Background and aims
The outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has recently spread worldwide and been ...declared a pandemic. We aim to describe here the various clinical presentations of this disease by examining eleven cases.
Methods
Electronic medical records of 11 patients with COVID‐19 were collected, and demographics, clinical manifestations, outcomes, key laboratory results, and radiological images are discussed.
Results
The clinical course of the eleven cases demonstrated the complexity of the COVID‐19 profile with different clinical presentations. Clinical manifestations range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe.
Conclusion
All different clinical characteristics of COVID‐19 should be taken into consideration to identify patients that need to be in strict quarantine for the efficient containment of the pandemic.
Clinical manifestations of COVID‐19 range from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Laboratory detection of the viral nucleic acid can yield false‐negative results, and serological testing of virus‐specific IgG and IgM antibodies should be used as an alternative for diagnosis. Patients with common allergic diseases did not develop distinct symptoms and severe courses. Cases with a pre‐existing condition of chronic obstructive pulmonary disease or complicated with a secondary bacterial pneumonia were more severe.
Background
Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has been widely spread. We aim to investigate the clinical ...characteristic and allergy status of patients infected with SARS‐CoV‐2.
Methods
Electronic medical records including demographics, clinical manifestation, comorbidities, laboratory data, and radiological materials of 140 hospitalized COVID‐19 patients, with confirmed result of SARS‐CoV‐2 viral infection, were extracted and analyzed.
Results
An approximately 1:1 ratio of male (50.7%) and female COVID‐19 patients was found, with an overall median age of 57.0 years. All patients were community‐acquired cases. Fever (91.7%), cough (75.0%), fatigue (75.0%), and gastrointestinal symptoms (39.6%) were the most common clinical manifestations, whereas hypertension (30.0%) and diabetes mellitus (12.1%) were the most common comorbidities. Drug hypersensitivity (11.4%) and urticaria (1.4%) were self‐reported by several patients. Asthma or other allergic diseases were not reported by any of the patients. Chronic obstructive pulmonary disease (COPD, 1.4%) patients and current smokers (1.4%) were rare. Bilateral ground‐glass or patchy opacity (89.6%) was the most common sign of radiological finding. Lymphopenia (75.4%) and eosinopenia (52.9%) were observed in most patients. Blood eosinophil counts correlate positively with lymphocyte counts in severe (r = .486, P < .001) and nonsevere (r = .469, P < .001) patients after hospital admission. Significantly higher levels of D‐dimer, C‐reactive protein, and procalcitonin were associated with severe patients compared to nonsevere patients (all P < .001).
Conclusion
Detailed clinical investigation of 140 hospitalized COVID‐19 cases suggests eosinopenia together with lymphopenia may be a potential indicator for diagnosis. Allergic diseases, asthma, and COPD are not risk factors for SARS‐CoV‐2 infection. Older age, high number of comorbidities, and more prominent laboratory abnormalities were associated with severe patients.
Decreased eosinophil count, which was positively correlated with lymphocyte counts, may be a potential biological indicator for diagnosing
COVID‐19 patients. Low prevalence of allergic diseases, COPD and patients with smoking history indicated they may not be the predisposing
factors of COVID‐19. Elder age, high number of comorbidities and more prominent laboratory abnormalities were associated with severe
patientsz.
Abstract
Background
Encephalitis in hand, foot, and mouth disease (HFMD) is a serious threat to children’s health and life. Toll-like receptor 3 (TLR3) is an innate immune-recognition receptor that ...can recognize virus and initiate innate immune responses. Emodin has the effects of anti-inflammatory and regulating immune function, but the mechanism is not very clear.
Methods
Cells and mice were pretreated with coxsackievirus B3m (CVB3) and treated with emodin. The messenger ribonucleic acid (mRNA) and protein levels of TLR3 and downstream molecules were detected by quantitative real-time polymearse chain reaction and western blotting analysis, respectively. TLR3 expression was also downregulated by anti-TLR3 antibody (TLR3Ab) or small interfering RNA (siRNA). Pathological changes were assessed with hematoxylin and eosin staining. Immunohistochemistry was used to examine the expression of TLR3 in brain tissues. The expression of interleukin (IL)-6, nuclear factor (NF)-κB, and interferon (IFN)-β in serum were tested with enzyme-linked immunosorbent assay.
Results
Emodin decreased the mRNA and protein levels of TLR3 and downstream molecules in vitro and in vivo. After downregulating TLR3 using anti-TLR3Ab or siRNA, emodin could still decrease the mRNA and protein levels of TLR3 and downstream molecules. Emodin also displayed notable effects on pathology, TLR3 protein in brain tissues, and expression of IL-6, NF-κB, IFN-β, in serum.
Conclusions
Emodin exerts a protective effect in CVB3-mediated encephalitis in HFMD by inhibiting the TLR3 pathway.
