Peripheral nerve regeneration and functional recovery remain major challenges in clinical practice. Nerve guidance conduits (NGCs) which can regulate the regenerative microenvironment are beneficial for peripheral nerve repair. Platelet-rich plasma (PRP) can secrete multiple growth factors to regulate the regenerative microenvironment. However, current administration methods of PRP are rapidly activated followed by the burst release of growth factors, causing low therapeutic efficiency in vivo. To overcome these disadvantages, a composite nerve conduit was fabricated by incorporating PRP into a gelatin methacrylate (GelMA) and sodium alginate (SA) hydrogel. The GelMA/SA-3/PRP-20 NGCs possess optimal mechanical properties, degradation rate, and superior biological performance. Importantly, GelMA/ SA-3/PRP-20 NGCs achieved the sustained release of two major growth factors (VEGF-A, PDGF-BB) from PRP. Moreover, the GelMA/SA-3/PRP-20 NGCs significantly promoted the migration of Schwann cells and the neovascularization of endothelial cells in vitro. While bridging 10 mm rat sciatic nerve defects, the GelMA/SA-3/PRP-20 NGCs promoted axonal regeneration and functional recovery of peripheral nerves. Therefore, the GelMA/SA-3/PRP-20 NGCs could regulate the regenerative microenvironment by sustained release of growth factors from PRP and shed new light on the clinical application of PRP in peripheral nerve repair.
High‐density lipoprotein (HDL), a well‐known atheroprotective factor, can be converted to proatherogenic particles in chronic inflammation. HDL‐targeted therapeutic strategy for atherosclerotic cardiovascular disease (CVD) is currently under development. This study aims to assess the role of methionine sulfoxide reductase A (MsrA) in abnormal HDL and its related disorders in scavenger receptor class B type I deficient (SR‐BI−/−) mice. First, we demonstrated that MsrA overexpression attenuated ROS level and inflammation in HepG2 cells. For the in vivo study, SR‐BI−/− mice were intravenously injected with lentivirus to achieve hepatic MsrA overexpression. High‐level hepatic MsrA significantly reduced the plasma free cholesterol contents, improved HDL functional proteins apolipoprotein A‐I (apoAI), apoE, paraoxonase1 (PON1), and lecithin:cholesterol acyltransferase (LCAT), while decreased the pro‐inflammatory property of dysfunctional HDL, contributing to reduced atherosclerosis and hepatic steatosis in Western diet‐fed mice. Furthermore, the study revealed that hepatic MsrA altered the expression of several genes controlling HDL biogenesis, cholesterol esterification, cholesterol uptake mediated by low‐density lipoprotein receptor (LDLR) and biliary excretion, as well as suppressed nuclear factor κB (NF‐κB) signaling pathway, which largely relied on liver X receptor alpha (LXRα)‐upregulation. These results provide original evidence that MsrA may be a promising target for the therapy of dysfunctional HDL‐related CVD.
The response spectra are widely used in the damage assessment of non-Gaussian random vibration environments and the derivation of damage equivalent accelerated test spectrum. The effectiveness of the latter is strongly affected by modal parameter uncertainties, multiple field data processing, and the nonsmooth shape of the derived power spectral density (PSD). Optimization of accelerated test spectrum derivation based on dynamic parameter selection and iterative update of spectrum envelope is presented in this paper. The extreme response spectrum (ERS) envelope of the field data is firstly taken as the limiting spectrum, and the corresponding relationship between damping coefficient, fatigue exponent, and damage equivalent PSD under different test times is constructed to achieve the dynamic selection of uncertain parameters in the response spectrum model. Then, an iterative update model based on the weighted sum of fatigue damage spectrum (FDS) error is presented to reduce the error introduced by the nonsmooth shape of the derived PSD. The case study shows that undertest can be effectively avoided by the dynamic selection of model parameters. The weighted error is reduced from 80.1% to 7.5% after 7 iterations. Particularly, the error is close to 0 within the peak and valley frequency band.
Nasopharyngeal carcinoma (NPC) is more common among women in Southeast Asia. An important issue is whether it is safe for them to bear children after treatment and when it is safe to do so. We conducted this study to explore the relation between fertility and prognosis in child-bearing women with NPC. Patients and Methods: Child-bearing women were defined as young women between the ages of 18 and 30. A total of 127 eligible child-bearing NPC patients were identified from December 2003 to December 2014. The patients were divided into two groups, depending on whether or not they had post-therapeutic births. The Kaplan-Meier method was used for survival analyses. The Log rank test was used to compare two survival curves and the independent significances of different prognostic factors were assessed by Cox proportional hazards regression analysis. Results: The 5-year overall survival (OS) and disease-free survival (DFS) in the Childbirth group were significantly higher than those in the Non-Childbirth group (100% vs 88.8%, P = 0.026 and 100% vs 77.5%, P = 0.007, respectively). In the Childbirth group, no difference was found in the 5-year DFS between different birth interval times, from 1 to 5 years after treatment. The clinical stage was identified as the risk factor of OS (HR = 101.725, 95% CI: 2.160-4790.910, P = 0.019), and consequent childbirth after treatment was associated with favorable DFS (HR = 0.148, 95% CI: 0.034-0.643, P = 0.011). Conclusion: Post-therapeutic birth did not increase the mortality risk of child-bearing women with NPC. There was no significant correlation between the subsequent birth time window after treatment and the prognosis.
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