Automated interpretation of retinal vein occlusion based on fundus fluorescein angiography images using deep learning: A retrospective, multi-center study.

Purpose: Fundus fluorescein angiography (FFA) is the gold standard for retinal vein occlusion (RVO) diagnosis. This study aims to develop a deep learning-based system to diagnose and classify RVO using FFA images, addressing the challenges of time-consuming and variable interpretations by ophthalmologists. Methods: 4028 FFA images of 467 eyes from 463 patients were collected and annotated. Three convolutional neural networks (CNN) models (ResNet50, VGG19, InceptionV3) were trained to generate the label of image quality, eye, location, phase, lesions, diagnosis, and macular involvement. The performance of the models was evaluated by accuracy, precision, recall, F-1 score, the area under the curve, confusion matrix, human-machine comparison, and Clinical validation on three external data sets. Results: The InceptionV3 model outperformed ResNet50 and VGG19 in labeling and interpreting FFA images for RVO diagnosis, achieving 77.63%-96.45% accuracy for basic information labels and 81.72%-96.45% for RVO-relevant labels. The comparison between the best CNN and ophthalmologists showed up to 19% accuracy improvement with the inceptionV3. Conclusion: This study developed a deep learning model capable of automatically multi-label and multi-classification of FFA images for RVO diagnosis. The proposed system is anticipated to serve as a new tool for diagnosing RVO in places short of medical resources.

An electrospun scaffold functionalized with a ROS-scavenging hydrogel stimulates ocular wound healing.

Ocular alkali burn is a serious ophthalmic emergency. Highly penetrative alkalis cause strong inflammatory responses leading to persistent epithelial defects, acute corneal perforation and severe scarring, and thereby persistent pain, loss of vision and cicatricial sequelae. Early and effective anti-inflammation management is vital in reducing the severity of injury. In this study, a double network biomaterial was prepared by compounding electrospinning nanofibres of thioketal-containing polyurethane (PUTK) with a reactive oxygen species (ROS)-scavenging hydrogel (RH) fabricated by crosslinking poly(poly(ethylene glycol) methyl ether methacrylate-co-glycidyl methacrylate) with thioketal diamine and 3,3'-dithiobis(propionohydrazide). The developed PUTK/RH patch exhibited good transparency, high tensile strength and increased hydrophilicity. Most importantly, it demonstrated strong antioxidant activity against H2O2 and 2,2-di(4-tert-octylphenyl)-1-picryl-hydrazyl (DPPH). Next, a rat corneal alkali burn model was established, and the PUTK/RH patch was transplanted on the injured cornea. Reduced inflammatory cell infiltration was revealed by confocal microscopy, and lower expression levels of genes relative to inflammation, vascularization and scarring were identified by qRT-PCR and western blot. Fluorescein sodium dyeing, hematoxylin and eosin (H&E) staining and immunohistochemical staining confirmed that the PUTK/RH patch could accelerate corneal wound healing by inhibiting inflammation, promoting epithelial regeneration and decreasing scar formation. STATEMENT OF SIGNIFICANCE: Ocular alkali burn is a serious ophthalmic emergency, characterized with persistent inflammation and irreversible vision loss. Oxidative stress is the main pathological process at the acute inflammatory stage, during which combined use of glucocorticoids and amniotic membrane transplantation is the most widely accepted treatment. In this study, we fabricated a polyurethane electrospun nanofiber membrane functionalized with a ROS-scavenging hydrogel. This composite patch could be a promising amniotic membrane substitute, possessing with a transparent appearance, elasticity and anti-inflammation effect. It could be easily transplanted onto the alkali-burned corneas, resulting in a significant inhibition of stromal inflammation and accelerating the recovery of corneal transparency. The conception of ROS-scavenging wound patch may offer a new way for ocular alkali burn.

Zwitterionic hydrogel-coated heart valves with improved endothelialization and anti-calcification properties.

