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Purpose This study aimed to assess the relationship between the cardiac rhythm response to ibutilide infusion after pulmonary vein isolation and the recurrence of long-term atrial arrhythmias. Methods One hundred and thirty-eight patients with non-paroxysmal atrial fibrillation who had had their first catheter ablation were retrospectively included. All patients whose atrial fibrillation did not terminate after pulmonary vein isolation were administered intravenous ibutilide (1.0 mg). Those with termination of atrial fibrillation after ibutilide administration were defined as responders (n = 86); those without termination of atrial fibrillation, as non-responders ( n = 52). The primary endpoint was any documented recurrence of atrial arrhythmia lasting more than 30 seconds after the initial catheter ablation. Results Conversion of atrial fibrillation to sinus rhythm, directly or via atrial flutter, with ibutilide administration was achieved in 62.3% of patients. A longer duration of atrial fibrillation was associated with failed termination of atrial fibrillation (odds ratio 1.009, 95% confidence interval 1.002-1.017, p = 0.011). During a median follow-up period of 610 days (interquartile range 475-1 106) post ablation, non-responders (n = 24, 46.2%) had a higher recurrence rate of atrial arrhythmia than the responders (n = 26, 30.2%; log-rank, p = 0.011) after the initial catheter ablation. Multivariate Cox regression analysis revealed that non-responders (hazard ratio 1.994, 95% confidence interval 1.117-3.561, p = 0.020) was significantly correlated with recurrence of atrial arrhythmias. Conclusions In patients whose atrial fibrillation persisted after pulmonary vein isolation, the response to ibutilide administration could predict the recurrence of atrial arrhythmias after catheter ablation, which may be useful for risk stratification for recurrence of atrial fibrillation and individualised management of atrial fibrillation.

Objectives Early acute kidney injury (AKI) after burn contributes to disastrous prognoses for severely burned patients. Burn-induced renal oxidative stress and secondary proinflammatory mediator release contribute to early AKI development, and Toll-like receptor (TLR) 4 regulates inflammation. Heme oxygenase-1 (HO-1) is a stress-responsive enzyme that plays a vital role in protecting against ischemia-induced organ injury via its antioxidant properties and regulation of inflammation. We investigated the potential effect of HO-1 induction in preventing burn-induced early AKI and its related mechanism. Methods A classic major-burn rat model was established using a 100 °C water bath, and hemin was injected intraperitoneally immediately after the injury to induce HO-1. Histological staining and blood tests were used to assess AKI progression based on structural changes and function. Renal levels of HO-1, oxidative stress, proinflammatory mediators and TLR4-related signals were detected using ELISA, immunostaining, qRT-PCR, and western blotting. The selective TLR4 inhibitor TAK242 and TLR4 inducer LPS were introduced to determine the roles of HO-1 in burn-related renal inflammation and the TLR4 pathway. Results Hemin improved burn-induced renal histological damage and dysfunction, and this beneficial effect was related to reduced renal oxidative stress and the release of proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and intracellular adhesion molecule-1 (ICAM-1). Hemin downregulated the expression of TLR4 and the subsequent phosphorylation of IKKα/β, IκBα, and NF-κB p65;. TAK242 exerted an effect similar to but weaker than hemin; and LPS reversed the antiinflammatory effect of hemin and the regulation of TLR4 signals. These results suggested that the TLR4 signaling pathway mediated the HO-1-facilitated regulation of renal inflammation after burn. Conclusion The present study demonstrated that HO-1 induction prevented burn-induced early AKI by targeting renal inflammation, which was mediated via regulation of the TLR4/NF-κB signaling pathway.

With the rapid development of social media platforms and the increasing scale of the social media data, the rumor detection task has become vitally important since the authenticity of posts cannot be guaranteed. To date, many approaches have been proposed to facilitate the rumor detection process by utilizing the multi-task learning mechanism, which aims to improve the performance of rumor detection task by leveraging the useful information contained in stance detection task. However, most of the existing approaches suffer from three limitations: (1) only focus on the textual content and ignore the multi-modal information which is key component contained in social media data; (2) ignore the difference of feature space between the stance detection task and rumor detection task, resulting in the unsatisfactory usage of stance information; (3) largely neglect the semantic information hidden in the finegrained stance labels. Therefore, in this paper, we design a Multi-modal Meta Multi-Task Learning (MM-MTL) framework for social media rumor detection task. To make use of multiple modalities, we design a multi-modal post embedding layer which considers both textual and visual content. To overcome the feature sharing problem of the stance detection task and rumor detection task, we propose a meta knowledge-sharing scheme to share some higher meta network layers and capture the metaknowledge behind the multi-modal post. To better utilize the semantic information hidden in the fine-grained stance labels, we employ the attention mechanism to estimate the weight of each reply. Extensive experiments on two Twitter benchmark datasets demonstrate that our proposed method achieves state-of-the-art performance.

Background Low voltage zones (LVZ) are associated with poor outcomes in patients with atrial fibrillation (AF). The APPLE and DR-FLASH scores predict LVZ in patients undergoing catheter ablation. This study aimed to assess the relationship of mitral valve regurgitation (MR) and LVZ after adjusting for APPLE or DR-FLASH scores. Methods This was a retrospective study on patients with AF who underwent their first catheter ablation. All patients underwent a transthoracic echocardiographic examination before ablation. The APPLE and DR-FLASH scores were calculated at baseline. LVZ determined by high-density mapping was defined as bipolar voltage amplitude 5% of the left atrial surface area. Results Altogether, 152 patients (mean age 62.0 ± 10.8 years, 65.8% men, and 36.2% with persistent AF) were included. Of the 152 patients, 47 (30.9%) had LVZ. The patients with LVZ had more moderate-to-severe MR (17.0% vs. 3.8%, P = 0.014) and higher APPLE scores (1.7 ± 1.1 vs. 1.2 ± 1.1, P = 0.009) and DR-FLASH scores (3.0 ± 1.5 vs. 2.4 ± 1.4, P = 0.010). Using multivariate logistic regression analysis, we found moderate-to-severe MR was related to LVZ presence after adjusting for the APPLE (OR 4.040, P = 0.034) or DR-FLASH (OR 4.487, P = 0.020) scores. Furthermore, moderate-to-severe MR had an incremental predictive value for LVZ presence in addition to the APPLE (P = 0.03) or DR-FLASH (P = 0.02) scores. Conclusion In patients with AF, MR severity was related to LVZ after adjusting the APPLE score or DR-FLASH score.

In this article, we focus on fake news detection task and aim to automatically identify the fake news from vast amount of social media posts. To date, many approaches have been proposed to detect fake news, which includes traditional learning methods and deep learning-based models. However, there are three existing challenges: (i) How to represent social media posts effectively, since the post content is various and highly complicated; (ii) how to propose a data-driven method to increase the flexibility of the model to deal with the samples in different contexts and news backgrounds; and (iii) how to fully utilize the additional auxiliary information (the background knowledge and multi-modal information) of posts for better representation learning. To tackle the above challenges, we propose a novel Knowledge-aware Multi-modal Adaptive Graph Convolutional Networks (KMAGCN) to capture the semantic representations by jointly modeling the textual information, knowledge concepts, and visual information into a unified framework for fake news detection. We model posts as graphs and use a knowledge-aware multi-modal adaptive graph learning principal for the effective feature learning. Compared with existing methods, the proposed KMAGCN addresses challenges from three aspects: (1) It models posts as graphs to capture the non-consecutive and long-range semantic relations; (2) it proposes a novel adaptive graph convolutional network to handle the variability of graph data; and (3) it leverages textual information, knowledge concepts and visual information jointly for model learning. We have conducted extensive experiments on three public real-world datasets and superior results demonstrate the effectiveness of KMAGCN compared with other state-of-the-art algorithms.

Studies have reported a positive association between hepatitis B surface antigen (HBsAg)-positive hepatitis B virus (HBV) infection and follicular lymphoma (FL). Nevertheless, clinical information concerning chronic HBV infection in FL is sparse. This retrospective cohort study investigated the prognostic impact of HBsAg in immunocompetent patients with FL treated with frontline rituximab-containing chemoimmunotherapy in an HBV-endemic area between 2006 and 2016. Among the 149 analyzed patients, 32 (21.5%) were HBsAg-positive. HBsAg positivity was positively associated with symptomatic splenomegaly, significant serous effusions, and peritreatment hepatic dysfunction. HBsAg-positive patients had a trend of lower complete remission rate (59.4% vs. 76.9%, P = 0.07), significantly poorer overall survival (hazard ratio for death, 2.68; 95% confidence interval, 1.21–5.92), and shorter progression-free survival than had HBsAg-negative patients. Multivariate analysis revealed that HBsAg is an independent adverse prognostic factor for overall survival. Intriguingly, HBsAg-positive patients had a higher incidence of progression of disease within 24 months (POD24) than had HBsAg-negative patients (cumulative incidence rate, 25.8% vs. 12.4%, P = 0.045). This study revealed that patients with FL and chronic HBV infection represent a distinct subgroup with a markedly poor prognosis. HBsAg was positively associated with POD24 and might serve as a new prognostic predictor of the survival of FL patients in endemic regions for HBV infection.

