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Background: During long-term antiplatelet agents (APAs) administration, patients with thrombotic diseases take a fairly high risk of life-threatening bleeding, especially when in need of urgent surgery. Rapid functional reversal of APAs remains an issue yet to be efficiently resolved by far due to the lack of any specific reversal agent in the clinic, which greatly restricts the use of APAs. Methods: Flow cytometry analysis was first applied to assess the dose-dependent reversal activity of platelet-mimicking perfluorocarbon-based nanosponges (PLT-PFCs) toward ticagrelor. The tail bleeding time of mice treated with APAs followed by PLT-PFCs was recorded at different time points, along with corresponding pharmacokinetic analysis of ticagrelor and tirofiban. A hemorrhagic transformation model was established in experimental stroke mice with thrombolytic/antiplatelet therapy. Magnetic resonance imaging was subsequently applied to observe hemorrhage and thrombosis in vivo. Further evaluation of the spontaneous clot formation activity of PLT-PFCs was achieved by clot retraction assay in vitro. Results: PLT-PFCs potently reversed the antiplatelet effect of APAs by competitively binding with APAs. PLT-PFCs showed high binding affinity comparable to fresh platelets in vitro with first-line APAs, ticagrelor and tirofiban, and efficiently reversed their function in both tail bleeding and postischemic-reperfusion models. Moreover, the deficiency of platelet intrinsic thrombotic activity diminished the risk of thrombogenesis. Conclusions: This study demonstrated the safety and effectiveness of platelet-mimicking nanosponges in ameliorating the bleeding risk of different APAs, which offers a promising strategy for the management of bleeding complications induced by antiplatelet therapy.

With the development of deep learning theory and the decrease of the cost of acquiring massive data, the image semantic segmentation algorithm based on Convolutional Neural Networks (CNNs) is gradually replacing the conventional segmentation algorithm by its high accuracy segmentation performance. By increasing the amount of training data and stacking more convolutional layers to form Deep Convolutional Neural Networks (DCNNs), a neural network model with higher segmentation accuracy can be obtained, but it faces the problems of serious memory consumption and long latency. For some special application scenarios, such as augmented reality and mobile interaction, real-time processing cannot be performed. To improve the speed of semantic segmentation while obtaining the most accurate segmentation results as possible, this paper proposes a semantic segmentation algorithm based on lightweight convolutional neural networks. Taking the computational complexity and segmentation accuracy into account, the algorithm starts from the perspective of extracting high-level semantic features and introduces a position-attention mechanism with richer contextual information to model the relationship between different pixels, avoiding the convolutional local perceptual field to be too small. To recover clearer target boundaries, a channel attention mechanism is introduced in the decoding part of the model to mine more useful feature channel information and effectively improve the fusion of low-level features with high-level features. By verifying the effectiveness of the above model on a publicly available dataset and comparing it with the more popular semantic segmentation methods, the model proposed in this paper has higher semantic segmentation accuracy and reflects certain advantages in objective evaluation.

Taxifolin inhibits breast cancer (BC) via novel mechanisms. In a syngeneic mouse BC model, taxifolin suppressed 4T-1 cell-derived allografts. RNA-seq of 4T-1 tumors identified 36 differentially expressed genes (DEGs) upregulated by taxifolin. Among their human homologues, 19, 7, and 2 genes were downregulated in BCs, high-proliferative BCs, and BCs with high-fatality risks, respectively. Three genes were established as tumor suppressors and eight were novel to BC, including HNRN, KPRP, CRCT1, and FLG2. These four genes exhibit tumor suppressive actions and reside in 1q21.3, a locus amplified in 70% recurrent BCs, revealing a unique vulnerability of primary and recurrent BCs with 1q21.3 amplification with respect to taxifolin. Furthermore, the 36 DEGs formed a multiple gene panel (DEG36) that effectively stratified the fatality risk in luminal, HER2+, and triple-negative (TN) equivalent BCs in two large cohorts: the METABRIC and TCGA datasets. 4T-1 cells model human TNBC cells. The DEG36 most robustly predicted the poor prognosis of TNBCs and associated it with the infiltration of CD8+ T, NK, macrophages, and Th2 cells. Of note, taxifolin increased the CD8+ T cell content in 4T-1 tumors. The DEG36 is a novel and effective prognostic biomarker of BCs, particularly TNBCs, and can be used to assess the BC-associated immunosuppressive microenvironment.

