immunotoxicity testing requirements, while also maximizing information and reducing animal use. Participants also acknowledged that in vitro evaluation of immunosuppression is complex and may require the use of multiple assays that are still being developed. These workshop discussions should contribute to developing an effective but more resource and animal efficient approach for evaluating chemical immunotoxicity.     

正交试验法优选复方当益颗粒成型工艺简

目的优选复方当益颗粒的最佳成型工艺。方法以颗粒的成型性、溶解性、吸湿性和流动性为考察指标,用La（34）正交试验优选成型工艺。结果最佳成型工艺为采用糊精作为稀释剂,水为润湿剂,混合粉末与润湿剂用量比为10：4.5。结论该工艺合理可行,稳定可靠,可为生产提供依据。