液相色谱-电喷雾串联质谱分析人全血中环孢素的基质效应评估及其机理探究

目的： 评估液相色谱-电喷雾串联质谱（LC-ESI-MS/MS）分析人全血中环孢素的基质效应，并探究其发生机理。方法： 全血裂解物的蛋白沉淀上清液用作全血基质。分别用乙腈水溶液和全血基质配制等浓度环孢素A（CyA）、环孢素C（CyC）的质控样品。分别在添加H⁺、NH₄⁺和Na⁺的流动相中，用LC-ESI-MS/MS的MRM模式检测质控样品中CyA，CyC的[M+H]⁺、[M+NH₄]⁺和[M+Na]⁺（M=CyA，CyC）峰面积，以其计算基质效应因子；用MS Scan模式检查质控样品中CyA、CyC色谱流出峰的质谱离子组成情况，用于判断基质效应原因。结果： 在添加H⁺、NH₄⁺和Na⁺的流动相中，全血基质中CyA、CyC基质效应因子分别为-76.6%~-54.0%、-86.0%~-55.3%和-42.8%~-34.1%。在加H⁺、加NH₄⁺流动相中，标准液加全血基质的CyA、CyC色谱峰的质谱中出现丰度很高的[M+Na]⁺和[M+K]⁺，在加Na⁺流动相中它们出现丰度很高的[M+K]⁺，而对应的定量离子[M+H]⁺、[M+NH₄]⁺或[M+Na]⁺的丰度显著降低。结论： 全血基质对环孢素的LC-ESI-MS/MS分析产生明显的基质效应，其原因与基质中Na⁺、K⁺同添加在流动相中用于辅助电离的H⁺、NH₄⁺或Na⁺竞争与环孢素加合，导致定量目标加合离子丰度显著降低有关。     

透析液钙离子浓度对肾功能衰竭血液透析患者血清钙离子水平及血压的影响

目的 观察不同钙离子浓度的透析液对血液透析患者透析后血清钙离子水平及血压变化的影响，为肾功能衰竭血液透析患者的高钙血症及高血压的防治提供依据。方法 选择不同钙离子浓度的透析液，将维持性血液透析患者分为高钙组（1．75mmol／L）和低钙组（1．25mmol／L），比较患者每次透析前后脉搏、血压，同时抽查患者透析前后血钙及血肌酐浓度的变化。结果透析后两组患者血肌酐浓度均显著下降，透析前后差异均具有统计学意义（P〈0．01）；高钙组患者透析后血钙较透析前升高，差异具有统计学意义（P〈0．01），而低钙组患者血钙比透析前略降低，差异无统计学意义（P〉0．05）。高钙组患者透析后较透析前收缩压、舒张压及平均动脉压都升高，差异均具有统计学意义（P〈0．05），而低钙组患者透析后较透析前收缩压、舒张压及平均动脉压都降低，差异均具有统计学意义（P〈0．05）。透析后两组血钙比较差异具有统计学意义（P〈0．01）；透析后低钙组较高钙组患者的收缩压、舒张压及平均动脉压都降低，三者差异均具有统计学意义（P〈0．01）。结论透析液钙离子浓度与血液透析患者血清钙离子水平及血压呈正相关，低钙透析液透析有助于维持性血液透析患者高血压的控制。     

重度苯妥英钠中毒的药学监护

目的首先确定中毒药物,然后通过测定血药浓度以了解中毒程度,为重度苯妥英钠中毒患者临床抢救治疗提供依据。方法间隔一定时间采集患者静脉血,萃取血中药物,在211 nm处以反相高效液相色谱法定性,明确中毒药物并测定血药浓度。结果在苯妥英中毒患者中最高血药浓度为68.94 mg.L-1,接近治疗浓度上限的3.5倍。结论患者为重度中毒,危及生命,需临床药师与临床医师积极配合,施行全程药学监护。     

检测子宫内膜异位症患者血清中差异表达蛋白的研究

目的：检测子宫内膜异位症（内异症）患者血清中差异表达的蛋白。方法：采用表面增强激光解吸／离子化飞行时间质谱（SELDI—TOF—MS）技术，选用WCX2蛋白质芯片对50例内异症及48例对照组血清标本进行检测以筛选内异症血清中差异表达的蛋白。结果：在Mr 0～50000范围内，检测出106个蛋白峰。内异症患者血清中差异表达的蛋白峰有4个。将发现的差异蛋白峰在Swiss蛋白数据库中搜索，发现Mr 9280蛋白峰与玻璃粘连蛋白Vitronectin相符。Vitronectin属于整合素家族，在内异症的粘附、侵袭、血管形成过程中起重要作用。其他的蛋白峰没有发现与之相匹配的蛋白，提示可能为新的蛋白质。结论：内异症患者血清中存在差异表达的蛋白，其对内异症的早期诊断具有一定的临床意义。SELDI蛋白芯片技术是一种快速、简单易行、样本用量少、高通量、重复性好的分析方法，具有广阔的临床应用前景。     

Correction of frequency and phase variations induced by eddy currents in localized spectroscopy with multiple echo times.