The aim of this study was to explore the most updated changing trends of non-rheumatic calcific aortic valve disease (nrCAVD) and reveal possible improvements. We analyzed the age-standardized rates (ASRs) of prevalence, incidence, disability-adjusted life-years (DALYs), and mortality trends of nrCAVD from 1990 to 2019 using data from the Global Burden of Disease (GBD) study 2019. The relations between ASRs and socio-demographic index (SDI) were analyzed with Pearson’s correlation coefficients. Decomposition and frontier analysis were employed to reveal the contribution proportion of influence factors and regions where improvement can be achieved. In 2019, there were 9.40 million (95% uncertainty interval (UI): 8.07 to 10.89 million) individuals with nrCAVD globally. From 1990 to 2019, the prevalence rate of nrCAVD increased by 155.47% (95% IU: 141.66% to 171.7%), with the largest increase observed in the middle SDI region (821.11%, 95% UI: 709.87% to 944.23%). Globally, there were no significant changes in the mortality rate of nrCAVD (0.37%, 95% UI: −8.85% to 7.99%). The global DALYs decreased by 10.97% (95% UI: −17.94% to −3.46%). The population attributable fraction (PAF) of high systolic blood pressure increased in the population aged 15–49 years, while it declined slightly in population aged 50+ years. Population growth was the main contributing factor to the increased DALYs across the globe (74.73%), while aging was the driving force in the high-SDI region (80.27%). The Netherlands, Finland, Luxembourg, Germany, and Norway could reduce DALY rates of nrCAVD using their socio-demographic resources. According to these results, we revealed that the burden of nrCAVD increased markedly from 1990 to 2019 in high-SDI and high-middle-SDI regions. There was a downward trend in the mortality due to nrCAVD since 2013, which is possibly owing to profound advances in transcatheter aortic valve replacement. Some countries may reduce burdens of nrCAVD using their socio-demographic resources.

Image recognition refers to the technology which processes, analyzes and understands images with computer so as to recognize various targets and objects of different patterns. To effectively combine image recognition and intelligent algorithm can enhance the efficiency of image feature analysis, improve the detection accuracy and guarantee real-time detection. In image feature recognition, the following problems exist: the description of accurate object features, object blockage, complex and changeable scenes. Whether these problems can be effectively solved has great significance in improving the stability and robustness of object recognition algorithm. This paper takes image salience as the fundamental framework, and makes in-depth study of the problems of effective object appearance description, multi-feature fusion and multi-feature adaptive combination. Then it proposes an image multi-scale feature recognition method based on image salience and it can better locate the saliency object in the image, and more evenly highlight the salient object and significantly suppress background noises. The experiment results prove that salient region detection algorithm can better stress the entire salient image.

Aim: To evaluate D-dimer levels in patients with hypertrophic cardiomyopathy (HCM). Patients & methods: A total of 346 patients with HCM were recruited. Plasma D-dimer was determined by clinical laboratory of our hospital. Left ventricular mass, stroke volume, cardiac output and cardiac index were assessed with cardiovascular magnetic resonance. Results: A total of 36 (10.4%) patients had elevated D-dimer levels. Age, female patients and statin therapy were independently associated with increasing D-dimer levels, and predictors of elevated D-dimer. Conclusion: Patients with HCM may have higher plasma D-dimer levels than subjects without HCM. D-dimer levels in patients with HCM are influenced by age, sex, atrial fibrillation, statin therapy and diastolic blood pressure.

