Since December 2019, the 2019 coronavirus disease (COVID-19) has expanded to cause a worldwide outbreak that more than 600,000 people infected and tens of thousands died. To date, the clinical ...characteristics of COVID-19 patients in the non-Wuhan areas of Hubei Province in China have not been described.
We retrospectively analyzed the clinical characteristics and treatment progress of 91 patients diagnosed with COVID-19 in Jingzhou Central Hospital.
Of the 91 patients diagnosed with COVID-19, 30 cases (33.0%) were severe and two patients (2.2%) died. The severe disease group tended to be older (50.5 vs. 42.0 years; p = 0.049) and have more chronic disease (40% vs. 14.8%; p = 0.009) relative to mild disease group. Only 73.6% of the patients were quantitative polymerase chain reaction (qPCR)-positive on their first tests, while typical chest computed tomography images were obtained for each patient. The most common complaints were cough (n = 75; 82.4%), fever (n = 59; 64.8%), fatigue (n = 35; 38.5%), and diarrhea (n = 14; 15.4%). Non-respiratory injury was identified by elevated levels of aspartate aminotransferase (n = 18; 19.8%), creatinine (n = 5; 5.5%), and creatine kinase (n = 14; 15.4%) in laboratory tests. Twenty-eight cases (30.8%) suffered non-respiratory injury, including 50% of the critically ill patients and 21.3% of the mild patients.
Overall, the mortality rate of patients in Jingzhou was lower than that of Wuhan. Importantly, we found liver, kidney, digestive tract, and heart injuries in COVID-19 cases besides respiratory problems. Combining chest computed tomography images with the qPCR analysis of throat swab samples can improve the accuracy of COVID-19 diagnosis.
Triggering receptor expressed on myeloid cells 2 (TREM2) is a single-pass transmembrane immune receptor that is mainly expressed on microglia in the brain and macrophages in the periphery. Recent ...studies have identified TREM2 as a risk factor for Alzheimer's disease (AD). Increasing evidence has shown that TREM2 can affect lipid metabolism both in the central nervous system (CNS) and in the periphery. In the CNS, TREM2 affects the metabolism of cholesterol, myelin, and phospholipids and promotes the transition of microglia into a disease-associated phenotype. In the periphery, TREM2 influences lipid metabolism by regulating the onset and progression of obesity and its complications, such as hypercholesterolemia, atherosclerosis, and nonalcoholic fatty liver disease. All these altered lipid metabolism processes could influence the pathogenesis of AD through several means, including affecting inflammation, insulin resistance, and AD pathologies. Herein, we will discuss a potential pathway that TREM2 mediates lipid metabolism to influence the pathogenesis of AD in both the CNS and periphery. Moreover, we discuss the possibility that TREM2 may be a key factor that links central and peripheral lipid metabolism under disease conditions, including AD. This link may be due to impacts on the integrity of the blood-brain barrier, and we introduce potential pathways by which TREM2 affects the blood-brain barrier. Moreover, we discuss the role of lipids in TREM2-associated treatments for AD. We propose some potential therapies targeting TREM2 and discuss the prospect and limitations of these therapies.
Quercetin, a typical flavonoid, possesses diverse biochemical and physiological actions, including antiplatelet, estrogenic, and anti-inflammatory properties. This review mainly centers on recent ten ...years findings with respect to intervening diabetes and its complications with the well-known flavonoid quercetin. After a short introduction of quercetin, major in vitro and in vivo findings are summarized showing that quercetin is a promising molecule for the treatment of these diseases. Finally, we contemplate future development and application prospects of quercetin. Despite the wealth of in animal research results suggesting the anti-diabetic and its complications potential of quercetin, its efficacy in diabetic human subjects is yet to be explored. The problem may become an important direction in the future research.
Improving the stability of cuprous oxide (Cu2O) is imperative to its practical applications in artificial photosynthesis. In this work, Cu2O nanowires are encapsulated by metal–organic frameworks ...(MOFs) of Cu3(BTC)2 (BTC=1,3,5‐benzene tricarboxylate) using a surfactant‐free method. Such MOFs not only suppress the water vapor‐induced corrosion of Cu2O but also facilitate charge separation and CO2 uptake, thus resulting in a nanocomposite representing 1.9 times improved activity and stability for selective photocatalytic CO2 reduction into CH4 under mild reaction conditions. Furthermore, direct transfer of photogenerated electrons from the conduction band of Cu2O to the LUMO level of non‐excited Cu3(BTC)2 has been evidenced by time‐resolved photoluminescence. This work proposes an effective strategy for CO2 conversion by a synergy of charge separation and CO2 adsorption, leading to the enhanced photocatalytic reaction when MOFs are integrated with metal oxide photocatalyst.
Cu2O nanowires are decorated with Cu3(BTC)2 by a surfactant‐free method. The Cu2O@Cu3(BTC)2 core–shell structure offers enlarged active surfaces and prolonged lifetime of separated electrons for CO2 reduction into CH4, exhibiting enhanced photocatalytic activity and stability compared to the bare Cu2O.
Chimeric antigen receptor (CAR) T cell therapy is one of the most promising immunotherapies in the past decade. It brings hope for cure to patients with previously refractory hematological ...malignancies. However, when translating this strategy into non-hematologic malignancies, the antitumor activity from multiple clinical studies seemed to be subtle or transient. The less satisfying efficacy in solid tumors might at least due to antigen heterogeneity, suboptimal CAR-T cell trafficking and tumor immunosuppressive environment. Here, we will review the updating strategies to challenge the therapeutic impediments of CAR-T therapy in non-hematologic malignancies. We mainly focus on the combination with oncolytic viruses (OV), the born allies for CAR-T cells. In addition to previously reported OVs-arming strategy, we discuss recently proposed tumor-tagging concept by OVs as CAR-T targets, as well as the possible improvements. Overall, tumor-tagging strategy by OVs combination with CAR-T would be a novel and promising solution for the heterogeneity and immunosuppressive microenvironment of solid tumors.
