Objective:The transcriptome data was utilized to screen cuproptosis-related genes(CRGs)in oral squamous cell car-cinoma(OSCC),and the characteristic genes were identified for constructing a prognostic model for predicting patients'survival time.Methods:OSCC transcriptome gene expression and clinical data were obtained from TCGA and GEO.Through Lasso regres-sion analysis and Cox regression analysis,relevant prognostic genes were screened and prognostic models were constructed.Ac-cording to the median value of risk scores,patients were divided into high and low risk groups,and their survival rates were com-pared.Finally,the predictive performance of the model was verified.Results:In this study,9 characteristic genes with prognostic value(ENO2,P4HA1,SLC2A3,AQP1,PLS1,NXPH4,CTSG,TRAC,THBS1)were screened out and a 9-gene prognostic model was constructed.The survival rate of high-risk group based on prognostic model was significantly lower than that of low-risk group.The area under curve(AUC)of receiver operating characteristic curve(ROC)was 0.701,0.729 and 0.702 at 1 year,3 years and 5 years,respectively,which verifies that the risk model has good predictive performance.The nomogram predicted that the 1-year,3-year,and 5-year survival probabilities of OSCC patients are 89.6％,72.4％,and 63.9％respectively,and the cal-ibration curve confirmed the accuracy of the nomogram prediction.Conclusion:The 9-gene prognostic model based on CRGs screening could predict the prognosis of OSCC patients,which is helpful for clinical personalized treatment of OSCC patients and prediction of their survival rate.

Objective:The transcriptome data was utilized to screen cuproptosis-related genes(CRGs)in oral squamous cell car-cinoma(OSCC),and the characteristic genes were identified for constructing a prognostic model for predicting patients'survival time.Methods:OSCC transcriptome gene expression and clinical data were obtained from TCGA and GEO.Through Lasso regres-sion analysis and Cox regression analysis,relevant prognostic genes were screened and prognostic models were constructed.Ac-cording to the median value of risk scores,patients were divided into high and low risk groups,and their survival rates were com-pared.Finally,the predictive performance of the model was verified.Results:In this study,9 characteristic genes with prognostic value(ENO2,P4HA1,SLC2A3,AQP1,PLS1,NXPH4,CTSG,TRAC,THBS1)were screened out and a 9-gene prognostic model was constructed.The survival rate of high-risk group based on prognostic model was significantly lower than that of low-risk group.The area under curve(AUC)of receiver operating characteristic curve(ROC)was 0.701,0.729 and 0.702 at 1 year,3 years and 5 years,respectively,which verifies that the risk model has good predictive performance.The nomogram predicted that the 1-year,3-year,and 5-year survival probabilities of OSCC patients are 89.6％,72.4％,and 63.9％respectively,and the cal-ibration curve confirmed the accuracy of the nomogram prediction.Conclusion:The 9-gene prognostic model based on CRGs screening could predict the prognosis of OSCC patients,which is helpful for clinical personalized treatment of OSCC patients and prediction of their survival rate.

Objective To understand the situation of knowledge,attitude and practice (KAP) of sheep farmers and field veterinarians towards brucellosis prevention,and find out the potentially influential factors.Methods From March to September in 2017,1 067 sheep farmers and 401 field veterinarians were selected as participates,and questionnaire survey was carried out.Percentage rate was used to describe the situation of KAP.Nonparametric test was used to compare the KAP score difference.Results The overall awareness in sheep farmers and field veterinarians was 64.2％ and 80.1％,respectively.In addition,there were 17.3％ (185/1067) sheep farmers and 12.2％ (49/401) field veterinarians had never heard of brucellosis.The knowledge awareness in sheep farmers and field veterinarians was 62.6％ and 79.0％,respectively,75.8％ and 83.8％ of them had positive attitude to brucellosis prevention,54.1％ and 77.6％ of them had good practice habit.They hoped in the future,more information could be received through TVs,and then was internet or broadcasting.Sheep farmers who from first class region,age less than 45 years,education higher than junior high school,feeding time less than 5 years and sheep ever infected with brucellosis (U =4.85,3.08,3.29,2.20,6.62,P ＜ 0.05 or ＜ 0.01),had higher KAP scores than others.Field veterinarians,who had lower education,had lower KAP scores (U =4.29,P ＜ 0.01).Conclusions The awareness of sheep farmers and field veterinarians still need to improve and strengthen.Some suggestions are put forward:improve intervention pattern,optimize content and method,pay attention to use new media.