Background The glycocalyx plays an important physiological role and may be damaged during cardiopulmonary bypass. Sevoflurane can protect the glycocalyx; however, its relevance in a clinical setting is unknown. Objective Glycocalyx degradation during cardiopulmonary bypass in patients was investigated. On the basis of the available experimental data, we hypothesised that sevoflurane-based anaesthesia would confer additional protection against cardiopulmonary bypass-induced glycocalyx damage. Design Randomised controlled study. Setting Clinical study at The First Affiliated Hospital of Wenzhou Medical University between June 2018 and March 2019. Patients Fifty-one patients. Interventions After intubation and mechanical ventilation, patients undergoing elective heart valve surgery were maintained under general anaesthesia with either propofol or sevoflurane during surgery. Main outcome measures Glycocalyx markers (such as syndecan-1, heparan sulphate and hyaluronan), sheddases responsible for the degradation of the endothelial glycocalyx (such as matrix metalloproteinase-9 and cathepsin-B), urine albumin-to-creatinine ratio and levels of lactic acid and myocardial enzymes were all measured. Postoperative mechanical ventilation time and length of stay in the cardiac care unit and hospital were also measured. Morbidity and mortality after 30 days and 1 year were evaluated. Results The vascular endothelial glycocalyx was damaged during cardiopulmonary bypass. The glycocalyx damage in the sevoflurane group was less extensive than that in the propofol group. The urine albumin-to-creatinine ratio increased in both groups but was lower in the sevoflurane group. Enzymes including matrix metalloproteinase-9 and cathepsin-B were positively correlated with glycocalyx marker concentrations. After operation, the sevoflurane group showed lower levels of lactic acid and myocardial enzyme, as well as shorter duration of postoperative mechanical ventilation than the propofol group. Conclusion Sevoflurane can decrease glycocalyx degradation in patients undergoing heart valve surgery under cardiopulmonary bypass. Trial registration Chinese Clinical Trial Registry, chictr.org.cn, identifier: ChiCTR1800016367.

Right ventricular (RV) failure is a major cause of death in patients with pulmonary arterial hypertension, and the mechanism of RV failure remains unclear. While the malfunction of RyR2 (ryanodine receptor type 2) on sarcoplasmic reticulum (SR) and aberrant Ca 2+ cycling in cardiomyocytes have been recognized in some cardiovascular diseases, their roles in RV failure secondary to pulmonary arterial hypertension require further investigation. In a monocrotaline-induced rat model of pulmonary arterial hypertension, the RV remodeling process was divided into normal, compensated, and decompensated stages according to the hemodynamic and morphological parameters. In both compensated and decompensated stages, significant diastolic SR Ca 2+ leakage was detected along with reduced intracellular Ca 2+ transient amplitude and SR Ca 2+ contents in RV myocytes. RyR2 protein levels decreased progressively during the process, and the thiol oxidation proportions of RyR2 were higher in compensated and decompensated stages than in normal stage. Inhibition of RyR2 oxidation by dithiothreitol or repairing RyR2 directly by dantrolene could restore Ca 2+ homeostasis in RV myocytes. Daily intraperitoneal injection of dantrolene delayed decompensation progression and significantly improved the survival rate of pulmonary hypertension rats in decompensated stage (79.3% versus 55.9%; P =0.026). Our findings suggest that diastolic SR Ca 2+ leakage via oxidized RyR2 facilitates the development of RV failure. Dantrolene can inhibit diastolic SR Ca 2+ leakage in RV cardiomyocytes, delay right cardiac dysfunction, and improve the survival of rats with pulmonary arterial hypertension.

Aims This study aims to investigate the current status of biventricular pacemaker and defibrillator implantation in chronic heart failure (CHF) patients with indications for primary prevention of sudden cardiac death (SCD) in China and the effects of cardiac resynchronization therapy (CRT)‐pacemaker (P) and CRT‐defibrillator (D) implantation on the clinical prognosis of CHF among patients undergoing CRT. Methods and results Overall, 798 consecutive patients who had devices implanted (implantable cardioverter defibrillator: 199, CRT‐D: 362, and CRT‐P: 237) from May 2012 to July 2013 in POSCD‐China, a multicentric prospective cohort study, were enrolled. The primary endpoint was all‐cause death, and the secondary endpoint was SCD. In total, 71.3% of patients had non‐ischaemic CHF. The mean follow‐up time was 27.7 ± 12.0 months, and death occurred in 158 cases, with 35 cases of SCD. CHF was the main cause of death (68.4%), followed by sudden death (22.2%). In the CRT‐P group, the SCD rate was 8.0%, which was much higher than that in the CRT‐D (3.3%) and implantable cardioverter defibrillator (2.0%) groups. No significant differences were identified in the all‐cause death rate between the CRT‐D and CRT‐P groups (CRT‐D vs. CRT‐P, 20.4% vs. 19.4%, P = 0.840). Conclusions In China, among CHF patients with indications for primary prevention of SCD who received device implantation, non‐ischaemic CHF was the main aetiology, and the most important cause of death was heart failure. No differences in all‐cause death were observed between the CRT‐D and CRT‐P groups, but the CRT‐D group had a lower SCD rate than the CRT‐P group.

With the development of the Internet, more and more creators publish articles on social media. How to automatically filter high quality content from a large number of multimedia articles is one of the core functions of information recommendation, search engine, and other systems. However, existing approaches typically suffer from two limitations: (1) They usually model content as word sequences, which ignores the semantics provided by non-consecutive phrases, long-distance word dependency, and visual information. (2) They rely on a large amount of manually annotated data to train a quality assessment model while users may only provide labels of interest in a single class for a small number of samples in reality. To address these limitations, we propose a Multimodal Graph Convolutional Networks (MGCN) to model the semantic representations in a unified framework for High Quality Content Recognition. Instead of viewing text content as word sequences, we convert them into graphs, which can model non-consecutive phrases and long-distance word dependency for better obtaining the composition of semantics. Besides, visual content is also modeled into the graphs to provide complementary semantics. A well-designed graph convolutional network is proposed to capture the semantic representations based on these graphs. Furthermore, we employ a non-negative risk estimator for high quality content recognition and the loss is back-propagated for model learning. Experiments on real datasets validate the effectiveness of our approach.

Purpose Patients with malignancy are more likely to develop nutritional problems. The Geriatric Nutritional Risk Index (GNRI) is a new prognostic index for evaluating nutritional status. The objective of this study was to assess if preoperative GNRI could be a prognostic factor for patients with pancreatic ductal adenocarcinoma (PDAC) who underwent radical surgery. Patients and methods This study included 282 consecutive patients with incident pancreatic ductal adenocarcinoma who were treated with radical surgery. The Cox regression analysis was performed to calculate the overall survival (OS) and assess the prognostic factors. A nomogram was developed based on the results of the multivariate analysis, and the predictive accuracy of the nomogram was assessed. Results Among the 282 patients, there are 117 males and 165 females. The patients had a mean age of 58.7 ±13.5 years, with the median follow-up time of 72.9 months (interquartile range, 0.7 to 115.2 months). They were classified into abnormal (GNRI ≤ 98) and normal (GNRI > 98) GNRI groups, respectively. Multivariate Cox analysis showed that age (HR = 1.023), drinking history (HR = 1.453), tumor grade (HR = 1.633), TNM stage (HR = 1.921), and GNRI (HR = 1.757) were significantly associated with OS. Based on the above variables, the nomogram was established. The concordance index (C-index) and time-dependent receiver operating characteristics curve (tdROC) showed the nomogram was superior to TNM grade and tumor grade in predicting the OS of patients with PDAC. Conclusion GNRI could be a useful prognostic indicator in patients with PDAC who received surgery. Based on the GNRI and the other clinical indicators, we developed a nomogram model that can provide an accurate estimation of OS in patients with PDAC after radical surgery.

Background China is facing a more severe stroke challenge. In 2017, China fully implemented the zero-margin drug policy (ZMDP), cancelling 15% of drug markups in public hospitals. Based on the "System of Health Accounts 2011" (SHA 2011), this paper explores the changes in the economic burden of stroke in China after implementing ZMDP to provide an accurate reference for policymakers. Methods Stroke patients from 2016 to 2018 were selected by multistage stratification probability-proportional random sampling in Shanxi Province. A total of 223 187 samples were included. Regression discontinuity design (RDD) was used to measure the change of drug proportion and cost. Sensitivity analysis and subgroup analysis were implied to determine the stability of the results. Results The current curative expenditure on stroke from 2016 to 2018 was 4374.69, 3727.22, and 3752.52 million Chinese Yuan (CNY). About 90% of the cost occurred during hospitalization, and 60% in general hospitals. After the implementation of ZMDP, the drug proportion from 46.54% (interquartile range (IQR) = 37.10%, 55.14%) in 2016 to 36.40% (IQR = 25.82%, 48.58%) in 2018, and average hospitalization cost per stay was from 7950.02 (IQR = 4938.76, 12 639.90) CNY in 2016 to 7362.08 (IQR = 4892.82, 11 501.40) CNY in 2018. RDD showed the drug proportion decreased by 2.76% (95% confidence interval (CI) = 1.17%, 4.35%, P = 0.001), and the expense decreased by 4698.34 (95% CI = 3047.59, 6349.09, P

We introduce tf_geometric, an efficient and friendly library for graph deep learning, which is compatible with both TensorFlow 1.x and 2.x. tf_geometric provides kernel libraries for building Graph Neural Networks (GNNs) as well as implementations of popular GNNs. The kernel libraries consist of infrastructures for building efficient GNNs, including graph data structures, graph map-reduce framework, graph mini-batch strategy, etc. These infrastructures enable tf_geometric to support single-graph computation, multi-graph computation, graph mini-batch, distributed training, etc.; therefore, tf_geometric can be used for a variety of graph deep learning tasks, such as transductive node classification, inductive node classification, link prediction, and graph classification. Based on the kernel libraries, tf_geometric implements a variety of popular GNN models for different tasks. To facilitate the implementation of GNNs, tf_geometric also provides some other libraries for dataset management, graph sampling, etc. Different from existing popular GNN libraries, tf_geometric provides not only Object-Oriented Programming (OOP) APIs, but also Functional APIs, which enable tf_geometric to handle advanced graph deep learning tasks such as graph meta-learning. The APIs of tf_geometric are friendly, and they are suitable for both beginners and experts. In this paper, we first present an overview of tf_geometric's framework. Then, we conduct experiments on some benchmark datasets and report the performance of several popular GNN models implemented by tf_geometric., Comment: 7 pages, 5 figures

Cardiac amyloidosis is a rare disease due to the deposition of amyloid fibrils in the heart. Clinical manifestation of the heart includes restrictive heart failure and arrhythmia, when myocardium and conduction system are involved respectively. Arrhythmia can present as atrioventricular block (AVB), and sick sinus syndrome (SSS), therefore cardiac amyloidosis may require permanent pacemaker implantation. However, the stability of pacemaker parameters in cardiac amyloidosis patients remains unknown. We conducted an observational retrospective study of patients diagnosed with cardiac amyloidosis who underwent permanent pacemaker implantation from January 1, 2011 to December 31, 2019. Base-line data were obtained via Medical Record System. Data of pacemaker parameters were obtained via pacemaker programming at the time of implantation and last follow-up at the clinic. A total of 10 patients were included in our study, among which 5 patients underwent cardiac biopsy and showed positive result, 4 patients showed positive biopsy result of other tissue and characteristic echocardiography result of restrictive diastolic dysfunction, 1 patient was diagnosed with primary systematic amyloidosis (AL) involving kidney and advanced atrioventricular block. Amyloidosis type of the 10 patients were primary systemic amyloidosis (AL). Among the 10 patients, 3 were female (30.0%), and the mean age was 61.3±3.9. All patients met the indication for permanent pacemaker implantation, including 9 SSS and 1 advanced AVB. 9 patients were implanted with DDD, and 1 with VVI. The middle survival time was 446 (331, 728) days from the time of implantation to last follow-up (June 30, 2020). Two patients died due to disease progression. As for the 7 patients whose baseline and follow-up data were both obtained, pacemaker parameters at baseline were as followed: Atrial Impedance 477.8±115.0 Ω, Atrial P Wave 1.30±0.70 mV, Atrial Threshold 0.75±0.16 V@0.4ms, Ventricular Impedance 551.3±233.4 Ω, Ventricular R Wave 7.99±4.66 mV, Ventricular Threshold 0.76±0.15 V@0.4ms. Pacemaker parameters at follow-up were as followed: Atrial Impedance 426.2±93.2 Ω, Atrial P Wave 1.34±0.71 mV, Atrial Threshold 1.59±1.51 V@0.4ms, Ventricular Impedance 405.8±41.6 Ω, Ventricular R Wave 10.69±6.53 mV, Ventricular Threshold 1.80±1.88 V@0.4ms. Most patients relieved from cardiac symptoms and severe cardiac complications. A relatively short-term follow-up indicated elevation of Ventricular Threshold (P=0.028), and analysis of other parameters showed insignificant results. Elevation of Ventricular Threshold may be explained by the progression of amyloid fibrils deposition in the heart. Ventricular Threshold of one patient significantly increased from 1.0 V to 6.0 V at 3-month follow-up. Since all patients underwent chemotherapy for the primary amyloidosis, stability of pacemaker parameters may be another way for evaluation. Long-term follow-up is needed for further evaluation. Funding Acknowledgement Type of funding sources: None.

Background: Noncommunicable diseases (NCDs) are the leading causes of morbidity and mortality worldwide. Understanding the distribution of diseases can provide a basis for policy formulation and intervention. This study analyses the current curative expenditure (CCE) of NCDs in China to provide health policy advice.Methods: Data were collected by multi-stage stratified random sampling from 2017-2019. The medical expenses of patients with NCDs were calculated based on “System of Health Accounts 2011”(SHA 2011), Analyze from funding sources, dimensions of institutional flow, and financing scheme. Linear regression analysis was conducted by controlling factors influencing hospitalization expenses. All analyses were performed by STATA 15.0.Results: 408 institutions and 8,104,233 valid items were included in the study. The CCE of NCDs was 14.205 billion China Yuan (CNY) in 2017, 15.914 billion CNY in 2018, and 18.055 billion CNY in 2019. More than 60% came from public financing. The proportion of family health financing continued to decline, reaching 31.16% in 2019. The expenditures were mainly in general hospitals, above 70%. Elderly patients account for the majority. Diseases of the circulatory system, Diseases of the digestive system, and Neoplasms were the main NCDs. Year, age, gender, length of stay, surgery, insurance, and institution level were the factors affecting hospitalization expenses.Conclusions: NCDs are the main CCE of diseases in China, and their resources are not allocated reasonably. To reduce the CCE of NCDs, the government needs to optimize resource allocation and rationalize institutional flows and functions.

The cross-modal image-text retrieval has attracted extensive attention in recent years, which contributes to the development of search engine. Fine-grained features and cross-attention have been widely used in past researches to reach the goal of cross-modal image-text matching. Although cross-related methods have achieved remarkable results, the features must be encoded again in evaluation phase due to the interaction of the two modalities, which is unsuitable for actual scenarios of search engine development. In addition, the aggregated feature does not contain sufficient semantics since it is merely obtained by simple mean pooling. Furthermore, connecting weights of self-attention blocks are target position invariant, which lacks the expected adaptability. To tackle these limitations, in this paper, we propose a novel Global Relation-aware Attention Network (GRAN) for image-text retrieval by designing Global Attention Module (GAM) and Relation-aware Attention Module (RAM) which play an important role in modeling the global feature and the relationships of local fragments. Firstly, we propose Global Attention Module (GAM) followed the fine-grained features to obtain meaningful global feature. Secondly, we use several stacked transformer encoders to further encode features separately. Finally, we propose Relation-aware Attention Module (RAM) to generate a vector which represents the relation information to infer the attention intensity of pairwise fragments. The local features, the global feature, and their relations are considered jointly to conduct an efficient image-text retrieval. Extensive experiments are conducted on the benchmark datasets of Flickr30K and MSCOCO, demonstrating the superiority of our method. On the Flickr30K, compared to the state-of-the-art method TERAN, we improve Recall@K(K=1) metric by 5.8% and 4.0 on the image and text retrieval tasks, respectively.

Orofacial pain is one of the most common medical challenges. A preliminary report indicates that the NOP receptor may act as a therapeutic target in orofacial pain. Previous studies have shown that [(pF)Phe4, Aib7, Aib11, Arg14, Lys15]N/OFQ-NH2 (NOP01) functions as a potent NOP receptor peptide agonist. This work aims to investigate the antinociception of NOP01 and its possible action mechanisms in a formalin-induced mouse orofacial pain model at different levels. Our results demonstrated that local, intraperitoneal (i.p.) or intrathecal (i.t.) injection of NOP01 produced dose-related antinociception in both phases of the formalin pain, which could be inhibited by the NOP receptor antagonist but not the classical opioid receptor antagonist. Furthermore, the antinociception induced by systemic NOP01 was blocked by local but not spinal pretreatment with the NOP receptor antagonist, suggesting the involvement of the peripheral NOP receptor in NOP01-induced systemic antinociception. Moreover, local injection of NOP01 markedly suppressed the expression of c-Fos protein induced by formalin in ipsilateral trigeminal ganglion (TG) neurons. In conclusion, this work suggests that NOP01 exerts significant antinociception on orofacial pain at both peripheral and spinal levels via the NOP receptor. Notably, NOP01 cannot readily penetrate the blood-brain barrier. Thus, NOP01 may behave as a potential compound for developing peripherally restricted analgesics.

