RESCUE BT Trial Investigators E ndovascular treatment has been shown to significantly increase the reperfusion rate and improve the functional outcomes of patients with acute ischemic stroke due to large vessel occlusion. [1][2][3][4] However, endovascular thrombectomy has historically failed to yield successful reperfusion in approximately 30% of patients. 5 Unsuccessful reperfusion likely arises in part from mechanical thrombectomy devices causing traumatic damage to the vascular endothelium with subendothelial matrix exposure, leading to platelet activation, adhesion, and aggregation and potentially resulting in reocclusion and thromboembolic complications. 6,7 Tirofiban, a highly selective nonpeptide platelet glycoprotein IIb/IIIa inhibitor with a relatively short half-life that can reversibly prevent platelet aggregation, has been proven to reduce the risk of thrombotic complications during percutaneous coronary intervention. [8][9][10] Given the benefit of treatment of acute coronary syndromes, a growing number of studies have evaluated tirofiban as an adjunctive treatment in patients with large vessel occlusion ischemic stroke IMPORTANCE Tirofiban is a highly selective nonpeptide antagonist of glycoprotein IIb/IIIa receptor, which reversibly inhibits platelet aggregation. It remains uncertain whether intravenous tirofiban is effective to improve functional outcomes for patients with large vessel occlusion ischemic stroke undergoing endovascular thrombectomy.OBJECTIVE To assess the efficacy and adverse events of intravenous tirofiban before endovascular thrombectomy for acute ischemic stroke secondary to large vessel occlusion.DESIGN, SETTING, AND PARTICIPANTS This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 55 hospitals in China, enrolling 948 patients with stroke and proximal intracranial large vessel occlusion presenting within 24 hours of time last known well.

CD133 is widely expressed in colorectal cancer (CRC) tissues and cell lines. This protein has been used as a marker of CRC cancer stem cells, although the function and mechanism of CD133 in CRC invasion and metastasis remain unclear. In our study, we examined the role of CD133 in CRC invasion in vitro and investigated the mechanism involved in CD133-related invasion. CD133(high) and CD133(low) HCT116 cells were isolated, and the proliferation and invasive ability of these two subpopulations were tested. CD133(high) HCT116 cells exhibited greater proliferation and invasion compared with CD133(low) HCT116 cells. CD133 knockdown (using CD133 small-interfering [si]RNA) inhibited the invasive activity of CD133si-HCT116 cells. For the first time, we found that the expression of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) was down-regulated in CD133si-HCT116 cells. In addition, for the TIMP-2si-HCT116 cells (transfected with TIMP-2 siRNA), in vitro invasion was significantly decreased, whereas the expression of CD133 remained unchanged. Finally, the metalloproteinase 2 and MEK/ERK signaling pathways were examined, and no significant change was observed after the knockdown of CD133 or TIMP-2 in HCT116 cells. In conclusion, we demonstrated that CD133 plays an important role in HCT116 cell invasion, and for the first time, we found that CD133 knockdown significantly down-regulated TIMP-2 expression, which suggests that CD133 affects the invasive ability of HCT116 cells by regulating TIMP-2.

The aim of the present study was to investigated the construction of polycaprolactone-lecithin (PCL-L) electrospun fibers as a novel scaffold material for a tissue-engineered ureter. The effect of bone marrow mesenchymal stem cells (BM-MSCs) on the neovascularization of the scaffolds and the viability of planted urothelial cells (UCs) on PCL-L were also studied. UCs were obtained from New Zealand rabbit bladders, cultured and then seeded onto the lumen of the tubular scaffolds before being subcutaneously transplanted into the space of nude mice. The cultured UCs showed vacuolar degeneration after 7 days of transplantation and they gradually degraded thereafter. To facilitate the regeneration of the tissue-engineered ureter and the survival of UCs in the implant, MSCs were seeded into the tubular grafts by rolling up the nanofibrous membrane, followed by the seeding of UCs. This facilitated the survival of the UCs, which formed several cellular layers after 30 days. The mean microvessel density was significantly increased in tissues seeded with MSCs. Cell-tracking experiments revealed that the transplanted MSCs did not integrate directly into capillaries for angiogenesis. Our results demonstrated that the PCL-L electrospun fibrous scaffold has a high potential for a tissue-engineered ureter especially when seeded with BM-MSCs, which enhanced angiogenesis.

Background: Deteriorated bone-graft interaction at the tunnel entrance following ACL reconstruction (ACLR) is considered one of the primary causes of long-term tunnel enlargement and graft wear. Methods have been introduced to improve the long-term outcome, such as novel graft materials or alternative fixation methods, but have been met with varying degrees of success. This study aims to design a protection liner to improve the bonegraft interaction at the tunnel entrances. Methods: A finite element model of a human cadaveric knee was used to simulate traditional ACLR and ACLR using the protection liner. Stress distribution around the tunnel entrances and on the ACL graft were calculated under a combined loading of 103 N anterior tibial load, 7.5 Nm internal tibial moment, and 6.9 Nm valgus tibial moment at a joint flexion angle of 20°. Results were compared between the traditional ACLR and ACLR using a double liner (femoral and tibial) setup, as well as between the ACLR using a double liner setup and a single liner (femoral side) setup. Different materials (PEEK, Ti-6Al-4V, CoCrMo) for the liner were also evaluated. Results: The traditional ACLR resulted in concentrated stress on the graft where it contacted the tunnel entrance. Correspondingly, there were stress concentrations at the distal posterior zone of the femoral tunnel entrance and medial posterior zone of the tibial tunnel entrance, while the other zones suffered from a stress reduction. Use of the protection liner reduced the stress concentration around the tunnel entrances by up to 89% and increased the stress at the unloaded zones by up to 106%. Also, stress concentration on the graft was slightly decreased (15.4 vs 15.1 MPa) after using the liner. The single liner setup increased the stress concentration around the tibial tunnel entrance. Stiffer materials improved the stress distribution around tunnel entrances but had little effect on the stress on the graft. Conclusions: The novel protection liner can improve the stress distribution on the graft and at the tunnel entrances, which may be beneficial for improving the clinical outcome of ACLR.