Herb induced liver injury by Xianling Gubao Tablets: A case assessed for causality using updated RUCAM and integrated evidence chain

Objective:A typical case of Xianling Gubao(XLGB)Tablets-induced liver injury was systematically studied in the clinic and the laboratory.Methods:A patient with herb-induced liver injury(HILI)and a history of taking XLGB Tablets before disease onset was engaged as the study subject,and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method(RUCAM)and the integrated evidence chain(iEC)method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury(HILI Guidelines).Results:Clinical history,biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral,alcoholic and autoimmune liver diseases on the diagnosis.Based on an investigation of the patient’s medication history,she was suspected to have HILI caused by XLGB Tablets,as the patient was only taking an oral preparation of XLGB Tablets,and the influence of other drugs on the diagnosis was excluded.This patient with alanine aminotransferase(ALT)3 upper limit of normal(ULN)and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury.The relationship was considered“highly probable”(score of 9)using the updated RUCAM of 2016.Moreover,the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99,suggesting that the patient was consuming XLGB Tablets rather than another drug.LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug,and no chemical additions were found.Examination of the drug for pesticide residues,heavy metals,aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia.Conclusion:In summary,the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC.Therefore,this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

Fair Non-Repudiation for Web Services Transactions

To safeguard the interests of transacting parties,non-repudiation mechanisms need to assure fairness and timeliness.The non-repudiation service currently implemented usually does not consider the requirement of fairness and the fair non-repudiation protocols to date can not be suitably applied in real environment due to its complex interaction.This paper discusses the transaction-oriented non-repudiation requirement for Web services transaction,analyzes the constraints of the traditional model for the available fair non-repudiation protocols and designs a new Online-TTP fair non-repudiation protocol.The new protocol provides a fair non-repudiation solution to secure Web services transactions and can be embedded into a single Web service call.The protocol adopts evidence chained to decreasing the overhead of evidence verification and management and alleviates the overhead of certificate revocation checking and time-stamp generation for signatures.The protocol has strong fairness,timeliness,efficiency and practicability.