The evaluation and treatment of acute anterior circulation occlusion stroke with high clot burden: Progressive stratified aspiration thrombectomy vs. stent retriever thrombectomy.

OBJECTIVE: To evaluate the safety and effectiveness of the progressive stratified aspiration thrombectomy (PSAT) in treatment of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). METHODS: 117 AIS-LVO patients with high clot burden who underwent emergency endovascular treatment were included. All patients were divided into two groups according to surgical technique: PSAT group, stent retriever thrombectomy (SRT) group. The primary outcome was the 90-day mRS, the secondary outcomes included recanalization rate, the 24-h and 7-day NIHSS, the 7-day symptomatic intracranial hemorrhage (SICH) rate and 90-days mortality. RESULTS: 65 patients underwent PSAT, and 52 patients underwent SRT. The PSAT group performed better than SRT group regarding the successful recanalization rate (86.3 % vs. 71.2 %, P < 0.05) and time from puncture to recanalization (70 min [IQR, 58-87 min] vs. 87 min [IQR, 68-103 min], P < 0.05). The 7-day NIHSS score of the PSAT group was lower than that of the SRT group (12 [10-18] vs. 12 [8-25], P < 0.05). It was worth noting that at the 90-day follow-up, the favorable functional outcome (mRS 0-2) rate of PSAT group was higher (P < 0.05). There was no significant difference in terms of the 24-h NIHSS score after surgery (15 [10-18] vs. 15 [10-22], P > 0.05), SICH (23.1 % vs. 26.9 %, P > 0.05) and mortality rate between the two groups (13.4 % vs. 19.2 %, P > 0.05). CONCLUSIONS: It is safe and effective to treat high clot burden AIS-LVO patients with PSAT, which has a better reperfusion rate and prognostic outcome than SRT.

Identification and Characterization of the Amphioxus Lck and Its Associated Tyrosine Phosphorylation-Dependent Inhibitory LRR Receptor.

Amphioxus (e.g., Branchiostoma belcheri, Bb) has recently emerged as a new model for studying the origin and evolution of vertebrate immunity. Mammalian lymphocyte-specific tyrosine kinase (Lck) plays crucial roles in T cell activation, differentiation and homeostasis, and is reported to phosphorylate both the ITIM and ITSM of PD-1 to induce the recruitment of phosphatases and thus the inhibitory function of PD-1. Here, we identified and cloned the amphioxus homolog of human Lck. By generating and using an antibody against BbLck, we found that BbLck is expressed in the amphioxus gut and gill. Through overexpression of BbLck in Jurkat T cells, we found that upon TCR stimulation, BbLck was subjected to tyrosine phosphorylation and could partially rescue Lck-dependent tyrosine phosphorylation in Lck-knockdown T cells. Mass spectrometric analysis of BbLck immunoprecipitates from immunostimulants-treated amphioxus, revealed a BbLck-associated membrane-bound receptor LRR (BbLcLRR). By overexpressing BbLcLRR in Jurkat T cells, we demonstrated that BbLcLRR was tyrosine phosphorylated upon TCR stimulation, which was inhibited by Lck knockdown and was rescued by overexpression of BbLck. By mutating single tyrosine to phenylalanine (Y-F), we identified three tyrosine residues (Y539, Y655, and Y690) (3Y) of BbLcLRR as the major Lck phosphorylation sites. Reporter gene assays showed that overexpression of BbLcLRR but not the BbLcLRR-3YF mutant inhibited TCR-induced NF-κB activation. In Lck-knockdown T cells, the decline of TCR-induced IL-2 production was reversed by overexpression of BbLck, and this reversion was inhibited by co-expression of BbLcLRR but not the BbLcLRR-3YF mutant. Sequence analysis showed that the three tyrosine-containing sequences were conserved with the tyrosine-based inhibition motifs (ITIMs) or ITIM-like motifs. And TCR stimulation induced the association of BbLcLRR with tyrosine phosphatases SHIP1 and to a lesser extent with SHP1/2. Moreover, overexpression of wild-type BbLcLRR but not its 3YF mutant inhibited TCR-induced tyrosine phosphorylation of multiple signaling proteins probably via recruiting SHIP1. Thus, we identified a novel immunoreceptor BbLcLRR, which is phosphorylated by Lck and then exerts a phosphorylation-dependent inhibitory role in TCR-mediated T-cell activation, implying a mechanism for the maintenance of self-tolerance and homeostasis of amphioxus immune system and the evolutionary conservatism of Lck-regulated inhibitory receptor pathway.

Sevoflurane Suppresses Colon Cancer Cell Malignancy by Regulating circ-PI4KA.

PURPOSE: To explore the effect of SEV on colon cancer cells through circ-PI4KA. METHODS: The RNA level of circular RNA_0062389, microRNA-331-3p and LIM and SH3 protein 1 was determined by quantitative real-time polymerase chain reaction. Protein expression was detected by Western blot. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide, cell colony formation and 5-ethynyl-29-deoxyuridine assays. Cell apoptosis was demonstrated using Annexin V-fluorescein isothiocyanate/propidium iodide double staining assay. Cell migration and invasion were detected by transwell assay. The target relationship between miR-331-3p and circ-PI4KA or LASP1 was predicted by starBase v2.0 online database, and identified by a dual-luciferase reporter assay. The effects between SEV treatment and circ-PI4KA knockdown on tumor formation were presented by in vivo tumor formation assay. RESULTS: Circ-PI4KA and LASP1 expressions were dramatically upregulated, while miR-331-3p was downregulated in colon cancer tissues and cells, respectively. SEV exposure significantly decreased the expression of circ-PI4KA and LASP1, but increased miR-331-3p expression. SEV inhibited cell proliferation, migration and invasion, and induced cell apoptosis by regulating circ-PI4KA. Furthermore, circ-PI4KA interacted with miR-331-3p, and miR-331-3p interacted with LASP1. SEV inhibited tumor growth by controlling circ-PI4KA in vivo. CONCLUSION: Circ-PI4KA attenuated SEV-treated colon cancer cell malignancy by upregulating LASP1 through binding to miR-331-3p, which provided a new mechanism for studying surgery-mediated therapy of colon cancer.