过滤对一种IgG2亚型EGFR单抗中不溶性微粒的影响

目的：探讨过滤操作对一种免疫球蛋白G2（immunoglobin G2,IgG2）亚型表皮生长因子受体（epidermal growth factor receptor,EGFR）单克隆抗体（单抗）生物类似药（similar biotherapeutic product,SBP）候选药中不溶性微粒的影响。方法：利用微流数字成像（microflow digital imaging,MDI）技术对某厂家生产的IgG2亚型EGFR单抗SBP候选药与其原研药（reference biotherapeutic product,RBP）中不同粒径的不溶性微粒进行比较;采用0.22 μm的滤器对EGFR单抗SBP候选药进行过滤,并采用MDI法立即对不同粒径和性质的不溶性微粒进行检测和分析;再将过滤后的EGFR单抗SBP候选药在室温静置2 h,并采用MDI法对不同粒径和性质的不溶性微粒进行检测和分析。结果：某IgG2亚型EGFR单抗SBP候选药中不同粒径的不溶性微粒数量明显高于RBP;用0.22 μm的滤器过滤后,EGFR单抗SBP候选药中的不溶性微粒数由8.51×10⁵粒·mL^-1降为1.52×10⁴粒·mL^-1,且主要成分蛋白聚体、气泡和纤维均明显减少;室温静置2 h后,其中的不溶性微粒数由1.52×10⁴粒·mL^-1增加至3.23×10⁴粒·mL^-1,且增加的微粒主要为蛋白聚体。结论：与原研药相比,该EGFR单抗SBP候选药蛋白聚体水平较高,过滤后有明显改善,但随着放置时间延长,蛋白聚体含量又有明显增加。这提示我们需加强研发,以提高SBP候选药的产品质量、安全性和有效性。     

扎那米韦鼻用粉雾剂粉体性质研究

目的 考察3种方法制备扎那米韦鼻用粉雾剂粉体的性质。方法 分别采用研磨法、气流粉碎法和喷雾干燥法制备不同粒径扎那米韦的粉体,并与吸入乳糖混合,对混合粉体的粒径、微观形态、流动性、堆密度和吸湿性进行考察。结果 研磨法、喷雾干燥法和气流粉碎法得到的扎那米韦原料粉末粒径依次减小;与乳糖相比,3种混合粉体松密度逐渐减小,振实密度依次增加,流动性仅喷雾干燥略增加,研磨法和气流粉碎法无影响; 3种方式得到的混合粉末均没有明显的吸湿性。结论 研磨筛分法比较适合扎那米韦鼻用粉雾剂的进一步开发。     

星点设计-效应面法优化盐酸溴己新吸入粉雾剂的处方

摘 要 目的：优化盐酸溴己新吸入粉雾剂的处方。方法: 采用冷冻干燥 气流粉碎法制备盐酸溴己新吸入粉雾剂,通过星点设计考察甘露醇（X1）,亮氨酸（X2）和泊洛沙姆188（X3）在辅料中的用量对盐酸溴己新吸入粉雾剂的休止角（Y1）、细微粒子剂量（Y2）和空气动力学粒径（Y3）的影响。根据最佳数学模型绘制效应面,通过重叠等高线图确定最优处方。结果:影响因素和考察指标之间存在定量关系,优化处方为甘露醇：亮氨酸：泊洛沙姆188在处方中的比例为2.4∶〖KG-*2〗2.22∶〖KG-*2〗0.05。较优处方的各指标实测值与预测值较接近。结论:采用星点设计 效应面法完成了盐酸溴己新吸入粉雾剂的多目标同步优化。     

Characterization of the innate stimulatory capacity of plant-derived virus-like particles bearing influenza hemagglutinin

Cell-mediated immunity is an important component of immediate and long-term anti-viral protection. Dendritic cells (DCs) are essential for the induction of cell-mediated immunity by instructing the activation and differentiation of antigen-specific T cell responses. Activated DCs that express co-stimulatory molecules and pro-inflammatory cytokines are necessary to promote the development of type 1 immune responses required for viral control. Here we report that plant-derived virus-like particles (VLPs) bearing influenza hemagglutinins (HA) directly stimulate mouse and human DCs. DCs exposed to H1- and, to a lesser extent, H5-VLPs in vitro rapidly express co-stimulatory molecules and produce pro-inflammatory cytokines including IL-12, IL-6 and TNFα. Furthermore, these VLPs support the activation and differentiation of antigen-specific T cell responses. Mechanistically, H1-VLPs stimulate the activation of kinases typically activated downstream of pattern recognition receptors including AKT, p38, and p42/44 ERK. In vivo, immunization with plant-derived VLPs induce the accumulation of both cDC1s and cDC2 in the draining lymph node and a corresponding increase in T and B cells. VLPs devoid of HA protein activate DCs, suggesting they are intrinsically immunostimulatory. Together, the results demonstrate that these candidate plant-derived VLP vaccines have an inherent and direct stimulatory effect on DCs and can enhance the ability of DCs to promote Type 1 immune responses.     

