Simultaneous Detection of Two Extracellular Vesicle Subpopulations in Saliva Assisting Tumor T Staging of Oral Squamous Cell Carcinoma.

Extracellular vesicles (EVs), acting as important mediators of intercellular communication, play an essential role in physiological processes, which have unique potential in the medical field. However, the heterogeneity of EVs limits their development for disease diagnosis and therapy, making the EV subpopulation analysis extremely valuable. In this article, a simple microfluidic approach was presented for the on-chip specific isolation and detection of two phenotypes of EVs (Annexin V+ EGFR+ EVs and Annexin V- EGFR+ EVs) based on different biomolecule-modified magnetic nanospheres and a fluorescence labeling technique. Combined with the control of the magnetic field in the microzone and fluid flow, it was easy to form two separate functional regions in the chip to capture different EV subpopulations. This method was successfully applied to the tests of clinical saliva samples in 75 oral squamous cell carcinoma (OSCC) patients and 10 healthy people. The results showed that the total level of EGFR+ EVs was much higher in OSCC patients that in healthy people. Meantime, the ratio of Annexin V+ EGFR+ EVs to Annexin V- EGFR+ EVs was found to be negatively correlated with tumor T stage of OSCC patients with a statistical difference, which suggested the ratio as a clinical index for monitoring the progression of OSCC in real time based on a noninvasive method. The approach provided a novel idea for evaluating the tumor T stage of OSCC and a powerful tool for clinical application.

Three-Dimensional Magnetic Chip with Extracorporeal Circulation for Circulating Tumor Cell In Vivo Detection and Tumor Growth Inhibition.

Liquid biopsy technology involves taking samples from body fluids in a minimally invasive way and analyzing tumor markers to achieve early diagnosis and efficacy evaluation of tumors. The development of real-time cancer diagnosis and treatment strategies based on liquid biopsy technology is of great significance to cancer management. This paper described an extracorporeal circulation based on a three-dimensional (3D) magnetic chip (3DMC-system) for in vivo detection and real-time monitoring of circulating tumor cells (CTCs). Utilizing biofunctionalized magnetic nanospheres (MNs) with CTC recognition function, this 3DMC-system could effectively achieve the real-time monitoring of CTCs in vivo with good stability and strong anti-interference. Compared with in vitro CTC detection, in vivo detection could not only detect more CTCs but also detect the presence of CTCs in the blood at an early stage of the tumor, when tumor metastasis is not observed in imaging. In addition, due to the flexibility of the chip design, the system can easily add a treatment module to integrate cancer diagnosis and treatment together. With good biocompatibility and high stability, this 3DMC-system is expected to provide a new personalized medical program for cancer patients.

One-to-Many Single Entity Electrochemistry Biosensing for Ultrasensitive Detection of microRNA.

Single-entity electrochemistry (SEEC), a promising method for biosensing, has an intrinsic limitation on sensitivity since at most one colliding entity can be successfully triggered by one target. Here, we take advantage of one-to-many (1:n) signal amplification to develop a new single-entity electrochemistry biosensing (SEECBS), integrating satellite magnetic nanoparticle (MN)-DNA-Pt nanoparticle (NP) conjugates, duplex-specific nuclease (DSN) assisted Pt NPs releasing with stabilization, and effective collision of small sized and nearly naked Pt NPs. Compared with conventional SEECBS, the 1:n SEECBS can successfully enrich ∼2 nM Pt NPs by adding 50 aM microRNA (miRNA), in other words, ∼4 × 107 Pt NPs can be triggered by one target. The proposed SEECBS allows the detection of 47 aM miRNA-21, nearly 6 orders of magnitude lower than the previous work, and discrimination of nontarget miRNAs containing even single-nucleotide mismatch. Besides, this method has also been successfully demonstrated for quantification of miRNA in different cell lines. Therefore, the proposed method holds great potential for the application of SEECBS in early diagnosis and prognosis monitoring of cancer.

Magnetic Chip Based Extracorporeal Circulation: A New Tool for Circulating Tumor Cell in Vivo Detection.

In vivo detection of circulating tumor cells (CTCs) which inspect all of the circulating blood in body seems to have more advantages on cell capture, especially in earlier cancer diagnosis. Herein, based on in vivo microfluidic chip detection system (IV-chip-system), an extracorporeal circulation was constructed to effectively detect and monitor CTCs in vivo. Combined with microfluidic chip and immunomagnetic nanosphere (IMN), this system not only acts as a window for CTC monitoring but also serves as a collector for further cancer diagnosis and research on CTCs. Compared with the current in vivo detection method, this system can capture and detect CTCs in the bloodstream without any pretreatments, and it also has a higher CTC capture efficiency. It is worth mentioning that this system is stable and biocompatible without any irreversible damage to living animals. Taking use of this system, the mimicked CTC cleanup process in the blood vessel is monitored, which may open new insights in cancer research and early cancer diagnosis.

Continuous magnetic separation microfluidic chip for tumor cell in vivo detection.

Continuously recording the dynamic changes of circulating tumor cells (CTCs) is crucial for tumor metastasis. This paper creates a continuous magnetic separation microfluidic chip that enables rapid and continuous in vivo cell detection. The chip shows its potential to study tumor cell circulation in the blood, offering a new platform for studying the cellular mechanism of tumor metastasis.