Objective To study the antipyretic effect of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules on the fever model induced by LPS and dry yeast in rats.Methods Fever was induced by ip injecting LPS (100 μg/kg) or sc injecting dry yeast (20％) in rats.We observed the changes of temperature of the rats after administration of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets (the acetaminophen contents were 205.67,102.83,and 51.42 mg/kg)and Chaiqin Qingning Capsules (1110.60,555.30,and 277.65 mg/kg).Maximum temperature rise height (△T) and temperature response index (TRI) were calculated,and the curve of average rise in temperature was drawn.Results Each dose group of Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules had obvious antipyretic effect on the fever model induced by LPS and dry yeast in rats,and there was a certain dose-effect relationship.Conclusion Paracetamol Tablets,Compound Paracetamol and Amantadine Hydrochloride Tablets,Compound Dextromethorphan Hydrobromide Tablets,and Chaiqin Qingning Capsules has certain antipyretic effect on LPS and dry yeast fever model in rats,and on the whole,the Western medicine acts rapid but continue for a short time,while the traditional Chinese medicine acts slow but continues for a long time.

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 investigate the "dose-time-toxicity" relationship of liver injury in mice induced by multiple dose of Chaiqin Qingning Capsule and Ganmaoling capsule. Methods Three hundred and ten healthy SPF mice were divided into 7 groups randomly, in which 3 groups were low, medium and high dose subgroups of Chaiqin Qingning capsule ( 50 mice with male and female half in each subgroup) . The doses of Chaiqin Qingning capsule subgroups were 1437. 70, 2300. 31 and 3680. 50 mg/kg, which were 1. 63 , 1. 64 and 1. 65 times of clinically equivalent dose ( ED) respectively. Three groups were low, medium and high dose subgroups of Ganmaoling capsule (50 mice with male and female half in each subgroup). The doses of Ganmaoling capsule subgroups were 1452. 31, 2251. 08 and 3489. 18 mg/kg, which were 1. 553 , 1. 554 and 1. 555 times of ED respectively. One group was the normal control group (10 mice, half were male). Each subgroup mice were treated with intragastric administration of the corresponding concentration drug suspension by 0. 20 ml per 10 g body weight, and the normal control group mice were treated with intragastric administration of equal volume of distilled water. All mice were treated once daily for 14 days. The general state of mice in each group was observed during the experiment. Ten mice randomly selected on the 1st, 3rd, 7th, 11th and 14th day after multiple administration of the medicine in each subgroup respectively and 10 mice in the normal control group after 14 days multiple administration of distilled water were weighed, and the serum alanine aminotransferase ( ALT) , aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB) and total bilirubin (TBil) levels were tested. Then the mice were executed and the organs, i. e. , liver, thymus, and spleen were taken to weigh and calculate the organ index. Results The general state of mice in the normal control group, Chaiqin Qingning capsule subgroups and Ganmaoling capsule low dose subgroup were not abnormal during the administration period. Ganmaoling capsule high dose subgroup appeared 8 mice died within 1 day after first administration, the overall mortality rate was 16%. The high dose and medium dose subgroup of mice showed decrease in activities, dietary, water and body weight significantly on 1st to 3rd day. The symptoms gradually disappeared on 4th to 7th day, and the state gradually returned to normal on 8th to 14th day. The difference of serum level of ALT, AST, ALP, ALB, TBil and liver, thymus and spleen organ index of Chaiqin Qingning capsule subgroups and Ganmaoling capsule low dose subgroup on the 1st, 3rd, 7th, 11th and 14th days after multiple administration compared with those of the normal control group were not statistically significant (all P>0. 05). The levels of serum ALT, ALP and TBil of Ganmaoling capsule high dose subgroup mice after multiple administration on 1st, 3rd, 7th day and the serum AST of mice on 1st and 3rd day were significantly higher than those in the normal control group (P<0. 05, P<0. 01). The serum ALB level of Ganmaoling capsule high dose subgroup mice on 3rd, 7th, 11th and 14th day were significantly lower than those in normal control group (P<0. 05, P<0. 01). The levels of serum ALT, AST, ALP and TBil of Ganmaoling capsule medium dose subgroup mice after multiple administration on 1st and 3rd day were significantly higher than those in the normal control group (P<0. 05, P<0. 01). The serum ALB level of Ganmaoling capsule medium dose subgroup mice after multiple administration on 3rd and 7th day were significantly lower than those in normal control group (P<0. 05, P<0. 01). The liver organ index of mice in Ganmaoling capsule high dose subgroup after multiple administration on 1st , 3rd and Ganmaoling capsule medium dose subgroup after multiple administration on 1st day were significantly higher than that in the normal control group (all P<0. 01). Conclusions Multiple intragastric administration of Chaiqin Qingning capsule in different doses did not induce significant hepatotoxicity. Multiple intragastric administration of Ganmaoling capsule in medium dose or high dose could induce hepatotoxicity in mice, and showed an obvious "dose-time-toxicity" relationship.