Background: Noncommunicable diseases (NCDs) are the leading causes of morbidity and mortality worldwide. Understanding the financing and distribution of diseases can provide a basis for policy formulation and intervention. This study analyses the expenditure of NCDs in China to provide health policy advice.Methods: Data were collected by multi-stage stratified random sampling from 2017-2019. The medical expenses of patients with NCDs were calculated based on “System of Health Accounts 2011”(SHA 2011), Analyze from funding sources, dimensions of institutional flow, and financing scheme. Linear regression analysis was conducted by controlling factors influencing hospitalization expenses. All analyses were performed by STATA 15.0.Results: 408 institutions and 8,104,233 valid items were included in the study. The current curative expenditure (CCE) of NCDs was 14.205 billion China Yuan (CNY) in 2017, 15.914 billion CNY in 2018, and 18.055 billion CNY in 2019. More than 60% came from public financing. The proportion of family health financing continued to decline, reaching 31.16% in 2019. The expenditures were mainly in general hospitals, above 70%. Elderly patients account for the majority. Diseases of the circulatory system, Diseases of the digestive system, and Neoplasms were the main NCDs. Year, age, gender, length of stay, surgery, insurance, and institution level were the factors affecting hospitalization expenses.Conclusions: NCDs are the main economic burden of diseases in China, and their financing and distribution are inequality. To reduce the economic burden of NCDs, the government needs to optimize resource allocation and rationalize institutional flows and functions.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are an effective treatment for common EGFR mutations in non-small-cell lung cancer (NSCLC). Rarer EGFR mutations such as kinase domain duplications (KDDs) have been identified, but the optimal therapy following treatment resistance remains unknown. We report two patients who were diagnosed with NSCLC including KDD. For case 1, afatinib (40 mg once daily) was at first effective but then became ineffective. Consequently, osimertinib therapy (80 mg once daily) was administered. As of 26 May 2021, the osimertinib therapy achieved a stable disease state according to the chest computed tomography scan. As for case 2, the patient received second-line chemotherapy and anlotinib (12 mg once daily) for 6 months and died in May 2020. Here, we describe osimertinib as an effective therapy for EGFR-KDD positive lung adenocarcinoma and thereby provide a new alternative for further treatment following resistance to first- and second-generation EGFR-TKIs.

Nowadays, detecting fake news on social media platforms has become a top priority since the widespread dissemination of fake news may mislead readers and have negative effects. To date, many algorithms have been proposed to facilitate the detection of fake news from the hand-crafted feature extraction methods to deep learning approaches. However, these methods may suffer from the following limitations: (1) fail to utilize the multi-modal context information and extract high-order complementary information for each news to enhance the detection of fake news; (2) largely ignore the full hierarchical semantics of textual content to assist in learning a better news representation. To overcome these limitations, this paper proposes a novel hierarchical multi-modal contextual attention network (HMCAN) for fake news detection by jointly modeling the multi-modal context information and the hierarchical semantics of text in a unified deep model. Specifically, we employ BERT and ResNet to learn better representations for text and images, respectively. Then, we feed the obtained representations of images and text into a multi-modal contextual attention network to fuse both inter-modality and intra-modality relationships. Finally, we design a hierarchical encoding network to capture the rich hierarchical semantics for fake news detection. Extensive experiments on three public real datasets demonstrate that our proposed HMCAN achieves state-of-the-art performance.

ALK-positive disease is characterized by the presence of ALK gene rearrangements that encode driver fusion oncoproteins. EML4-ALK fusion is regarded as the most common type in advanced nonsmall cell lung cancers. STRN-ALK is a novel ALK fusion partner in NSCLC and is considered sensitive to targeted therapy. However, there was no study regarding effective therapy for EML4-ALK and STRN-ALK double fusion variants in EGFR-resistant mutant lung cancer. TP53, RB1, and EGFR exon 21 L858R were found in tumor tissues and plasma from patients with capture-based NGS. After 3 months of gefitinib treatment, an NGS of plasma circulating tumor DNA showed that all variants disappeared significantly, and the tumor mass regressed on CT. However, after 10 months, the patient developed drug resistance and the disease progressed with the appearance of new metastatic lesions in the liver and bones. A repeated NGS test revealed EGFR exon20 T790M and the appearance of a novel double-fusion EML4-ALK and STRN-ALK. A combined therapeutic regimen of crizotinib plus osimertinib showed a promising prognosis confirmed with lung CT scans showing stable lesions without any new metastasis. Moreover, a subsequent genotype by NGS also showed the disappearance of STRN-ALK and EGFR exon20 T790M. The therapeutic efficacy of crizotinib plus osimertinib on EML4-ALK and STRN-ALK double-fusion variant in patients with EGFR-resistant mutant lung cancer may provide a supportive reference for the patients with such genetic alteration.

AimsPulmonary arterial hypertension (PAH) is a serious and devastating complication of systemic lupus erythematosus (SLE), especially when the right ventricle (RV) fails. Whether the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) measured by echocardiography as a simple surrogate of RV to pulmonary circulation (PC) coupling predicts the outcome of SLE-associated PAH has not been investigated.Methods and resultsBetween February 2010 and August 2015, 112 consecutive patients with a diagnosis of SLE-associated PAH confirmed by right heart catheterization were enrolled prospectively. The endpoint was a composite of all-cause mortality and clinical worsening. Baseline clinical characteristics and echocardiographic assessment were analysed. Among all the patients, 47 (42%) patients experienced the endpoint (mean follow-up period 18.1 ± 12.0 months), including 20 patients who died during a median follow-up period of 48.5 months. Multivariable Cox regression analysis showed that TAPSE/PASP ratio [hazard ratio (HR) 0.004, P = 0.017] and 6-min walk distance (6MWD) (HR 0.997, P = 0.036) were the independent predictors for the endpoint. A three-group prediction risk was created based on combined assessment of the TAPSE/PASP ratio and 6MWD relative to their cut-off values. The patients with the worse RV-PC coupling (TAPSE/PASP ConclusionThe TAPSE/PASP ratio, combined with 6MWD, provides clinical and prognostic insights into patients with SLE-associated PAH. A low TAPSE/PASP and low 6MWD identifies the subgroup of patients with high risk of poor prognosis.

Objective The association between the shedding of the endothelial glycocalyx (EG) and the pathogenesis of microcirculatory perfusion disturbances has been discussed in experimental studies. This discussion, however, has limited relevance in a clinical setting. We investigated EG shedding in patients undergoing cardiopulmonary bypass (CPB) and its association with alterations in microvascular perfusion. Methods The plasma levels of syndecan-1, heparan sulfate, and hyaluronan were used as markers of glycocalyx degradation. Microcirculatory parameters included perfused vessel density (PVD) and De Backer Scores. Sidestream dark field imaging (SDF) was applied to visualize sublingual microcirculation during the preoperative resting state (T0), after sternum splitting, after aortic clamping, 5 min before aortal declamping, 1 h after CPB (T4), 4 h after CPB, 24 h after CPB (T6), and 48 h after CPB. Results Thirty patients undergoing cardiac surgery were recruited. The plasma levels of glycocalyx degradation markers increased after CPB. This increase indicated severe glycocalyx shedding at T4 relative to that at T0. By T6, the plasma levels of glycocalyx degradation markers had decreased to baseline levels in a stepwise manner. PVD and the De Backer Scores decreased at T4 and recovered at T6. Glycocalyx marker concentrations were correlated with microvascular alterations during cardiac surgery. Conclusions Glycocalyx components are closely related to microcirculation perfusion disorders. Damage to the glycocalyx during surgery with CPB may play a key role in microcirculation perfusion dysfunction.

Network representation learning is playing an important role in network analysis due to its effectiveness in a variety of applications. However, most existing network embedding models focus on homogeneous networks and neglect the diverse properties such as different types of network structures and associated multimedia content information. In this article, we learn node representations for multimodal heterogeneous networks, which contain multiple types of nodes and/or links as well as multimodal content such as texts and images. We propose a novel attention-aware collaborative multimodal heterogeneous network embedding method (A 2 CMHNE), where an attention-based collaborative representation learning approach is proposed to promote the collaboration of structure-based embedding and content-based embedding, and generate the robust node representation by introducing an attention mechanism that enables informative embedding integration. In experiments, we compare our model with existing network embedding models on two real-world datasets. Our method leads to dramatic improvements in performance by 5%, and 9% compared with five state-of-the-art embedding methods on one benchmark (M10 Dataset), and on a multi-modal heterogeneous network dataset (WeChat dataset) for node classification, respectively. Experimental results demonstrate the effectiveness of our proposed method on both node classification and link prediction tasks.

