Characterization of Blasts in Clinical Samples Containing Few Blasts

Characterization (eg, phenotyping) of blasts present at low percentages in clinical samples is often required for decisions regarding the approach to therapy. However, the available methods for cell characterization do not yield reliable data when the target cells are scant, and the existing methods for blast enrichment, such as cell sorting by flow cytometry (FCM), cannot enrich blasts of unknown immunophenotype. Blastretriever is a newly developed density centrifugation reagent for retrieving blasts. We examined the utility of Blastretriever in clinical practice. When normal bone marrow (BM) cells were separated with this reagent, myeloblasts and B-cell precursors were enriched and detected as clusters on the FCM cytogram. Compared with a conventional reagent for mononuclear cell preparation, the Blastretriever reagent markedly enriched leukemic myeloblasts, leukemic lymphoblasts, and blastoid lymphoma cells from 36 test samples (BM cells and peripheral blood). We then applied the Blastretriever reagent to samples from 11 consecutive patients who had been referred to us because they exhibited low percentages of blasts (1 patient had only 0.2% blasts). Characterization was needed but impossible with conventional analyses. Blast enrichment was achieved for all 11 samples, allowing reliable blast characterization by FCM, fluorescence in situ hybridization, and/or G-banding determinations. The revealed blast characteristics were valuable for choosing appropriate therapy for the patients.     

水产品中副溶血性弧菌检测增菌方法改良探讨

目的探讨水产品中副溶血性弧菌的高效增菌方法,提高检出率。方法以国标法为基础,在增菌液中加入鱼蛋白胨作为改良法1;以氯化钠多黏菌素B肉汤进行二次增菌为改良法2。分别对人工污染样品和实际水产样品进行检测,比较不同增菌液的检出率。结果改良法1的检出率高于国标法(χ2=4.50,P0.05),改良法2与国标法相比检出率一致。结论通过对增菌液的改良,建立高效增菌方法,可以提高水产品中副溶血性弧菌的检出率。     

基于网络药理学及体外实验验证研究茯苓-白术药对治疗胃癌的作用机制

目的：基于网络药理学及实验验证,探讨茯苓-白术药对治疗胃癌的作用机制。方法：根据口服生物利用度和类药性,在中药系统药理学数据库与分析平台(TCMSP)筛选茯苓-白术药对活性成分,借助Swiss Target Prediction数据库,预测茯苓-白术药对活性成分的潜在靶点。在疾病相关基因数据库（DisGeNET）检索胃癌相关靶点,将2个靶点集导入Cytoscape软件做交集,通过筛选拓扑特征值获取茯苓-白术药对治疗胃癌的核心靶点集,构建蛋白质-蛋白质相互作用（PPI）网络。并进行基因本体（GO）及京都基因和基因组百科全书（KEGG）富集分析。最后,通过体外实验对有效靶点及通路进行验证。结果：茯苓-白术药对含有36个有效活性成分,PPI网络关键靶点主要为MAPK3、PTGS2、EGFR、MAPK8、MAPK14、PPARG、ESR1等。预测茯苓-白术药对活性成分通过“Viral carcinogenesis”“PI3K-AKT signaling pathway”“Proteoglycans in cancer”等信号通路发挥作用。结论：茯苓-白术药对通过多成分、多靶点、多途径治疗胃癌,可通过靶向于PI3K-AKT信号通路及促分裂原活化的蛋白激酶3蛋白表达参与细胞增殖、侵袭,为进一步研究茯苓-白术药对治疗胃癌奠定了坚实基础。     

Immunomagnetic enrichment of disseminated tumor cells in bone marrow and blood of breast cancer patients by the Thomsen-Friedenreich-Antigen

Purpose The presence of disseminated tumor cells in the bone marrow (DTC-BM) of breast cancer patients has shown independent prognostic impact. Immunomagnetic enrichment of such cells is an approach to increase the number of detected cells with limited sample volume, especially for circulating tumor cells (CTCs) in blood. The Thomsen-Friedenreich (TF) antigen (CD 176) is a specific oncofetal carbohydrate epitope (Galβ1-3GalNAcα-O) expressed on the surface of various carcinomas. Own studies demonstrated a nearly complete TF expression on DTC-BM, indicating its suitability as marker for immunomagnetic enrichment. Methods BM samples of 65 and peripheral blood samples of 11 breast cancer patients were examined immunocytochemically by staining with the anti-Cytokeratin antibody A45-B/B3 before and after immunomagnetic enrichment. Enrichment was done by incubation with the primary antibody TF 2 (IgM), followed by secondary magnetically labelled rat-anti mouse IgM. Cytospin slides were screened manually by bright-field microscopy. Results 15/65 pts (23%) showed DTC-BM in primary screening with a median of 2/2 mio cells (range 1–10). By enrichment, a median of 23.3 mio cells (0.8–218) could be analysed, increasing positivity to 72% (47/65 pts) with a med. of 4 DTCs (1–105, P < .0001). Blood from 1/11 pts before and 5/11 (45%) after enrichment showed CTCs (med. 2, 1–20), at a med. of 12.4 mio (2.6–38.5) cells analysed. Comparing BM and blood of the same patients after enrichment, 5 were positive in both compartments, 4 showed DTC-BM without presence of CTCs. Conclusion The positive immunomagnetic enrichment technique with TF-antibodies enables to analyse larger sample volumes and increase tumor cell detection rate. This could allow monitoring and characterisation of CTCs as targets for therapies.     

药用动植物重金属富集作用的利与弊

目的探讨药用动植物中重金属的富集作用,促进中药材的合理应用。方法对近10余年来药用动植物重金属富集作用的相关研究进行综述,重点比较药用动植物富集重金属作用的利与弊。结果有许多临床常用的中药材的原植物或原动物对重金属离子都具有超富集作用或者是对重金属离子具有高耐受性。结论在今后的GAP关键技术的研究中要注意考查药材对重金属的生理特性,并有针对性地制定防范策略,确保中药材生产的优质高产和临床用药的安全有效。     

南芪北芪抗应激与免疫调节作用的研究

目的观察南芪与北芪在抗应激、免疫调节及补血方面效果的差异。方法通过抗疲劳实验、耐常压缺氧实验、耐脑缺血缺氧实验及对失血性和环磷酰胺性贫血的保护作用等实验考察南、北芪抗应激及补血作用；通过巨噬细胞吞噬功能、血清溶血素水平和皮肤迟发性过敏实验观察两者对免疫调节功能的影响。结果南、北芪均可延长小鼠负重游泳、耐常压缺氧及耐脑缺血缺氧的时间；升高贫血小鼠的红细胞和血红蛋白；提高巨噬细胞吞噬功能、血清溶血素水平，增强皮肤迟发性过敏反应。两者药效强弱无统计学差异。结论南、北芪均具有提高小鼠抗应激的能力、增强免疫功能及补血作用，作用效果无显著性差异     

Multidimensional endotyping using nasal proteomics predicts molecular phenotypes in the asthmatic airways

1. Download : Download high-res image (254KB)
2. Download : Download full-size image

     

Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction

Aims

In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

Methods and results

Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.8% females), and registry patients ineligible for RCT inclusion (n = 20 810; 30.2% females). Clinical endpoints included all-cause mortality, cardiovascular mortality, and first HF hospitalization at 1 year. Males and females were equally eligible for trial enrolment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups, respectively. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (standardized mortality ratio [SMR] 0.72; 95% confidence interval [CI] 0.62–0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09–1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95% CI 0.76–1.03 for females, SMR 1.43; 95% CI 1.33–1.53 for males).

Conclusion

Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and female trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries.