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Objective: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune‐mediated disorder with aquaporin 4‐immunoglobulin G (AQP4‐IgG) in most settings. Soluble programmed death‐1 (sPD‐1) and soluble programmed death ligand 1 (sPD‐L1) play key roles in immunomodulation. We aim to assess the association of sPD‐1 and sPD‐L1 with cytokines and their clinical significance in AQP4‐IgG (+) NMOSD. Method: We measured plasma sPD‐1, sPD‐L1, and 10 cytokines levels of 66 AQP4‐IgG (+) NMOSD patients, including 40 patients in attack (attack‐NMOSD) and 26 patients in remission (remission‐NMOSD) phases, and 28 healthy controls through ultrasensitive Simoa and SP‐X platform, respectively. We also performed >2 years (median) of follow‐up after testing and analyzed the relationship between the detection index and current and future clinical parameters. Result: Plasma sPD‐1 level discriminated attack‐NMOSD from remission‐NMOSD (AUC = 0.692, p = 0.009). sPD‐1 and sPD‐L1 levels positively correlated with IL‐6 (rsPD‐1 = 0.313; rsPD‐L1 = 0.508), IFN‐γ (rsPD‐1 = 0.331; rsPD‐L1 = 0.456), and TNF‐α (rsPD‐1 = 0.451; rsPD‐L1 = 0.531) expression, as well as clinical indicators, including the EDSS score (rsPD‐1 = 0.331; rsPD‐L1 = 0.402), number of attacks (rsPD‐1 = 0.431) and segments of spinal cord involvement (rsPD‐1 = 0.462; rsPD‐L1 = 0.508). The risk of relapse within 2 years after sampling was associated with higher sPD‐1/sPD‐L1 ratio in attack‐NMOSD (p = 0.022; Exp(B) = 1.589). Interpretation: Plasma sPD‐1 and sPD‐L1 levels reflected current disease severity and activity, and predicted future relapses in AQP4‐IgG (+) NMOSD, suggesting that they hold the potential to guide timely and targeted treatment. [ABSTRACT FROM AUTHOR]

In this paper, a partially linear model based on the fused lasso method is proposed to solve the problem of high correlation between adjacent variables, and then the idea of the two-stage estimation method is used to study the solution of this model. Firstly, the non-parametric part of the partially linear model is estimated using the kernel function method and transforming the semiparametric model into a parametric model. Secondly, the fused lasso regularization term is introduced into the model to construct the least squares parameter estimation based on the fused lasso penalty. Then, due to the non-smooth terms of the model, the subproblems may not have closed-form solutions, so the linearized alternating direction multiplier method (LADMM) is used to solve the model, and the convergence of the algorithm and the asymptotic properties of the model are analyzed. Finally, the applicability of this model was demonstrated through two types of simulation data and practical problems in predicting worker wages. [ABSTRACT FROM AUTHOR]

Son of sevenless (SOS) is one of the guanine nucleotide exchange factors that can regulate the mitogen‐activated protein kinase/extracellular signal regulated kinase signal pathway via controlling the activation of Ras. microRNAs are key regulon of gene expression and would be treated as tumor biomarkers or therapeutic targets. In this study, we find that miR‐148a‐3p acts as a tumor‐suppressor in the development and progression of non‐small‐cell lung cancer (NSCLC). miR‐148a‐3p inhibits NSCLC cells proliferation and epithelial–mesenchymal transition by reducing the expression of SOS2, which refers Ras activating. Our findings demonstrate that the miR‐148a‐3p may play a significant role in NSCLC including the kind of lung cancer with K‐Ras gene mutation, and it exerted the tumor inhibitor function by targeting SOS2. Because of that, miR‐148a‐3p and SOS2 may be an efficient target in developing more useful therapies against NSCLC. [ABSTRACT FROM AUTHOR]

Background: Bioprosthetic valve thrombosis is previously considered as an extremely rare complication which hasn't been systemically recognized and understood.Case Presentation: Herein, we present an unusual case of a patient manifesting with acute heart failure, secondary to thrombus formation in a porcine aortic bioprosthesis which was implanted 11 months prior to hospitalization. Due to the patient's poor heart function and intraoperative findings, thrombectomy was performed. For our best knowledge, cases of early bioprosthetic valve thrombosis presenting with acute heart failure have seldomly been reported.Conclusion: Our study reviews predisposing factors, typical echocardiographic features and treatment for bioprosthetic valve thrombosis and it should be considered as a reason for bioprosthetic malfunction. A combination of clinical and echocardiographic features can help for diagnosis preoperatively. In some certain circumstances, early reoperation can be avoided if anticoagulant therapy works. [ABSTRACT FROM AUTHOR]

The preclinical studies using animal models play a very important role in the evaluation of facial nerve regeneration. Good models need to recapitulate the distance and time for axons to regenerate in humans. Compared with the most used rodent animals, the structure of facial nerve in mini-pigs shares more similarities with humans in microanatomy. To evaluate the feasibility of repairing facial nerve defects by collagen scaffolds combined with ciliary neurotrophic factor (CNTF), 10-mm-long gaps were made in the buccal branch of mini-pigs' facial nerve. Three months after surgery, electrophysiological assessment and histological examination were performed to evaluate facial nerve regeneration. Immunohistochemistry and transmission electron microscope observation showed that collagen scaffolds with collagen binding (CBD)-CNTF could promote better axon regeneration, Schwann cell migration, and remyelination at the site of implant device than using scaffolds alone. Electrophysiological assessment also showed higher recovery rate in the CNTF group. In summary, combination of collagen scaffolds and CBD-CNTF showed promising effects on facial nerve regeneration in mini-pig models. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1669-1676, 2015. [ABSTRACT FROM AUTHOR]