[Acupuncture of revised acupoint combination around the skull base for post-stroke mild cognitive impairment: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of acupuncture of revised acupoint combination around the skull base in treating post-stroke mild cognitive impairment (PSMCI), and preliminary explore its action mechanism. METHODS: A total of 76 PSMCI patients were randomly divided into an observation group (38 cases, 4 cases dropped off) and a control group (38 cases, 3 cases dropped off, 1 case was removed). In the observation group, acupuncture of revised acupoint combination around the skull base (bilateral Fengchi [GB 20], Wangu [GB 12], Tianzhu [BL 10] and Yamen [GV 15], Baihui [GV 20]) was used for treatment. In the control group, 8 non-meridian and non-acupoint points at the distal end were selected for shallow puncture treatment. Retaining the needles of 30 min, once every other day,3 times a week for 4 weeks in both groups. The scores of Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), Barthel index (BI) and serum levels of cystatin C (Cys-C) and homocysteine (Hcy) were compared in the two groups before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the scores of MoCA were increased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was higher than that in the control group (P<0.05). The scores of MMSE and BI were increased compared with those before treatment in the observation group (P<0.05), and the score of MMSE in the observation group was higher than that in the control group (P<0.05). After treatment, the serum levels of Cys-C and Hcy were decreased compared with those before treatment in the observation group (P<0.05), and lower than those in the control group (P<0.05). After treatment, the serum level of Cys-C was increased compared with that before treatment in the control group (P<0.05). The total effective rate of the observation group was 88.2% (30/34), which was higher than 32.4% (11/34) of the control group (P<0.05). CONCLUSION: Acupuncture of revised acupoint combination around the skull base can improve cognitive function and daily living ability of PSMCI patients, which may be related to the down regulation of serum levels of Cys-C and Hcy.

Chemically Edited Exosomes with Dual Ligand Purified by Microfluidic Device for Active Targeted Drug Delivery to Tumor Cells.

Exosomes, which are lipid membrane-bound nanovesicles (50-150 nm in diameter), have aroused extensive attention for their potential applications in invasive molecular and stand for a new therapeutic delivery system. However, they are limited by poor targeting ability and a lack of efficient isolation techniques. Here, we present a three-dimensional nanostructured microfluidic chip, in which arrays of micropillars were functionalized with crisscrossed multiwall carbon nanotubes by chemical deposition, to capture exosomes with high efficiency through a combination of a specific recognition molecule (CD63) and the unique topography of the nanomaterials. As is proven, this nanostructured interface substantially made the immuno capturing of exosomes more efficient. A high percentage of intact vesicles <150 nm were readily purified. As a further application, we added functionality to the exosomes by a chemical editing approach for targeted drug delivery. Donor cells were labeled chemically with dual ligands (biotin and avidin) in the phospholipid membrane and encapsulated drugs in the cytosol. Though the engineered donor cells secreted exosomes, the dual ligands, together with the drugs, were inherited by the exosomes, which were then isolated with the microfluidic chip. Then, the isolated exosomes were used as drug delivery vehicles and showed strong targeting abilities to tumor cells and highly efficient receptor-mediated cellular uptake when exposed to recipient cells. Thus, the anticancer effect of chemotherapeutic drugs was improved significantly. It suggested that this platform could provide a useful tool for isolating intact exosomes with high efficiency and exploiting their natural carrier function to deliver chemotherapeutic drugs to tumor cells with increased efficacy and targeting capacity.

Single Cell Chemical Proteomics with Membrane-Permeable Activity-Based Probe for Identification of Functional Proteins in Lysosome of Tumors.

Proteomics at single-cell resolution can help to identify the heterogeneity among cell populations, shows more and more significance in current chemistry and biology. In this work, we demonstrated a new single cell chemical proteomic (SCCP) strategy with a membrane-permeable activity-based probe (ABP) to characterize the functional proteins in lysosome located in the cytosol. The ABP targeted to the cysteine cathepsin family protein, CpFABP-G, was designed for cysteine cathepsins labeling. The labeled HeLa cell of a cancer cell line was injected into a capillary and was lysed by SDS solution with heating. The lysate was then online readout by capillary electrophoresis-laser-induced fluorescence method. Due to the employment of highly specified ABP kicking out the uncorrelated proteins, the expression of cysteine cathepsins in individual HeLa cells was easily detected, and heterogeneity among those HeLa cells was readily discriminated. Further work was concentrated on SCCP analysis of the mouse leukemia cell of monocyte macrophage (RAW264.7). It was for the first time identifying two expression modes of cysteine cathepsins in RAW264.7, which could be undermined by the analysis of cell populations. We believed that SCCP would be one of the powerful alternatives for proteomics at single-cell resolution.