The aim of this study was to evaluate the effects of intravitreal injection of neural stem cells (NSCs) originating from human umbilical cord-derived mesenchymal stem cells (UC-MSCs) on neurodegeneration of diabetic retinopathy (DR) in rats. UC-MSCs were isolated and passaged, followed by induction to NSCs in neural differentiation medium. Four weeks following NSC transplantation, treatment attenuated retinal vascular dysfunction compared with non-treated rats, and BDNF and Thy-1 expression was significantly higher in the treated group than in the control group. Treatment of diabetic rats with NSCs prevented the decrease in BDNF levels caused by diabetes. The average leakage of Evans Blue (EB) dye in the treated group was significantly less than that in the control group. These morphological improvements were accompanied by a restoration of vision, as documented by F-ERG. NSCs originating from MSCs demonstrated a neuroprotective effect by increasing the number of surviving RGCs and significantly reducing the progression of DR. Thus, transplantation of NSCs could be a novel strategy for the treatment of neurodegeneration in DR.

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The purpose of this study was to establish a deep learning model for automated sub-basal corneal nerve fiber (CNF) segmentation and evaluation with in vivo confocal microscopy (IVCM). Methods: A corneal nerve segmentation network (CNS-Net) was established with convolutional neural networks based on a deep learning algorithm for sub-basal corneal nerve segmentation and evaluation. CNS-Net was trained with 552 and tested on 139 labeled IVCM images as supervision information collected from July 2017 to December 2018 in Peking University Third Hospital. These images were labeled by three senior ophthalmologists with ImageJ software and then considered ground truth. The areas under the receiver operating characteristic curves (AUCs), mean average precision (mAP), sensitivity, and specificity were applied to evaluate the efficiency of corneal nerve segmentation. The relative deviation ratio (RDR) was leveraged to evaluate the accuracy of the corneal nerve fiber length (CNFL) evaluation task. Results: The model achieved an AUC of 0.96 (95% confidence interval [CI] = 0.935-0.983) and an mAP of 94% with minimum dice coefficient loss at 0.12. For our dataset, the sensitivity was 96% and specificity was 75% in the CNF segmentation task, and an RDR of 16% was reported in the CNFL evaluation task. Moreover, the model was able to segment and evaluate as many as 32 images per second, much faster than skilled ophthalmologists. Conclusions: We established a deep learning model, CNS-Net, which demonstrated a high accuracy and fast speed in sub-basal corneal nerve segmentation with IVCM. The results highlight the potential of the system in assisting clinical practice for corneal nerves segmentation and evaluation. Translational Relevance: The deep learning model for IVCM images may enable rapid segmentation and evaluation of the corneal nerve and may provide the basis for the diagnosis and treatment of ocular surface diseases associated with corneal nerves.

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Myeloid-derived suppressor cells (MDSCs), which are activated under pathological conditions, are a group of heterogeneous immature myeloid cells. MDSCs have potent capacities to support tumor growth via inhibition of the antitumoral immune response and/or the induction of immunosuppressive cells. In addition, multiple studies have demonstrated that MDSCs provide potential therapeutic targets for the elimination of immunosuppressive functions and the inhibition of tumor growth. The combination of targeting MDSCs and other therapeutic approaches has also demonstrated powerful antitumor effects. In this review, we summarize the characteristics of MDSCs in the tumor microenvironment (TME) and current strategies of cancer treatment by targeting MDSCs.

Allograft rejection is the major cause of corneal allograft failure. Rapamycin (RAPA) has been reported as an effective and novel immunosuppressive agent for patients undergoing corneal transplantation. However, its high water insolubility and low bioavailability have strongly constrained its clinical application. In this study, we successfully developed a RAPA nano-micelle ophthalmic solution and found that corneal allograft survival in recipients treated with RAPA nano-micelle ophthalmic solution was significantly prolonged for more than 2 months, with less inflammatory infiltration, decreased production of pro-inflammatory factors, and elevated recruitment of myeloid-derived suppressor cells (MDSCs). MDSCs from mice treated with RAPA nano-micelle ophthalmic solution could significantly inhibit the proliferation of CD4+T cells through increased expressions of inducible nitric oxidase (iNOS) and arginase-1 (Arg-1). The activity blockade of Arg-1 and iNOS pharmacologically reversed their immunosuppressive ability. Moreover, the effects of RAPA were antagonized by the administration of anti-Gr-1 antibody or by inhibiting the activity of iNOS pharmacologically. In addition, RAPA nano-micelle also effectively alleviated allograft rejection in high-risk rabbit penetrating keratoplasty (PKP) models with corneal vascularization. Collectively, our results demonstrate that RAPA nano-micelle ophthalmic solution could improve the immunosuppressive activity of MDSCs through elevated expression of Arg-1 and iNOS, which highlights the possible therapeutic applications of RAPA against corneal allograft rejection.

Background: Bilateral synchronous multiple primary lung adenocarcinoma (BSMPLA) is a rapidly increasing disease for which timely and accurate treatment is required. We describe our experience which we hope to establish optimal therapeutic options for patients with BSMPLA. Methods: This study aimed to explore the feasibility and safety of simultaneous bilateral video-assisted thoracoscopic surgery (VATS) in 56 patients who received histological diagnoses of BSMPLA at our hospital between January 2016 and January 2018. In this retrospective analysis of clinical outcomes, we observed no serious postoperative complications or perioperative death. Results: Four and 28 patients respectively underwent bilateral lobectomy and lobectomy with contralateral sublobar resection, whereas the remaining 24 patients underwent bilateral sublobar resection. Sublobar resection means anatomical segmentectomy or wedge resection. The mean postoperative hospital stay duration was 5.39±2.67 days. Postoperative complications comprising persistent air leakage for more than 5 days was observed in 8 (14.2%) of 56 patients. No severe postoperative complications or deaths occurred. Conclusions: Our results suggest that simultaneous bilateral VATS is feasible, safe, and reproducible. This therapeutic strategy appears to confer considerable benefits on patients with BSMPLA.

Macrophages differentiated into a classically activated (M1) or alternatively activated phenotype (M2) in infection and tumor, but the precise effects of glycolysis and oxidative phosphorylation (OXPHOS) metabolic pathway remain unclear. Herein, the effects of glycolysis or OXPHOS on macrophage polarizations were investigated using a pharmacological approach in mice. 2-Deoxy-D-glucose (2-DG) treatments, which blocks the key enzyme hexokinase of glycolysis, efficiently inhibits a specific switch to M1 lineage, decreasing the secretion of pro-inflammatory cytokines and expressions of co-stimulatory molecules associated with relieving infectious inflammation in vitro and in vivo. Glycolytic activation through the hypoxia-inducible factor-1α (HIF-1α) pathway was required for differentiation to the M1 phenotype, which conferred protection against infection. Dimethyl malonate (DMM) treatment, which blocks the key element succinate of OXPHOS, efficiently inhibits a specific switch to M2 lineage when macrophages receiving M2 stimulation, decreasing the secretion of anti-inflammatory cytokine and CD206 expressions. Mitochondrial dynamic alterations including mitochondrial mass, mitochondrial membrane potential (Dym) and ROS productions were critically for differentiation to the M2 phenotype, which conferred protection against anti-tumor immunity. Glycolysis is also required for macrophage M2 differentiation. Thus, these data provide a basis for a comprehensively understanding the role of glycolysis and OXPHOS in macrophage differentiation during anti-infection and anti-tumor inflammation.