High energy density and rechargeable lithium ion batteries are attracting widely interest in renewable energy fields. The preparation of the high performance materials for electrodes has been regarded as the most challenging and innovative aspect. By utilizing a facile combustion synthesis method, pure nanostructure LiNi0.5Mn1.5O4 cathode material for lithium ion batteries were successfully fabricated. The crystal phase of the samples were characterized by X-Ray Diffraction, and micro-morphology as well as electrochemistry properties were also evaluated using FE-SEM, electrochemical charge-discharge test. The result shows the fabricated LiNi0.5Mn1.5O4 cathode materials had outstanding crystallinity and near-spherical morphologies. That obtained LiNi0.5Mn1.5O4 samples delivered an initial discharge capacity of 137.2 mAhg-1 at the 0.1 C together with excellent cycling stability and rate capability as positive electrodes in a lithium cell. The superior electrochemical performance of the as-prepared samples are owing to nanostructure particles possessing the shorter diffusion path for Li+ transport, and the nanostructure lead to large contact area to effectively improve the charge/discharge properties and the rate property. It is demonstrated that the as-prepared nanostructure LiNi0.5Mn1.5O4 samples have potential as cathode materials of lithium-ion battery for future new energy vehicles.

BACKGROUND Cardiac involvement occurs in more than half of the patients with light-chain amyloidosis (AL), but the characteristics, treatment and prognosis of cardiac AL (CAL) are not fully described. Methods and Results: A total of 227 patients with CAL diagnosis between January 2009 and March 2017 at Peking Union Medical College Hospital were included. Patients with Mayo stages I, II and III AL accounted for 0.9%, 49.8% and 49.3%, respectively. Autologous stem cell transplantation, bortezomib combinations, non-bortezomib regimens and palliative treatment were given as first line therapy in 3.1%, 44.1%, 30.8% and 22.0% of patients, respectively. Overall hematological response and cardiac response were achieved in 60.6% and 37.2% of evaluable patients, respectively. The median overall survival (OS) was 17 months in all patients, and 10 months in those with Mayo stage III. In patients with Mayo stage III disease who survived for >1 month, the bortezomib group survived significantly longer than the non-bortezomib group (median OS, not reached vs. 12 months, P=0.019). Three independent prognostic factors for survival were identified: N-terminal fragment of B-type natriuretic peptide (NT-proBNP) ≥5,000 pg/mL, bone marrow plasma cells ≥10%, and systolic blood pressure

IntroductionHepatic sarcomatoid carcinoma (HSC) is a rare type of liver cancer with a high malignant grade and poor prognosis. This study compared the clinical characteristics and magnetic resonance imaging (MRI) features of HSCs with those of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), aiming to identify valuable features for HSC diagnosis.MethodsIn total, 17 pathologically confirmed HSC cases, 50 HCC cases and 50 common ICC cases were enrolled from two hospitals. The clinical characteristics and MRI features of all cases were summarized and statistically analyzed.ResultsOn the one hand, the incidence rates of elevated carbohydrate antigen (CA) 19-9 and elevated carcinoembryonic antigen (CEA) were significantly higher in the HSC cases than in the HCC cases (29.4% vs. 0%; 17.6% vs. 0%). The HSC enhancement patterns, primarily including progressive enhancement, were also significantly different from HCC cases. The incidence rates of heterogeneous signals on T2-weighted imaging and during the arterial phase were significantly higher in the HSC cases than in the HCC cases (94.1% vs. 66.0%; 100.0% vs. 72.0%). The diameter of HSCs was significantly larger than that in the HCC cases (6.12 cm vs. 4.21 cm), and the incidence rates of adjacent cholangiectasis, intrahepatic metastasis and lymph node enlargement were considerably higher in the HSC cases than in the HCC cases (52.9% vs. 6.0%; 47.1% vs. 12.0%; 41.2% vs. 2.0%). On the other hand, the incidence rate of elevated CA199 was significantly lower in the HSC cases than in the ICC cases (29.4% vs. 60.0%). The incidence rates of intratumoral necrosis and pseudocapsules were significantly higher in the HSC cases than in the HCC cases (35.3% vs. 8.0%; 47.1% vs. 12.0%). However, the incidence rates of target signs were significantly lower in the HSC cases than in the HCC cases (11.8% vs. 42.0%). In addition, there was no significant difference in the enhancement patterns between HSC cases and ICC cases.ConclusionsHSCs were frequently seen in elderly men with clinical symptoms and elevated CA199 levels. The MRI features, including large size, obvious heterogeneity, hemorrhage, progressive enhancement, pseudocapsule and lymph node enlargement, contributed to the diagnosis of HSC.

Background Coronavirus disease 2019 (COVID‐19) has reached a pandemic level. Cardiac injury is not uncommon among COVID‐19 patients. We sought to describe the electrocardiographic characteristics and to identify the prognostic significance of electrocardiography (ECG) findings of patients with COVID‐19. Hypothesis ECG abnormality was associated with higher risk of death. Methods Consecutive patients with laboratory‐confirmed COVID‐19 and definite in‐hospital outcome were retrospectively included. Demographic characteristics and clinical data were extracted from medical record. Initial ECGs at admission or during hospitalization were reviewed. A point‐based scoring system of abnormal ECG findings was formed, in which 1 point each was assigned for the presence of axis deviation, arrhythmias, atrioventricular block, conduction tissue disease, QTc interval prolongation, pathological Q wave, ST‐segment change, and T‐wave change. The association between abnormal ECG scores and in‐hospital mortality was assessed in multivariable Cox regression models. Results A total of 306 patients (mean 62.84 ± 14.69 years old, 48.0% male) were included. T‐wave change (31.7%), QTc interval prolongation (30.1%), and arrhythmias (16.3%) were three most common found ECG abnormalities. 30 (9.80%) patients died during hospitalization. Abnormal ECG scores were significantly higher among non‐survivors (median 2 points vs 1 point, p

Early acute kidney injury (AKI) contributes to severe morbidity and mortality in critically burned patients. Renal inflammation plays a vital role in the progression of early AKI, acting as a therapeutic target. Astaxanthin (ATX) is a strong antioxidant widely distributed in marine organisms that exerts many biological effects in trauma and disease. ATX is also suggested to have anti-inflammatory activity. Hence, we attempted to explore the role of ATX in protecting against early postburn AKI via its anti-inflammatory effects and the related mechanisms. A severely burned model was established for histological and biochemical assessments based on adult male rats. We found that oxidative stress-induced tissue inflammation participated in the development of early AKI after burn injury and that the MyD88-dependent TLR4/NF-κB pathway was activated to regulate renal inflammation. The TLR4 and NF-κB inhibitors TAK242 and PDTC showed similar effects in attenuating burn-induced renal inflammation and early AKI. Upon ATX treatment, the release of inflammatory mediators in the kidneys was downregulated, while the TLR4/MyD88/NF-κB axis was inhibited in a dose-related manner. TAK242 and PDTC could enhance the anti-inflammatory effect of high-dose ATX, whereas lipopolysaccharide (LPS) reversed its action. Furthermore, the expression of heme oxygenase (HO)-1 was upregulated by ATX in a dose-related manner. Collectively, the above data suggest that ATX protects against renal inflammation in a dose-related manner by regulating the TLR4/MyD88/NF-κB axis and HO-1 and ultimately prevents early AKI following severe burns.

Burn wounds present an evolutionary progression, in which the initial wound tissue deepens and expands following thermal injury. Progressive tissue damage in the zone of stasis may worsen burn injury, which is associated with oxidative stress and secondary apoptosis, and worsen the prognosis of patients with burn wounds. The mitochondrial apoptotic pathway is involved in receiving oxidative signals and regulating tissue apoptosis. Previously, Abnormal Savda Munziq (ASMq), a natural compound of traditional Uyghur Medicine, which includes ten types of herb, has been reported to exhibit a number of effects, including anti‑inflammatory, antioxidative and anti‑apoptotic activities. The present study demonstrated that ASMq protected against early burn wound progression following thermal injury in rats; this effect may be mediated by its ability to attenuate oxidative stress‑induced mitochondria‑associated apoptosis. The present study may provide a novel therapeutic method to prevent early burn wound progression following burn injury.

