Xanthohumol improves cognitive impairment by regulating miRNA-532-3p/Mpped1 in ovariectomized mice.

RATIONALE: Studies have shown the potential neuroprotective effect of xanthohumol, while whether xanthohumol has the ability of repairing cognitive impairment and its underlying mechanism still remains obscure. OBJECTIVES: To unravel the mechanism of xanthohumol repairing cognitive impairment caused by estrogen deprivation. METHODS: C57BL/6 J female mice that underwent bilateral ovariectomy to establish cognitive decline model were randomly divided into three xanthohumol-treated groups and a saline-treated model group. For identifying the neuroprotective function of xanthohumol, Morris water maze (MWM) test and open field test (OFT) were conducted. After extracting total RNA of mouse hippocampus of different groups, mRNA-seq and microRNA (miRNA)-seq analysis were performed, and the differentially expressed miRNAs (DEMIs) and their target genes were further validated by qPCR. MiR-532-3p and its downstream gene Mpped1 were screened as targets of xanthohumol. Influence of miR-532-3p/Mpped1 to cognitive ability was examined via MWM test and OFT after stereotactic brain injection of Mpped1 overexpressed adeno-associated virus. The regulation of miR-532-3p on Mpped1 was confirmed in hippocampal neuronal cell line HT22 by luciferase reporter gene assay. RESULTS: Xanthohumol treatment reversed the cognitive decline of OVX mice according to behavioral tests. By comparing miRNA levels of xanthohumol-treated groups with saline-treated group, we found that the main changed miRNAs were miR-122-5p, miR-532-3p, and miR-539-3p. Increased miR-532-3p in OVX mice was suppressed by xanthohumol treatment. Furthermore, the downstream gene of miR-532-3p, Mpped1, was also increased by xanthohumol and showed the capability of relieving cognitive impairment of OVX mice after overexpressed in hippocampus. The 3' untranslated region of Mpped1 was identified as the target region of miR-532-3p, and agomiR-532-3p remarkably reduced the expression of Mpped1 mRNA. CONCLUSIONS: Xanthohumol has the ability of repairing cognitive impairment through removing the inhibition of miR-532-3p on Mpped1 in mouse hippocampus. This finding not only advances the understanding of neuroprotective mechanism of xanthohumol, but also provides novel treatment targets for dementia of postmenopausal women.

Development and Application of a Standardized Testset for an Artificial Intelligence Medical Device Intended for the Computer-Aided Diagnosis of Diabetic Retinopathy.

Objective: To explore a centralized approach to build test sets and assess the performance of an artificial intelligence medical device (AIMD) which is intended for computer-aided diagnosis of diabetic retinopathy (DR). Method: A framework was proposed to conduct data collection, data curation, and annotation. Deidentified colour fundus photographs were collected from 11 partner hospitals with raw labels. Photographs with sensitive information or authenticity issues were excluded during vetting. A team of annotators was recruited through qualification examinations and trained. The annotation process included three steps: initial annotation, review, and arbitration. The annotated data then composed a standardized test set, which was further imported to algorithms under test (AUT) from different developers. The algorithm outputs were compared with the final annotation results (reference standard). Result: The test set consists of 6327 digital colour fundus photographs. The final labels include 5 stages of DR and non-DR, as well as other ocular diseases and photographs with unacceptable quality. The Fleiss Kappa was 0.75 among the annotators. The Cohen's kappa between raw labels and final labels is 0.5. Using this test set, five AUTs were tested and compared quantitatively. The metrics include accuracy, sensitivity, and specificity. The AUTs showed inhomogeneous capabilities to classify different types of fundus photographs. Conclusions: This article demonstrated a workflow to build standardized test sets and conduct algorithm testing of the AIMD for computer-aided diagnosis of diabetic retinopathy. It may provide a reference to develop technical standards that promote product verification and quality control, improving the comparability of products.

Practice toward standardized performance testing of computer-aided detection algorithms for pulmonary nodule.

This study aimed at implementing practice to build a standardized protocol to test the performance of computer-aided detection (CAD) algorithms for pulmonary nodules. A test dataset was established according to a standardized procedure, including data collection, curation and annotation. Six types of pulmonary nodules were manually annotated as reference standard. Three specific rules to match algorithm output with reference standard were applied and compared. These rules included: (1) "center hit" [whether the center of algorithm highlighted region of interest (ROI) hit the ROI of reference standard]; (2) "center distance" (whether the distance between algorithm highlighted ROI center and reference standard center was below a certain threshold); (3) "area overlap" (whether the overlap between algorithm highlighted ROI and reference standard was above a certain threshold). Performance metrics were calculated and the results were compared among ten algorithms under test (AUTs). The test set currently consisted of CT sequences from 593 patients. Under "center hit" rule, the average recall rate, average precision, and average F1 score of ten algorithms under test were 54.68, 38.19, and 42.39%, respectively. Correspondingly, the results under "center distance" rule were 55.43, 38.69, and 42.96%, and the results under "area overlap" rule were 40.35, 27.75, and 31.13%. Among the six types of pulmonary nodules, the AUTs showed the highest miss rate for pure ground-glass nodules, with an average of 59.32%, followed by pleural nodules and solid nodules, with an average of 49.80 and 42.21%, respectively. The algorithm testing results changed along with specific matching methods adopted in the testing process. The AUTs showed uneven performance on different types of pulmonary nodules. This centralized testing protocol supports the comparison between algorithms with similar intended use, and helps evaluate algorithm performance.

