BackgroundThe shape of the patella has been considered to be a predisposing factor resulting in patellar instability, but the effects of abnormal patella position during its development are unclear. The present study evaluated patellar morphological changes after patella instability and evaluated the influence of patellar instability on the patella shape.MethodsTwenty rabbits that were 2 months old were included in the study. The left knee of each rabbit, defined as the experimental group (N = 20 knees/group), underwent a medial soft tissue restraint release. The right knee of each rabbit, defined as the control group (N = 20 knees/group), did not undergo any surgical procedures. A CT scan was performed on each knee before surgery and 6 months post-surgery to measure the transverse diameter, thickness, Wiberg index, and Wiberg angle for analysis of the patellar morphological changes. Cross-specimen examination was conducted to evaluate the differences between the experimental group and the control group.ResultsThe four indices remained the same between the two groups before surgery. However, 6 months after surgery, the mean transverse diameter of the patellae in the experimental group was significantly longer than that in the control group (P < 0.001), while the mean thickness in the experimental group was not significantly greater than that in the control group (P = 0.314), resulting in a flattened shape. The Wiberg indices were not significantly different between the two groups. However, the mean Wiberg angle was higher in the experimental group than in the control group (P < 0.001), which resulted in a flattened articular surface of the patella.ConclusionThe sectional shape and articular surface of the patella became more flattened after patella instability in this study, which indicates that patella dysplasia could be caused by patella instability. Clinically, early intervention for adolescent patients with patella instability is important.
N-Demethylation is a key step in the preparation of a number of semisynthetic opiate pharmaceuticals. Herein we report a high-yielding, catalytic procedure for the N-demethylation of opiates which has a number of advantages over existing methods. For example, tetrasodium 5,10,15,20-tetra(4-sulfophenyl)porphyrinatoiron(II) (0.3 molar equiv) effected the transformation of codeine methyl ether to the corresponding N-nor analogue in 91% yield. The catalyst was readily removed and recycled.
The increased PD-L1 expression induces poorer prognosis in melanoma. The small molecule inhibitors of PD-1/PD-L1 pathways have been an encouraging drug development strategy because of good affinity and oral bioavailability without immunogenicity and immunotoxicities of PD-1/PD-L1 antibodies. In this study, we studied the effects of PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, on PD-1/PD-L1 binding and the cytokines secretion in human CD3 + cells in vitro. We also investigated the antitumor and immunomodulatory activity of PCC0208025 and the pharmacokinetics properties in B16-F10 melanoma-bearing mice. The results showed that PCC0208025 inhibited the PD-1/PD-L1 proteins binding, and rescued PD-L1-mediated inhibition of IFN-γ production in human CD3 + T cells in vitro. Furthermore, in B16-F10 melanoma-bearing mice, PCC0208025 presented the antitumor effects, enhanced IFN-γ levels in plasma, increased the frequency of CD3 + CD8 + T and CD8 + IFN-γ + T and the ratios of CD8 + /Treg, and deceased the CD4 + CD25 + CD127 low/− (Treg) number in tumor. Pharmacokinetics study found that PCC0208025 was absorbed and distributed into the tumors with much higher concentrations than those of the blockade against PD-1/PD-L1 binding. Our work suggests that PCC0208025 exhibited anti-tumor effects through inhibiting Treg expansion and increasing cytotoxic activity of tumor-infiltrating CD8 + T cells by the blockade of PD-1/PD-L1 binding, which may provide the pharmacological basis to develop small molecule inhibitors of PD-1/PD-L1 binding for PCC0208025 as a lead compound.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.