Objective Pulmonary arterial hypertension (PAH) is a serious complication of SSc with high mortality. Interventricular systolic asynchrony (IVSA) is observed in PAH patients, but the effect of IVSA and its association with long-term mortality and clinical events in SSc-associated PAH are unclear. This study aimed to investigate the impact of IVSA on the prognosis of SSc-associated PAH. Methods Between March 2010 and July 2018, a total of 60 consecutive patients with SSc-associated PAH were enrolled. The end point was a composite of all-cause mortality and clinical worsening. Asynchrony was assessed by colour-coded tissue Doppler imaging (TDI) echocardiography. The myocardial sustained systole curves (Sm) of the basal portion of the right ventricular (RV) free wall and left ventricular (LV) lateral wall were obtained. IVSA was defined as the time difference from the onset of the QRS complex to the end of Sm between LV and RV. Results Patients with greater IVSA time differences presented with advanced pulmonary vascular resistance (PVR). The IVSA time difference was an independent predictive factor (Hazard Ratio (HR) = 1.018, 95% CI: 1.005, 1.031, P =0.005) for the composite end point and was significantly associated with PVR (r = 0.399, R2=0.092, P =0.002). Kaplan–Meier survival curves showed that patients with greater IVSA had worse prognoses (log-rank P =0.001). Conclusion In conclusion, IVSA analysed by colour-coded TDI echocardiography provided added value as a noninvasive, easy-to-use approach for assessing the prognosis of patients with SSc-associated PAH. A significant IVSA time difference identifies the subgroup of patients at high risk of a poor prognosis.

Rack scale design is a promising trend towards customized hardware design, where high density clusters of SoCs are integrated in the rack. One of the biggest challenges for rack scale computing is the interconnection network. Traditional data center topologies require too many ToR switches to support hundreds of SoCs, while distributed fabrics deliver a considerably high end-to-end latency and network oversubscription. Since no one topology fits all kinds of workloads, a flexible in-rack topology requires a careful redesign to dynamically adapt to diverse data center traffic within tight cost and space constraints in the rack. SRFabric is a semi-reconfigurable rack scale network topology that exploits the high path diversity, the cost-effectiveness of distributed fabrics, and the dynamic reconfigurability of circuit switches. This is accomplished by enabling multiple static ports and dynamic ports for each SoC. Leveraging the partial link reconfigurability, SRFabric is able to optimize its topology to dynamically adapt to various workload patterns. We further propose the design of SRFabric to decide the nearly optimal number of dynamic ports and static ports for expected communication density and performance. Extensive evaluations demonstrate that SRFabric can deliver lower average path length, i.e., 2.21 hops on average, and higher bisection bandwidth, i.e., up to 77% nonblocking bandwidth, and provide comparable performance with state-of-the-art strategy XFabric at a lower cost, i.e., XFabric costs up to 3 times more than that of SRFabric.

CA extern - Weitere Nicht-UDE-Autoren sind nicht genannt. Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007. © 2020 Hellenic Society of Cardiology

Aims: Systemic light-chain (AL) amyloidosis is a multisystemic disorder leading to multiple organ dysfunction and mortality that is often caused by cardiac involvement. Soluble suppression of tumorigenicity 2 (sST2) is a novel biomarker identified for risk stratification of heart disease. The aim of this study was to investigate the value of circulating sST2 levels in prognosis and mortality risk assessments for the AL amyloidosis population.Methods and Results: A total of 56 patients diagnosed with AL amyloidosis were enrolled in Peking Union Medical College Hospital (PUMCH) from January 2015 to May 2018. The relationships between the clinical parameters and overall survival (OS) and risk factors for disease progression were assessed. Additionally, receiver operating characteristic (ROC) curves, Kaplan–Meier analysis, and Cox hazard models were performed to explore the predictive value of sST2 in mortality rates. We found that the median OS of all patients was 7.3 [interquartile range (IQR) 4.4, 15.9] months. The median baseline sST2 level was 12.2 (IQR 5.1, 31.1) ng/ml, and the sST2 high group had more severe patients with a higher Mayo stage. In the ROC analysis, the area under the curve (AUC) was 0.728 [95% confidence interval (CI) 0.603–0.853] for sST2 to predict the outcomes of AL amyloidosis patients, and the optimal cutoff value was 12.34 ng/ml (sensitivity 80.2%, specificity 61.1%). Moreover, in multivariate Cox proportional hazards regression analysis, sST2 acted as an independent predictor of poor functional outcome in patients with AL amyloidosis.Conclusion: In AL amyloidosis patients, sST2 was a strong and independent prognostic biomarker for all-cause mortality, providing complementary prognostic information of a novel scoring system for risk stratification.

In a cloud-edge system, mobile users submit comprehensive service requests, on-the-fly service composition to orchestrate service components from different edge nodes is a promising way to achieve a quick response to these requests. Since several mobile applications consume large amount of energy during waiting for the responses, it is critical to achieve less service delay for energy saving as well as improve QoE (Quality of Experience). However, the service completion time in an edge is quite unstable, which increases the overall response time of the composite service. This paper argues that we may accelerate services through service clone via different edges, so that we can guarantee the overall response time of the composite service. And since the data fetch is also time consuming, we propose an effective data-aware service composition algorithm via service cloning to minimize the overall response time. We implement the algorithm and evaluate the performance with extensive simulations. The simulation results show that the proposed algorithm has a good performance improvement on service delay and energy consumption reduction, compared to the traditional algorithms.

Nowadays, millions of users use community question answering (CQA) systems to share valuable knowledge. An essential function of CQA systems is the accurate matching of answers w.r.t a given question. Recent research exhibits the superior advantages of graph neural networks (GNNs) on modeling content semantics for CQA matching. However, existing GNN-based approaches are insufficient to deal with the multi-modal and redundant properties of CQA systems. In this paper, we propose a multi-modal attentive graph pooling approach (MMAGP) to model the multi-modal content of questions and answers with GNNs in a unified framework, which explores the multi-modal and redundant properties of CQA systems. Our model converts each question/answer into a multi-modal content graph, which can preserve the relational information within multi-modal content. Specifically, to exploit the visual information, we propose an unsupervised meta-path link prediction approach to extract labels from visual content and model them into the multi-modal graph. An attentive graph pooling network is proposed to select vertices in the multi-modal content graph that are significant for the matching adaptively, and generate a pooled graph via aggregating context information for selected vertices. An interaction pooling network is designed to infer the final matching score based on the interactions between the pooled graphs of the input question and answer. Experimental results on two real-world datasets demonstrate the superior performance of MMAGP compared with other state-of-the-art CQA matching models.

Backgrounds: Deep burn-wounds undergo a dynamic progression in the initial or periburn area after insults. The zone of stasis has a higher risk of deterioration and is considered a salvageable target. Few studies have explored the role of mitochondrial damage in this process and potential “built-in” self-defense within the human body. Methods: A classic “comb” scald rat model was established. Histological and blood-flow observation were processed based on hematoxylin-eosin staining and laser analysis. Oxidative and apoptotic status were analyzed by commercial kits. Transmission electron microscope, immunofluorescence staining, and western blot were applied to detect the mitophagy happened in the zone of stasis and potential regulators. Adenovirus-based gene-silence contributed to determine the role of HIF-1α as a regulatory mediator. Findings: We found that burn insults caused typical ischemia and histological deterioration in the zone of stasis, in parallel with increases in oxidative stress and apoptosis. Mitochondrial damage was also involved in the aforementioned changes. Furthermore, we detected typical mitophagy in burn-wounds, which was contradictory to the burn-wound conversion. HIF-1α expression was closely related to the level of mitophagy, while BNIP3 and PARKIN are involved downstream. Interpretation: Accordingly, burn-induced mitochondrial impairment contributes to the mobilization of injurious mechanisms in the zone of stasis and that mitophagy provides a more beneficial way to protect against burn-wound progression via the elimination of damaged mitochondria. Our findings offer insights into mitochondrial quality control in burn-wound progression and suggest the novel concept that HIF-1α may be a potential therapeutic target due to its possible regulatory effects on BNIP3- or PARKIN-mediated mitophagy. Funding Statement: This work was supported by the following grants: National Natural Science Foundation of China (NSFC) Grants 81671909, 81901958 and Zhejiang Provincial Natural Science Foundation of China Grants: LY18H150004, LY19H150004, LY20H150010. Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: The present study was performed according to protocols approved by the Committee on Animal Care and Use of the Second Affiliated Hospital Zhejiang University School of Medicine (2019-331), and strictly followed the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals.

