The Evaluation of Multiple Linear Regression–Based Limited Sampling Strategies for Mycophenolic Acid in Children with Nephrotic Syndrome

We evaluated mycophenolic acid (MPA) limited sampling strategies (LSSs) established using multiple linear regression (MLR) in children with nephrotic syndrome treated with mycophenolate mofetil (MMF). MLR-LSS is an easy-to-determine approach of therapeutic drug monitoring (TDM). We assessed the practicability of different LSSs for the estimation of MPA exposure as well as the optimal time points for MPA TDM. The literature search returned 29 studies dated 1998–2020. We applied 53 LSSs (n = 48 for MPA, n = 5 for free MPA [fMPA]) to predict the area under the time-concentration curve (AUC_pred) in 24 children with nephrotic syndrome, for whom we previously determined MPA and fMPA concentrations, and compare the results with the determined AUC (AUC_total). Nine equations met the requirements for bias and precision ±15%. The MPA AUC in children with nephrotic syndrome was predicted the best by four time-point LSSs developed for renal transplant recipients. Out of five LSSs evaluated for fMPA, none fulfilled the ±15% criteria for bias and precision probably due to very high percentage of bound MPA (99.64%). MPA LSS for children with nephrotic syndrome should include blood samples collected 1 h, 2 h and near the second MPA maximum concentration. MPA concentrations determined with the high performance liquid chromatography after multiplying by 1.175 may be used in LSSs based on MPA concentrations determined with the immunoassay technique. MPA LSS may facilitate TDM in the case of MMF, however, more studies on fMPA LSS are required for children with nephrotic syndrome.     

枸橼酸咖啡因药物动力学模型定量分析用药方案可行性

基于枸橼酸咖啡因标准用药方案,结合临床用药经验设计了三种常规用药方案及两种个性用药方案.利用药物动力学模型给定的血药浓度随时间变化规律,以有效治疗浓度为判据,分析了方案的可行性.结合临床用药案例分析了有效用药周期.     

A Multifunctional Nanomicelle for Real‐Time Targeted Imaging and Precise Near‐Infrared Cancer Therapy

Simultaneous targeted cancer imaging, therapy and real‐time therapeutic monitoring can prevent over‐ or undertreatment. This work describes the design of a multifunctional nanomicelle for recognition and precise near‐infrared (NIR) cancer therapy. The nanomicelle encapsulates a new pH‐activatable fluorescent probe and a robust NIR photosensitizer, R16FP, and is functionalized with a newly screened cancer‐specific aptamer for targeting viable cancer cells. The fluorescent probe can light up the lysosomes for real‐time imaging. Upon NIR irradiation, R16FP‐mediated generation of reactive oxygen species causes lysosomal destruction and subsequently trigger lysosomal cell death. Meanwhile the fluorescent probe can reflect the cellular status and in situ visualize the treatment process. This protocol can provide molecular information for precise therapy and therapeutic monitoring.     

The Necessity of Having a Tetradentate Ligand to Extract Copper(II) Ions from Amyloids

The accumulation of redox-active metal ions, in particular copper, in amyloid plaques is considered to the cause of the intensive oxidation damage to the brain of patients with Alzheimers disease (AD). Drug candidates based on a bis(8-aminoquinoline) tetradentate ligand are able to efficiently extract Cu²⁺ from copper-loaded amyloids (Cu–Aβ). Contrarily, in the presence of a bidentate hydroxyquinoline, such as clioquinol, the copper is not released from Aβ, but remains sequestrated within a Aβ–Cu–clioquinol ternary complex that has been characterized by mass spectrometry. Facile extraction of copper(II) at a low amyloid/ligand ratio is essential for the re-introduction of copper in regular metal circulation in the brain. As, upon reduction, the Cu⁺ is easily released from the bis(8-aminoquinoline) ligand unable to accommodate Cu^I, it should be taken by proteins with an affinity for copper. So, the tetradentate bis(8-aminoquinoline) described here might act as a regulator of copper homeostasis.     

Targeted Antithrombotic Protein Micelles

Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site‐specific delivery of a variety of therapeutic agents. Multifunctional protein micelles bearing targeting and therapeutic proteins were now obtained by one‐pot transpeptidation using an evolved sortase A. Conjugation to the corona of a single‐chain antibody (scFv), which binds to the ligand‐induced binding site (LIBS) of activated GPIIb/IIIa receptors, enabled the efficient detection of thrombi. The inhibition of thrombus formation was subsequently accomplished by incorporating the catalytically active domain of thrombomodulin (TM) onto the micelle corona for the local generation of activated protein C, which inhibits the formation of thrombin. An effective strategy has been developed for the preparation of protein micelles that can be targeted to sites of activated platelets with broad potential for treatment of acute thrombotic events.     

Chemical biology beyond binary codes

The cellular chemical machinery controlling all living processes is mediated by macroassemblies of enzymes and nucleic acids. These complexes form, break up in different orders and reorganize in ways that result in the chain of events that we call a biochemical 'pathway'. However, all of the methods available to study protein interactions in living cells allow only the observation or recreation of binary complexes. Two recent reports and earlier studies describe the use of chemical 'dimerizers' that can dynamically induce assembly or disassemby of protein complexes. The dimerizer tools create the opportunity to understand the 'real' biology of macromolecular assembly.     

A Research Review on Strategic Alliance of Industrial Technology Innovation

As technological innovation has been taking a predominant role in today 's industry,strategic alliance of industrial technology innovation is an expansion in the layer of technological development and strategic alliance industry.In China,the national innovation system hasn 't been perfect yet,strategic alliance of industrial technology innovation is still a new-born object which needs further theoretical studies and practical explorations.     

中国汽车产业企业与跨国汽车企业战略联盟治理模式研究

从中国汽车产业企业的立场出发,阐述了中国汽车产业战略联盟治理模式,结合联盟的现状,分析了中国本土汽车企业(包括零部件企业)与跨国汽车企业战略联盟管理的治理模式的问题和可能的选择。     

示踪元素钐对磷酸盐玻璃微球性质的影响

引入少量的示踪物氧化钐,磷酸盐玻璃的工艺性能不会发生大的变化,制成玻璃微球的方法可以不变。这种微球经中子活化后,在发生β衰变的同时,还伴随γ衰变,放射出的低能氧化钐后,磷酸盐玻璃微球的化学稳定性得到了很好的改善,进一步提高了使用的安全性,这是一种多功能的内放射医疗玻璃微球。     

中国银行业跨国经营的过渡性选择

针对中国银行跨国经营存在的不足,从价值链和博弈论的角度,就中国银行业的跨国战略联盟所采用的市场关系型银行联盟和产权关系型银行联盟两种方式进行比较分析,得出采取产权关系型的银行联盟为佳的结论。