利用LC-MS/MS法快速鉴定盐酸头孢吡肟中的同分异构体杂质

目的建立应用LC-MS/MS技术快速鉴定盐酸头孢吡肟原料药中的同分异构体杂质的方法。方法以乙腈-10 mmol·L^-1乙酸铵(5∶95)为流动相经C₁₈柱分离,通过电喷雾串联质谱在线检测，获得相关的色谱和质谱信息。结果在所建立的条件下，盐酸头孢吡肟及其同分异构体杂质获得有效分离，主成分和其同分异构体杂质的保留时间分别为15.28 min和9.18 min，同时它们的二级质谱产物离子信息及其裂解方式呈现明显的差异。结论本法能快速、准确地分离鉴定盐酸头孢吡肟原料药中的同分异构体杂质，从而可以对其原料药进行质量控制。     

液相色谱-质谱联用法同时测定人血浆中雷米普利和雷米普利拉的浓度

目的:建立同时测定人血浆中雷米普利和雷米普利拉浓度的液相色谱-质谱方法。方法:以喹那普利为内标,血浆样品经固相萃取小柱提取后,采用HPLC-MS(TOF)联用技术,以电喷雾(ESI)作为接口技术,以宽的m/z为数据采集范围检测后,选择准分子离子[M H] 作为检测离子,进行滤过、积分的方式检测,同时测定人血浆中雷米普利和雷米普利拉的浓度。结果:雷米普利和雷米普利拉的线性范围分别为1~80μg·L-1和0.5~40μg·L-1,日内精密度与日间RSD均小于10%。结论:该测定方法具有灵敏、专一和快速的优点,可满足雷米普利在人体内药动学研究的要求。     

Liquid chromatography–tandem mass spectrometric assay for the quantitation in human plasma of the novel indenoisoquinoline topoisomerase I inhibitors,NSC 743400 and NSC 725776

Topoisomerase I (Topo I) is a recognized target for ovarian, lung, and colorectal cancer therapy. The FDA-approved camptothecin (CPT) Topo I inhibitors, topotecan and irinotecan are labile and their effects are rapidly reversible. The indenoisoquinoline topoisomerase I inhibitors, NSC 743400 and NSC 725776, have been developed as a new generation of Topo I inhibitors and are being advanced to clinical evaluation. To support the clinical development of NSC 743400 and NSC 725776, we developed and validated, according to FDA guidelines, LC–MS/MS assays for the sensitive, accurate and precise quantitation of NSC 743400 and NSC 725776 in 0.2 mL human plasma. After ethyl acetate extraction, separation was achieved with a Synergi Polar RP column and a gradient of 0.1% formic acid in acetonitrile:water. NSC 743400 and NSC 725776 eluted at approximately 3 min, and the total run time was 14 min. Detection consisted of electrospray, positive-mode ionization mass spectrometry. Between 3 and 1000 ng/mL, accuracy was 96.9–108.2% for NSC 743400 and 95.1–106.7% for NSC 725776, and precision was <11.4% for NSC 743400 and <5.9% for NSC 725776. Extraction recovery was >80% for both analytes, and ion suppression ranged from −46.7 to 5.7%. The use of isotopically labeled internal standards and a wash phase at the end of the run were necessary to achieve adequate assay performance. Protein binding in human plasma as assessed by equilibrium dialysis showed both indenoisoquinolines to be more than 98% protein bound.     

测定胃癌患者肿瘤组织与外周血中前列腺素E2的临床意义

目的 测定胃癌患者肿瘤组织及外周血中前列腺素E2(prostaglandin E2,PGE2)含量.方法 用PGE2酶联免疫试剂盒分别测定40例胃癌患者肿瘤组织、癌旁切缘组织及术前外周血中PGE2含量.结果 胃癌组织的PGE2含量明显高于癌旁切缘组织,分别为(8.225±2.425)、(1.669±0.287)ng/g,两者差异有统计学意义(P<0.01),低分化和高中分化胃癌组织PGE2含量分别为(9.02±2.28)、(5.38±0.35)ng/g,两者有显著性差异(P<0.05).外周血中PGE2含量与胃癌组织PGE2含量呈正相关(r=0.889,P<0.01).肿瘤直径≥5 cm和<5 cm的胃癌患者外周血中PGE2含量差异有统计学意义(P<0.05).低分化和高中分化胃癌患者外周血中PGE2含量差异也有统计学意义(P<0.05).胃癌组织及外周血中PGE2含量与患者年龄、性别无关,与肿瘤部位、浸润深度、临床病理分期及是否淋巴结转移也无关.结论 胃癌患者肿瘤组织中PGE2含量增高,其外周血PGE2含量也随之增高,表明外周血PGE:水平与胃癌组织释放的PGE2含量成正比.测定外周血中PGE2可以间接评估胃癌患者的肿瘤大小与分化程度.     

