OBJECTIVE The inhibitory effect of active ingredients of Tripterygium wilfordii Hook.F.(TWHF)(celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine)on human carboxylester-ase 1(CES1)and CES2 was detected to investigate the herb-drug interactions(HDIs)of TWHF.METHODS Human liver microsomes catalysed hydrolysis of 2-(2-benzoyl-3-methoxyphenyl)benzothi-azole(BMBT)and fluorescein diacetate(FD)were used as the probe reaction to phenotype the activity of CES1 and CES2,respectively.The residual activities of CES1 and CES2 were detected by ultra-high performance liquid chromatography(UPLC)after intervention with celastrol,triptolide,triptonide,wilforlide A,wilforgine and wilforine(100 μmol·L-1).Kinetics analysis,involving half inhibitory concentra-tion(IC50),inhibition type and kinetic parameter(Ki),and in vitro-in vivo extrapolation(IVIVE),was carried out to predict the HDIs between these compounds and CES-metabolizing drugs.Molecular docking was performed to analyze the ligand-enzyme interaction.RESULTS Out of the six main con-stituents of TWHF,only celastrol exhibited strong inhibition towards both CES1 and CES2,with the inhibitory rates of 97.45%(P<0.05)and 95.62%(P<0.05),respectively.The IC50 was 9.95 and 4.02 mol·L-1,respectively,and the types of inhibition were all non-competitive inhibition.Based on the kinetics analysis,the Ki values were calculated to be 5.10 and 10.55 μmol·L-1 for the inhibition of celastrol on CES1 and CES2,respectively.IVIVE indicated that celastrol might disturb the metabolic hydrolysis of clinical drugs in vivo by inhibiting CES1.Molecular docking results showed that hydrogen bonds and hydrophobic contacts contributed to the interaction of celastrol and CESs.CONCLUSION The inhibitory effect of celastrol on CES1 and CES2 might cause HDIs with clinical drugs hydrolysed by CESs.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.