美国生物类似药的使用与医疗保险支付策略分析——基于Pfizer vs. Johnson案的思考 *

近几年全球生物类似药发展如火如荼,各国出台积极政策响应与推动生物类似药的研发和应用,大型制药企业也通过一系列对生物医药公司的收购完成生物类似药研发先机的抢占。以Pfizer vs. Johnson案为研究对象,对美国生物类似药的保障政策、诉讼案件发展和系列焦点问题进行整体描述与深入分析。研究发现,来自原研企业的竞争压力及临床对生物类似药可替代性的质疑与保守态度,都在一定程度上对类似药的应用和推广构成威胁,而其价格优势和越来越明朗的政策环境使得生物类似药的未来可期。     

Glycine metabolomic changes induced by anticancer agents in A549 cells

Amino Acids - Glycine plays a key role in rapidly proliferating cancer cells such as A549 cells. Targeting glycine metabolism is considered as a potential means for cancer treatment. However, the...     

土壤干旱胁迫对九头狮子草和圆苞金足草幼苗形态和生理特性的影响

采用称重控水法控制土壤相对含水量分别为(85.0±2.5)％(对照)、(67.5±2.5)％(轻度干旱)、(50.0±2.5)％(中度干旱)和(32.5±2.5)％(重度干旱),对土壤干旱胁迫条件下九头狮子草[Peristrophe japonica (Thunb.)Bremek.]和圆苞金足草(Goldfussia pentstemonoides Nees)2年生苗的植株形态及生理特性变化进行了研究.结果表明:经土壤干旱胁迫处理30 d后供试2种植物的外部形态均有一定变化,其中九头狮子草主要变化为叶片失绿、变薄且萎蔫、枝条下垂;圆苞金足草主要变化为茎干倒伏、叶片变软且叶柄低垂.随土壤干旱胁迫程度的增加,供试2种植物叶片的自然饱和亏、临界饱和亏、需水程度、束缚水含量、束缚水与自由水的含量比值、脯氨酸含量和可溶性糖含量均呈逐渐增加的趋势且均高于对照,而自由水含量、最高水势、最低水势和可溶性蛋白质含量均逐渐降低且总体上低于对照.总体上看,在重度干旱胁迫条件下供试2种植物各生理特性均与对照有极显著或显著差异,而在轻度或中度干旱胁迫条件下部分指标与对照无显著差异.供试2种植物各生理指标的变化幅度有明显差异,在同一干旱胁迫条件下九头狮子草叶片的自然饱和亏、需水程度、自由水含量、最高水势和最低水势的降幅、脯氨酸含量和可溶性蛋白质含量的降幅均高于圆苞金足草,其临界饱和亏、束缚水含量、束缚水与自由水的含量比值和可溶性糖含量均低于圆苞金足草.综合分析结果表明:供试2种植物对土壤干旱胁迫均具有一定的耐性,但圆苞金足草具有更强的抵御干旱的生理机制.     

大白菜部分形态性状的QTL定位与分析

应用352个标记位点的大白菜AFLP和RAPD图谱和一套栽培品种间杂交获得的重组自交系群体,采用复合区间作图的方法对大白菜9个形态性状进行QTL定位及遗传效应研究。在14个连锁群上检测到50个QTL:其中控制株型的QTL有5个;控制株高的QTL有6个;控制开展度的QTL有5个;控制最大叶长的QTL有7个;控制最大叶宽的QTL有4个;控制叶形指数的QTL有6个;控制中肋长的QTL有7个;控制中肋宽的QTL有4个;控制抽苔的QTL有6个。另外,估算了单个QTL的遗传贡献率和加性效应。这将为大白菜品种改良中形态性状的分子标记辅助选择提供理论依据。     

大兴安岭林区针叶林的生长方程及火灾林木死亡率

本文用随机模拟的方法建立了北方针叶林的生长方程及其受到火灾侵害后的林木死亡率,定量地研究了火灾对这种林分变动的影响．     

中国盾脸姬蜂亚科一新种及一新记录(膜翅目：姬蜂科)

