BACKGROUND:With social progress,the incidence rate of knee osteoarthritis is getting higher and higher in the face of the rapidly developing aging problem in the social population,and the number of total knee replacement operations is gradually increasing. OBJECTIVE:To study the relationship between prosthesis size and stress shielding by improving the tibial prosthesis base. METHODS:A female patient with severe knee osteoarthritis was selected.Based on Mimics,through extracting the bone structure of the knee joint and simulating the total knee replacement surgery,osteotomy,positioning,and implantation operations were carried out to establish the geometric modeling of the total knee replacement prosthesis(including the femoral prosthesis,tibial bracket,and tibial pad),and improve the design of the tibial prosthesis base,analyze the effect of different tibial prosthesis bases on stress shielding of surrounding bone tissue. RESULTS AND CONCLUSION:(1)Compared with single-stem tibial intramedullary stem prosthesis,the design of four-post tibial intramedullary stem prosthesis created a certain degree of stress shielding around the short stem.However,compared with a thicker single long stem,this stress shielding effect was significantly reduced,and the load was evenly distributed among the four short stems,so there was no stress concentration at the bottom of the pile.(2)The design with a rectangular hole in the middle not only provided relatively good stability,but also helped to reduce stress shielding of cancellous bone to a certain extent,with a reduction rate of 77.5%.(3)Compared with a single-stem tibial intramedullary stem prosthesis,both the four-post tibial intramedullary stem prosthesis and the four-post tibial intramedullary stem prosthesis with a hole in the middle have good stability,which can reduce stress shielding to a certain extent without causing stress concentration,providing theoretical guidance for the design of the tibial intramedullary stem.

BACKGROUND:Total knee arthroplasty serves as an effective intervention for the treatment of late-stage knee joint disorders.However,prosthetic liners are prone to wear and failure due to internal stress variations,resulting in limited lifespan and decreased postoperative patient activity.Addressing how to enhance prosthetic design to meet a broader range of patient needs constitutes a significant focus in prosthesis research. OBJECTIVE:Based on the morphological design of the meniscus,we propose an asymmetric design prosthesis and compare it with a symmetric posterior stabilized prosthesis.The stress distribution patterns and variations in the contact area of the liners for both prostheses were analyzed to explore whether the asymmetric prosthesis design offers advantages over the symmetric design. METHODS:Using the finite element method,we simulated the osteotomy and prosthesis assembly in a knee osteoarthritis patient.Two different prostheses(asymmetric design and posterior stabilized)were employed to establish post-total knee arthroplasty knee joint models.Under flexion conditions at 0°,10°,20°,and 30°,we investigated the Mises stress on the femoral and tibial components as well as the liner.Additionally,by comparing the contact area on the inner and outer sides of the liner,we aimed to explore the changes in biomechanics and alterations in motion behavior in the post-total knee arthroplasty knee joint. RESULTS AND CONCLUSION:(1)Throughout the flexion range from 0 to 30 degrees,the Mises stress peak on the liner exhibited a trend of initial decrease followed by an increase,with the stress on the medial side consistently surpassing that on the lateral side.(2)In comparison to the posterior stabilized prosthesis,the asymmetrically designed prosthesis demonstrated smaller stress peaks.At a flexion angle of 30 degrees,the Mises stress peak values of the medial and lateral parts of the asymmetric prosthesis were 15.81 MPa and 11.95 MPa,and those of the posterior stabilization prosthesis were 16.70 MPa and 13.76 MPa.The difference of Mises stress on the medial part was 5.33%,and the difference of Mises stress on the lateral part was 13.15%.Comparing the peak Mises stress on the femoral and tibial components,the asymmetric component was always lower than the posterior stable component during knee flexion.(3)In the upright position at 0 degrees,the medial contact area of the posterior stabilization prosthesis was 17.96 mm2,and the lateral contact area was 34.10 mm2.The contact area on the inner and outer sides of the asymmetric design prosthesis liner was 105.47 mm2 and 107.80 mm2,respectively,indicating a larger contact area with a smaller difference between the inner and outer sides.(4)These results suggest that the biomechanical performance of the asymmetric prosthesis is superior,contributing to the maintenance of knee joint stability and improved joint mobility.This design,to a certain extent,mimics the rotational motion mechanism of the knee joint about the medial condyle as an axis,making it a more effective choice for knee joint prosthesis selection.