Pulmonary arterial hypertension is a serious complication of systemic lupus erythematosus. It is characterized by increased right ventricular afterload which mainly comprises pulmonary arterial compliance (PAC) and pulmonary vascular resistance. The role of PAC in predicting the outcome of systemic lupus erythematosus-associated pulmonary arterial hypertension has not been investigated yet. Between February 2012 to December 2016, 120 consecutive patients diagnosed with systemic lupus erythematosus-associated pulmonary arterial hypertension based on right heart catheterization were enrolled, prospectively. Baseline clinical characteristics and hemodynamic assessment were analyzed. Baseline right ventricular afterload was stratified according to the PAC and pulmonary vascular resistance. The end point was a composite of all-cause mortality and clinical worsening. Among them, end points occurred in 49 (41%) patients after 15 months (interquartile range, 8.5–24.0). Patients with a PAC P=0.001) of the end point events than the patients with a PAC ≥1.39 mL/mm Hg. Multivariable Cox regression analysis showed that stratified right ventricular afterload was the only independent predictor for the end point (hazard ratio, 2.009 [95% CI, 1.390–2.904],P2, 6.10;P

Background Atrial fibrillation (AF) is the most common sustained arrhythmia, and catheter ablation has been shown to be a highly effective treatment for patients with symptomatic AF. Very early recurrence (VER) of AF within 7 days after catheter ablation is common, but the clinical significance of VER remains unclear. We have examined the usefulness of the noninvasive electrocardiography monitor for the detection of VER and the relationship between VER and late recurrence (LR). Methods Eighty‐eight patients with paroxysmal or persistent atrial fibrillation were retrospectively included. All patients underwent primary catheter ablation at a large general hospital between March 2016 and August 2018. All patients were followed up in atrial fibrillation clinic at an interval of every 3 months for late recurrence of AF. VER was evaluated by one‐lead continuous noninvasive electrocardiography monitoring device for 7 days after ablation. The association between VER and LR was analyzed by univariate and multivariate Cox regression model. Results Mean age was 62.9 ± 9.7 years, and 39.8% were female. Thirty‐two patients (36.4%) experienced VER. After a mean follow‐up of 539.36 ± 211.66 days, 17 patients (19.3%) experienced LR. Multivariate Cox regression analysis revealed VER was an independent predictor of LR: HR 3.6 (95% CI, 1.2–10.8), p = .020. In addition, diabetes was also associated with LR of atrial fibrillation. Conclusions Noninvasive electrocardiography monitoring was a useful tool for detecting VER and VER after catheter ablation was associated with LR.

Background In the past two decades, chronic non-communicable diseases have become the leading disease burden, and cardio-cerebrovascular diseases (CCVD) are the main causes of death in chronic diseases. It has become the focus of global public health attention, in this study, System of Health Accounts 2011 (SHA 2011) is used to calculate health expenditure, discuss its economic burden, and put forward countermeasures. Methods Data were collected by multi-stage stratified random sampling and the medical expenses of patients with CCVD were calculated based on SHA 2011, from the dimensions of the financing plan, institutional flow, and service function. Correlation and regression analysis were conducted by controlling factors influencing hospitalization expenses. All analysis were conducted by software SPSS. Results The current health expenditure (CHE) of CCVD in Dalian was 3.986 billion Yuan, accounting for 12.88% of the CHE (30.947 billion Yuan). The current curative expenditure (CCE) of CCVD was 2.947 billion Yuan. 40.39% of CCVD financing came from social medical insurance, and the proportion of family health financing was higher (39.06%). The expenditures were consumed by general hospitals and elderly patients. Conclusions The expenditure burden of CCVD in Dalian was massive, and wasted the health resource severely. It is necessary for the government to adjust the financing structure, reallocate the expenses of CCVD, and make institutional flow and functional distribution more reasonable.

BackgroundSince December 2019, a cluster of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China and spread rapidly from China to other countries. In-hospital mortality are high in severe cases and cardiac injury characterized by elevated cardiac troponin are common among them. The mechanism of cardiac injury and the relationship between cardiac injury and in-hospital mortality remained unclear. Studies focused on cardiac injury in COVID-19 patients are scarce.ObjectivesTo investigate the association between cardiac injury and in-hospital mortality of patients with confirmed or suspected COVID-19.MethodsDemographic, clinical, treatment, and laboratory data of consecutive confirmed or suspected COVID-19 patients admitted in Wuhan No.1 Hospital from 25thDecember, 2019 to 15thFebruary, 2020 were extracted from electronic medical records and were retrospectively reviewed and analyzed. Univariate and multivariate Cox regression analysis were used to explore the risk factors associated with in-hospital death.ResultsA total of 110 patients with confirmed (n=80) or suspected (n=30) COVID-19 were screened and 48 patients (female 31.3%, mean age 70.58±13.38 year old) among them with high-sensitivity cardiac troponin I (hs-cTnI) test within 48 hours after admission were included, of whom 17 (17/48, 35.4%) died in hospital while 31 (31/48, 64.6%) were discharged or transferred to other hospital. High-sensitivity cardiac troponin I was elevated in 13 (13/48, 27.1%) patents. Multivariate Cox regression analysis showed pulse oximetry of oxygen saturation (SpO2) on admission (HR 0.704, 95% CI 0.546-0.909, per 1% decrease, p=0.007), elevated hs-cTnI (HR 10.902, 95% 1.279-92.927, p=0.029) and elevated d-dimer (HR 1.103, 95%CI 1.034-1.176, per 1mg/L increase, p=0.003) on admission were independently associated with in-hospital mortality.ConclusionsCardiac injury defined by hs-cTnI elevation and elevated d-dimer on admission were risk factors for in-hospital death, while higher SpO2could be seen as a protective factor, which could help clinicians to identify patients with adverse outcome at the early stage of COVID-19.

To investigated the role of HIF-1α in myocardial inflammatory injury in rats induced by CME and its possible mechanism. Forty SD rats were separated randomly and equally into four groups, i.e. CME+HIF-1α stabilizer dimethyloxalyl glycine (CME+DMOG) group, CME+HIF-1α inhibitor YC-1 (CME+YC-1) group, CME group, and Sham group. HBFP staining, myocardial enzyme assessment, and cardiac ultrasound were used to measure microinfarct, serum c-troponin I (cTnI) level, and Cardiac function. ELISA and western blot were applied for detecting NLRP3 inflammasome pathway and TLR4/MyD88/NF-κB signaling level.Pro-inflammatory factors of IL-18, IL-1β and TNF-α increased their expression levels after CME, which indicated inflammatory responses in the myocardium. Additionally, in the inflammatory process, NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling were involved. DMOG reverses these effects of CME, whereas YC-1 aggravates these effects. HIF-1α may attenuate myocardial inflammatory injury induced by CME and improve cardiac function, which can perhaps be explained by the fact that TLR4/MyD88/NF-κB signaling pathway activation is inhibited.

Background. Acute kidney injury (AKI) has long been recognized as a common and important complication of acute pancreatitis (AP). In the study, machine learning (ML) techniques were used to establish predictive models for AKI in AP patients during hospitalization. This is a retrospective review of prospectively collected data of AP patients admitted within one week after the onset of abdominal pain to our department from January 2014 to January 2019. Eighty patients developed AKI after admission (AKI group) and 254 patients did not (non-AKI group) in the hospital. With the provision of additional information such as demographic characteristics or laboratory data, support vector machine (SVM), random forest (RF), classification and regression tree (CART), and extreme gradient boosting (XGBoost) were used to build models of AKI prediction and compared to the predictive performance of the classic model using logistic regression (LR). XGBoost performed best in predicting AKI with an AUC of 91.93% among the machine learning models. The AUC of logistic regression analysis was 87.28%. Present findings suggest that compared to the classical logistic regression model, machine learning models using features that can be easily obtained at admission had a better performance in predicting AKI in the AP patients.

Orofacial pain is one of the most common pain conditions and compromises the quality of life of the sufferer. Several studies have shown that opioid agonists produced significant analgesia in the orofacial pain, and combination of opioids with drugs belonging to other classes induced synergism in the orofacial pain. However, combination therapy of different analgesic drugs improves the risk of drug-drug interactions. Against this background, we sought to investigate the analgesic effects of the multi-functional opioid peptide DN-9, a mixed opioid and NPFF receptors agonist that produced robust analgesia in acute and inflammatory pain models, on formalin-induced orofacial pain. Our results showed that formalin injection caused significant spontaneous pain behaviors and increased the expressions of the mu-opioid receptor, c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK1/2) in the ipsilateral trigeminal ganglion (TG). In mice pretreated with DN-9, there was a significant reduction in nociceptive behaviors, which was selectively mediated by the mu- and kappa-opioid receptors, independently of the NPFF system. Four hours after formalin injection, the level of c-Fos immunoreactivity in the ipsilateral TG neurons was much lower in mice pretreated with DN-9 or morphine. In addition, DN-9 exhibited a significant inhibition in the expression of p-ERK1/2, which was reversed by the selective antagonists of the mu- and kappa-opioid receptors. In conclusion, our present results demonstrate that central administration of DN-9 produces potential antinociceptive effects via the mu- and kappa-opioid receptors, independently of the NPFF system, and this antinociceptive action is tightly linked with the intracellular ERK activation in TG neurons.