中国盾脸姬蜂亚科一新种及一新记录（膜翅目：姬蜂科）盛茂领章英（林业部森林病虫害防治总站沈阳１１００３４）１９９５－０４－２０收稿,１９９６－０１－１７收修改稿·９２·黄脸姬蜂属ＣｈｏｒｉｎａｅｕｓＨｏｌｍｇｒｅｎ,１８５６和突唇姬蜂属Ｉｓｃｈｙｒｏｃ...     

Identification and characterization of Escherichia coli thioesterase III that functions in fatty acid beta-oxidation

When Escherichia coli is grown on oleic acid as the sole carbon source, most of this fatty acid is completely degraded by beta-oxidation. However, approximately 10% of the oleic acid is only partially degraded to 3,5- cis-tetradecadienoyl-CoA, which is hydrolyzed to 3,5- cis-tetradecadienoic acid and released into the growth medium. An investigation of thioesterases involved in this novel pathway of beta-oxidation led to the identification of a new thioesterase (thioesterase III) that is induced by growth of E. coli on oleic acid. This enzyme was partially purified and identified as the ybaW gene product by mass spectrometric analysis of tryptic peptides. The ybaW gene, which has a putative consensus sequence for binding the fatty acid degradation repressor, was cloned and expressed in E. coli. Thioesterase III was shown to be a long-chain acyl-CoA thioesterase that is most active with 3,5-tetradecadienoyl-CoA, a minor metabolite of oleate beta-oxidation. Its substrate specificity and induction by fatty acids agree with its proposed function in the thioesterase-dependent pathway of beta-oxidation. Thioesterase III is proposed to hydrolyze metabolites of beta-oxidation that are resistant to further degradation and that would inhibit the flux through the pathway if they were allowed to accumulate.     

Tetranor PGDM, an abundant urinary metabolite reflects biosynthesis of prostaglandin D2 in mice and humans

Prostaglandin D(2) (PGD(2)) is a cyclooxygenase (COX) product of arachidonic acid that activates D prostanoid receptors to modulate vascular, platelet, and leukocyte function in vitro. However, little is known about its enzymatic origin or its formation in vivo in cardiovascular or inflammatory disease. 11,15-dioxo-9alpha-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor PGDM) was identified by mass spectrometry as a metabolite of infused PGD(2) that is detectable in mouse and human urine. Using liquid chromatography-tandem mass spectrometry, tetranor PGDM was much more abundant than the PGD(2) metabolites, 11beta-PGF(2alpha) and 2,3-dinor-11beta-PGF(2alpha), in human urine and was the only endogenous metabolite detectable in mouse urine. Infusion of PGD(2) dose dependently increased urinary tetranor PGDM > 2,3-dinor-11beta-PGF(2alpha) > 11beta-PGF(2alpha) in mice. Deletion of either lipocalin-type or hemopoietic PGD synthase enzymes decreased urinary tetranor PGDM. Deletion or knockdown of COX-1, but not deletion of COX-2, decreased urinary tetranor PGDM in mice. Correspondingly, both PGDM and 2,3-dinor-11beta-PGF(2alpha) were suppressed by inhibition of COX-1 and COX-2, but not by selective inhibition of COX-2 in humans. PGD(2) has been implicated in both the development and resolution of inflammation. Administration of bacterial lipopolysaccharide coordinately elevated tetranor PGDM and 2,3-dinor-11beta-PGF(2alpha) in volunteers, coincident with a pyrexial and systemic inflammatory response, but both metabolites fell during the resolution phase. Niacin increased tetranor PGDM and 2,3-dinor-11beta-PGF(2alpha) in humans coincident with facial flushing. Tetranor PGDM is an abundant metabolite in urine that reflects modulated biosynthesis of PGD(2) in humans and mice.