Abstract
Aims
To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19).
Methods and results
We enrolled 671 ...eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years. Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors. Risk factors of death and myocardial injury were analysed using multivariable regression models. A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs. 9.7%; P < 0.001) than survivors. The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 95% confidence interval (CI), 0.87–0.96; sensitivity, 0.86; specificity, 0.86; P < 0.001. The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28–16.28; P = 0.019) and 1.25 (95% CI, 1.07–1.46; P = 0.004), respectively. In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury.
Conclusion
The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities.
•We propose a novel multiscale graph convolutional network (MSGCN) combining the multiscale.•object-based technique and GCN;•The multiscale decision fusion strategy can make full use of the ...comprehensive information of objects.•with various sizes and shapes;•The designed feature extractor can automatically obtain object-wise high level features;•We show the effectiveness of the proposed method by extensive experiments.
To date, although numerous methods of Change detection (CD) in remote sensing images have been proposed, accurately identifying changes is still a great challenge, due to the difficulties in effectively modeling the features from ground objects with different patterns. In this paper, a novel CD method based on the graph convolutional network (GCN) and multiscale object-based technique is proposed for both homogeneous and heterogeneous images. First, the object-wise high level features are obtained through a pre-trained U-net and the multiscale segmentations. Second, by treating each parcel as a node, the graph representations can be formed and then fed into the proposed multiscale graph convolutional network with each channel corresponding to one scale. The multiscale GCN propagates the label information from a small amount of labeled nodes to the other unlabeled ones. Finally, to comprehensively incorporate the information from the output channels of multiscale GCN, a fusion strategy is designed using the parent–child relationships between scales. Extensive experiments on optical, SAR and heterogeneous optical/SAR data sets demonstrate that the proposed method outperforms some state-of-the-art methods in both qualitative and quantitative evaluations.
Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is ...limited.
To explore the association between cardiac injury and mortality in patients with COVID-19.
This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study.
Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed.
A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients 80.3%), cough (144 34.6%), and shortness of breath (117 28.1%). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median range age, 74 34-95 vs 60 21-90 years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 59.8% vs 78 of 334 23.4%; P < .001); had higher leukocyte counts (median interquartile range (IQR), 9400 6900-13 800 vs 5500 4200-7400 cells/μL) and levels of C-reactive protein (median IQR, 10.2 6.4-17.0 vs 3.7 1.0-7.3 mg/dL), procalcitonin (median IQR, 0.27 0.10-1.22 vs 0.06 0.03-0.10 ng/mL), creatinine kinase-myocardial band (median IQR, 3.2 1.8-6.2 vs 0.9 0.6-1.3 ng/mL), myohemoglobin (median IQR, 128 68-305 vs 39 27-65 μg/L), high-sensitivity troponin I (median IQR, 0.19 0.08-1.12 vs <0.006 <0.006-0.009 μg/L), N-terminal pro-B-type natriuretic peptide (median IQR, 1689 698-3327 vs 139 51-335 pg/mL), aspartate aminotransferase (median IQR, 40 27-60 vs 29 21-40 U/L), and creatinine (median IQR, 1.15 0.72-1.92 vs 0.64 0.54-0.78 mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients 64.6% vs 15 of 334 patients 4.5%). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 46.3% vs 13 of 334 3.9%; P < .001) or invasive mechanical ventilation (18 of 82 22.0% vs 14 of 334 4.2%; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 58.5% vs 49 of 334 14.7%; P < .001), acute kidney injury (7 of 82 8.5% vs 1 of 334 0.3%; P < .001), electrolyte disturbances (13 of 82 15.9% vs 17 of 334 5.1%; P = .003), hypoproteinemia (11 of 82 13.4% vs 16 of 334 4.8%; P = .01), and coagulation disorders (6 of 82 7.3% vs 6 of 334 1.8%; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 51.2% vs 15 of 334 4.5%; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 95% CI, 1.92-9.49) and from admission to end point (hazard ratio, 3.41 95% CI, 1.62-7.16).
Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.