Combined Use of Texture Features and Morphological Classification Based on Dynamic Contrast-enhanced MR Imaging: Differentiating Benign and Malignant Breast Masses with High Negative Predictive Value

Purpose: We evaluated the diagnostic performance of the texture features of dynamic contrast-enhanced (DCE) MRI for breast cancer diagnosis in which the discriminator was optimized, so that the specificity was maximized via the restriction of the negative predictive value (NPV) to greater than 98%.Methods: Histologically proven benign and malignant mass lesions of DCE MRI were enrolled retrospectively. Training and testing sets consist of 166 masses (49 benign, 117 malignant) and 50 masses (15 benign, 35 malignant), respectively. Lesions were classified via MRI review by a radiologist into 4 shape types: smooth (S-type, 34 masses in training set and 8 masses in testing set), irregular without rim-enhancement (I-type, 60 in training and 14 in testing), irregular with rim-enhancement (R-type, 56 in training and 22 in testing), and spicula (16 in training and 6 in testing). Spicula were immediately classified as malignant. For the remaining masses, 298 texture features were calculated using a parametric map of DCE MRI in 3D mass regions. Masses were classified into malignant or benign using two thresholds on a feature pair. On the training set, several feature pairs and their thresholds were selected and optimized for each mass shape type to maximize specificity with the restriction of NPV > 98%. NPV and specificity were computed using the testing set by comparison with histopathologic results and averaged on the selected feature pairs.Results: In the training set, 27, 12, and 15 texture feature pairs are selected for S-type, I-type, and R-type masses, respectively, and thresholds are determined. In the testing set, average NPV and specificity using the selected texture features were 99.0% and 45.2%, respectively, compared to the NPV (85.7%) and specificity (40.0%) in visually assessed MRI category-based diagnosis.Conclusion: We, therefore, suggest that the NPV of our texture-based features method described performs similarly to or greater than the NPV of the MRI category-based diagnosis.     

基体辅助激光解吸质谱法在生物大分子质量研究中的应用

研究了基体辅助激光解析飞行时间质谱法(MALDI-TOF MS)测定蛋白和糖蛋白的实验条件,实测了重组人白细胞介素2、肿瘤坏死因子、粒细胞巨噬细胞集落刺激因子、白细胞干扰素α2b、白细胞干扰素α₁、促红细胞生成素、钙调蛋白及其片段、大鼠脑型一氧化氮合成酶和天然牛精液蛋白提取物的分子量和纯度,鉴定了蛋白质混合物中各单个成分,结果表明MALDI-TOF MS可有效地研究基因工程蛋白质和天然蛋白提取物等生物大分子的质量。     

Timely follow‐up of positive cancer screening results: A systematic review and recommendations from the PROSPR Consortium

Timely follow‐up for positive cancer screening results remains suboptimal, and the evidence base to inform decisions on optimizing the timeliness of diagnostic testing is unclear. This systematic review evaluated published studies regarding time to follow‐up after a positive screening for breast, cervical, colorectal, and lung cancers. The quality of available evidence was very low or low across cancers, with potential attenuated or reversed associations from confounding by indication in most studies. Overall, evidence suggested that the risk for poorer cancer outcomes rises with longer wait times that vary within and across cancer types, which supports performing diagnostic testing as soon as feasible after the positive result, but evidence for specific time targets is limited. Within these limitations, we provide our opinion on cancer‐specific recommendations for times to follow‐up and how existing guidelines relate to the current evidence. Thresholds set should consider patient worry, potential for loss to follow‐up with prolonged wait times, and available resources. Research is needed to better guide the timeliness of diagnostic follow‐up, including considerations for patient preferences and existing barriers, while addressing methodological weaknesses. Research is also needed to identify effective interventions for reducing wait times for diagnostic testing, particularly in underserved or low‐resource settings. CA Cancer J Clin 2018;68:199–216 . © 2018 American Cancer Society .     

探究三维超声成像诊断乳腺肿块的临床应用价值

目的：探究与分析三维超声成像诊断乳腺肿块的临床应用价值。方法方便选取并回顾性分析该院自2013年9月—2015年9月收治的90例乳腺肿块患者的临床资料,该组患者均接受了二维超声、三维超声及弹性成像检查,将上述3种检查结果与术后病理结果进行对照。结果二维超声敏感性为79.03%,特异性为70.83%,准确性为74.63%,三维超声敏感性为89.83%,特异性为78.95%,准确性为84.33%,弹性超声成像敏感性为92.60%,特异性为82.5%,准确性为86.57%,三维超声与弹性超声成像敏感性、特异性及准确性相比均差异无统计学意义(P>0.05)。三维超声与弹性超声成像敏感性、特异性及准确性与二维超声相比均明显增高,差异有统计学意义(P<0.05)。结论三维超声的诊断准确率明显高于二维超声,且与弹性超声成像无明显差异,临床医生可将其应用于乳腺肿块的诊断过程中,为进一步治疗提供合理依据。