This study indicated that TLR3 pathway is a viable therapeutic target for CVB3-mediated encephalitis in HFMD and certified the efficacy of emodin via inhibiting the TLR3 signaling pathway to alleviate CVB3-mediated encephalitis in HFMD in vitro and in vivo.
Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are two important cellular components in the tumor microenvironment, which may modify the cancer phenotype and affect patient ...survival. However, the crosstalk between MDSCs and multiple myeloma stem cells (MMSCs) are relatively poorly understood.
The frequencies of granulocytic-MDSCs (G-MDSCs) in MM patients were detected by flow cytometry and their association with the disease stage and patient survival were analyzed. RT-PCR, flow cytometry, western blot and sphere formation assays were performed to investigate the effects of G-MDSCs, piRNA-823 and DNA methylation on the maintenance of stemness in MM. Then a subcutaneous tumor mouse model was constructed to analyze tumor growth and angiogenesis after G-MDSCs induction and/or piRNA-823 knockdown in MM cells.
Our clinical dataset validated the association between high G-MDSCs levels and poor overall survival in MM patients. In addition, for the first time we showed that G-MDSCs enhanced the side population, sphere formation and expression of CSCs core genes in MM cells. Moreover, the mechanism study showed that G-MDSCs triggered piRNA-823 expression, which then promoted DNA methylation and increased the tumorigenic potential of MM cells. Furthermore, silencing of piRNA-823 in MM cells reduced the stemness of MMSCs maintained by G-MDSCs, resulting in decreased tumor burden and angiogenesis in vivo.
Altogether, these data established a cellular, molecular, and clinical network among G-MDSCs, piRNA-823, DNA methylation and CSCs core genes, suggesting a new anti-cancer strategy targeting both G-MDSCs and CSCs in MM microenvironment.
ObjectivesAs early prediction of severe illness and death for patients with coronavirus disease 2019 (COVID-19) is important, we aim to explore the clinical value of laboratory indicators in ...evaluating the progression and prognosis of patients with COVID-19.DesignRetrospective cohort study.SettingHospital-based study in China.ParticipantsAdult patients with COVID-19 from December 15, 2019 to March 15, 2020.End pointDisease severity and mortality.MethodsClinical data of 638 patients with COVID-19 were collected and compared between severe and non-severe groups. The predictive ability of laboratory indicators in disease progression and prognosis of COVID-19 was analysed using the receiver operating characteristic curve. The survival differences of COVID-19 patients with different levels of laboratory indicators were analysed utilising Kaplan-Meier analysis.Results29.8% (190/638) of patients with COVID-19 progressed to severe. Compared with patients with no adverse events, C reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and D-dimer were significantly higher in severe patients with adverse events, such as acute myocardial injury, respiratory failure, acute kidney injury, mechanical ventilation, intensive care unit admission, multiple organ dysfunction syndromes and death (all p<0.05). The multivariate logistic analysis suggested that CRP, NLR and D-dimer were independent risk factors for the disease progression of COVID-19 (all p<0.05). The model combining all of them owned the highest area under the receiver operating characteristic curve (AUC) predicting disease progression and death of COVID-19, with AUC of 0.894 (95% CI 0.857 to 0.931) and 0.918 (95% CI 0.873 to 0.962), respectively. Survival analysis suggested that the patients with a high level of CRP, NLR or D-dimer performed shorter overall survival time (all p<0.05).ConclusionsThe combination of CRP, NLR and D-dimer could be an effective predictor for the aggravation and death in patients with COVID-19. The abnormal expression of these indicators might suggest a strong inflammatory response and multiple adverse events in patients with severe COVID-19.
20(S)‐protopanaxadiol (PPD)‐type ginsenosides are generally believed to be the most pharmacologically active components of Panax ginseng. These compounds induce apoptotic cell death in various cancer ...cells, which suggests that they have anti‐cancer activity. Anti‐angiogenesis is a promising therapeutic approach for controlling angiogenesis‐related diseases such as malignant tumors, age‐related macular degeneration, and atherosclerosis. Studies showed that 20(S)‐PPD at low concentrations induces endothelial cell growth, but in our present study, we found 20(S)‐PPD at high concentrations inhibited cell growth and mediated apoptosis in human umbilical vein endothelial cells (HUVECs). The mechanism by which high concentrations of 20(S)‐PPD mediate endothelial cell apoptosis remains elusive. The present current study investigated how 20(S)‐PPD induces apoptosis in HUVECs for the first time. We found that caspase‐9 and its downstream caspase, caspase‐3, were cleaved into their active forms after 20(S)‐PPD treatment. Treatment with 20(S)‐PPD decreased the level of Bcl‐2 expression but did not change the level of Bax expression. 20(S)‐PPD induced endoplasmic reticulum stress in HUVECs and stimulated UPR signaling, initiated by protein kinase R‐like endoplasmic reticulum kinase (PERK) activation. Total protein expression and ATF4 nuclear import were increased, and CEBP‐homologous protein (CHOP) expression increased after treatment with 20(S)‐PPD. Furthermore, siRNA‐mediated knockdown of PERK or ATF4 inhibited the induction of CHOP expression and 20(s)‐PPD‐induced apoptosis. Collectively, our findings show that 20(S)‐PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK‐eIF2α signaling pathway is essential for this process. These findings suggest that high concentrations of 20(S)‐PPD could be used to treat angiogenesis‐related diseases.
