Molecular profiling of circulating extracellular vesicles (EVs) provides a promising noninvasive means to diagnose, monitor, and predict the course of metastatic breast cancer (MBC). However, the analysis of EV protein markers has been confounded by the presence of soluble protein counterparts in peripheral blood. Here we use a rapid, sensitive, and low-cost thermophoretic aptasensor (TAS) to profile cancer-associated protein profiles of plasma EVs without the interference of soluble proteins. We show that the EV signature (a weighted sum of eight EV protein markers) has a high accuracy (91.1 %) for discrimination of MBC, non-metastatic breast cancer (NMBC), and healthy donors (HD). For MBC patients undergoing therapies, the EV signature can accurately monitor the treatment response across the training, validation, and prospective cohorts, and serve as an independent prognostic factor for progression free survival in MBC patients. Together, this work highlights the potential clinical utility of EVs in management of MBC.
Tumor-derived extracellular vesicles (EVs) hold the potential to substantially improve noninvasive early diagnosis of cancer. However, analysis of nanosized EVs in blood samples has been hampered by lack of effective, rapid, and standardized methods for isolating and detecting EVs. To address this difficulty, here we use the electric-hydraulic analogy to design cascaded microfluidic circuits for pulsatile filtration of EVs via integration of a cell-removal circuit and an EV-isolation circuit. The microfluidic device is solely driven by a pneumatic clock pulse generator, allowing for preprogrammed, clog-free, gentle, high-yield, and high-purity isolation of EVs directly from blood within 30 minutes. We demonstrate its clinical utility by detecting protein markers of isolated EVs from patient blood using a polyethylene glycol–enhanced thermophoretic aptasensor, with 91% accuracy for diagnosis of early-stage breast cancer. The cascaded microfluidic circuits can have broad applications in the field of EV research.
Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.
To systemically evaluate the clinical efficacy of Fuke Qianjin tablets combined with antibiotics in the treatment of endometritis. The databases such as PubMed, CNKI, VIP and WanFang Data were searched to collect the randomized controlled trials(RCTs) about Fuke Qianjin tablets combined with antibiotics for endometritis since 2010. According to the Cochrane Reviewer's Handbook, two reviewers independently screened the literature, extracted the data and assessed the methodological quality of the included studies. Then the Meta-analysis was performed by using RevMan 5.3 software. 16 RCTs were included, involving 2 299 patients. Meta-analysis showed that after endometritis was treated by Fuke Qianjin tablets combined with antibiotics, the thickness of endometrium was higher than that in antibiotics group[MD=1.20, 95%CI (1.10, 1.29), P<0.000 01]; the occurrence rate of normal menstrual cycle[OR=1.46,95%CI (1.21, 1.77), P=0.000 1] and total effective rate [OR=1.19, 95%CI (1.15, 1.24), P<0.000 01] were increased ; the irregular vaginal bleeding [OR=0.21, 95%CI (0.14, 0.30), P<0.000 01] and inflammatory reactions[OR=0.19, 95%CI (0.10, 0.37)] were reduced. In short, Fuke Qianjin tablets combined with antibiotics have better effects than antibiotics alone for endometritis, so it is worthy to be recommended for clinical application.