Synthesis of imatinib,a tyrosine kinase inhibitor,labeled with carbon-14

Imatinib (Gleevec) is a multiple tyrosine kinase inhibitor that decreases the activity of the fusion oncogene called BCR-ABL (breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog) and is clinically used for the treatment of chronic myelogenous leukemia and acute lymphocytic leukemia. Small molecule drugs, such as imatinib, can bind to several cellular proteins including the target proteins in the cells, inducing undesirable effects along with the effects against the disease. In this study, we report the synthetic optimization for ¹⁴C-labeling and radiosynthesis of [¹⁴C]imatinib to analyze binding with cellular proteins using accelerator mass spectroscopy. ¹⁴C-labeling of imatinib was performed by the synthesis of ¹⁴C-labeld 2-aminopyrimidine intermediate using [¹⁴C]guanidine·HCl, which includes an in situ reduction of an inseparable byproduct for easy purification by HPLC, followed by a cross-coupling reaction with aryl bromide precursor. The radiosynthesis of [¹⁴C]imatinib (specific activity, 631 MBq/mmol; radiochemical purity, 99.6%) was achieved in six steps with a total chemical yield of 29.2%.     

复合PCR鉴别葡萄球菌及其多重耐药基因

目的　建立既可鉴别金黄色葡萄球菌又可同时检测其耐药基因的分子诊断方法。方法　对应于femB、mecA、ileS基因的 3对引物与快速提取的单菌落模板DNA进行单管同步扩增 ,电泳观察PCR片段 ;mecA、ileS耐药基因扩增结果分别与苯唑西林、莫匹罗星药敏试验对比 ,分析菌株的耐药性。结果　检测femB基因可快速特异性地筛选出金黄色葡萄球菌 ,mecA基因的检出与常规药敏试验鉴定耐甲氧西林葡萄球菌 (MRS)的结果基本一致 ,而拥有ileS基因的全部葡萄球菌分离株对莫匹罗星耐药。结论　复合PCR可快速敏感地从葡萄球菌中区分金黄色葡萄菌 ,并同时检出MRSA和耐莫匹罗星的多重耐药菌株。     

返魂草药材的鉴别研究现状

目的：返魂草为我国长白山地区的一种特色药材资源,为保证其质量,为该药材的鉴定提供理论依据。方法查阅总结文献资料,对返魂草药材的鉴别进行综述。结果为返魂草药材提供了来源鉴定、性状鉴定、显微鉴定、理化鉴定方法。结论阐述了返魂草药材的鉴定研究现状。     

600例肺炎支原体感染咽拭子培养结果的分析

目的 探讨肺炎支原体（MP）快速鉴定培养基在肺炎支原体感染鉴定中的临床价值.方法 采用肺炎支原体快速鉴定培养基对600例急性呼吸道感染患者的咽拭子标本进行肺炎支原体培养,并对结果进行统计学分析.结果 600例急性呼吸道感染患者的咽拭子标本肺炎支原体培养阳性148例,总阳性率为24.7％;男性阳性例数为76例,阳性率为25.3％,女性阳性例数为72例,阳性率为24.0％,男、女阳性率比较,差异无统计学意义（P＞0.05）.在各年龄组中,0～15岁组、16～35岁组、36 ～70岁组阳性例数分别为123例、16例、9例,阳性率分别为61.5％、8.0％、5.0％;0～15岁组阳性率与16～35岁组、36～70岁组组间比较,差异有统计学意义（P＜0.01）,16～35岁组与36～70岁组比较,差异无统计学意义（P＞0.05）.结论 肺炎支原体快速鉴定培养基检测结果准确、简便、快速,尤其对0～15岁患者检出阳性率高,可作为一般实验室诊断肺炎支原体感染的首选试验.     