Sepsis is the principal cause of fatality in the intensive care units worldwide. It involves uncontrolled inflammatory response resulting in multi-organ failure and even death. Micheliolide (MCL), a ...sesquiterpene lactone, was reported to inhibit dextran sodium sulphate (DSS)-induced inflammatory intestinal disease, colitis-associated cancer and rheumatic arthritis. Nevertheless, the role of MCL in microbial infection and sepsis is unclear. We demonstrated that MCL decreased lipopolysaccharide (LPS, the main cell wall component of Gram-negative bacteria)-mediated production of cytokines (IL-6, TNF-α, MCP-1, etc) in Raw264.7 cells, primary macrophages, dendritic cells and human monocytes. MCL plays an anti-inflammatory role by inhibiting LPS-induced activation of NF-κB and PI3K/Akt/p70S6K pathways. It has negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. In the acute peritonitis mouse model, MCL reduced the secretion of IL-6, TNF-α, IL-1β, MCP-1, IFN-β and IL-10 in sera, and ameliorated lung and liver damage. MCL down-regulated the high mortality rate caused by lethal LPS challenge. Collectively, our data illustrated that MCL enabled maintenance of immune equilibrium may represent a potentially new anti-inflammatory and immunosuppressive drug candidate in the treatment of sepsis and septic shock.
MALAT1 was reported to sponge miR-30e, miR-126 and miR-155 in the pathogenesis of many diseases. Plasma miR-30e can indicate the risk of no-reflow during primary percutaneous coronary intervention ...(pPCI), while miR-126 can be used as a predictor of coronary slow flow phenomenon. In this study, we compared the diagnostic value of above genes in the prediction of no-reflow phenomenon in ST-segment elevation myocardial infarction (STEMI) subjects receiving pPCI. Quantitative real-time PCR, ELISA, Western blot and luciferase assays were performed to explore the regulatory relationship of MALAT1/miR-30e, MALAT1/miR-126, MALAT1/miR-155, miR-126/HPSE, and miR-155/EDN1. ROC analysis was carried out to evaluate the potential value of MALAT1, miRNAs and target genes in differentiating normal reflow and no-reflow in STEMI patients receiving pPCI. Elevated MALAT1, CRP, HPSE, and EDN1 expression and suppressed miR-30e, miR-155 and miR-126 expression was found in the plasma of STEMI patients receiving pPCI who were diagnosed with no-reflow phenomenon. ROC analysis showed that the expression of MALAT1, miR-30e, miR-126 and CRP could be used as predictive biomarkers to differentiate normal reflow and no-reflow in STEMI patients receiving pPCI. MALAT1 was found to suppress the expression of miR-30e, miR-126 and miR-155, and HPSE and EDN1 were respectively targeted by miR-126 and miR-155. This study demonstrated that MALAT1 could respectively sponge the expression of miR-30e, miR-126 and miR-155. And miR-30e, miR-126 and miR-155 respectively targeted CRP, HPSE and EDN1 negatively. Moreover, MALAT1 could function as an effective biomarker of no-reflow phenomenon in STEMI patients receiving pPCI.
•The impact response of self-locked systems is studied by impact experiment and simulations.•A one-dimensional theoretical crushing model for the system is developed.•Three deformation modes of the ...system are predicted and investigated.•The criterion to predict the deformation mode of system is established analytically.•A guideline on the design of the self-locked system is provided.
The self-locked energy absorbing system can prevent lateral splash of tubes from impact loadings without any requirements for boundary constraints or inter-tube fasteners, thus breaking through the limitation of widely-used round tube systems. To reveal the mechanism of the impact response of self-locked systems, both impact experiment and FEM simulations are carried out. Based on the experimental and simulation results, a one-dimensional theoretical crushing model of the system is developed to analyze the dynamic response of the system, in which a plastic hinge model of the unit cell is proposed for the force-deformation relation. Three deformation modes of the system are predicted and observed, and moreover, the criteria to determine the deformation mode of the system are established analytically. A guideline on the design of the self-locked system is summarized, which is helpful in practical applications.
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•The residual bearing capacity of the immersed tunnel of HZMB was greatly reduced under the car bomb.•The corner and the concrete cover were seriously damaged.•The initiation at the mid-span of the ...middle wall can reduce the roof deformation.•Four disaster damage levels were identified and categorized.
With the completion of the subsea immersed tunnel of the Hong Kong–Zhuhai–Macao Bridge (HZMB), the tunnel structure in a closed environment for a long time will inevitably be threatened by sudden extreme accidents such as car accidents and car bombs. However, intensive research efforts have been devoted to understanding their performance under service and seismic loads, and the vulnerability of the tunnels against accidental blast loads is seldom discussed. The present study performs an immersed tunnel model of HZMB was constructed at a scale of 1:5 to carry out the explosion test. The results showed that after an internal explosion of a van-type bomb, the roof subsidence of the tunnel model doubled under the same water pressure. The test also revealed that the peak overpressure load on the roof was up to 50 MPa, which showed the multi-peak characteristics, and evident cracks appeared on the top slab and at the junction of the roof and middle wall. In addition, based on the fully verified constitutive model of high strain rate materials, a refined finite element model was established. The propagation characteristics of the blast wave in the tunnel, dynamic response characteristics, and failure process and modes of the tunnel structure were discussed in the developed FE model. The results showed that the ultimate blast resistance of the tunnel model was 41.8 kg TNT (scaled distance is 0.363 m/kg1/3). Furthermore, a resonance effect was observed between the middle wall and roof. The deformation and damage of the roof could be significantly reduced for the explosion height of 1.06–1.25 m. This height range could be very useful for developing traffic standards guiding the safe transportation of hazardous chemicals in tunnels. Based on the numerical and test data, four blast damage levels were finally identified and categorized according to the scaled distance to the tunnel roof.
