Intervertebral disc degeneration (IDD) is characterized by the decrease of nucleus pulposus cells (NPCs).With the increase of the degree of degeneration, the reactive oxygen species (ROS) in nucleus pulposus tissue increases. Pyroptosis is a newly discovered form of cell death and its relationship with oxidative stress in NPCs remains unclear. This study was performed to investigate the mechanisms of pyroptosis of NPCs under oxidative stress. NPCs were isolated from IDD patients by surgical treatment. Pyroptosis related proteins like NLR family pyrin domain containing 3(NLRP3) and PYD and CARD domain containing (PYCARD) were detected by western blot, and membrane pore formation was observed by hochest33342/PI double staining or scanning electron microscope. The results showed that ROS induced the pyroptosis of NPCs and it depended on the expression of NLRP3 and PYCARD. The increased ROS level also increased transcription factor nuclear factor, erythroid 2 like 2 (NFE2L2, Nrf2) and the autophagy of NPCs, both of which attenuated the pyroptosis. In summary, ROS induces the pyroptosis of NPCs through the NLRP3/ PYCARD pathway, and establishes negative regulation by increasing autophagy and NFE2L2. These findings may provide a better understanding of the mechanism of IDD and potential therapeutic approaches for IDD treatment.

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To investigate the biocompatibility and bone ingrowth properties of a novel trabecular bone mimic porous tantalum scaffold which holds potential for bone tissue engineering, a novel three-dimensional, multiscale interconnected porous tantalum scaffold was designed and manufactured. The morphology of the novel scaffold was observed with the use of scanning electron microscopy (SEM) and industrial computerized tomography. Mesenchymal stem cells (MSCs) were cultured with novel porous tantalum powder, SEM was carried out for the observation of cell morphology and adhesion, and cytotoxicity was evaluated by the MTT assay. Canine femoral shaft bone defect models were established, and novel porous tantalum rods were used to repair the bone defect. Repair effects and bone integration were evaluated by hard tissue slice examination and push-out tests at the indicated time. We found that the novel porous tantalum scaffold is a trabecular bone mimic, having the characteristics of being three-dimensional, multiscaled, and interconnected. The MSCs adhered to the surface of tantalum and proliferated with time, the tantalum extract did not have a cytotoxic effect on MSCs. In the bone defect model, porous tantalum rods integrated tightly with the host bone, and new bone formation was found on the scaffold-host bone interface both 3 and 6 months after the implantation. Favorable bone ingrowth was observed in the center of the tantalum rod. The push-out test showed that the strength needed to push out the tantalum rod is comparable for both 3 and 6 months when compared with the normal femoral shaft bone tissue. These findings suggested that the novel trabecular bone mimic porous tantalum scaffold is biocompatible and osteoinductive, which holds potential for bone tissue engineering application.

Background: The application of tranexamic acid (TXA) in total hip arthroplasty (THA) and total knee arthroplasty (TKA) has brought momentous changes in blood management. However, the optimal regimen of TXA has not yet been identified. This study aimed to compare the efficacy of a three-day prolongedcourse of multiple-dose of TXA with a single pre-operative dose of TXA in patients who undergo THA and TKA.Method: We retrospectively analyzed two groups of consecutive patients who received primary unilateral THA and TKA from 2015 to 2017. One group received a three-day prolonged-course of multiple-dose of TXA, while another group received a single-dose of TXA. The primary outcomes included the changes in hemoglobin (Hb), estimated total blood loss (TBL), and transfusion rate; the secondary outcomes included the platelet (PLT) counts, inflammatory markers, and fibrinolysis parameters.Results: A total of 193 THA and 166 TKA procedures were included for comparison. Compared with the patients who received a single-dose of TXA, the patients who received a three-day prolonged-course of multiple-dose of TXA had smaller post-operative drops in Hb levels, which led to consistently significantly higher Hb levels in both THA and TKA. Therefore, the use of multiple-dose of TXA was associated with significantly lower maximum Hb drops and estimated TBL in both THA (24.58±11.43 vs. 30.38±11.33 g/L, P=0.001; 685.88±412.02 vs. 968.94±479.9 mL, P<0.0001) and TKA (18.04±9.75 vs. 27.24±10.99 g/L, P<0.0001; 497.35±291.03 vs. 816.51±354.38 mL, P<0.0001), and marginally reduced transfusion requirements (THA: 1/65 vs. 10/128; TKA: 0/70 vs. 2/96). The multiple-dose group also showed higher PLT counts, continuously reduced inflammatory responses, and significantly and durably attenuated fibrinolytic responses.Conclusions: A three-day prolonged-course of multiple-dose of TXA was consistently effective in reducing post-operative Hb drops, estimated TBL, inflammatory responses, and fibrinolytic responses, which could be recommended for clinical practice. However, these findings need to be confirmed by prospective studies.