Historical continuity in the methodology of modern medical science: Leonardo leads the way

Early modern medical science did not arise ex nihilo, but was the culmination of a long history stretching back through the Renaissance, the Middle Ages, Byzantium and Roman times, into Greek Antiquity. The long interval between Aristotle and Galen and Harvey and Descartes was punctuated by outstanding visionaries, including Leonardo, the ultimate Renaissance man. His attitude and mindset were based on Aristotelian pursuit of empirical fact and rational thought. He declared himself to be a “man without letters” to underscore his disdain for those whose culture was only mnemonics and philosophical inferences from authoritative books. Leonardo read the Book of Nature with the immense curiosity of the pioneering scientist, ushering in the methodology of modern medical science with help from forerunners. He left no publications, but extensive personal Notebooks: on his scientific research, hydrodynamics, physiological anatomy, etc. Apparently, numerous successors availed themselves of his methodologies and insights, albeit without attribution. In his Notebooks, disordered and fragmentary, Leonardo manifests the exactitude of the engineer and scientist, the spontaneous freshness of one speaking of what he has at heart and that he knows well. His style is unrefined, but intensely personal, rich with emotion and, sometimes, poetic. Leonardo, the visionary anatomist, strived consistently not merely to imitate nature by depicting body structures, but to perceive through analysis and simulations the intimate physiologic processes; i.e., the biomechanics underlying the workings of all bodily organs and components, even the mysterious beating heart. It is fitting to regard him as the first modern medical scientist.     

The role of emotion identification skill in the formation of male and female friendships: A longitudinal study

The present study explored the relationship between emotion identification skill (EIS) and friendships in adolescence. Students from five Australian high schools completed questionnaires annually from Grade 8 to Grade 12 including subjective measures of EIS and a peer-based objective measure of social functioning (e.g., friendship nominations). The total sample of participants was 795 (406 males; 389 females) with 468 (225 males; 243 females) completing questionnaires in Grade 12. EIS in early adolescence was predictive of friendships for females in late adolescence. Specifically, girls starting out with low EIS in Grade 8 tended to have fewer female friendships and more male friendships in Grade 12. There were no effects for males. Lower initial EIS was associated with significant improvements in awareness over time, but these improvements had no effect on friendships in Grade 12. The EIS that girls enter high school with may influence their friendship composition into late adolescence.     

A new method for muscle fatigue assessment: Online model identification techniques

Introduction: The purpose of this study was to propose a method that allows extraction of the current muscle state under electrically induced fatigue. Methods: The triceps surae muscle of 5 subjects paralyzed by spinal cord injury was fatigued by intermittent electrical stimulation (5 × 5 trains at 30 Hz ). Classical fatigue indices representing muscle contractile properties [peak twitch (Pt) and half‐relaxation time (HRT)] were assessed before and after each 5‐train series and were used to identify 2 relevant parameters (F_m, U_r) of a previously developed mathematical model using the Sigma‐Point Kalman Filter. Results: Pt declined significantly during the protocol, whereas HRT remained unchanged. Identification of the model parameters with experimental data yielded a model‐based fatigue assessment that gave a more stable evaluation of fatigue than classical parameters. Conclusions: This work reinforces clinical research by providing a tool that clinicians can use to monitor fatigue development during stimulation. Muscle Nerve 50: 556–563, 2014     

BioAge: Toward a multi-determined,mechanistic account of cognitive aging

The search for reliable early indicators of age-related cognitive decline represents a critical avenue for progress in aging research. Chronological age is a commonly used developmental index; however, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological systems, represents a promising operationalization of developmental time. Current BioAge models have successfully predicted age-related cognitive deficits. Research on aging-related cognitive function indicates that the interaction of multiple risk and protective factors across the human lifespan confers individual risk for late-life cognitive decline, implicating a multi-causal explanation. In this review, we explore current BioAge models, describe three broad yet pathologically relevant biological processes linked to cognitive decline, and propose a novel operationalization of BioAge accounting for both moderating and causal mechanisms of cognitive decline and dementia. We argue that a multivariate and mechanistic BioAge approach will lead to a greater understanding of disease pathology as well as more accurate prediction and early identification of late-life cognitive decline.