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BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization, while several key epidemiological parameters of the disease remain to be clarified. This study aimed to obtain robust estimates of the incubation period, upper limit of latent period (interval between infectors exposure and infectees exposure), serial interval, time point of exposure (the day of infectees exposure to infector relative to the latters symptom onset date) and basic reproduction number (R0) of COVID-19. MethodsBetween late February and early March of 2020, the individual data of laboratory confirmed cases of COVID-19 were retrieved from 10728 publicly available reports released by the health authorities of and outside China and from 1790 publications identified in PubMed and CNKI. To be eligible, a report had to contain the data that allowed for estimation of at least one parameter. As relevant data mainly came from clustering cases, the clusters for which no evidence was available to establish transmission order were all excluded to ensure accuracy of estimates. Additionally, only the cases with an exposure period spanning 3 days or less were included in the estimation of parameters involving exposure date, and a simple method for determining exposure date was adopted to ensure the error of estimates be small (< 0.3 day). Depending on specific parameters, three or four of normal, lognormal, Weibull, and gamma distributions were fitted to the datasets and the results from appropriate models were presented. FindingsIn total, 1155 cases from China, Japan, Singapore, South Korea, Vietnam, Germany and Malaysia were included for the final analysis. The mean and standard deviation were 7.44 days and 4.39 days for incubation period, 2.52 days and 3.95 days for the upper limit of latent period, 6.70 days and 5.20 days for serial interval, and -0.19 day (i.e., 0.19 day before infectors symptom onset) and 3.32 days for time point of exposure. R0 was estimated to be 1.70 and 1.78 based on two different formulas. For 39 (6.64%) cases, the incubation periods were longer than 14 days. In 102 (43.78%) infector-infectee pairs, transmission occurred before infectors symptom onsets. In 27 (3.92%) infector-infectee pairs, infectees symptom onsets occurred before those of infectors. Stratified analysis showed that incubation period and serial interval were consistently longer for those with less severe disease and for those whose primary cases had less severe disease. Asymptomatic transmission was also observed. InterpretationThis study obtained robust estimates of several key epidemiological parameters of COVID-19. The findings support current practice of 14-day quarantine of persons with potential exposure, but also suggest that longer monitoring periods might be needed for selected groups. The estimates of serial interval, time point of exposure and latent period provide consistent evidence on pre-symptomatic transmission. This together with asymptomatic transmission and the generally longer incubation and serial interval of less severe cases suggests a high risk of long-term epidemic in the absence of appropriate control measures. FundingThis work received no funding from any source.
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Mediation analysis is mainly used to explore the causal mechanism between independent variable X and dependent variable Y. It determines whether mediator M plays a role and evaluate the role’s degree in the causal path by decomposing the causal path between the independent variable X and the dependent variable Y. However, the classical mediation analysis is generally used for single mediator. This paper introduces a new mediation analysis method for multiple mediators.
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At present, traditional methods on statistics have limitations in controlling time- varying confounding. This paper introduces an analysis method, parametric g-formula, which would adjust time-varying confounding, and also exemplifies the steps of its implementation for purpose to provide a new reference for researchers to deal with long-term observational data.
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Objective:To explore the inhibitory effects of gomisin A(GA)in combination with carboplatin (CBP)on the proliferation,invasion and metastasis of human ovarian cancer Skov3 cells and their mechanisms,and to illustrate the synergistic antitumor effect of GA.Methods:The ovarian cancer Skov3 cells were treated with different concentrations of GA combined with different concentrations of CBP.MTT assay was used to detect the inhibitory rates of proliferation.According to the results,the appropriate concentrations of GA and CBP were conformed.The Skov3 cells were treated with PBS,GA(0.04 μmol·L-1),CBP(16 mg·L-1)and GA (0.04 μmol·L-1)in combination with CBP(16 mg·L-1),respectively,and used as control group,GA group, CBP group and GA+CBP group.After 48 h of treatment,the cell morphology was observed by optical microscope, the cell reproductive ability was determined by clonogenic cell survival assay,and the cell migration ability was measured by cell wound healing test;Transwell experiment was used to detect the cell invasion ability.The expression levels of MMP-2 and MMP-9 mRNA were determined by RT-PCR and the protein expression levels of MMP-2,MMP-9,AKT1 and pAKT1 were determined by Western blotting method.Results:Compared with GA and CBP groups,the inhibitory rate of proliferation of Skov3 cells in GA + CBP group was significantly increased (P<0.01).The concentrations of GA and CBP for the best dose ratio were 0.04 μmol·L-1and 16 mg·L-1, respectively.The results of clone formation assay showed that the colony formation rates in CBP and GA+CBP groups were decreased compared with control group(P<0.05 or P<0.01);the colony formation rate of cells in GA + CBP group was significantly decreased compared with GA and CBP groups(P<0.01);the wound scratch assay results suggested that the number of metastic Skov3 cells in GA and CBP groups were decreased compared with control group;and the number of metastic Skov3 cells in GA+ CBP group was decreased compared with GA and CBP groups.The results of Transwell expriment showed that the capacities of cells passing the ECM in GA and CBP groups were decreased compared with control group;the capacity of cells passing the ECM was decreased compared with GA and CBP groups.The RT-PCR and Western blotting results showed that the expression levels of MMP-2 and MMP-9 mRNA in GA+CBP group were down-regulated compared with GA and CBP groups(P<0.01),and the expression levels of MMP-2,MMP-9,AKT1 and pAKT1 protein were down-regulated(P<0.01).Conclusion:GA can enhance the ability of CBP to inhibit the proliferation,invasion and metastasis of human ovarian cancer Skov3 cells,and thus play a role in decreasing the toxicity and increasing the efficacy of chemotherapy.