Image semantic segmentation is a visual scene understanding task. The goal is to predict the category label of each pixel in the input image, so as to achieve object segmentation at the pixel level. Semantic segmentation is widely used in automatic driving, robotics, medical image analysis, video surveillance, and other fields. Therefore, improving the effect and accuracy of image semantic segmentation has important theoretical research significance and practical application value. This paper mainly introduces the pyramid scene parsing network PSPNet based on pyramid pooling and proposes a parameter optimization method based on PSPNet model using GPU distributed computing method. Finally, it is compared with other models in the field of semantic segmentation. The experimental results show that the accuracy of the improved PSPNet model in this paper has been significantly improved on Pascal VOC 2012 + 2017 data set.

Objective. To clarify the effect of LINC00460 on mediating the proliferative ability of vascular endothelial cells (ECs) by targeting microRNA-24-3p (miRNA-24-3p), thus influencing the progression of atherosclerotic diseases. Methods. Relative levels of LINC00460 and miRNA-24-3p in ECs induced with different doses of ox-LDL (oxidized low density lipoprotein) for different time points were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Influences of LINC00460 and miRNA-24-3p on the viability of ECs were assessed by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2 ′ -deoxyuridine (EdU) assay. Through dual-luciferase reporter gene assay, the binding between LINC00460 and miRNA-24-3p was evaluated. At last, rescue experiments were performed to identify the function of the LINC00460/miRNA-24-3p axis in regulating the proliferative ability of ECs. Results. LINC00460 was upregulated after ox-LDL treatment in a dose- and time-dependent manner. Viability of ECs gradually increased with the prolongation of ox-LDL treatment and the treatment of increased dose. The overexpression of LINC00460 enhanced the viability and EdU-positive rate in ECs treated with ox-LDL. miRNA-24-3p was the direct target of LINC00460, which was negatively regulated by LINC00460. miRNA-24-3p was downregulated with the prolongation of ox-LDL treatment. The overexpression of miRNA-24-3p could reverse the effect of LINC00460 on regulating the proliferative ability of ECs. Conclusions. LINC00460 regulates the proliferative ability of ECs and thus the occurrence and development of coronary atherosclerotic diseases by targeting miRNA-24-3p.

The present study aims to determine the expression of interleukin (IL)-10 in peripheral blood of patients with sepsis, and investigate its effects on the biological function of vascular endothelial cells.Thirty-six sepsis patients and 20 healthy subjects were included. Peripheral blood was collected from all subjects. ELISA was used to determine IL-10 content in serum. A ratio of IL-10⁺ T cells was determined by flow cytometry. CCK-8 assay was used to investigate proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. Western blotting was used to examine the expression of phosphorylated STAT3 protein.The content of IL-10 and the ratio of IL-10⁺ T cells were enhanced in pa-tients with sepsis. Serum from patients with sepsis inhibited the proliferation of HU-VECs, and addition of IL-10 antibody reversed this effect. IL-10 in the serum from patients with sepsis promoted the apoptosis of HUVECs. IL-10 inhibited the proliferation and promoted the apoptosis of HUVECs by enhancing the phosphorylation of STAT3.The present study demonstrates that the content of IL-10 and the ratio of IL-10⁺ T cells in peripheral blood of patients with sepsis are up-regulated, and this inhibits HUVEC proliferation and promotes HUVEC apoptosis through STAT3 sig-naling pathway. The results in this study provide a new experimental basis for further understanding the molecular mechanism of sepsis-induced vascular injury.

