精脒对SW620细胞增殖及糖酵解的影响

目的 探讨精脒对人结肠癌SW620细胞增殖及糖酵解的影响.方法 以SW620细胞为研究对象,用0.625～2.5 μmoL/L精脒(SPD)作用于细胞,细胞密度以104个/mL接种于96孔培养板,分别培养24 h后,MTT法检测细胞增殖情况;同时,取6孔板培养24 h的细胞上清液,用试剂盒检测SW620细胞葡萄糖消耗及乳酸水平;细胞密度以1.2× 105个/mL接种于6孔培养板中,培养24 h后加入不同浓度SPD,继续培养24 h后,Western blot检测缺氧诱导因子(HIF-1)、乳酸脱氢酶(LDHA)及葡萄糖转运蛋白1(GLUT1)表达的变化.结果 与对照组比较,精脒各浓度组均能促进SW620细胞的增殖(P＜0.01),且促进作用呈剂量依赖性;精脒各浓度组作用后SW620细胞内葡萄糖的消耗及乳酸含量明显增多(P＜0.01),呈剂量依赖性;与对照组比较,LDHA、HIF-1及GLUT1蛋白表达水平随着精脒浓度的升高而增加(P＜0.01),且呈剂量依赖性.结论 精脒具有促进人结肠癌SW620细胞增殖及糖酵解的作用.     

Lisdexamfetamine: chemistry,pharmacodynamics, pharmacokinetics,and clinical efficacy,safety, and tolerability in the treatment of binge eating disorder

Introduction: The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED).

Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED.

Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.     

Improvement of Pitting-Corrosion Resistance of Ultrafine-Grained 7475 Al Alloy by Aging

The effect of aging on the resistance to pitting corrosion of ultrafine-grained 7475 aluminium (Al) alloy processed by hydrostatic extrusion (HE) is studied. Differences in the microstructure were investigated using secondary electron (SEM) and transmission electron microscopy (TEM). Corrosion tests were performed in 0.1 M NaCl, and characterization of corroded surface was performed. The results of this work show that the pitting susceptibility of ultra-fine grained 7475Al is related to the distribution of MgZn₂ precipitates. After HE, the formation of An ultrafine-grained microstructure at the grain boundaries of ultrafine grains is observed, while subsequent aging results in the formation of MgZn₂ precipitates in the grain interior. Grain refinement increases susceptibility to localized attack, while the subsequent aging improves the overall corrosion resistance and limits the propagation of corrosion attack.     

Influence of Strain Route Changes on the Microstructure and Mechanical Properties of CuZn36 Alloy during Cross Channel Extrusion CCE

This study evaluates the impact of changing the deformation routes of the extrusion process in a cross-shaped die (CCE) on the structure and properties of a CuZn36 alloy (% at.). Samples with dimensions of Ø8 × 36 mm were subjected to extrusion at room temperature according to two variants: straight extrusion in the A route (2-, 4-, 8- and 12-pass) and extrusion with interoperative rotation by 90° in the B_C route (2- and 4-pass). The improvement of strength properties was obtained as a result of grain fragmentation in the CCE process. Changes in the microstructure were observed using a light microscope, and mechanical properties were measured in the microhardness test and a static tensile test. The obtained results showed that the mechanical properties of the alloy depend on the number of passes and the material deformation route. This observation was related to the fragmentation of its structure and strengthening, which resulted in changes in its properties. The highest strength was characterized by the material pressed four times with the rotation of 90° (B_C route), whose properties were comparable and even slightly better than the material squeezed twelve times without rotation (A route).     

Guided motor training induces dendritic spine plastic changes in adult rat cerebellar purkinje cells

Schizophrenia is a complex disorder with a high heritability. Relatives with schizophrenia have an increased risk not only for schizophrenia but also for schizophrenia spectrum disorders, such as schizotypal personality disorder. A single nucleotide polymorphism (SNP), rs1344706, in the Zinc Finger Protein 804A (ZNF804A) gene, has been implicated in susceptibility to schizophrenia by several genome-wide association studies, follow-up association studies and meta-analyses. This SNP has been shown to affect neuronal connectivities and cognitive abilities. We investigated an association between the ZNF804A genotype of rs1344706 and schizotypal personality traits using the Schizotypal Personality Questionnaire (SPQ) in 176 healthy subjects. We also looked for specific associations among ZNF804A polymorphisms and the three factors of schizotypy-cognitive/perceptual, interpersonal and disorganization-assessed by the SPQ. The total score for the SPQ in carriers of the risk T allele was significantly higher than that in individuals with the G/G genotype (p=0.042). For the three factors derived from the SPQ, carriers with the risk T allele showed a higher disorganization factor (p=0.011), but there were no differences in the cognitive/perceptual or interpersonal factors between genotype groups (p>0.30). These results suggest that the genetic variation in ZNF804A might increase susceptibility not only for schizophrenia but also for schizotypal personality traits in healthy subjects.     

Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia

An enlarged volume of the pituitary gland has been reported in the schizophrenia spectrum, possibly reflecting the hypothalamic-pituitary-adrenal (HPA) hyperactivity. However, it remains largely unknown whether the pituitary size longitudinally changes in the course of the spectrum disorders. In the present study, longitudinal magnetic resonance imaging (MRI) data were obtained from 18 patients with first-episode schizophrenia, 13 patients with schizotypal disorder, and 20 healthy controls. The pituitary volume was measured at baseline and follow-up (mean, 2.7 years) scans and was compared across groups. The pituitary volume was larger in the schizophrenia patients than controls at baseline, and both patient groups had significantly larger pituitary volume than controls at follow-up. In a longitudinal comparison, both schizophrenia (3.6%/year) and schizotypal (2.7%/year) patients showed significant pituitary enlargement compared with controls (− 1.8%/year). In the schizophrenia patients, greater pituitary enlargement over time was associated with less improvement of delusions and higher scores for thought disorders at the follow-up. These findings suggest that the pituitary gland exhibits ongoing volume changes during the early course of the schizophrenia spectrum as a possible marker of state-related impairments.     

信息药师在药品SPD系统功能优化中的实践

目的：信息药师参与优化药品供应、管理和配送（SPD）系统,以提升药品流转效率。方法：从分析需求、拟定解决方案、绘制流程图、协调相关科室等方面分析信息药师的职能。结果与结论：信息药师参与SPD系统的运行和维护工作,可顺利将各临床部门的需求与工程师的技术实践相对接,优化药品的采购验收、出入库和库存管理的自动化水平,保障药学信息准确、合理,沟通顺畅。     

基于SPD的检验试剂二级库管理系统设计探讨

目的:优化检验试剂的采购流程,达到检验试剂的精细化管理、降低医院检验试剂的库存成本。方法:在医院现有的供应链管理管理系统的下面增加检验试剂二级库管理模块,再与医院LIS系统的收费端口对接,精确测算项目收入。结果:所有检验试剂的信息可以溯源。检验科内部以设备为中心,分组管理。所有检验项目的收费和试剂成本均可准确统计,帮助绩效分析。结论:检验试剂的二级库精细化管理,可以提高检验试剂的管理效率、保证检验项目合同的准确执行,还可以降低医院的库存成本。     

Formation of DHP-derived DNA adducts from metabolic activation of the prototype heliotridine-type pyrrolizidine alkaloid, heliotrine

Pyrrolizidine alkaloid-containing plants are widespread in the world and may be the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids require metabolism to exert their genotoxicity and tumorigenicity. Our mechanistic studies have determined that metabolism of the retronecine-type (riddelliine, retrorsine, and monocrotaline), heliotridine-type (lasiocarpine), and otonecine-type (clivorine) tumorigenic pyrrolizidine alkaloids in vivo and/or in vitro all generates a common set of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts responsible for tumor induction. All the pyrrolizidine alkaloids studied previously are diesters with an ester linkage at the C7 and C9 positions of the necine base. In this study, we report that F344 rat liver microsomal metabolism of heliotrine, a tumorigenic monoester bearing a hydroxyl group at the C7 of the necine base, resulted in the formation of the dehydroheliotridine (DHH) metabolite. When incubations of heliotrine were carried out in the presence of calf thymus DNA, the same set of DHP-derived DNA adducts was formed. These results support that DHP-derived DNA adducts are potential common biomarkers of pyrrolizidine alkaloid exposure and tumorigenicity. For comparison, the dehydroretronecine (DHR)-derived DNA adducts formed from metabolism of riddleiine, retrorsine, monocrotaline, riddelleiine N-oxide, and retrorsine N-oxide were measured in parallel; the levels of DHP-derived DNA adduct formation were in the order: riddelliine approximately retrorsine>monocrotaline>retrorsine N-oxide>or=riddelliine N-oxide>heliotrine.