Effects of the information-knowledge-attitude-practice nursing model combined with predictability intervention on patients with cerebrovascular disease.

BACKGROUND: Cerebrovascular disease (CVD) poses a serious threat to human health and safety. Thus, developing a reasonable exercise program plays an important role in the long-term recovery and prognosis for patients with CVD. Studies have shown that predictive nursing can improve the quality of care and that the information -knowledge-attitude-practice (IKAP) nursing model has a positive impact on patients who suffered a stroke. Few studies have combined these two nursing models to treat CVD. AIM: To explore the effect of the IKAP nursing model combined with predictive nursing on the Fugl-Meyer motor function (FMA) score, Barthel index score, and disease knowledge mastery rate in patients with CVD. METHODS: A total of 140 patients with CVD treated at our hospital between December 2019 and September 2021 were randomly divided into two groups, with 70 patients in each. The control group received routine nursing, while the observation group received the IKAP nursing model combined with predictive nursing. Both groups were observed for self-care ability, motor function, and disease knowledge mastery rate after one month of nursing. RESULTS: There was no clear difference between the Barthel index and FMA scores of the two groups before nursing (P > 0.05); however, their scores increased after nursing. This increase was more apparent in the observation group, and the difference was statistically significant (P < 0.05). The rates of disease knowledge mastery, timely medication, appropriate exercise, and reasonable diet were significantly higher in the observation group than in the control group (P < 0.05). The satisfaction rate in the observation group (97.14%) was significantly higher than that in the control group (81.43%; P < 0.05). CONCLUSION: The IKAP nursing model, combined with predictive nursing, is more effective than routine nursing in the care of patients with CVD, and it can significantly improve the Barthel index and FMA scores with better knowledge acquisition, as well as produce high satisfaction in patients. Moreover, they can be widely used in the clinical setting.

A liquid biopsy-guided drug release system for cancer theranostics: integrating rapid circulating tumor cell detection and precision tumor therapy.

Theranostics combining precision diagnosis and concurrent therapy has attracted significant attention as a promising strategy against life-threatening cancer. Liquid biopsy provides a real-time assessment of cancer by the analysis of tumor biomarkers, among which circulating tumor cells (CTCs) have been widely used to monitor disease progression and therapeutic response. In this study, a liquid biopsy-guided drug release system (LBDR system) integrating cancer diagnostic and therapeutic functions on a magnetically controlled microfluidic platform is presented. Two kinds of magnetic nanospheres (MNs), recognition MNs and drug-loaded MNs, are loaded onto the microfluidic chip to integrate the rapid detection of CTCs and controlled drug release. When CTCs bind to aptamers on the recognition MNs, complementary strands (cDNAs) hybridized with the aptamers are released and then conjugated with drug-loaded MNs to further trigger the release of anti-cancer drugs. The amount of drug released is controlled according to the number of detected CTCs, which can provide effective treatment for individual patients according to the diagnostic results. This LBDR system provides a novel strategy for cancer therapy and may facilitate the development of personalized cancer therapy.

Incorporating luminescence-concentrating upconversion nanoparticles and DNA walkers into optical tweezers assisted imaging: a highly stable and ultrasensitive bead supported assay.

We incorporate three conceptual components including luminescence-concentrating upconversion nanoparticles, optical tweezers, and DNA walkers into bead carriers to establish a new imaging analysis.

Integrating optical tweezers with up-converting luminescence: a non-amplification analytical platform for quantitative detection of microRNA-21 sequences.

We report a single-microsphere based imaging assay method by integrating up-converting luminescence with optical tweezers for detecting microRNA-21 sequences. This method achieves a competitive detection limit of 12 fM with good selectivity and no dedicated signal amplification designs.

A chip assisted immunomagnetic separation system for the efficient capture and in situ identification of circulating tumor cells.

The detection of circulating tumor cells (CTCs), a kind of "liquid biopsy", represents a potential alternative to noninvasive detection, characterization and monitoring of carcinoma. Many previous studies have shown that the number of CTCs has a significant relationship with the stage of cancer. However, CTC enrichment and detection remain notoriously difficult because they are extremely rare in the bloodstream. Herein, aided by a microfluidic device, an immunomagnetic separation system was applied to efficiently capture and in situ identify circulating tumor cells. Magnetic nanospheres (MNs) were modified with an anti-epithelial-cell-adhesion-molecule (anti-EpCAM) antibody to fabricate immunomagnetic nanospheres (IMNs). IMNs were then loaded into the magnetic field controllable microfluidic chip to form uniform IMN patterns. The IMN patterns maintained good stability during the whole processes including enrichment, washing and identification. Apart from its simple manufacture process, the obtained microfluidic device was capable of capturing CTCs from the bloodstream with an efficiency higher than 94%. The captured cells could be directly visualized with an inverted fluorescence microscope in situ by immunocytochemistry (ICC) identification, which decreased cell loss effectively. Besides that, the CTCs could be recovered completely just by PBS washing after removal of the permanent magnets. It was observed that all the processes showed negligible influence on cell viability (viability up to 93%) and that the captured cells could be re-cultured for more than 5 passages after release without disassociating IMNs. In addition, the device was applied to clinical samples and almost all the samples from patients showed positive results, which suggests it could serve as a valuable tool for CTC enrichment and detection in the clinic.