•The less satisfying efficacy of CAR-T cell therapy in solid tumors might at least due to antigen heterogeneity, suboptimal CAR-T cell trafficking and tumor immunosuppressive environment.•Instead of hunting CAR-T cell targets, tagging tumor cells by oncolytic viruses (OV) provides more choices.•Oncolytic viruses can deliver novel CAR-T targets specifically to tumor cells, redirecting single-target CAR-T cells to previously antigen-mismatched tumor cells.•Adopt the gene circuit idea by inserting the RNA-based AND gate to realize better tumor-tagging specificity.
Psychologic depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychologic depression alters the immune profiles in ...prostate cancer.
We used a murine model of depression in Myc-CaP tumor-bearing immunocompetent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Transwell migration and coculture assays were used to evaluate myeloid cell trafficking and cytokine profile changes evoked by Myc-CaP cells that had been treated with norepinephrine (NE), a major elevated neurotransmitter in depression. Chemoattractant, which correlated with immune cell infiltration, was screened by RNA-seq. The chemoattractant and immune cell infiltration were further confirmed using clinical samples of patients with prostate cancer with a high score of psychologic depression.
Psychologic depression predominantly promoted tumor-associated macrophage (TAM) intratumor infiltrations, which resulted from spleen and circulating monocytic myeloid-derived suppressor cell mobilization. Neuropeptide Y (NPY) released from NE-treated Myc-CaP cells promotes macrophage trafficking and IL6 releasing, which activates STAT3 signaling pathway in prostate cancer cells. Clinical specimens from patients with prostate cancer with higher score of depression revealed higher CD68
TAM infiltration and stronger NPY and IL6 expression.
Depression promotes myeloid cell infiltration and increases IL6 levels by a sympathetic-NPY signal. Sympathetic-NPY inhibition may be a promising strategy for patients with prostate cancer with high score of psychologic depression.
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The two-parameter Rayleigh distribution, as an extended distribution of the Rayleigh distribution, has been widely applied in reliability analysis. With the introduction of the location parameter, ...two-parameter Rayleigh distribution becomes more flexible in fitting real-data. In this paper, based on generalized progressively hybrid censored(GPHC) sample from the two-parameter Rayleigh distribution, Classical and Bayesian inferences are discussed. The Newton-Raphson(NR) and Expectation-Maximization(EM) algorithms are used to compute the maximum likelihood estimates(MLEs). As well as the asymptotic confidence interval(ACI) estimation is obtained through the asymptotic distribution theory of maximum likelihood estimation(MLE) and computation of the observed Fisher information matrix. In Bayesian frame, the estimation of unknown parameters and prediction of future observable are taken into consideration. Due to Bayesian estimation is challenging to compute precisely and for the purpose of comparison, the Lindley's approximation, the Tierney-Kadane(TK) approximation and Markov chain Monte Carlo(MCMC) method are employed to obtain Bayesian estimates. Then, combining the MCMC algorithm mentioned in the article, the one- and two- samples Bayesian prediction are obtained. Finally, the simulation results are provided and a real-life data set is used for illustration purpose.
The re‐emergence of influenza raises a global concern that viral pandemics can unpredictably occur. However, effective approaches that can probe the infection risk of influenza viruses for humans are ...rare. In this work, we develop a glycofoldamer that can rapidly identify the glycan‐receptor specificity of influenza viruses in a high‐throughput manner. The coupling of glycan receptors that can be recognized by hemagglutinin (a surface protein on the virion capsid of influenza) to a fluorogenic‐dye foldamer produces the glycofoldamers with minimal fluorescence in aqueous solution. After interaction with human‐infecting virus strains for only five minutes, the fluorescence intensity of the glycofoldamer is remarkably enhanced with a blue‐shifted emission peak. The probes have also proven effective for the rapid identification of 1) the human‐ or bird‐infecting properties of influenza viruses in a high‐throughput manner and 2) the receptor‐specificity switch of a virus strain by mutations.
Glycofoldamers: The coupling of sialylglycans to a unique dye foldamer produces glycofoldamers that can rapidly identify the human‐ or avian‐infecting properties of influenza viruses in a high‐throughput screening. The mutation‐induced receptor‐specificity switch of a virus was also identified with this approach.
Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of ...disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.
We performed targeted next-generation sequencing of the four CP-associated genes in 1061 Han Chinese CP patients and 1196 controls. To evaluate gene-environment interactions, the patients were divided into three subgroups, idiopathic CP (ICP; n = 715), alcoholic CP (ACP; n = 206), and smoking-associated CP (SCP; n = 140). The potential impact of rare pathogenic variants on the age of onset of CP and clinical outcomes was evaluated using the Kaplan-Meier model.
We identified rare pathogenic genotypes involving the SPINK1, PRSS1, CTRC, and/or CFTR genes in 535 (50.42%) CP patients but in only 71 (5.94%) controls (odds ratio = 16.12; P < 0.001). Mutation-positive patients had significantly earlier median ages at disease onset and at diagnosis of pancreatic stones, diabetes mellitus and steatorrhea than mutation-negative ICP patients. Pathogenic genotypes were present in 57.1, 39.8, and 32.1% of the ICP, ACP, and SCP patients, respectively, and influenced age at disease onset and clinical outcomes in all subgroups.
We provide evidence that rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes significantly influence the age of onset and clinical outcomes of CP. Extensive gene-environment interactions were also identified.
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