In this study, we show that 20(S)‐PPD inhibits HUVEC growth by inducing apoptosis and that ATF4 expression activated by the PERK‐eIF2α signaling pathway is essential for this process.
Defects can introduce atomic structural modulation and tailor performance of materials. Herein, it demonstrates that semiconductor WO
with inert electrocatalytic behavior can be activated through ...defect-induced tensile strains. Structural characterizations reveal that when simply treated in Ar/H
atmosphere, oxygen vacancies will generate in WO
and cause defective structures. Stacking faults are found in defects, thus modulating electronic structure and transforming electrocatalytic-inert WO
into highly active electrocatalysts. Density functional theory (DFT) calculations are performed to calculate
H adsorption energies on various WO
surfaces, revealing the oxygen vacancy composition and strain predicted to optimize the catalytic activity of hydrogen evolution reaction (HER). Such defective tungsten oxides can be integrated into commercial proton exchange membrane (PEM) electrolyser with comparable performance toward Pt-based PEM. This work demonstrates defective metal oxides as promising non-noble metal catalysts for commercial PEM green-hydrogen generation.
Deregulated microRNAs (miRNAs) and their roles in cancer development have attracted much attention. Two miRNAs, miR-15a and miR-16, which act as putative tumor suppressor by targeting the oncogene ...BCL2, have been implicated in cell cycle, apoptosis and proliferation. In this study, we investigated the possible role of miR-15a/16 in the angiogenesis of multiple myeloma (MM). Using a stem-loop quantitative reverse transcription-PCR, we analyzed miR-15a/16 expressions in bone marrow samples from newly diagnosed MM patients and a panel of MM cell lines. miRNA transfection, western blotting analysis and assay of luciferase activity were used to examine whether vascular endothelial growth factor (VEGF) is the target of miR-15a/16. The functional roles of miR-15a/16 on tumorigenesis and angiogenesis were examined by in vitro angiogenesis models and in vivo tumor xenograft model. We showed that miR-15a and miR-16 were significantly underexpressed in primary MM cells as well as in MM cell lines. The aberrant expression of miR-15a/16 was detected especially in advanced stage MM. In human MM cell lines and normal plasma cells, expression of miR-15a/16 inversely correlated with the expression of VEGF-A. Western blotting combined with the luciferase reporter assay demonstrated that VEGF-A was a direct target of miR-15a/16. Ectopic overexpression of miR-15a/16 led to decreased pro-angiogenic activity of MM cells. Finally, infection of lentivirus-miR-15a or lentivirus-miR-16 resulted in significant inhibition of tumor growth and angiogenesis in nude mice. This study suggest that miR-15a/16 could play a role in the tumorigenesis of MM at least in part by modulation of angiogenesis through targeting VEGF-A.
Emodin is an anthraquinone with potential anti-inflammatory properties. However, the possible molecular mechanisms and protective effects of emodin are not clear. The objective of this study was to ...investigate the possible molecular mechanisms and protective effects of emodin on lipopolysaccharide (LPS)-induced acute liver injury (ALI) via the Toll-like receptor 4 (TLR4) signaling pathway in the Raw264.7 cell line and in Balb/c mice.
This study established an inflammatory cellular model and induced an ALI animal model. TLR4 was overexpressed by lentivirus and downregulated by small interfering RNA (siRNA) technology. The mRNA and protein levels of TLR4 and downstream molecules were detected in cells and liver tissue. The tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 levels in supernatant and serum were determined by ELISA. The distribution and expression of mannose receptor C type 1 (CD206) and arginase 1 (ARG1) in the liver were tested by immunofluorescence. Mouse liver function and histopathological observations were assessed.
Administration of emodin reduced the protein and/or mRNA levels of TLR4 and its downstream molecules following LPS challenge in Raw264.7 cells and in an animal model. Additionally, emodin suppressed the expression of TNF-α and IL-6 in cell culture supernatant and serum. The inhibitory effect of emodin was also confirmed in RAW264.7 cells, in which TLR4 was overexpressed or knocked down. Additionally, ARG1 and CD206 were elevated in the emodin groups. Emodin also decreased serum ALT and AST levels and alleviated the liver histopathological damage induced by LPS.
Emodin showed excellent hepatoprotective effects against LPS-induced ALI, possibly by inhibiting TLR4 signaling pathways.
PDF
