Diterpenoids with an unusual tricyclo[10.3.0.02,9]pentadecane skeleton from Pedilanthus tithymaloides as multidrug resistance modulators.

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.

Changes in hip joint contact stress during a gait cycle based on the individualized modeling method of "gait-musculoskeletal system-finite element".

OBJECTIVE: To construct a comprehensive simulation method of "gait-musculoskeletal system (MS)-finite element (FE)" for analysis of hip joint dynamics characteristics and the changes in the contact stress in the hip throughout a gait cycle. METHODS: Two healthy volunteers (male and female) were recruited. The 3D gait trajectories during normal walking and the CT images including the hip and femur of the volunteers were obtained. CT imaging data in the DICOM format were extracted for subjected 3D hip joint reconstruction. The reconstructed 3D model files were used to realize the subject-specific registration of the pelvis and thigh segment of general musculoskeletal model. The captured marker trajectory data were used to drive subject-specific musculoskeletal model to complete inverse dynamic analysis. Results of inverse dynamic analysis were exported and applied as boundary and load settings of the hip joint finite element in ABAQUS. Finally, the finite element analysis (FEA) was performed to analyze contact stress of hip joint during a gait cycle of left foot. RESULTS: In the inverse dynamic analysis, the dynamic changes of the main hip-femoral muscle force with respect to each phase of a single gait cycle were plotted. The hip joint reaction force reached a maximum value of 2.9%BW (body weight) and appeared at the end of the terminal stance phase. Twin peaks appeared at the initial contact phase and the end of the terminal stance phase, respectively. FEA showed the temporal changes in contact stress in the acetabulum. In the visual stress cloud chart, the acetabular contact stress was mainly distributed in the dome of the acetabulum and in the anterolateral area at the top of the femoral head during a single gait cycle. The acetabular contact area was between 293.8 and 998.4 mm2, and the maximum contact area appear at the mid-stance phase or the loading response phase of gait. The maximum contact stress of the acetabulum reached 6.91 MPa for the model 1 and 6.92 MPa for the model 2 at the terminal stance phase. CONCLUSIONS: The "Gait-MS-FE" technology is integrated to construct a comprehensive simulation framework. Based on human gait trajectories and their CT images, individualized simulation modeling can be achieved. Subject-specific gait in combination with an inverse dynamic analysis of the MS provides pre-processing parameters for FE simulation for more accurate biomechanical analysis of hip joint.

Prior Intra-articular Corticosteroid Injection Within 3 Months May Increase the Risk of Deep Infection in Subsequent Joint Arthroplasty: A Meta-analysis.

BACKGROUND: Intra-articular injections containing a corticosteroid are used frequently, and periprosthetic joint infection is a serious complication after total joint arthroplasty. There is debate regarding whether intra-articular corticosteroid injections before arthroplasty increase periprosthetic joint infection after surgery. QUESTIONS/PURPOSES: (1) Does a previous intra-articular corticosteroid injection increase the odds of infection after subsequent hip or knee arthroplasty? (2) Does this risk vary based on how soon before the arthroplasty (such as less than 3 months before surgery) the injection is administered? METHODS: Using the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to July 2021, we searched for comparative studies in English on patients who received intra-articular corticosteroid injections before arthroplasty and that tracked the frequency of infection after arthroplasty. We extracted data on the risk of infection after subsequent joint arthroplasty. The keywords included "corticosteroid," "steroid," "arthroplasty," "knee replacement," and "hip replacement." Eleven retrospective, comparative studies from four countries were included, of which 10 reported the specific diagnosis criteria and one did not. These articles included data on 173,465 arthroplasties in the hip or knee, as well as of 73,049 injections and 100,416 control patients. The methodologic quality of the included studies was evaluated according to the Newcastle-Ottawa Quality Assessment Scale; the articles' scores ranged from 6 to 7 (the score itself spans 0 to 9, with higher scores representing better study quality). We found no evidence of publication bias based on the Egger test, and tests of heterogeneity generally found heterogeneity, so a random-effects model was used of our meta-analyses. A meta-analysis was performed with Review Manager 5.3 software and Stata version 12.0 software. RESULTS: Overall, there were no differences in the odds of periprosthetic joint infection between the injection group and the control group among patients who received any kind of injection (odds ratio 1.22 [95% CI 0.95 to 1.58]; p = 0.12). However, in a subgroup analysis, there was a higher OR for postoperative PJI in patients with an intra-articular corticosteroid injection in the knee or hip within 3 months (OR 1.39 [95% CI 1.04 to 1.87]; p = 0.03). There were no differences in the infection risk in patients who had injections between 3 and 6 months before arthroplasty (OR 1.19 [95% CI 0.95 to 1.48]; p = 0.13) or between 6 and 12 months before arthroplasty. CONCLUSION: The current evidence suggests ipsilateral intra-articular corticosteroid injections within 3 months before arthroplasty were associated with an increased risk of periprosthetic joint infection during subsequent joint arthroplasty. We recommend against performing total joint arthroplasty on a patient who has received an intra-articular corticosteroid injection within 3 months. Further high-quality studies on this topic from registries, national databases, or insurance company data are still required to confirm and extend our findings. LEVEL OF EVIDENCE: Level III, therapeutic study.