放化同步治疗中老年局部晚期非小细胞肺癌时紫杉醇剂量选择的研究

目的探讨放化同步治疗中老年非小细胞肺癌（NSCLC）时紫杉醇剂量的选择。方法选择60例NSCLC患者,其中男性36例,女性24例;年龄55~65岁。随机分为A、B、C、D、E 5组,每组12例患者。所有患者先经过3个周期的诱导化学治疗,1个月后进行放化同步治疗。三维适形放射治疗在5~6周内完成,控制总剂量在60 Gy;化学治疗时使用紫杉醇,A组2次/周,每次10mg/m2;B组2次/周,每次15 mg/m2;C组2次/周,每次20 mg/m2;D组3次/周,每次10 mg/m2;E组3次/周,每次15 mg/m2,6周完成治疗。当任何一组患者在治疗期间出现半数以上的患者发生3度以上急性不良反应即停止该组试验。结果 A、B、D 3组出现3度以上不良反应的患者均未超过半数,完成所有治疗,近期总有效率分别为41.67%、75.00%、66.67%;C、E两组因出现3度以上不良反应的患者超过半数而停止试验。结论在诱导化疗后使用放化同步治疗中老年局部晚期NSCLC患者时紫杉醇最佳使用剂量的选择为每周30 mg/m2,可根据患者具体身体状况调整每次给药剂量和给药次数,并于5~6周完成治疗。     

Gene transfection in complex media using PCBMAEE-PCBMA copolymer with both hydrolytic and zwitterionic blocks

Safety and high efficacy of vectors are essential requirements for gene therapy. To address these challenges, poly(carboxy betaine methacrylate ethyl ester)-poly(carboxy betaine methacrylate) (PCBMAEE-PCBMA) diblock copolymers were synthesized to form core–shell vector for gene delivery. The hydrophobic PCBMAEE segment, a polyzwitterionic precursor, can condense plasmid DNA (pDNA) into a hydrophobic core, which improves pDNA protection from nuclease attack and maintains the condensed structure against dilution. Moreover, the hydrolysis of PCBMAEE in uptaken gene vectors can enhance the pDNA release and reduce the cytotoxicity caused by the cationic polymer accumulation in the host cells. The PCBMA segment, zwitterionic fouling resistant material, is utilized to stabilize the gene vector in the complex medium and reduce the interference from serum proteins without impeding the endocytosis of DNA vector like PEG protection layer. Results showed that the complex formed by PCBMAEE₅₀-PCBMA₁₄ with luciferase or pEGFP gene exhibit higher transfection efficacy of pDNA than that formed by PEI 25 kDa or Lipofectamine^® 2000 in tested cell lines (COS-7, HepG-2, HeLa, and HUVEC), especially, in difficult-to-transfect ones, such as HeLa and HUVEC. The luciferase expression level infected by the vectors of PCBMAEE₅₀-PCBMA₁₄/pGL-4 at N/P = 20/1 is 27 times of the branched PEI 25 kDa in COS-7 cells and 16 times of Lipofectamine^® 2000 in HUVEC. Furthermore, the complex formed by PCBMAEE₅₀-PCBMA₁₄ also show advantages in transfection rate, dosage effectiveness and preservation of transfecting activity in serum contained growth medium. The luciferase expression of the vectors of PCBMAEE₅₀-PCBMA₁₄/pGL-4 at N/P = 20/1 is 230 times higher than that of PEI complex at low vector dosage (the 5% standard dosage). And the transfection rate is 25 times higher than that of PEI complex in 10% serum contained growth medium. In short, all these results indicated that the polymeric gene vector, consisted of convertible hydrophobic polyzwitterionic precursor and fixed polyzwitterionic fouling resistant segment, is a promising candidate for high and stable gene transfection in complex growth medium.     

Improving adherence to malaria treatment for children: the use of pre-packed chloroquine tablets vs. chloroquine syrup

Malaria is a major cause of morbidity and mortality among children under five in sub-Saharan Africa. Prompt diagnosis and adequate treatment of acute clinical episodes are essential to reduce morbidity and prevent complications and mortality. In many countries, chloroquine syrup is the mainstay of malaria treatment for children under five. Not only is syrup more expensive than tablets, adherence to the prescribed dose at home is a problem because mothers use wrongly sized measuring devices or have difficulty with the instructions. We investigated the impact of introducing pre-packed tablets for children on adherence to treatment and compared the total cost of the tablets with that of syrup. Children aged 0--5 years diagnosed with malaria at the clinic over a 6-week period received either pre-packed tablets or syrup by random assignment. The principal caregivers were interviewed at home on day 4 after attending the clinic. Of the 155 caregivers given pre-packed tablets, 91% (n=141) adhered to the recommended dosage, while only 42% (n=61) of 144 who were provided syrup did. Only 20% of caregivers who received syrup used an accurate 5 ml measure. The cost of treatment with tablets was about one-quarter that of syrup and 62% (n=96) of caregivers preferred tablets. Pre-packed chloroquine tablets are a viable alternative to syrup.     

An in vivo database model for pharmacological and physiological dosage for experimental animals

We developed a database compiling in vivo doses of compounds for various activities in certain animal species. The related database covers almost 100 years of experiments. The conceptual scheme of the database was created using concepts of the entity-relationship modeling principles. Using published references, dosages and their effects on laboratory animals were entered as data. As the next stage of our work, we have started to examine the available literature to information about the experimental dosages of various drugs used in other studies.The database provides various interfaces, including graphical-user interfaces and interfaces for Internet access. The database will be useful as a knowledge infrastructure for researchers who have to perform dose-scan experiments for a specific pharmacological activity. The basic benefit of that knowledge infrastructure is that it will enable virtual pharmacological experiments that will be considerably less expensive than conventional laboratory experiments, because the number of animals used and the number of dose-scan experiments will be greatly reduced. The developed database will also be helpful for new drug development studies and for responding to queries about animal types, drugs used, drug interactions, and results.     

药品应急检验中如何进行急性毒性试验研究

急性毒性试验在药品的应急检验中得到了广泛的应用。本文介绍了在应急检验中如何进行药品的急性毒性试验（最大耐受量以及半数致死量测定）,试图为药品的应急检验以及临床应用提供有益的经验。     

Quantitative three‐dimensional imaging of live avian embryonic morphogenesis via micro‐computed tomography

Many clinically relevant congenital malformations arise during mid to late embryonic stages. This period is challenging to image quantitatively in live embryos, necessitating the use of multiple specimens with increased experimental variability. Here we establish X‐ray and blood‐pool computed tomography (CT) contrast agent toxicity and teratogenesis thresholds for 3D Micro‐CT imaging of live avian embryos. Day 4 chick embryos micro‐injected with Visipaque? (VP) developed for an additional 6 days without defect. X‐ray radiation up to 798 mGy was nontoxic. Peak average contrast of 1,060 HU occurred within 1 hr of imaging at 50 μm resolution. VP‐enhanced contrast persisted past 24 hr with delayed accumulation in the allantois. Regional volumes of VP‐injected embryos were statistically identical to those of fixed embryos perfused with osmium tetroxide. We further quantified longitudinal volumetric morphogenesis of the allantois over 30 hr. These results demonstrate the safety and efficacy of contrast enhanced quantitative micro‐CT imaging for live embryos. Developmental Dynamics 240:1949–1957, 2011. © 2011 Wiley‐Liss, Inc.