Ultrasonographic diagnosis of ovarian tumors through the deep convolutional neural network.

OBJECTIVES: The objective of this study was to develop and validate an ovarian tumor ultrasonographic diagnostic model based on deep convolutional neural networks (DCNN) and compare its diagnostic performance with that of human experts. MATERIAL AND METHODS: We collected 486 ultrasound images of 192 women with malignant ovarian tumors and 617 ultrasound images of 213 women with benign ovarian tumors, all confirmed by pathological examination. The image dataset was split into a training set and a validation set according to a 7:3 ratio. We selected 5 DCNNs to develop our model: MobileNet, Xception, Inception, ResNet and DenseNet. We compared the performance of the five models through the area under the curve (AUC), sensitivity, specificity, and accuracy. We then randomly selected 200 images from the validation set as the test set. We asked three expert radiologists to diagnose the images to compare the performance of radiologists and the DCNN model. RESULTS: In the validation set, AUC of DenseNet was 0.997 while AUC was 0.988 of ResNet, 0.987 of Inception, 0.968 of Xception and 0.836 of MobileNet. In the test set, the accuracy was 0.975 with the DenseNet model versus 0.825 (p < 0.0001) with the radiologists, and sensitivity was 0.975 versus 0.700 (p < 0.0001), and specificity was 0.975 versus 0.908 (p < 0.001). CONCLUSIONS: DensNet performed better than other DCNNs and expert radiologists in identifying malignant ovarian tumors from benign ovarian tumors based on ultrasound images, a finding that needs to be further explored in clinical trials.

Potential Therapeutic Value of the STING Inhibitors.

The stimulator of interferon genes (STING) is a critical protein in the activation of the immune system in response to DNA. It can participate the inflammatory response process by modulating the inflammation-preferred translation program through the STING-PKR-like endoplasmic reticulum kinase (PERK)-eIF2α pathway or by inducing the secretion of type I interferons (IFNs) and a variety of proinflammatory factors through the recruitment of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) or the regulation of the nuclear factor kappa-B (NF-κB) pathway. Based on the structure, location, function, genotype, and regulatory mechanism of STING, this review summarizes the potential value of STING inhibitors in the prevention and treatment of infectious diseases, psoriasis, systemic lupus erythematosus, non-alcoholic fatty liver disease, and other inflammatory and autoimmune diseases.

Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis.

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.

Design, Synthesis, and Biological Evaluation of Triazolone Derivatives as Potent PPARα/δ Dual Agonists for the Treatment of Nonalcoholic Steatohepatitis.

Peroxisome proliferator-activator receptors α/δ (PPARα/δ) are regarded as potential therapeutic targets for nonalcoholic steatohepatitis (NASH). However, PPARα/δ dual agonist GFT-505 exhibited poor anti-NASH effects in a phase III clinical trial, probably due to its weak PPARα/δ agonistic activity and poor metabolic stability. Other reported PPARα/δ dual agonists either exhibited limited potency or had unbalanced PPARα/δ agonistic activity. Herein, we report a series of novel triazolone derivatives as PPARα/δ dual agonists. Among them, compound H11 exhibited potent and well-balanced PPARα/δ agonistic activity (PPARα EC50 = 7.0 nM; PPARδ EC50 = 8.4 nM) and a high selectivity over PPARγ (PPARγ EC50 = 1316.1 nM) in PPAR transactivation assays. The crystal structure of PPARδ in complex with H11 revealed a unique PPARδ-agonist interaction. H11, which had excellent PK properties and a good safety profile, showed potent in vivo anti-NASH effects in preclinical models. Together, H11 holds a great promise for treating NASH or other inflammatory and fibrotic diseases.