Objective To study the time-toxicity and dose-toxicity relationship of hepatotoxicity induced by Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning Capsules (CQC) with single dose in mice.Methods In the Time-Toxicity relationship study,Kunming mice were randomly divided into control,PT,CPAH,CDH,and CQC group,and mice of.each drug administration group were randomly divided into nine subgroups according to the time (1,2,4,8,12,24,48,72 and 96 h after administration) of blood collection.The acetaminophen contents in PT,CPAH,and CDH groups were 425.98 mg/kg,and the dose of CQC group was 3 680.50 mg/kg.In the Dosage-Time relationship study,mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium and low dose group.The acetaminophen contents of high,medium,and low dose were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH group,and the dose of CQC group was 1437.70,2300.31,and 3680.50 mg/kg,10 mice in each group,sex in half.Blood was collected 12 h after administration.Animal behavior was observed every day,blood and organs were collected at the corresponding time points,serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),and alkaline phosphatase (ALP) level were detected,and the organs index of spleen and thymus,liver were calculated.Results There were no significant changes of ALT,AST,ALP,and organs index after once ig administration of CQC at dosage of 1437.70 mg/kg to 3680.50 mg/kg in mice.The study on time-toxicity relationship indicated that,after once administration of PT,CPAH,and CDH at 425.98 mg/kg,mice showed toxic symptom such as hypokinesia,dry hair and so on,12 h was the most obvious,24 ～ 72 h disappeared.The level of ALT,AST,and ALP in serum increased and reached to the peak at 12 h and then restored near normality after 72,24,and 24 h in PT,CPAH,and CDH group.Their organ index of liver,spleen and thymus all had no significant changes.The study on the dosage-toxicity relationship indicated that,there were no significant changes of animal behavior,ALT,AST,ALP,and organs index after once ig administration of PT,CPAH,and CDH at 266.24 mg/kg.Obvious liver injury can be induced by the three drugs with dosage of 425.98 to 681.57 mg/kg and the level of ALT,AST,and ALP increased significantly with the increase of dosage.Their liver index increased significantly with dosage of 681.57 mg/kg,but the organs index of spleen,thymus had no significant changes.Conclusion There was no hepatotoxicity after once ig administration of CQC with dosage of 3680.50 mg/kg in mice.Mice were once ig administration ofPT,CPAH,and CDH with a large dose,may induce acute liver injury and show obvious time-toxicity and dose-toxicity relationships.

Objective To study the dose-time-toxicity relationship of hepatotoxicity in mice with multiple administration of Paracetamol Tablets (PT),Compound Paracetamol and Amantadine Hydrochloride Tablets (CPAH),Compound Dextromethorphan Hydrobromide Tablets (CDH),and Chaiqin Qingning capsules (CQC).Methods Mice were randomly divided into control,PT,CPAH,CDH,and CQC high,medium,and low dose groups.The acetaminophen contents of high,medium,and low doses were 266.24,425.98,and 681.57 mg/kg in PT,CPAH,and CDH groups,and the doses of CQC group were 1437.70,2300.31,and 3 680.50 mg/kg,ig administration,once daily for 5 d.General state and toxicity of mice were observed.The changes of ALT,AST,AKP,TBIL,and ALB levels in serum and organ indexes of liver,spleen,thymus,and kidney were tested on day 1,3,7,11,and 14 after multiple administration.Results CQC with the dosage range of 1 437.70-3 680.50 mg/kg to mice within 14 d,has not yet induced the increase of AST,ALT,AKP,TBIL,and ALB levels and changes of organ indexes of liver,thymus spleen,and kidney compared with normal control (P ＞ 0.05).PT,CPAH,and CDH with repeated dose of 425.98-681.57 mg/kg could induce significant increase of the levels ofALT,AST,AKP,and TBIL which reached the peak on day 1 (P ＜ 0.05),and then gradually decreased on day 3-14.The level of ALB significant decreased on day 1-11 (P ＜ 0.05),and then gradually recovered on day 11-14.The liver index significant increased on day 1-3 (P ＜ 0.05),and recovered on day 7-14.Conclusion Multiple administration of CQC could not induce liver injury in mice within 14 d,while multiple administration ofPT,CPAH,and CDH could induce hepatotocixity in mice with a certain dose,and show an obvious dose-time-toxicity relationship.

Objective To optimize the fermentation conditions for Enterococcus faecalis (E.faecalis) and Saccharomyces cerevisiae (S.cerevisiae) mixed culture.Methods The optimum fermentation conditions for E.faecalis and S.cerevisiae mixed culture were identified by investigating the influence of initial pH,inoculum size,and ventilation rate of the culture broth on mixed microbial growth.Results The optimal initial pH of mixed microbial culture was 7.0 and the inoculation amounts of E.faecalis and S.cerevisiae were 4％ and 10％ respectively,when fermented in 600-mL pilot fermentor (liquid volume 40％) at 30 ℃,with ventilation rate of 0.2 L/min,for 20 h.At the end of the fermentation,the E.faecalis and S.cerevisiae counts were approximately 3.8 × 108 CFU/mL and 2.4 × 108 CFU/mL,respectively.Ventilation for the amount difference of E.faecalis was no significant (P ＞ 0.05),and for the amount difference of S.cerevisiae was statistically significant (P ＜ 0.05).Conclusion The E.faecalis and S.cerevisiae counts increased by 32.2％ and 31.5％ respectively,when the optimized conditions of fermentation culture were used.In this study,high mixed microbial counts were obtained,thus providing a reference for the preparation of large-scale production of mixed microbes.

