An Automatic Method Framework for Personalized Knee Prosthetic Modeling Based on Kinematic Geometry.

The shape of a knee prosthesis has an important impact on the effect of total knee arthroplasty. Comparing to a standard common prosthesis, the personalized prosthesis has inherent advantages. However, how to construct a personalized knee prosthesis has not been studied deeply. In this paper, we present an automatic method framework of modeling personalized knee prostheses based on shape statistics and kinematic geometry. Firstly, the average healthy knee model is established through an unsupervised process. Secondly, the sTEA (Surgical Transecpicondylar Axis) is calculated, and the average healthy knee model is resized according to it. Thirdly, the resized model is used to simulate the knee's motion in a healthy state. Fourthly, according to the target patient's condition, an excising operation is simulated on both patient's knee model and the resized model to generate an initial knee prosthesis model. Finally, the initial prosthesis model is adjusted according to the simulated motion results. The average maximum error between the resized healthy knee model and the patient's own knee model is less than 2 mm, and the average maximum error between the motion simulation results and actual motion results is less than 3 mm. This framework can generate personalized knee prosthesis models according to the patient's different conditions, which makes up for the deficiencies of standard common prostheses.

Holomycin, a novel NLRP3 inhibitor, attenuates cartilage degeneration and inflammation in osteoarthritis.

The contribution of the NLRP3 inflammasome in osteoarthritis (OA) pathogenesis has been uncovered in recent years. Holomycin (HL) has recently been identified as a novel NLRP3 inflammasome inhibitor. Herein, we aimed to explore the benefits of HL for OA. A chondrocyte-macrophage co-culture system and the destabilization of the medial meniscus (DMM) mouse model were established to study the effect of HL on OA in vitro and in vivo. ECM degradation-related proteins (MMP-13, aggrecan, and Collagen II) were detected by Western blot (WB) and immunohistochemistry (IHC). The chondrocyte senescence was determined by cell cycle, p16 and p21 expressions, and SA-ß-Gal staining. The cartilage degeneration was evaluated by OARSI score and Safranin O and H&E staining. Inflammation and NLRP3 inflammasome activation were investigated via RT-PCR, ELISA, WB, and IHC. In vitro studies showed that IL-1ß stimulation caused a significant increase of MMP13, p16, p21, and ß-galactosidase expressions, a G1-phase arrest, and a down-regulation of aggrecan and Collagen II in chondrocytes, and the increased expressions of IL-6, CXCL-1, IL-1ß, NLRP3, and Caspase 1 p20 in both chondrocyte and macrophage. Meanwhile, HL administration could partly reverse these effects induced by IL-1ß. In DMM mouse models, intra-articular administration of HL alleviated cartilage degeneration and inflammation, as evidenced by the decrease of OARSI score and MMP13, p16, p21, Collagen II, IL-6, and CXCL-1 expressions and the restoration of chondrocyte number, proteoglycan, and MMP13 expression in cartilage tissues. This study identified HL as a promising agent for OA.

A rapid and simple high-performance liquid chromatography assay for the leflunomide metabolite, teriflunomide (A77 1726), in renal transplant recipients.

Leflunomide (Arava), a drug with immunosuppressive and antiviral effects, is being used in renal transplant recipients, primarily for its action against BK polyomavirus (BKV), which affects 1% to 10% of renal transplant recipients and often causes failure of grafted kidneys. Leflunomide effects are solely due to an active metabolite, teriflunomide (formerly A77 1726). Trough blood concentrations of teriflunomide exceeding 40 microg/mL (148 micromol/L) are associated with progressive clearance of BKV. Toxic effects become increasingly apparent at higher concentrations. We have developed a rapid, simple, and robust high-performance liquid chromatography (HPLC) method for therapeutic monitoring of teriflunomide in renal transplant recipients. Sample preparation is rapid, and each HPLC separation takes about 7 minutes. Intraday and interday coefficients of variation were 1.5% or less and 5.6% or less, respectively. The method was linear to 200 microg/mL (740 micromol/L), which is well above teriflunomide concentrations that are likely to be observed.