Objective To investigate the "dose-time-toxicity" relationship of liver injury in mice induced by multiple dose of Chaiqin Qingning Capsule and Ganmaoling capsule. Methods Three hundred and ten healthy SPF mice were divided into 7 groups randomly, in which 3 groups were low, medium and high dose subgroups of Chaiqin Qingning capsule ( 50 mice with male and female half in each subgroup) . The doses of Chaiqin Qingning capsule subgroups were 1437. 70, 2300. 31 and 3680. 50 mg/kg, which were 1. 63 , 1. 64 and 1. 65 times of clinically equivalent dose ( ED) respectively. Three groups were low, medium and high dose subgroups of Ganmaoling capsule (50 mice with male and female half in each subgroup). The doses of Ganmaoling capsule subgroups were 1452. 31, 2251. 08 and 3489. 18 mg/kg, which were 1. 553 , 1. 554 and 1. 555 times of ED respectively. One group was the normal control group (10 mice, half were male). Each subgroup mice were treated with intragastric administration of the corresponding concentration drug suspension by 0. 20 ml per 10 g body weight, and the normal control group mice were treated with intragastric administration of equal volume of distilled water. All mice were treated once daily for 14 days. The general state of mice in each group was observed during the experiment. Ten mice randomly selected on the 1st, 3rd, 7th, 11th and 14th day after multiple administration of the medicine in each subgroup respectively and 10 mice in the normal control group after 14 days multiple administration of distilled water were weighed, and the serum alanine aminotransferase ( ALT) , aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB) and total bilirubin (TBil) levels were tested. Then the mice were executed and the organs, i. e. , liver, thymus, and spleen were taken to weigh and calculate the organ index. Results The general state of mice in the normal control group, Chaiqin Qingning capsule subgroups and Ganmaoling capsule low dose subgroup were not abnormal during the administration period. Ganmaoling capsule high dose subgroup appeared 8 mice died within 1 day after first administration, the overall mortality rate was 16%. The high dose and medium dose subgroup of mice showed decrease in activities, dietary, water and body weight significantly on 1st to 3rd day. The symptoms gradually disappeared on 4th to 7th day, and the state gradually returned to normal on 8th to 14th day. The difference of serum level of ALT, AST, ALP, ALB, TBil and liver, thymus and spleen organ index of Chaiqin Qingning capsule subgroups and Ganmaoling capsule low dose subgroup on the 1st, 3rd, 7th, 11th and 14th days after multiple administration compared with those of the normal control group were not statistically significant (all P>0. 05). The levels of serum ALT, ALP and TBil of Ganmaoling capsule high dose subgroup mice after multiple administration on 1st, 3rd, 7th day and the serum AST of mice on 1st and 3rd day were significantly higher than those in the normal control group (P<0. 05, P<0. 01). The serum ALB level of Ganmaoling capsule high dose subgroup mice on 3rd, 7th, 11th and 14th day were significantly lower than those in normal control group (P<0. 05, P<0. 01). The levels of serum ALT, AST, ALP and TBil of Ganmaoling capsule medium dose subgroup mice after multiple administration on 1st and 3rd day were significantly higher than those in the normal control group (P<0. 05, P<0. 01). The serum ALB level of Ganmaoling capsule medium dose subgroup mice after multiple administration on 3rd and 7th day were significantly lower than those in normal control group (P<0. 05, P<0. 01). The liver organ index of mice in Ganmaoling capsule high dose subgroup after multiple administration on 1st , 3rd and Ganmaoling capsule medium dose subgroup after multiple administration on 1st day were significantly higher than that in the normal control group (all P<0. 01). Conclusions Multiple intragastric administration of Chaiqin Qingning capsule in different doses did not induce significant hepatotoxicity. Multiple intragastric administration of Ganmaoling capsule in medium dose or high dose could induce hepatotoxicity in mice, and showed an obvious "dose-time-toxicity" relationship.