Objective:To investigate the protective effect of racanisodamine on lung injury in mice exposed to irradiation.Methods:C57BL/6 mice were randomly divided into control group, racanisodamine group, 18 Gy irradiation group (model group) and racanisodamine combined with 18 Gy irradiation group (treatment group), with 5 mice in each group. The mice in the treatment group received racanisodamine (5 mg/kg) intraperitoneally 3 d before irradiation and contained the whole experiments. Then, single chest irradiation of 18 Gy X-rays was performed both in the model and treatment groups. The racanisodamine group and treatment group received racanisodamine intraperitoneally once a day until 6 weeks after irradiation. The mice were killed at 6 weeks after irradiation. The lung histopathology was observed by HE staining. Serum and bronchial alveolar lavage fluid (BALF) inflammatory cytokines such as TNF-α, IL-1β and IL-6 were determined by ELISA method. Cell senescence was detected by SA-β-Gal staining. The expressions of Nrf2, p-Nrf2 and p62 in lung tissue were performed by immunehistochemistry and Western blot assays.Results:Compared with the model group, the scores of HE staining were decreased ( t=8.66, P<0.01), the number of infiltrated inflammatory cells in BALF were decreased ( t=10.70, P<0.01), and protein concentration in BALF had lower levels ( t=6.75, P<0.01), the serum TNF-α, IL-1β and IL-6 were decreased significantly ( t=8.17, 4.58, 6.54, P<0.01), the activity of SA-β-gal was decreased, and the expressions of Nrf2, p-Nrf2 were enhanced ( t=6.42, 7.30, P<0.01), while the expression of p62 was reduced ( t=4.62, P<0.01) in the treatment group. Conclusions:Racanisodamine plays the protective effect of radiation-induced lung injury by alleviating inflammation associating with the activating of Nrf2-related pathway, which reversed radiation-induced cell senescence.

Objective:To investigate the protective effect of racanisodamine (654-2) on lung epithelial cell injury induced by X-ray in mice and unravel the underlying mechanism.Methods:Mouse alveolar epithelial cells MLE-12 were used to establish radiation-induced lung injury (RILI) model in vitro and divided into 4 groups as follows: control (no irradiation), radiation (16 Gy radiation), treatment 1 (16 Gy radiation + 2 μmol/L 654-2), treatment 2 (16 Gy radiation + 10 μmol/L 654-2), and inhibitor (16 Gy radiation + 10 μmol/L 654-2 + 2 μmol/L ML385), respectively. Cells were sampled at different time points after radiation. Cell senescence was detected with senescence-associated β-galactosidase (SA-β-Gal) staining. Cell colony-forming ability was detected to observe the recovery capability of cells after treatment. The expression levels of p21, p16, phosphorylated histone H2AX(γH2AX), nuclear factor erythroid-2 related factor 2 (Nrf2), Nrf2 Ser40 site phosphorylation (p-Nrf2), p62, heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) proteins were measured by Western blot. Cell apoptosis and the production of intracellular reactive oxygen species (ROS) were determined by flow cytometry. The expression levels of glutathione (GSH) and superoxide dismutase (SOD) were detected according to the manufectuer instructions. The expression levels of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) mRNA were determined by real time reverse transcription PCR. Measurement data were expressed as Mean ±SD. Comparison between two groups was conducted by independent sample t-test, and comparison among multiple groups was performed by one-way ANOVA. Results:Compared with the radiation group, the proportion of cells with positive staining of SA-β-Gal was significantly lower and cell senescence were alleviated in the treatment 1 and 2 groups (all P<0.001). Compared with the radiation group, the expression level of γH2AX protein was significantly down-regulated ( P=0.037), cell apoptosis rate was significantly decreased ( P=0.026), the proliferation capacity of MLE-12 was enhanced ( P=0.004), GSH ( P=0.002) and SOD ( P<0.001) activity was enhanced and ROS production was declined ( P=0.001) in the treatment 2 group. The expression levels of Nrf2 and p-Nrf2 in total protein were up-regulated over the time of 654-2 intervention. Meanwhile, the expression levels of antioxidant proteins of NQO1 and HO-1 were up-regulated and that of GCLC and GCLM mRNA was also up-regulated. There were no significant differences in the number of cells with positive staining of SA-β-Gal ( P=0.145) and ROS production ( P=0.317) between the inhibitor and radiation groups after supplement of ML385, small-molecule inhibitor of Nrf2. Conclusion:654-2 can activate the Nrf2 pathway, enhance cell antioxidant capacity and inhibit cell senescence, thereby playing a protective role on radiation- induced lung injury.