Valve replacement surgery is the golden standard for end-stage valvular disease due to the lack of self-repair ability. Currently, bioprosthetic heart valves (BHVs) crosslinked by glutaraldehyde (GA) have been the most popular choice in clinic, especially after the emerge of transcatheter aortic valve replacement (TAVR). Nevertheless, the lifespan of BHVs is limited due to severe calcification and deterioration. In this study, to improve the anti-calcification property of BHVs, decellularized heart valves were modified by methacrylic anhydride to introduce double bonds (MADHVs), and a hybrid hydrogel made of sulfobetaine methacrylate (SBMA) and methacrylated hyaluronic acid (MAHA) was then coated onto the surface of MADHVs. Followed by grafting of Arg-Glu-Asp-Val (REDV), an endothelial cell-affinity peptide, the BHVs with improved affinity to endothelial cell (SMHVs-REDV) was obtained. SMHVs-REDV exhibited excellent collagen stability, reliable mechanical property and superior hemocompatibility. Moreover, enhanced biocompatibility and endothelialization potential compared with GA-crosslinked BHVs were achieved. After subcutaneous implantation for 30 days, SMHVs-REDV showed significantly reduced immune response and calcification compared with GA-crosslinked BHVs. Overall, simultaneous endothelialization and anti-calcification can be realized by this strategy, which was supposed to be benefit for improving the main drawbacks for available commercial BHVs products.

A novel detergent-based decellularization combined with carbodiimide crosslinking for improving anti-calcification of bioprosthetic heart valve.

Currently, valve replacement surgery is the only therapy for the end-stage valvular diseases because of the inability of regeneration for diseased heart valves. Bioprosthetic heart valves (BHVs), which are mainly derived from glutaraldehyde (GA) crosslinked porcine aortic heart valves or bovine pericardium, have been widely used in the last decades. However, it is inevitable that calcification and deterioration may occur within 10-15 years, which are still the main challenges for the BHVs in clinic. In this study, N-Lauroylsarcosine sodium salt (SLS) combined with N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) were utilized to decellularize and crosslink the heart valves instead of GA treatment. The obtained BHVs exhibited excellent extracellular matrix stability and mechanical properties, which were similar with GA treatment. Moreover, the obtained BHVs exhibited betterin vitrobiocompatibilities than GA treatment. After subcutaneous implantation for 30 d, the obtained BHVs showed mitigated immune response and reduced calcification compare with GA treatment. Therefore, all the above results indicated that the treatment of SLS-based decellularization combined with EDC/NHS crosslink should be a promising method to fabricate BHVs which can be used in clinic in future.

Human epidermal growth factor-functionalized cocoon silk with improved cell proliferation activity for the fabrication of wound dressings.

Human epidermal growth factor (hEGF) is a key factor involved in wound healing owing to its powerful ability to stimulate cell proliferation. In this study, we used piggyBac transposon technology to produce transgenic silkworms expressing the hEGF protein fused to truncated heavy chain (FibH-hEGF). The FibH-hEGF fusion protein was successfully expressed and secreted into silkworm cocoons. Compared to wild-type silk, the transgenic silkworm silk had the similar morphology about silks fiber surface and cocoon nets, while the secondary structure between the transgenic silk and wild-type silk was different. Most importantly, transgenic silkworm cocoon silk powder extract significantly increased human fibroblast FIB cell proliferation for a long duration with no apparent cytotoxicity. Our study provides a promising method for obtaining cost-effective and functional biomaterials for the fabrication of wound dressings.

Liposomal C6 Ceramide Activates Protein Phosphatase 1 to Inhibit Melanoma Cells.

Melanoma is one common skin cancer. In the present study, the potential anti-melanoma activity by a liposomal C6 ceramide was tested in vitro. We showed that the liposomal C6 (ceramide) was cytotoxic and anti-proliferative against a panel of human melanoma cell lines (SK-Mel2, WM-266.4 and A-375 and WM-115). In addition, liposomal C6 induced caspase-dependent apoptotic death in the melanoma cells. Reversely, its cytotoxicity was attenuated by several caspase inhibitors. Intriguingly, liposomal C6 was non-cytotoxic to B10BR mouse melanocytes and primary human melanocytes. Molecularly, liposomal C6 activated protein phosphatase 1 (PP1) to inactivate Akt-mammalian target of rapamycin (mTOR) signaling in melanoma cells. On the other hand, PP1 shRNA knockdown or exogenous expression of constitutively activate Akt1 (CA-Akt1) restored Akt-mTOR activation and significantly attenuated liposomal C6-mediated cytotoxicity and apoptosis in melanoma cells. Our results suggest that liposomal C6 activates PP1 to inhibit melanoma cells.