Uniaxial compressive properties of rocks are very important for designing and constructing engineering projects. Based on the available standards for determining these properties, high quality core specimens with proper geometry are needed. In many cases, the standard specimens, especially in clay-bearing, fractured, and weathered rocks, are always not able to be prepared. On the other hand, in some natural conditions, rocks with different size, shape, and cross-section are undergoing uniaxial compressive loading. Therefore, in order to evaluate the uniaxial compressive strength dependency behaviors of rocks on the shape and cross-section of tested specimens, some marble specimens with three different cross-sections, including circular, square, and rectangular, as well as four different shape ratios (height to diameter/width ratio) of 0.5, 1, 2, and 3 were prepared and tested. Axial and lateral strains, acoustic emission (AE), and camera photographs were recorded during the tests. Rock strength behavior was evaluated based on several stress thresholds, including crack closure stress (σcc), crack initiation stress (σci), damage stress (σcd), and peak stress (σucs). The results indicated that σcc was not dependent on the cross-sectional shape of specimens. With increasing shape ratio, σcc gradually increased, while σcd and σucs greatly decreased, and σci remained at a constant value. The cross-sectional shape effect became operative when r was less than or equal to 1. Moreover, the values of σcd and σucs of rectangular prism specimens and square prism specimens are lower than those of cylindrical specimens, indicating that the unstable crack propagation of prism specimens occurs earlier. The difference gap of σcd and σucs between specimens with different cross-sectional shapes was dramatically decreased with increasing shape ratio. The AE and camera recorded data indicated that the fracture modes of rectangular and square prism specimens are more likely to change from shearing to slabbing fracture when the shape ratio decreased from 3 to 0.5. The main crack developed surface turned from wide surface to narrow surface with the shape ratio of rectangular prism specimens changing from 3 to 1 and 0.5. The research results are of referential meaning to the design of pillars in underground hard rock mines.

Biocompatible, small-sized but well-dispersed gold nanoparticles (Au NPs) remain a major challenge for their synthesis. Here a convenient solution impregnation technique is developed to prepare such Au NPs under the regulation of degummed silk fibroin fibers (SFFs) extracted from Bombyx mori cocoons. SFFs play multiple roles in the formation of Au NPs such as reactive substrate to capture AuCl4- ions by the chelation of -C = O, reducing agent for Au(0) by the reduction of -OH, and modifiers to render biocompatible Au NPs by some functional groups and biomolecules. The as-prepared Au NPs with a size of 7–10 nm are embedded in the solid SFF substrate, and can disperse well in the liquid system by the disintegration of SFFs into silk fibroin (SF) in a certain CaCl2 solution. The biocompatible Au NPs exhibit uniform small size and distribute stably in both solid and solution states, which have distinctive properties and functional advantages, and bring great convenience to their storage and transportation.

Background The mortality rate of patients with hemodynamic instability due to severe pelvic fracture remains substantial and massive transfusion happens frequently. Angio-embolization, external fixation and preperitoneal pelvic packing of the pelvis are the main managements used to control bleeding in these patients. In this paper, we aimed at characterizing the rationale of these surgical managements, and placed them in optimal management algorithm to compose a new guideline. Methods We selected controlled trials, assessing safety of management for the intervention of hemorrhagic shock from mortality data, and assessing efficacy from volume of first 24 h blood transfusion following hospitalization. Six single and combined managements were extracted as comparison. A pairwise meta-analysis was conducted using a random effect model, and then the analysis was extended to a network meta-analysis. Pooled effect sizes were ranked and demonstrated the probability of being the best treatments for safety and efficacy. Results 13 clinical trials and 24,396 participants were identified for this analysis. The assessment of rank probability indicated that pelvic packing presented the greatest likelihood of improving safety, while external fixation was indicated most efficient among the interventions for controlling hemorrhage. Conclusions Clinical protocols for guidelines of hemodynamically unstable pelvic fracture patients have been multidirectionally developed. We strongly support the initial application of an external fixator. Provided that patients remain hemodynamically unstable after application of an external fixation, pelvic packing is the next procedure to consider. Angio-embolization is the complementary but not alternative method of choice subsequently.