Background Preemptive administration of analgesic drugs reduces perceived pain and prolongs duration of antinociceptive action. Whereas several lines of evidence suggest that endomorphins, the endogenous mu-opioid agonists, attenuate acute and chronic pain at the spinal level, their preemptive analgesic effects remain to be determined. In this study, we evaluated the anti-allodynic activities of endomorphins and explored their mechanisms of action after preemptive administration in a mouse model of inflammatory pain. Methods The anti-allodynic activities of preemptive intrathecal administration of endomorphin-1 and endomorphin-2 were investigated in complete Freund’s adjuvant (CFA)-induced inflammatory pain model and paw incision-induced postoperative pain model. The modulating effects of endomorphins on the expression of p38 mitogen-activated protein kinase (p38 MAPK) and inflammatory mediators in dorsal root ganglion (DRG) of CFA-treated mice were assayed by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, or immunofluorescence staining. Results Preemptive intrathecal injection of endomorphins dose-dependently attenuated CFA-induced mechanical allodynia via the mu-opioid receptor and significantly reversed paw incision-induced allodynia. In addition, CFA-caused increase of phosphorylated p38 MAPK in DRG was dramatically reduced by preemptive administration of endomorphins. Repeated intrathecal application of the specific p38 MAPK inhibitor SB203580 reduced CFA-induced mechanical allodynia as well. Further RT-PCR assay showed that endomorphins regulated the mRNA expression of inflammatory cytokines in DRGs induced by peripheral inflammation. Conclusions Our findings reveal a novel mechanism by which preemptive treatment of endomorphins attenuates inflammatory pain through regulating the production of inflammatory cytokines in DRG neurons via inhibition of p38 MAPK phosphorylation. Electronic supplementary material The online version of this article (10.1186/s12974-018-1358-3) contains supplementary material, which is available to authorized users.

Background Atrial fibrillation (AF) is an important arrhythmia associated with cardiovascular morbidity and mortality. This study is focused on exploring the potential relationship between short-term air pollution exposure and occurrence of AF. Methods A case-crossover design was used to investigate the effect of pollutants on AF occurrence among 100 patients from 2013 to 2014. The air pollutants included ambient particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5 ), particulate matter less than 10 μm in aerodynamic diameter (PM10 ), nitrogen dioxide (NO2 ), sulfur dioxide (SO2 ), carbon monoxide (CO), and ozone (O3 ). Participants with cardiac implantable electronic devices implanted were followed-up to December 31, 2014. Results A 10 μg/m3 increase of PM2.5 and PM10 was associated with 3.8% (95% confidence interval [CI]: 1.4-6.2) and 2.7% (95% CI: 0.6-4.8) increase in the risk of AF occurrence, respectively. No statistically significant association was noted with SO2 , NO2 , CO, and O3 . Conclusions Short-term exposure to particular matter, both PM2.5 and PM10 , is associated with an increased risk of AF. This further demonstrates the urgency for air quality monitoring and control in geographical area with intense pollution.

We recently characterized a novel bifunctional agonist for opioid and neuropeptide FF receptors, named BN-9, which exhibited potent analgesia in the mouse tail-flick test when given centrally. To further evaluate its potential therapeutic efficacy for translational-medical development, the current work was performed to explore the antinociceptive activities of intraperitoneal (i.p.) administration of BN-9 in mouse models of tail-flick assay, formalin pain, visceral pain and post-operative pain. In the tail-flick test, BN-9 induced a dose-related antinociceptive effect, which was fully blocked by systemic pretreatment with the peripheral acting opioid receptor antagonist naloxone methiodide, but not supraspinal naloxone methiodide, implying the involvement of the peripheral opioid receptors. In addition, the systemic antinociception of BN-9 was antagonized by the selective antagonists of the μ- and κ-opioid receptors, independently of the δ-opioid and neuropeptide FF receptors. Similarly, dose-dependent analgesia was also produced by systemic BN-9 in different pain models via the peripheral opioid receptors, independently of the neuropeptide FF receptors. Furthermore, the side-effects of systemic BN-9 on motor performance, tolerance development and gastrointestinal transit inhibition were also evaluated. Repeated systemic injection of BN-9 produced non-tolerance analgesia over 8 days. Compared with morphine, intraperitoneal administration of BN-9 exerted less inhibition of gastrointestinal transit. These data show that BN-9 induced systemic analgesia with reduced side-effects on tolerance and constipation. This article suggests that systemic injection of BN-9 causes effective antinociception in different preclinical pain models via the peripheral opioid receptors, providing an attractive approach to develop peripherally acting opioid analgesics with multiple targeting properties.

Background and purpose The voltage-gated sodium channel NaV 1.7 is considered a therapeutic target for pain treatment based on human genetic evidence. GpTx-1 and its potent analogue [Ala5 , Phe6 , Leu26 , Arg28 ]GpTx-1 (GpTx-1-71) were recently characterized as NaV 1.7 inhibitors in vitro. Furthermore, the present work was conducted to investigate the analgesic properties of these two peptides in different pain models after spinal administration. Experimental approach The antinociceptive activities of both GpTx-1 and GpTx-1-71 were investigated in mouse models of acute, visceral, inflammatory and neuropathic pain. Furthermore, the side effects of GpTx-1 and GpTx-1-71 were evaluated in rotarod, antinociceptive tolerance, acute hyperlocomotion and gastrointestinal transit tests. Key results The i.t. administration of both GpTx-1 and GpTx-1-71 dose-dependently produced powerful antinociception in the different pain models. This effect was attenuated by the opioid receptor antagonist naloxone, suggesting the involvement of the opioid system. In this study, repeated administration of these two_peptides produced spinal analgesia without a loss of potency over 8 days in mouse models of acute, inflammatory and neuropathic pain. Moreover, spinal administration of GpTx-1 and GpTx-1-71 did not induce significant effects on motor coordination, evoke acute hyperlocomotion or increase gastrointestinal transit time. Conclusions and implications Our data indicate that the NaV 1.7 peptide inhibitors GpTx-1 and GpTx-1-71 produce powerful, nontolerance-forming analgesia in preclinical pain models, which might be dependent on the endogenous opioid system. In addition, at the spinal level, the limited side effects imply that these NaV 1.7 peptide inhibitors could be potentially developed as GpTx-1-based drugs for pain relief.

The authors sought to evaluate the safety and effectiveness of the NeoVas bioresorbable scaffold (BRS) compared with metallic drug-eluting stents.BRS have the potential to improve very late outcomes compared with metallic drug-eluting stents, but some BRS have been associated with increased rates of device thrombosis before complete bioresorption. NeoVas is a new poly-l-lactic acid BRS that elutes sirolimus from a poly-D, l-lactide coating.Eligible patients with a single de novo native coronary artery lesion with a reference vessel diameter 2.5 to 3.75 mm and a lesion length ≤20 mm were randomized 1:1 to NeoVas BRS versus cobalt-chromium everolimus-eluting stents (CoCr-EES). Angiographic follow-up was performed in all patients at 1 year. The primary endpoint was angiographic in-segment late loss (LL), and the major secondary endpoint was the rate of angina. Baseline and follow-up optical coherence tomography and fractional flow reserve were performed in a pre-specified subgroup of patients.The authors randomized 560 patients at 32 centers to treatment with NeoVas (n = 278) versus CoCr-EES (n = 282). One-year in-segment LL with NeoVas and CoCr-EES were 0.14 ± 0.36 mm versus 0.11 ± 0.34 mm (difference 0.03 mm; upper 1-sided 97.5% confidence interval 0.09 mm; pThe NeoVas BRS was noninferior to CoCr-EES for the primary endpoint of 1-year angiographic in-segment LL, and resulted in comparable 1-year clinical outcomes, including recurrent angina. (NeoVas Bioresorbable Coronary Scaffold Randomized Controlled Trial; NCT02305485).

Background: The study aimed to analyze the hospital charges of the inpatients with acute ischemic stroke in Beijing and determine the factors associated with hospital costs. Methods: Medical records of hospitalized patients with a primary diagnosis of ischemic stroke according to International Classification of Diseases 10th Revision codes were collected from 121 hospitals in Beijing from March 1, 2012, to February 28, 2015. Distribution characteristics of hospital charges for different hospital levels (level 2 hospitals and level 3 hospitals) and types (Western medicine hospitals and Chinese medicine hospitals) were studied. Linear regression analysis was used to examine the association among hospital costs and factors that influenced total hospital charges. Results: There were 158,781 admissions for ischemic stroke, 63.1% of the patients were male and their mean age was 67.7 ± 12.4 years, the median length of hospital stay (LOHS) was 13.5 days (interquartile range 9.9–18.1 days). The median hospital charge was 2,112 (1,436–3,147) US dollars. Of these, 46.7% were for medicine, 21.1% for laboratory and examination, and 16.3% for therapy. LOHS, hospital level, and pulmonary infection were key determinants of the hospital charges. Conclusions: The proportion of medicine fees for the ischemic stroke inpatients showed a downward trend during the period from 2012 to 2015, but medicine fees still accounted for the largest percentage of hospital charges in China. LOHS emerged to be the main determinant of the cost. Decreasing medicine fees and LOHS might be strategies to decrease hospital charges and reduce economic burden of stroke in China.