As a consequence of the time-varying magnetic field induced by eddy currents, frequency drifting occurs when the sampling window of localized spectroscopy continuously shifts. The frequency drifting and the concomitant phase variations can severely affect spectroscopy results when data are acquired with multiple echo times (TEs), such as in the measurement of glutamate (Glu) concentration using the TE-averaged method. Specifically, the averaged spectra are further broadened and distorted in the presence of residual eddy currents, and editing of the coupled spins of Glu C4 protons is affected, resulting in errors in the measured relative intensity ratio. Postacquisition correction using unsuppressed water as reference can effectively minimize this detrimental effect, as manifested by the significantly enhanced signal intensity. Also, it is demonstrated that the methyl signals of creatine (Cr) at 3.0 ppm and choline (Cho) at 3.2 ppm can be used as internal references in finding frequency and phase disparities between different TEs.     

An experimentally supported, mathematical explanation of the gas chromatographic elution behaviour of the long-chain carbon members of the homologous series

By substituting the saturated vapour phase tension of the pure normal hydrocarbons described by the Clausius-Clapeyron law into the accepted expression of the specific retention volume (V_g,T), a theoretically coherent and relatively simple mathematical evidence of the elution behaviour of the homologous members has been deduced. It gives exponential retention time dependence on carbon number for isothermal, and nearly equidistant (i.e., approximately linear retention-time dependence on carbon number) elution for linear temperature programmed gas chromatographic runs. The final equations are in close correlation with the experimental results. Special emphasis is placed on the fact that a good approximation—not strict physical laws—have been found.     

不同输血方式对肺鳞癌患者围术期TNF—α和IL—lO的影响

[目的]探讨同种输血和自体输血对肺鳞癌患者围术期肿瘤坏死因子-α(TNF-α)和白细胞介素—10(IL—10)的影响和相互关系。[方法]2001年1月至2003年1月对31例肺鳞癌患者行肺癌根治术，将其分为两组，同种输血组(A组)17例，自体输血组14例(B组)。测定两组围术期血清中TNF-α和IL—10的浓度。[结果]A组输血后d1与输血前相比血清中TNF-α、IL-10浓度增高，以IL—10变化尤为明显，输血后d5TNF-α降低并接近输血前的水平，明显低于B组，IL—10仍明显高于输血前的水平。B组中不同时问IL—10无显著变化，TNF-α于ds明显高于输血前。[结论]肺鳞癌患者围术期同种输血后血清中TNF-α降低与IL—10升高有关，IL—10升高可能是同种输血后免疫抑制的重要原因。自体输血可减轻或去除这一作用。     

Measurement of kinetic parameters in skeletal muscle by magnetic resonance imaging with an intravascular agent.

The purpose of this work was to investigate the use of an intravascular contrast agent to determine perfusion kinetics in skeletal muscle. A two-compartment kinetic model was used to represent the flux of contrast agent between the intravascular space and extravascular extracellular space (EES). The relationship between the image signal-to-noise ratio (SNR) and errors in estimating permeability surface area product (Ktrans), interstitial volume (ve), and plasma volume (vp) for linear and nonlinear curve-fitting methods was estimated from Monte Carlo simulations. Similar results were obtained for both methods. For an image SNR of 60, the estimated errors in these parameters were 10%, 22%, and 17%, respectively. In vivo experiments were conducted in rabbits to examine physiological differences between these parameters in the soleus (SOL) and tibialis anterior (TA) muscles in the hind limb. Values for Ktrans were significantly higher in the SOL (3.2+/-0.9 vs. 2.0+/-0.5x10(-3) min-1), as were values for vp (3.4+/-0.8 vs. 2.1+/-0.7%). Differences in ve for the two muscles (8.7+/-2.2 vs. 8.5+/-1.6%) were not found to be significant. These results demonstrate that relevant physiological metrics can be calculated in skeletal muscle using MRI with an intravascular contrast agent.