Fatigue tests under high static pre-stress loads can provide meaningful results to better understand the time-dependent failure characteristics of rock and rock-like materials. However, fatigue tests under high static pre-stress loads are rarely reported in previous literature. In this study, the rock specimens were loaded with a high static pre-stress representing 70% and 80% of the uniaxial compressive strength (UCS), and cyclic fatigue loads with a low amplitude (i.e., 5%, 7.5% and 10% of the UCS) were applied. The results demonstrate that the fatigue life decreased as the static pre-stress level or amplitude of fatigue loads increased for different rock types. The high static pre-stress affected the fatigue life greatly when the static pre-stress was larger than the damage stress of rocks in uniaxial compression tests. The accumulative fatigue damage exhibited three stages during the fatigue failure process, i.e., crack initiation, uniform velocity, and acceleration, and the fatigue modulus showed an “S-type” change trend. The lateral and volumetric strains had a much higher sensitivity to the cyclic loading and could be used to predict fatigue failure characteristics. It was observed that volumetric strain $$\varepsilon _{{\text{v}}}$$ = 0 is a threshold for microcracks coalescence and is an important value for estimating the fatigue life.

Background: Previous studies have shown that heart failure is associated with hemostatic abnormalities and hypercoagulable state. Plasma D-dimer levels reflect both fibrin formation and degradation, and elevated D-dimer levels have been associated with poor prognosis in patients with heart failure. However, little is known about their roles in elderly patients with end-stage HF. In present study, we aimed to explore the clinical significance and determinants of plasma D-dimer in elderly patients with end-stage heart failure. Methods: A total of 177 patients with heart failure at Beijing Geriatric Hospital from November 1, 2015 to December 30, 2018 were enrolled. All hospitalized patients were obtained D-dimer levels within the first 24 h following admission after obtaining informed consent. Primary endpoint was all-cause mortality. Results: A total of 60 patients had elevated D-dimer levels. Blood urea nitrogen (β=1.106, 95% CI: 1.029-1.190, p = 0.006), NYHA functional class (β=2.179, 95% CI: 1.170-4.056, p = 0.014) and white blood cell counts (β = 1.188, 95% CI: 1.040-1.358, p = 0.011) were independent risk factors for elevated D-dimer in elderly patients with end-stage heart failure. Albumin (β=0.803, 95% CI: 0.728-0.885, P ＜ 0.001) was negative risk factor for elevated D-dimer in elderly patients with end-stage heart failure. Elevated D-dimer level was independently associated with increased risk of long-term all-cause mortality (P = 0.048). Conclusions: For elderly patients with end-stage heart failure, D-dimer levels were associated with white blood cell counts, blood urea nitrogen, albumin and NYHA functional class and elevated D-dimer level was independently associated with poor long-term outcome.

Seipin deficiency can induce hypertrophic cardiomyopathy and heart failure, which often leads to death in humans. To explore the effects and the possible mechanisms of Seipin deficiency in myocardial remodeling, Seipin knockout (SKO) mice underwent transverse aortic constriction (TAC) for 12 weeks. We found a more severe left ventricular hypertrophy and diastolic heart failure and increases in inflammatory cell infiltration, collagen deposition, and apoptotic bodies in the SKO group compared to those in the wild type (WT) group after TAC. Electron microscopy also showed a more extensive sarcoplasmic reticulum expansion, deformation of microtubules, and formation of mitochondrial lesions in the cardiomyocytes of SKO mice than in those of WT mice after TAC. Compared with the WT group, the SKO group showed increases in endoplasmic reticulum (ER) stress-, inflammation-, and fibrosis-related gene expression, while calcium ion-related factors, such as Serca2a and Ryr, were decreased in the SKO group after TAC. Increased levels of the ER stress-related protein GRP78 and decreased SERCA2a and P-RYR protein levels were detected in the SKO group compared with the WT group after TAC. Slowing of transient Ca2+ current decay and an increased SR Ca2+ content in myocytes were detected in the cardiomyocytes of SKO mice. Adipose tissue transplantation could not rescue the cardiac hypertrophy after TAC in SKO mice. In conclusion, we found that Seipin deficiency could promote cardiac hypertrophy and diastolic heart failure after TAC in mice. These changes may be related to the impairment of myocardial calcium handling, ER stress, inflammation, and apoptosis.

