Jia Liu

Purpose: To investigate whether a combination of radiomics and automatic machine learning applied to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of primary breast cancer can noninvasively predict axillary sentinel lymph node (SLN) metastasis. Methods: 62 patients who received a DCE-MRI breast scan were enrolled. Tumor resection and sentinel lymph node (SLN) biopsy were performed within 1 week after the DCE-MRI examination. According to the time signal intensity curve, the volumes of interest (VOIs) were delineated on the whole tumor in the images with the strongest enhanced phase. Datasets were randomly divided into two sets including a training set (~80%) and a validation set(~20%). A total of 1409 quantitative imaging features were extracted from each VOI. The select K best and least absolute shrinkage and selection operator (Lasso) were used to obtain the optimal features. Three classification models based on the logistic regression (LR), XGboost and support vector machine (SVM) classifiers were constructed. Receiver Operating Curve (ROC) analysis was used to analyze the prediction performance of the models. Both feature selection and models construction were firstly performed in the training set, then were further tested in the validation set by the same thresholds. Results: There is no significant difference between all clinical and pathological variables in breast cancer patients with and without SLN metastasis (P > 0.05), except histological grade (P = 0.03). Six features were obtained as optimal features for models construction. In the validation set, with respect to the accuracy and MSE, the SVM demonstrated the highest performance, with an accuracy, AUC, sensitivity (for positive SLN) , specificity (for positive SLN) and Mean Squared Error (MSE) of 0.85, 0.83, 0.71, 1, 0.26 respectively. Conclusions: We demonstrated the feasibility of combining artificial intelligence and radiomics from DCE-MRI of primary tumors to predict axillary SLN metastasis in breast cancer. This noninvasive approach could be very promising in application.

The optimization of the pharmacokinetic performance of various 2-pyridone-containing human rhinovirus (HRV) 3C protease (3CP) inhibitors following oral administration to either beagle dogs or CM-monkeys is described. The molecules described in this work are composed of a 2-pyridone-containing peptidomimetic binding determinant and an alpha,beta-unsaturated ester Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. Modification of the ester contained within these compounds is detailed along with alteration of the P(2) substituent present in the peptidomimetic portion of the inhibitors. The pharmacokinetics of several inhibitors in both dogs and monkeys are described (7 h plasma concentrations after oral administration) along with their human plasma stabilities, stabilities in incubations with human, dog, and monkey microsomes and hepatocytes, Caco-2 permeabilities, and aqueous solubilities. Compounds containing an alpha,beta-unsaturated ethyl ester fragment and either an ethyl or propargyl P(2) moiety displayed the most promising combination of 3C enzyme inhibition (k(obs)/[I] 170 000-223 000 M(-1) s(-1)), antiviral activity (EC(50) = 0.047-0.058 microM, mean vs seven HRV serotypes), and pharmacokinetics following oral administration (7 h dog plasma levels = 0.248-0.682 microM; 7 h CM-monkey plasma levels = 0.057-0.896 microM).

BACKGROUND: Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs. RESULTS: The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function. CONCLUSIONS: The PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases.

The damage of corneal epithelium may lead to the formation of irreversible corneal opacities and even blindness. The migration rate of corneal epithelial cells directly affects corneal repair. Here, we explored ocu-microRNA 24-3p (miRNA 24-3p) that can promote rabbit corneal epithelial cells migration and cornea repair. Exosomes, an excellent transport carrier, were exacted from adipose derived mesenchymal stem cells for loading with miRNA 24-3p to prepare miRNA 24-3p-rich exosomes (Exos-miRNA 24-3p). It can accelerate corneal epithelial migration in vitro and in vivo. For application in cornea alkali burns, we further modified hyaluronic acid with di(ethylene glycol) monomethyl ether methacrylate (DEGMA) to obtain a thermosensitive hydrogel, also reported a thermosensitive DEGMA-modified hyaluronic acid hydrogel (THH) for the controlled release of Exos-miRNA 24-3p. It formed a highly uniform and clear thin layer on the ocular surface to resist clearance from blinking and extended the drug–ocular–epithelium contact time. The use of THH-3/Exos-miRNA 24-3p for 28 days after alkali burn injury accelerated corneal epithelial defect healing and epithelial maturation. It also reduced corneal stromal fibrosis and macrophage activation. MiRNA 24-3p-rich exosomes functionalized DEGMA-modified hyaluronic acid hydrogel as a multilevel delivery strategy has a potential use for cell-free therapy of corneal epithelial regeneration.