Objective To compare the " dose-time-toxicity" relationship of acute liver injury in mice induced by a single-dose of Chaiqin Qingning capsule or Ganmaoling capsule.Methods " Time-toxicity" study:the mice were divided into 19 subgroups (10 mice in each subgroup),including 9 Chaiqin Qingning capsule subgroups,9 Ganmaoling capsule subgroups,and 1 normal control group (treated with distilled water).The mice in the Chaiqin Qingning capsule group were treated with a single intragastric administration with 1.65 times of clinically equivalent dose (ED) (equal to 95.42 times of 70 kg normal adult daily dose) of the drug suspension.The mice in the Ganmaoling capsule group were treated with a single intragastric administration with 1.554 times of ED (equal to 52.53 times of 70 kg normal adult daily dose) of the drug suspension.The mice in the Chaiqin Qingning capsule group and Ganmaoling capsule group were divided into 1 h,2 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h subgroups after administration,respectively." Dose-toxicity" study:the mice were divided into 13 subgroups (10 mice in each subgroup),including 6 Chaiqin Qingning capsule subgroups (according to dose,the mice were divided into ED,1.6ED,1.62ED,1.63ED,1.64ED and 1.65ED subgroups;351.00,561.60,898.56,1 437.70,2 300.31 and 3 680.50 mg/kg,respectively),6 Chaiqin Qingning capsule subgroups (according to dose,the mice were divided into ED,1.55ED,1.552ED,1.553ED,1.554ED and 1.555ED subgroups;390.00,604.50,936.98,1 452.31,2 251.08 and 3 489.18 mg/kg,respectively),and 1 normal control group (treated with distilled water)."Time-toxicity" was studied at different times after the drugs administration and " dose toxicity" was studied at 12 h after administration.General state and body weight of mice were observed.The changes of the levels of ALT,AST,and ALP in serum and organ index of liver,spleen,and thymus were tested.Results The difference of serum levels of ALT,AST,and ALP and liver,spleen,and thymus organ index of mice between the 9 different time subgroups and the 6 different dose subgroups in Chaiqin Qingning capsule group and the normal control group were not statistically significant (all P ＞ 0.05).The ALT,AST,and ALP levels in the 2 h,4 h,8 h,12 h,and 24 h subgroups and the 1.553ED,1.554ED,and 1.555ED subgroups,the serum levels of ALT in the 48 h subgroup,the serum levels of ALT and AST in the 1.552ED subgroup,and liver organ index in mice in the 8 h and 12 h subgroups and the 1.553ED,1.554ED,1.555ED subgroups in the Ganmaaoling capsule group were significantly higher than those in the normal control group (P ＜ 0.05,P ＜ 0.01).The serum levels of ALT,AST,ALP,and liver organ index in the 12 h subgroup were the highest in the " time-toxicity" study [(1 017.0 ±342.6) U/L,(281.3 ±60.1) U/L,(171.8 ±43.5) U/L,(6.76 ±0.60) g/100 g],and the serum levels of ALT,AST,ALP,and liver organ index in the 1.555ED subgroup were the highest in the "dose-toxicity" study [(2 930.6 ± 661.5) U/L,(888.8 ± 180.6) U/L,(392.7 ± 42.4) U/L,(7.21 ± 1.12) g/100 g].Conclusions A single large dose of Chaiqin Qingning capsule did not induce significant hepatotoxicity in mice.A single large dose of Ganmaoling capsule could induce acute liver injury in mice and showed a significant "dose-time-toxicity" relationship.