The surrounding rocks of underground engineering are generally subjected to a biaxial compressive stress condition. The failure properties of rocks under such a stress condition are worthy of being studied to ensure the stability of surrounding rock. This study aims to investigate the mechanical characteristics and acoustic emission (AE) properties of granite, marble, and sandstone in biaxial compression tests. Under biaxial confinements, it is evident that the elastic moduli of the three types of rocks decrease, and the plasticity increases monotonously with the increase of the intermediate principal stress &sigma, 2. As &sigma, 2 increases, the biaxial compressive strength &sigma, bcs of rock increases initially and subsequently decreases. The lateral strain &epsilon, 2 of rock under biaxial confinement is controlled by both &sigma, 1 and &sigma, 2, and the restrain degree in the development of microcracks and the constrain extent in the expansion along the direction of &sigma, 2 are both enhanced gradually with increase in &sigma, 2. The sharp increase points of AE hit and AE count indicate that the failure will occur soon. The AF-RA distribution of AE signals shows that the increase of &sigma, 2 causes more tensile cracks in rock. According to the dip failure angle of macro-cracks in rock under biaxial confinement, the failure modes of granite and marble are slabbing, while failure mode of sandstone is shear. In addition, the &sigma, 2 has a positive effect on the mass ratio of large size fragments after rock failure. An exponent relationship between the &sigma, bcs and &sigma, 2 was found, and the inner apices&ndash, inscribed Drucker&ndash, Prager criterion can be used to predict the &sigma, bcs of rock.

Background: The purpose of this meta-analysis is to compare the efficacy and safety of aspirin and rivaroxaban in the prevention of venous thromboembolism (VTE) following either total knee arthroplasty or total hip arthroplasty. Methods: A comprehensive literature search of several electronic databases (PubMed, Embase, and Web of Science) was conducted to identify relevant studies. Outcomes of interest included VTE rate, deep vein thrombosis (DVT) rate, pulmonary embolism rate, major bleeding events, mortality rate, blood transfusion, and wound complication. Risk ratio (RR) with 95% confidence intervals (95%CIs) were calculated using a fixed-effects model or random-effects model. Results: A total of 8 studies with 97,677 patients met the inclusion criteria and were included in this meta-analysis. Compared with rivaroxaban, aspirin had a significantly higher incidence of DVT (RR = 1.48, 95%CI: 1.27, 1.72; P

BACKGROUND This study investigated the effect of supernatant of endothelial cells stimulated by peripheral blood serum from sepsis patients on phenotype and function of peripheral NKT cells. MATERIAL AND METHODS Twenty-one patients with sepsis and 21 healthy subjects were included. Peripheral blood (5 ml) was collected from all patients and healthy subjects. To isolate peripheral blood mononuclear cells (PBMCs), Ficoll lymphocyte separation solution was used. Flow cytometry was carried out to determine NKT cell ratio, activity, and cytokine secretion. Human umbilical vein endothelial cells were cultured with serum from sepsis patients for 48 h before changing to fresh medium, and supernatant was collected. The supernatant was used to co-culture PBMCs before analyzing NKT activity and cytokines. RESULTS The ratios of CD3-CD56+NK cells and CD3+CD56+NKT cells were increased in peripheral blood from sepsis patients. Surface receptors p30, G2D, and p44 of CD3+CD56+NKT cells were elevated, while inhibitory receptors NKG2A and 158b were decreased. CD4+ NKT cells in peripheral blood from sepsis patients were enhanced. GranB, IFN-γ, IL-4, and IL-17 in NKT cells from sepsis patients were up-regulated. After co-culture with vascular endothelial cells treated with sepsis serum, expression of p30 and G2D in NKT cells was upregulated, and number of TCRVa24-positive cells was increased. In addition, ratio of CD4+NKT cells was increased, and intracellular expression of IL-4 and IFN-γ was elevated. CONCLUSIONS The study demonstrates that the level of NKT cells in peripheral blood from sepsis patients is increased, and their activity is enhanced. In addition, vascular endothelial cells from sepsis patients can regulate the activity of NKT cells.