低分子肝素钙预防腰椎退行性疾病术后深静脉血栓形成的有效性和安全性

目的探讨低分子肝素钙预防腰椎退行性疾病术后深静脉血栓形成(DVT)的有效性和安全性。方法回顾性分析广安市广安区人民医院68例腰椎退行性疾病患者的临床资料,术后均采用抗凝预防血栓形成,按照术后预防DVT所采用方式的不同分为对照组和低分子肝素钙组。分析比较2组患者术后引流量、切口愈合情况、DVT发生率、皮下瘀斑情况、血小板数值、凝血功能、D-二聚体。结果术后2组患者引流量、切口愈合情况、皮下瘀斑情况、凝血功能相关指标比较,差异无统计学意义(P>0.05)。术前和术后1、10 d 2组患者血小板数量的变化差异无统计学意义(P>0.05)。DVT发生率2组患者比较差异有统计学意义(P<0.05)。术前及术后1 d 2组患者D-二聚体比较,差异无统计学意义(P>0.05);术后10 d,对照组患者D-二聚体显著增加,2组比较差异有统计学意义(P<0.05)。结论腰椎退行性疾病术后使用低分子肝素钙进行抗凝,可以显著降低DVT的发生率,具有良好的安全性。     

MEMRI and tumors: a method for the evaluation of the contribution of Mn(II) ions in the extracellular compartment

The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn²⁺ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn²⁺ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn²⁺ ions, as the addition of Ca‐DO2A to a solution of MnCl₂ causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn²⁺ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T₁‐weighted images is taken as evidence of the sequestration of extracellular Mn²⁺ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T₁ decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd.     

工作相关肌肉骨骼疾患与人体工效学负荷研究进展

工作相关肌肉骨骼疾患(WMSDs)是常见的慢性非传染性疾病。WMSDs已成为影响工人健康、降低工人生命质量和造成经济损失的重要因素,可见于多个行业、工种。本文对WMSDs流行现状及人体工效学负荷相关研究进行综述,以期找到职业人群保护的可行方法。     

Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa

The objective of this study was to investigate the absorption behavior of chikusetsusaponin IVa (CHS‐IVa) in the rat intestine using single‐pass intestinal perfusion (SPIP) and to classify CHS‐IVa into the biopharmaceutics classification system (BCS). The equilibrium solubility of CHS‐IVa was determined by the shaker method. The absorption mechanism of CHS‐IVa in the intestine was studied by comparing the P_eff of different concentrations of CHS‐IVa. The intestinal site dependence of CHS‐IVa absorption was studied by comparing the P_eff of the same concentration of CHS‐IVa in different intestinal segments. The relationship between CHS‐IVa and intestinal efflux protein was studied by perfusion with an efflux protein inhibitor. The permeability of CHS‐IVa was investigated by comparing the P_eff of CHS‐IVa and the reported value. The solubility of CHS‐IVa over the pH range 1.0–7.5 was 14.4 ± 0.29 to 16.9 ± 0.34 mg/ml. The P_eff of CHS‐IVa in the duodenum was 1.76 × 10^?3 to 2.00 × 10^?3 cm/min. The P_eff of CHS‐IVa in the jejunum was 1.26 × 10^?3 to 1.39 × 10^?3 cm/min. The P_eff of CHS‐IVa in the ileum was 1.25 × 10^?3 to 1.31 × 10^?3 cm/min. The P_eff of CHS‐IVa in the colon was 1.02 × 10^?3 to 1.08 × 10^?3 cm/min. There was no statistical difference of the P_eff in the four segments at different CHS‐IVa concentrations. The P_eff of CHS‐IVa (0.07, 0.7 and 7.0 mg/ml) were all notably smaller than the reported P_eff (3.00 × 10^?3 cm/min) in the jejunum. The P_eff of CHS‐IVa was not influenced by verapamil (P‐gp inhibitor), indomethacin (MRP inhibitor) and pantoprazole (BCRP inhibitor). CHS‐IVa was classified as high solubility, low permeability and BCS III. The main absorptive tracts were the upper intestinal tracts and the rank order of intestinal permeability was duodenum > jejunum ≈ ileum > colon. The transport mechanism of CHS‐IVa in all intestinal segments might be primarily passive transport. CHS‐IVa was not a substrate of P‐gp, MRP and BCRP.     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

Decoding attention control and selection in visual spatial attention

Event‐related potentials (ERPs) are used extensively to investigate the neural mechanisms of attention control and selection. The univariate ERP approach, however, has left important questions inadequately answered. We addressed two questions by applying multivariate pattern classification to multichannel ERPs in two cued visual spatial attention experiments (N = 56): (a) impact of cueing strategies (instructional vs. probabilistic) on attention control and selection and (b) neural and behavioral effects of individual differences. Following cue onset, the decoding accuracy (cue left vs. cue right) began to rise above chance level earlier and remained higher in instructional cueing (~80 ms) than in probabilistic cueing (~160 ms), suggesting that unilateral attention focus leads to earlier and more distinct formation of the attention control set. A similar temporal sequence was also found for target‐related processing (cued target vs. uncued target), suggesting earlier and stronger attention selection under instructional cueing. Across the two experiments: (a) individuals with higher cue‐related decoding accuracy showed higher magnitude of attentional modulation of target‐evoked N1 amplitude, suggesting that better formation of anticipatory attentional state leads to stronger modulation of target processing, and (b) individuals with higher target‐related decoding accuracy showed faster reaction times (or larger cueing effects), suggesting that stronger selection of task‐relevant information leads to better behavioral performance. Taken together, multichannel ERPs combined with machine learning decoding yields new insights into attention control and selection that complement the univariate ERP approach, and along with the univariate ERP approach, provides a more comprehensive methodology to the study of visual spatial attention.     

Immunohistochemical and molecular analysis of PI3K/AKT/mTOR pathway in esophageal carcinoma

Among the numerous signaling pathways involved in tumorigenesis, PI3K‐AKT‐mTOR is a key one that regulates diverse cellular functions. However, its prognostic value in esophageal carcinoma remains unclear. In our study, we examined the immunohistochemical expression of phosphorylated (p‐) AKT, mTOR, p70S6K and 4E‐BP1 along with the mutational status of PIK3CA and AKT1 genes by High Resolution Melting Analysis and Pyrosequencing in 44 esophageal carcinomas. The results were correlated with the clinicopathological characteristics of the patients in an effort to define their possible prognostic significance. Total p‐mTOR cytoplasmic expression, assessed in 10 random areas, was positively correlated with tumor stage (Kruskal–Wallis ANOVA, I/II vs III/IV, p = 0.0500). Μoreover, maximum p‐mTOR cytoplasmic immunoexpression, estimated in hot spot areas, was positively associated with tumor grade (Mann–Whitney U test, I/II vs III, p = 0.0565). Interestingly, p‐4E‐BP1 immunoreactivity was negatively correlated with tumor histological grade (Mann–Whitney U test, I/II vs III, p = 0.0427). No mutation was observed in exons 9 and 20 of PIK3CA gene and in exon 4 of AKT1 gene. In conclusion, our findings depict the presence of activated PI3K/AKT/mTOR pathway in esophageal cancer bringing forward p‐mTOR and p‐4E‐BP1 for their potential role in esophageal carcinogenesis. Additional studies are warranted to validate our findings.     

Differentiating benign from malignant cardiac tumors with cardiac magnetic resonance imaging

Background

The purpose of this analysis is to describe the differences in cardiac magnetic resonance characteristics between benign and malignant tumors, which would be helpful for surgical planning.