Increasing evidence shows the oncogenic function of FAM83D in human cancer, but how FAM83D exerts its oncogenic function remains largely unclear. Here, we investigated the importance of FAM83D/FBXW7 ...interaction in breast cancer (BC). We systematically mapped the FBXW7-binding sites on FAM83D through a comprehensive mutational analysis together with co-immunoprecipitation assay. Mutations at the FBXW7-binding sites on FAM83D led to that FAM83D lost its capability to promote the ubiquitination and proteasomal degradation of FBXW7; cell proliferation, migration, and invasion in vitro; and tumor growth and metastasis in vivo, indicating that the FBXW7-binding sites on FAM83D are essential for its oncogenic functions. A meta-evaluation of FAM83D revealed that the prognostic impact of FAM83D was independent on molecular subtypes. The higher expression of FAM83D has poorer prognosis. Moreover, high expression of FAM83D confers resistance to chemotherapy in BCs, which is experimentally validated in vitro. We conclude that identification of FBXW7-binding sites on FAM83D not only reveals the importance for FAM83D oncogenic function, but also provides valuable insights for drug target.
A green, highly sensitive and selective electrochemical imprinted biosensor for horseradish peroxidase (HRP) was designed and prepared based on the combination of polyaniline nanotubes (PANTs) and ...self-assembly surface molecular imprinting technique. PANI nanotubes, as supporting material, could effectively enhance imprinting efficiency and the electrode conductivity and facilitate electron transfer. The imprinted biosensor was characterized by electrochemical methods, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). It showed a very highly electrocatalytical activity for reduction of hydrogen peroxide and could be used in amperometric determination of H2O2 in the ranges of 0–10 μM and 10–90 μM with a detection limit of 0.01 μM (S / N = 3). The imprinted sensor showed still an excellent selectivity for HRP and was successfully employed to detect different concentration levels of HRP from 1.0 × 10−9 to 0.10 mg/mL with a detection limit of 3.56 × 10−10 mg/mL(8.1fM) (S / N = 3) with Fe(CN)63/4− probe by differential pulse voltammetry(DPV). The developed method was successfully used in determination of H2O2 in human urine sample.
A HRP surface imprinting electrochemical sensor based PANTs film for sensitive and selective determination of hydrogen peroxide and horseradish peroxidase. Display omitted
•A new and simple electrochemical imprinting film biosensor for H2O2 and HRP was prepared.•The prepared sensor showed a good electrochemical response, high sensitivity and selectivity for HRP determination.•The sensor was also used to detect H2O2 in biological sample successfully.
We report the characterization and determination of 2,6-dichloro-1,4-benzoquinone and three new disinfection byproducts (DBPs): 2,6-dichloro-3-methyl-1,4-benzoquinone, ...2,3,6-trichloro-1,4-benzoquinone, and 2,6-dibromo-1,4-benzoquinone. These haloquinones are suspected bladder carcinogens and are likely produced during drinking water disinfection treatment. However, detection of these haloquinones is challenging, and consequently, they have not been characterized as DBPs until recently. We have developed an electrospray ionization tandem mass spectrometry technique based on our observation of unique ionization processes. These chloro- and bromo-quinones were ionized through a reduction step to form M + H− under negative electrospray ionization. Tandem mass spectra and accurate mass measurements of these compounds showed major product ions, M + H − HX−, M + H − HX − CO−, M + H − CO−, and/or X− (where X represents Cl or Br). The addition of 0.25% formic acid to water samples was found to effectively stabilize the haloquinones in water and to improve the ionization for analysis. These improvements were rationalized from the estimates of pK a values (5.8−6.3) of these haloquinones. The method of tandem mass spectrometry detection, combined with sample preservation, solid phase extraction, and liquid chromatography separation, enabled the detection of haloquinones in chlorinated water samples collected from a drinking water treatment plant. The four haloquinones were detected only in drinking water after chlorination treatment, with concentrations ranging from 0.5 to 165 ng/L, but were not detectable in the untreated water. This method will be useful for future studies of occurrence, formation pathways, toxicity, and control of these new halogenated DBPs.
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