Antibacterial, antioxidant and biocompatible nanosized quercetin-PVA xerogel films for wound dressing.

Topical use of antimicrobial agents to treat wounds to inhibit bacterial invasion and facilitate wound healing is an effective strategy. In this work, an antibacterial xerogel film for potential applications in wound dressings was developed. First, a natural antibacterial agent, quercetin (Qu), was made into water-soluble quercetin-borate (QuB) nanoparticles by merging a solvent exchange method with the borate esterification reaction. QuB nanoparticles were then employed as the cross-linking agent to achieve gelation of poly(vinyl alcohol) (PVA) to obtain antimicrobial QuB-PVA composite microgels. Furthermore, QuB-PVA microgels were utilized as raw materials to produce xerogel films via an electrospray technique. The as-prepared QuB-PVA xerogel films exhibited excellent bacteriostasis, antioxidation, biocompatibility, self-healing, accelerated skin regeneration and functional restoration, and promoted skin wound healing. The QuB-PVA films significantly facilitated the in vivo healing speed of full-thickness skin wounds compared to commercial dressings. We believe that the present multifunctional QuB-PVA xerogel film is an excellent candidate for the wound dressings.

Toward standardized premarket evaluation of computer aided diagnosis/detection products: insights from FDA-approved products.

INTRODUCTION: Computer aided detection and diagnosis (CADe and CADx) products are an emerging branch of medical device industry. However, limited technical standard has been developed for product verification and validation. It will be helpful to investigate the current practice of preclinical and clinical evaluation of approved products and provide insights for future standardization. AREAS COVERED: Document review was conducted on 56 products approved by the United States Food and Drug Administration, including Summary of Safety and Effectiveness Data, 510(k) decision and de novo decision summaries. Key parameters describing product characteristics, preclinical studies and clinical studies were collected. Evaluation strategies for CADe/CADx products were analyzed and assessed. EXPERT OPINION: Preclinical studies were widely adopted in the verification of CADe/CADx products. Standalone performance testing was a common procedure, but the selection of testing dataset and performance metrics showed significant variability and flexibility among manufacturers. Clinical studies were reported by all class III products and some class II products, and Multi-Reader Multi-Case design was commonly used. However, statistical analysis and presentation/interpretation of results was oftentimes incomplete. To resolve above issues, systematic development of standards of CADe/CADx is encouraged, which can be implemented at different aspects through the product lifecycle.

[Cluster application in PACS system].

How to use clustering techniques in PACS system is introduced. Two kinds of cluster solution to configure PACS system is proposed.

Silver nanoparticles crossing through and distribution in the blood-brain barrier in vitro.

Silver nanoparticles (SNPs) translocate to the brain through the blood stream after they are implanted in vivo. The aim of this study was to investigate the distribution of SNPs that crossed through the blood-brain barrier (BBB). An in vitro BBB model established by co-cultures of rat brain microvessel vascular endothelial cells (BMVECs) with astrocytes (ACs) was cultured with cell culture medium containing 100 microg/mL of either SNPs or silver microparticles (SMPs). After 4 hours of culture, the ultrastructure and its silver content of BBB was evaluated with transmission electronic microscopy (TEM) and inductively-coupled plasma mass spectrometry (ICP-MS) respectively. Results demonstrated that SNPs crossed the BBB and accumulated inside BMVECs, while the SMPs did not. The data indicated a special distribution of SNPs in the BBB and suggested that SNPs pass the BBB mainly by transcytosis of capillary endothelial cells. Further study would be necessary to evaluate the actual biological effects of SNPs on the brain.

Distribution, translocation and accumulation of silver nanoparticles in rats.

Silver nanoparticles (SNPs) are widely used in the field of biomedicine, but a comprehensive understanding of how SNPs distribute in the body and the induced toxicity remains largely unknown. The present study was designed to investigate the distribution and accumulation of SNPs in rats with subcutaneous injection. Rats were injected with either SNPs or silver microparticles (SMPs) at 62.8 mg/kg, and then sacrificed at predetermined time points. The main organs of the experimental animals were harvested for ultrastructural analysis by transmission electron microscopy (TEM) and for silver content analysis by inductively coupled plasma mass spectrometry (ICP-MS). Results indicated that SNPs translocated to the blood circulation and distributed throughout the main organs, especially in the kidney, liver, spleen, brain and lung in the form of particles. SMPs, however, could not invade the blood stream, or organ tissues. Ultrastructural observations indicate that those SNPs that had accumulated in organs could enter different kinds of cells, such as renal tubular epithelial cells and hepatic cells. Moreover, SNPs also induced blood-brain barrier (BBB) destruction and astrocyte swelling, and caused neuronal degeneration. The results suggest more cautions needed in biomedical applications of SNPs, in particular, the long-term uses.

[A long term accelerating corrosion fatigue texting of coronary stents in vitro].

According to the related standards, an in vitro corrosion fatigue testing of coronary stents was designed. The stents were fixed in the latex tubes, which were full of 0.9% saline solution, and radial stress was produced for simulating natural vessel. The accelerated fatigue test was performed with 4 x 10(8) cycles at a frequency of 60 Hz, which was equal to 10 years in vivo implantation. Twelve coronary stents made from stainless steel were adopted in the experiment. The bulk structure and surface morphology before and after testing were analysed by scanning electron microscopy. The structure damage and surface change caused by corrosion fatigue were identified and the probable reasons were proposed.