Objective:In the context of COVID-19 pandemic, the epidemic severities, non-pharmaceutical intervention intensities, individual behavior patterns and vaccination coverage vary with countries in the world. China has experienced a long period without indigenous cases, unfortunately, multi local outbreaks caused by imported cases and other factors have been reported, posing great challenges to COVID-19 prevention and control in China. Thus it is necessary to explore the mechanisms of the re-emerged COVID-19 epidemics and their differences.Methods:Based on susceptible exposed infectious recovered (SEIR) epidemic dynamics model, we developed a set of novel evolution equations which can describe the dynamic processes of integrated influence of interventions, vaccination coverage and individual behavior changes on the re-emergency of COVID-19 epidemic. We developed methods to calculate the optimal intervention intensity and vaccination rate at which the size of susceptible population can be reduced to less than threshold for the re-emergency of COVID-19 epidemic.Results:If strong interventions or super interventions are lifted too early, even a small cause can lead to the re-emergence of COVID-19 epidemic at different degrees. Moreover, the stronger the early control measures lifted are, the more severe the epidemic is. The individual behavior changes for the susceptibility to the epidemic and the enhancement or lifting of prevention and control measures are key factors to influence the incidence the multi outbreaks of COVID-19. The optimist early intervention measures and timely optimization of vaccination can not only prevent the re-emergency of COVID-19 epidemic, but also effectively lower the peak of the first wave of the epidemic and delay its arrival.Conclusion:The study revealed that factors for the re-emergence of COVID-19 epidemics included the intensity and lifting of interventions, the change of individual behavior to the response of the epidemic, external incentives and the transmissibility of COVID-19.

Since December 2019, the outbreak of COVID-19 in Wuhan has spread rapidly due to population movement during the Spring Festival holidays. Since January 23rd, 2020, the strategies of containment and contact tracing followed by quarantine and isolation has been implemented extensively in mainland China, and the rates of detection and confirmation have been continuously increased, which have effectively suppressed the rapid spread of the epidemic. In the early stage of the outbreak of COVID-19, it is of great practical significance to analyze the transmission risk of the epidemic and evaluate the effectiveness and timeliness of prevention and control strategies by using mathematical models and combining with a small amount of real-time updated multi-source data. On the basis of our previous research, we systematically introduce how to establish the transmission dynamic models in line with current Chinese prevention and control strategies step by step, according to the different epidemic stages and the improvement of the data. By summarized our modelling and assessing ideas, the model formulations vary from autonomous to non-autonomous dynamic systems, the risk assessment index changes from the basic regeneration number to the effective regeneration number, and the epidemic development and assessment evolve from the early SEIHR transmission model-based dynamics to the recent dynamics which are mainly associated with the variation of the isolated and suspected population sizes.

OBJECTIVE：To investigate the effects of dihydroartemisinin （DHA）on the metabolism of amino acid metabolites in human hepatocellular carcinoma cells Huh 7 and BEL- 7402，and to provide theoretic basis for clarifying the mechanism of DHA regulating the metabolism of hepatocellular carcinoma cells. METHODS ：CCK-8 method was taken to detect the effect of different concentrations of DHA （12.5，25，50，100 µmol/L）treating for 24，48，72 h on the two kinds of cells. Two kinds of cells were divided into control group and administration group （DHA，25 µmol/L），and then cultured with drug-free or drug-containing medium for 24 h，operated in parallel for three times. After derivatization of cell samples in each group ，GC-MS method was used to detect the content of amino acid metabolites ，combined with SIMCA-P software analysis and compound library comparison ，the differential metabolites in two kinds of cells were screened out. The pathway enrichment analysis of differential metabolism was conducted with Metaboanalyst 4.0 software. RESULTS ：Compared with control group ，the contents of glutamine ，glutathione， phenylalanine，fumaric acid and taurine were trending down in Huh 7 or BEL- 7402 cells. There were 28 and 29 differential metabolites obtained from the above two kinds of cells ，and 10 of them were common differential metabolites ，including glutamine，glutathione，taurine，fumaric acid ，phenylalanine，etc. The differential metabolites were enriched in 8 and 6 pathways respectively. The common enrichment pathways were amino acid-tRNA biosynthesis ，aspartate-alanine-glutamate metabolism ， nitrogen metabolism ，phenylalanine metabolism and pentose phosphate pathway ，etc. CONCLUSIONS ：DHA can significantly reduce the activities of Huh 7 cells and BEL- 7402 cells，and the contents of glutamine ，glutamic acid ，glutathione and phenylalanine，etc. It may regulate the growth of the two kinds of cells by influencing the mechanism of aspartic acid- alanine-glutamate metabolic pathway ，etc.

It is reported that dihydroartemisinin could reduce the expression of phosphorylated adhesion kinase and matrix metalloproteinase-2, inhibit the growth, migration and invasion of ovarian cancer cells, promote the formation of Treg cells through TGF-beta/Smad signaling pathway, and play an immunosuppressive role; dihydroartemisinin could also inhibit the growth of lung cancer cells by inhibiting the expression of vascular endothelial growth factor(VEGF) receptor KDR. However, there are few studies on dihydroartemisinin in hepatocellular carcinoma cells. In order to preliminarily explore the effect of dihydroartemisinin on invasion and metastasis of hepatocellular carcinoma cells, CCK-8 method and crystal violet staining were used to detect the effect of dihydroartemisinin on the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H. The effects of dihydroartemisinin on the invasion and metastasis of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H were studied by using cell wound healing and Transwell. Western blot was used to detect the protein expression of epidermal growth factor receptor(EGFR) and its downstream signaling pathway in cells treated with dihydroartemisinin for 48 hours. The results showed that dihydroartemisinin could inhibit the growth of hepatocellular carcinoma cell 7402 and highly metastatic hepatocellular carcinoma cell MHCC97 H at 25 μmol·L~(-1). As compared with the control group, the number of cell clones was significantly reduced, and the ability of cell migration and invasion was weakened. Western blot results showed that as compared with the control group, dihydroartemisinin group could down-regulate the protein expression of EGFR and its downstream signaling pathways p-AKT, p-ERK, N-cadherin, Snail and Slug, and up-regulate the expression of E-cadherin protein, thus affecting the migration, invasion and metastasis of hepatocellular carcinoma cells 7402 and MHCC97 H.
Artemisinins/pharmacology* ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; ErbB Receptors/metabolism* ; Humans ; Liver Neoplasms/pathology* ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Signal Transduction