空气细菌采样器室内采样效果比较

对不同工作原理的4种采样器进行空气中细菌采样效果比较。结果表明,安德森采样器对空气细菌的捕获率高,重复性好,并可测定细菌气溶胶粒子的大小,建议作为标准采样器使用。     

Treatment of chronic wounds with polyurethane sponges impregnated with boric acid particles: A randomised controlled trial

The objective of this study was to investigate the effectiveness of the sponge with boric acid particles combined with the negative pressure wound treatment (NPWT) system for chronic wounds with tissue defects. Our study was designed as a prospective randomised study. One hundred patients who were planned to have NPWT due to chronic wounds were included in this study from Orthopaedics and Traumatology and Plastic Surgery clinics. Patients were divided into two groups. In the first group, a new method, boric acid impregnated sponge, combined with the NPWT system, was used, and in the second group, sponge with silver nitrate was used. Besides the wide‐broad spectrum antibacterial properties of silver nitrate, the antimicrobial, angiogenetic, and epithelial effects of boric acid were aimed to investigate by macroscopically and histopathologically. Thirty‐six patients in the silver nitrate group and 44 patients in the boric acid group completed the study. A decrease in wound size and granulation was observed in both groups. Macroscopically, a decrease in wound size reduction, epithelialization and granulation were more prominent in the first group in which boric acid impregnated sponge was used than the second group in which silver sponge was used. Moreover, microscopically, the number of fibroblasts, collagen synthesis, and angiogenesis were significantly increased in Group 1. In this clinical study, the broad‐spectrum antimicrobial properties of boric acid and its positive effect on the cells responsible for wound healing were found to be more pronounced compared to silver nitrate sponges. A combination of boric acid sponges with the NPWT system may be an alternative method for chronic wounds.     

PVC材质一次性输注泵在常用局麻药应用中的安全性研究

目的考察一次性使用输注泵与常用局麻药的相容性,评定其在临床常用局麻药物使用中的安全性。方法3种常用局麻药分别与2种液体（生理盐水及乳酸林格氏液）按临床使用浓度配伍,在不同时间点分别采用LC-MS／MS法、光阻法、高效液相色谱法测定邻苯二甲酸二-（2-乙基己基）酯（DEHP）含量、不溶性微粒和药物浓度。结果DEHP含量低于LC-MS／MS测定方法定量下限（0．072gg·mL^-1）,更低于考核标准静脉晶体溶液输注成年人（70kg）DEHP剂量上界估算值（0．005mg·kg^-1·d^-1）;48h内各实验药物在一次性使用输注泵中药物含量相对0h均〉96．0％,受试输注泵与各种药物在48h内未见明显吸附;输注泵中溶液稳定,0h每1mL粒子直径≥10μm粒子数（n=30）（35．13±14．4）粒;每1mL粒子直径≥25μm粒子数（n=30）（0．61±0．49）粒,符合中国药典2010版标准。结论研究表明本一次性使用输注泵应用于3种常用局麻药物较为稳定,其DEHP溶出、不溶性微粒及药物吸附性等方面符合安全使用要求。     

Proton Therapy for Skull Base Chordomas: An Outcome Study from the University of Florida Proton Therapy Institute

Objectives Skull base chordoma is a rare, locally aggressive tumor located adjacent to critical structures. Gross total resection is difficult to achieve, and proton therapy has the conformal advantage of delivering a high postoperative dose to the tumor bed. We present our experience using proton therapy to treat 33 patients with skull base chordomas. Design Retrospective outcomes study. Setting University of Florida Proton Therapy Institute; 2007 to 2011. Participants A total of 33 patients with skull base chordomas received postoperative three-dimensional conformal proton therapy. The patients were 79% male and 6% diabetic; 27% had received a gross total resection. Main Outcome Measures The gross tumor/tumor bed received a dose between 77.4 CGE and 79.4 CGE. Local control and overall survival were tracked, and radiation toxicity was assessed using a modified Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme. Results Median follow-up for all patients was 21 months. Local control and overall survival rates at 2 years were 86% and 92%, respectively. Grade 2 toxicity was observed in 18% of our cohort in the form of unilateral hearing loss partially corrected with a hearing aid. No grade 2 or higher optic or brainstem toxicities were observed. Conclusions Proton therapy is an effective treatment modality for skull base chordomas.     

Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide

The objective of this study was to compare the short-term respiratory effects due to the inhalation of electronic and conventional tobacco cigarette-generated mainstream aerosols through the measurement of the exhaled nitric oxide (eNO). To this purpose, twenty-five smokers were asked to smoke a conventional cigarette and to vape an electronic cigarette (with and without nicotine), and an electronic cigarette without liquid (control session).     

Optimisation of Shrinkage and Strength on Thick Plate Part Using Recycled LDPE Materials

Achieving good quality of products from plastic injection moulding processes is very challenging, since the process comprises many affecting parameters. Common defects such as warpage are hard to avoid, and the defective parts will eventually go to waste, leading to unnecessary costs to the manufacturer. The use of recycled material from postindustrial waste has been studied by a few researchers. However, the application of an optimisation method by which to optimise processing parameters to mould parts using recycled materials remains lacking. In this study, Response Surface Methodology (RSM) and Particle Swarm Optimisation (PSO) methods were conducted on thick plate parts moulded using virgin and recycled low-density polyethylene (LDPE) materials (100:0, 70:30, 60:40 and 50:50; virgin to recycle material ratios) to find the optimal input parameters for each of the material ratios. Shrinkage in the x and y directions increased in correlation with the recycled ratio, compared to virgin material. Meanwhile, the tensile strength of the thick plate part continued to decrease when the recycled ratio increased. R30 (70:30) had the optimum shrinkage in the x direction with respect to R0 (100:0) material where the shrinkage increased by 24.49% (RSM) and 33.20% (PSO). On the other hand, the shrinkage in the y direction for R30 material increased by 4.48% (RSM) and decreased by 2.67% (PSO), while the tensile strength of R30 (70:30) material decreased by 0.51% (RSM) and 2.68% (PSO) as compared to R0 (100:0) material. Validation tests indicated that the optimal setting of processing parameter suggested by PSO and RSM for R0 (100:0), R30 (70:30), R40 (60:40) and R50 (50:50) was less than 10%.