Objective:To improve the teaching quality of Medical Microbiology by optimizing the teaching method,adjusting the teaching content and reforming the assessment model.Methods:The students of grade 2020 and 2021 of the same major were divided into the control group and the reform group.The control group received the traditional teaching method.The reform group received the"online + offline"blended teaching method,which integrates online learning resources and ideological and political education into the theoretical content of the curriculum.And the whole process assessment system was applied to the teaching method.The teaching quality was evaluated by the whole process examination results and questionnaire survey.Results:Compared with the control group,the score in the reform group was significantly improved(P＜0.01).Results of the questionnaire survey showed that students'satisfaction with the mixed teaching method reached 97.5% .The integration of hot issues of microbiology and curriculum ideological and political education significantly improved students'learning interest,and more students wanted to engage in the work of microbiology related fields in the future.Conclusion:The practice results show that optimizing the teaching method,adjusting the teaching content and reforming the assessment mode can stimulate the students'learning interest,improve the students'independent learning ability and improve the teaching quality.

This study aimed to quantitatively assess the effectiveness of the Wuhan lockdown measure on controlling the spread of coronavirus diesase 2019 (COVID-19). : Firstly，estimate the daily new infection rate in Wuhan before January 23，2020 when the city went into lockdown by consulting the data of Wuhan population mobility and the number of cases imported from Wuhan in 217 cities of Mainland China. Then estimate what the daily new infection rate would have been in Wuhan from January 24 to January 30th if the lockdown measure had been delayed for 7 days，assuming that the daily new infection in Wuhan after January 23 increased in a high，moderate and low trend respectively (using exponential, linear and logarithm growth models). Based on that，calculate the number of infection cases imported from Wuhan during this period. Finally，predict the possible impact of 7-day delayed lockdown in Wuhan on the epidemic situation in China using the susceptible-exposed-infectious-removed (SEIR) model. : The daily new infection rate in Wuhan was estimated to be 0.021%，0.026%，0.029%，0.033% and 0.070% respectively from January 19 to January 23. And there were at least 20 066 infection cases in Wuhan by January 23，2020. If Wuhan lockdown measure had been delayed for 7 days，the daily new infection rate on January 30 would have been 0.335% in the exponential growth model，0.129% in the linear growth model，and 0.070% in the logarithm growth model. Correspondingly，there would have been 32 075，24 819 and 20 334 infection cases travelling from Wuhan to other areas of Mainland China，and the number of cumulative confirmed cases as of March 19 in Mainland China would have been 3.3-3.9 times of the officially reported number. Conclusions: Timely taking city-level lockdown measure in Wuhan in the early stage of COVID-19 outbreak is essential in containing the spread of the disease in China.
COVID-19 ; China/epidemiology* ; Cities ; Communicable Disease Control ; Humans ; SARS-CoV-2

:To evaluate the impact of socioeconomic status，population mobility，prevention and control measures on the early-stage coronavirus disease 2019 (COVID-19) development in major cities of China. : The rate of daily new confirmed COVID-19 cases in the 51 cities with the largest number of cumulative confirmed cases as of February 19，2020 (except those in Hubei province) were collected and analyzed using the time series cluster analysis. It was then assessed according to three aspects，that is, socioeconomic status，population mobility，and control measures for the pandemic. : According to the analysis on the 51 cities，4 development patterns of COVID-19 were obtained，including a high-incidence pattern (in Xinyu)，a late high-incidence pattern (in Ganzi)，a moderate incidence pattern (in Wenzhou and other 12 cities)，and a low and stable incidence pattern (in Hangzhou and other 35 cities). Cities with different types and within the same type both had different scores on the three aspects. : There were relatively large difference on the COVID-19 development among different cities in China，possibly affected by socioeconomic status，population mobility and prevention and control measures that were taken. Therefore，a timely public health emergency response and travel restriction measures inside the city can interfere the development of the pandemic. Population flow from high risk area can largely affect the number of cumulative confirmed cases.
COVID-19 ; China/epidemiology* ; Cities ; Humans ; SARS-CoV-2 ; Social Class

:To predict the epidemiological trend of coronavirus disease 2019 (COVID-19) by mathematical modeling based on the population mobility and the epidemic prevention and control measures. : As of February 8，2020，the information of 151 confirmed cases in Yueqing，Zhejiang province were obtained，including patients' infection process，population mobility between Yueqing and Wuhan，etc. To simulate and predict the development trend of COVID-19 in Yueqing, the study established two-stage mathematical models，integrating the population mobility data with the date of symptom appearance of confirmed cases and the transmission dynamics of imported and local cases. : It was found that in the early stage of the pandemic，the number of daily imported cases from Wuhan (using the date of symptom appearance) was positively associated with the number of population travelling from Wuhan to Yueqing on the same day and 6 and 9 days before that. The study predicted that the final outbreak size in Yueqing would be 170 according to the number of imported cases estimated by consulting the population number travelling from Wuhan to Yueqing and the susceptible-exposed-infectious-recovered (SEIR) model; while the number would be 165 if using the reported daily number of imported cases. These estimates were close to the 170，the actual monitoring number of cases in Yueqing as of April 27，2020. : The two-stage modeling approach used in this study can accurately predict COVID-19 epidemiological trend.
COVID-19 ; China/epidemiology* ; Disease Outbreaks ; Humans ; Models, Theoretical ; Pandemics ; SARS-CoV-2

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl₄, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl₄-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl₄-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.