Objective To compare the " dose-time-toxicity" relationship of acute liver injury in mice induced by a single-dose of Chaiqin Qingning capsule or Ganmaoling capsule.Methods " Time-toxicity" study:the mice were divided into 19 subgroups (10 mice in each subgroup),including 9 Chaiqin Qingning capsule subgroups,9 Ganmaoling capsule subgroups,and 1 normal control group (treated with distilled water).The mice in the Chaiqin Qingning capsule group were treated with a single intragastric administration with 1.65 times of clinically equivalent dose (ED) (equal to 95.42 times of 70 kg normal adult daily dose) of the drug suspension.The mice in the Ganmaoling capsule group were treated with a single intragastric administration with 1.554 times of ED (equal to 52.53 times of 70 kg normal adult daily dose) of the drug suspension.The mice in the Chaiqin Qingning capsule group and Ganmaoling capsule group were divided into 1 h,2 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h subgroups after administration,respectively." Dose-toxicity" study:the mice were divided into 13 subgroups (10 mice in each subgroup),including 6 Chaiqin Qingning capsule subgroups (according to dose,the mice were divided into ED,1.6ED,1.62ED,1.63ED,1.64ED and 1.65ED subgroups;351.00,561.60,898.56,1 437.70,2 300.31 and 3 680.50 mg/kg,respectively),6 Chaiqin Qingning capsule subgroups (according to dose,the mice were divided into ED,1.55ED,1.552ED,1.553ED,1.554ED and 1.555ED subgroups;390.00,604.50,936.98,1 452.31,2 251.08 and 3 489.18 mg/kg,respectively),and 1 normal control group (treated with distilled water)."Time-toxicity" was studied at different times after the drugs administration and " dose toxicity" was studied at 12 h after administration.General state and body weight of mice were observed.The changes of the levels of ALT,AST,and ALP in serum and organ index of liver,spleen,and thymus were tested.Results The difference of serum levels of ALT,AST,and ALP and liver,spleen,and thymus organ index of mice between the 9 different time subgroups and the 6 different dose subgroups in Chaiqin Qingning capsule group and the normal control group were not statistically significant (all P ＞ 0.05).The ALT,AST,and ALP levels in the 2 h,4 h,8 h,12 h,and 24 h subgroups and the 1.553ED,1.554ED,and 1.555ED subgroups,the serum levels of ALT in the 48 h subgroup,the serum levels of ALT and AST in the 1.552ED subgroup,and liver organ index in mice in the 8 h and 12 h subgroups and the 1.553ED,1.554ED,1.555ED subgroups in the Ganmaaoling capsule group were significantly higher than those in the normal control group (P ＜ 0.05,P ＜ 0.01).The serum levels of ALT,AST,ALP,and liver organ index in the 12 h subgroup were the highest in the " time-toxicity" study [(1 017.0 ±342.6) U/L,(281.3 ±60.1) U/L,(171.8 ±43.5) U/L,(6.76 ±0.60) g/100 g],and the serum levels of ALT,AST,ALP,and liver organ index in the 1.555ED subgroup were the highest in the "dose-toxicity" study [(2 930.6 ± 661.5) U/L,(888.8 ± 180.6) U/L,(392.7 ± 42.4) U/L,(7.21 ± 1.12) g/100 g].Conclusions A single large dose of Chaiqin Qingning capsule did not induce significant hepatotoxicity in mice.A single large dose of Ganmaoling capsule could induce acute liver injury in mice and showed a significant "dose-time-toxicity" relationship.