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Objective:To explore the effect of gomisin A (GA) in combination with carboplatin (CBP) on the apoptosis of ovarian cancer Skov3 cells,and to illustrate the synergistic antitumor effect of GA.Methods:The ovarian cancer Skov3 cells were treated with GA combined with CBP.MTT assay was used to detect the inhibitory rates of proliferation and the appropriate concentrations of GA and CBP were selected according to the results.The Skov3 cells were divided into control group,GA (0.04 μmol · L-1) group,CBP (16 mg · L 1) group and GA (0.04 μmol· L-1)+ CBP (16 mg · L-1) group.After 48 h treatment,the cell morphology was observed by microscope,the apoptotic rate was measured by flow eytometry,the apoptotic index (AI) was observed by TUNEL staining,the mitochondrial membrane potential was detected by JC-1 staining,and the mRNA and protein expression levels of apoptosis-related genes (Bax,caspase-3,Stat3) were determined by RT PCR and Western blotting method.Results:The inhibitory rate of proliferation of Skov3 cells in GA + CBP group (52.1％) was significantly higher than those in GA and CBP groups (P＜0.01).The concentrations of GA and CBP for the best dose ratio were 0.04 μmol· L-1 and 16 mg · L-1,respectively.Compared with control group,the cell refractivities were decreased,the cells retracted,and part of cells were suspended in GA group and CBP groups;there were more suspended cells and cell retraction phenomenon was more prominent in GA + CBP group.The results of TUNEL staining and flow cytometry showed that the AI and apoptotic rate of cells in GA + CBP group were significantly increased compared with control group,GA and CBP group (P＜0.05 or P＜0.01);the JC-1staining results suggested that the mitochondrial membrane potential of Skov3 cells in GA + CBP group was decreased (P＜0.05 or P＜0.01).The RT-PCR and Western blotting results showed that the expression levels of Bax and caspase-3 mRNA and protein were up-regulated (P＜0.05) and the expression levels of Bcl-2 and Stat3mRNA and protein in GA + CBP group were down-regulated compared with control,GA and CBP groups (P＜0.05).Conclusion:GA can enhance the ability of CBP to induce the apoptosis of human ovarian cancer Skov3 cells,and its mechanisms may be related to the up-regulation of the Bax and Caspase-3 expressions and the down-reguation of the Bcl-2 expression;GA can synergize the induction of CBP on apoptosis.
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Basal metabolic rate (BMR) is of great significance to the setting of daily energy requirements and the scientific diet guidance for the population. There are 3 kinds of measurement methods for BMR, including the direct calorimetry, the indirect calorimetry, and the equation estimation. The direct calorimetry method is difficult to implement and is only used in some special populations. The indirect calorimetry and the equation estimation are two methods that are currently used commonly. The indirect calorimetry is highly accurate and suitable for individual for basal metabolic measurement or datum collection via equation estimation. The equation estimation is simple and convenient, which is suitable for large samples.
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Humanos , Metabolismo Basal , Fisiologia , Pesquisa Biomédica , Calorimetria Indireta , Metabolismo EnergéticoRESUMO
Objective:To investigate the preventive and protective effects of Schisandrin B in the mice of Alzheimer's disease (AD),and to clarify its mechanism.Methods:Fifty Balb/c mice were randomly divided into blank group,model group,pasitive control group,low dose of Schisandrin B group(0.1 g·kg-1)and high dose of Schisandrin B group(0.5 g·kg-1);there were 10 mice in each group.Step-through test was conducted after last administration to detect the latencies and number of errors of the mice in various groups,and the brain tissue was taken.Congo red staining was to detect the morphology changes of cells and neuronal amyloidosis in brain tissue of the mice.The levels of ROS in brain tissue of the mice were tested by Flow Cytometry.The contents of MDA,the levels of LDH,and the activities of CAT,GSH-Px and SOD in brain tissue of the mice were tested by biochemical method.Western blotting method was used to detect the expression levels of signaling pathway proteins Nrf2 and Keap1 in brain tissue of the mice.Results:Compared with model group,the latencies of the mice in low and high dose of Schisandrin B groups were increased (P<0.01) and the number of errors in step-through tests was decreased (P<0.05 or P<0.01).The Congo red staining results showed that compared with model group,the neuronal amyloidosis in brain tissue of the mice in Schisandrin B groups was decreased significantly.Compared with model group,the levels of ROS,LDH and the contents of MDA in brain tissue of the mice in low and high doses of Schisandrin B groups were decreased (P<0.05 or P<0.01),and the activities of CAT,SOD and GSH-Px were increased (P<0.01).Compared with low dose of Schisandrin B group,the content of MDA and the activities of SOD and GSH-Px in brain tissue of the mice in high dose of Schisandrin B group were increased (P<0.001).Compared with model group,the expression level of Nrf2 protein in brain tissue of the mice in low dose of Schisandrin B group was increased (P<0.01),while the expression level of Nrf2 protein in brain tissue of the mice in high dose of Schisandrin B group was decreased (P<0.01);the expression levels of Keap1 protein in brain tissue of the mice in low and high doses of Schisandrin B groups was decreased (P<0.01).Conclusion:Schisandrin B could decrease the level of peroxidation in brain tissue of the mice and reduce the oxidative damage and improve the memory function of the AD mice.The mechanism is related to the activation of Nrf2 signaling pathway which improve the activity of antioxidant enzymes.
