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OBJECTIVE：To excavate the safety warning signals induced by azole antifungal agents ，including fluconazole ， ketoconazole，itraconazole and voriconazole after marketing ，and to provide references for rational drug use in the clinic. METHODS：Reporting odds ratio （ROR）data mining algorithm was used to investigate signals of adverse drug event （ADE）for fluconazole，ketoconazole，itraconazole and voriconazole from FDA Adverse Event Reporting System （FAERS）during January 1st，2004 to March 30th，2019. ROR data mining method was used to excavate the ADR signals of the drugs ，and main ADR involved in the safety information of azole antifungal agents instructions were analyzed. RESULTS ：A total of 27 831，5 712， 5 381 and 11 333 reports were picked out for fluconazole ，ketoconazole，itraconazole and voriconazole ，respectively. All of these drugs had exhibited high-risk signals detection by ROR ，including medical examination ，blood and lymphatic system disorders ， renal and urinary disorders ，endocrine diseases ，hepatobiliary disorders. The hepatotoxic-related ADR signals were mainly concentrated in fluconazole and voriconazole （fluconazole ROR ＝6.51，voriconazole ROR ＝14.65）；ADR detection results of Cushing’s-like syndrome （ROR＝24.86） and adrenal suppression （ROR＝44.06） by itraconazole showed high-risk signals ； ketoconazole and itraconazole had showed a strong ADR signal in adrenocortical dysfunction （ketoconazole ROR ＝15.64， itraconazole ROR ＝23.26），and the signal intensity of ketoconazole （ROR＝2.81）in skin and subcutaneous tissue disorders was significantly higher than that of other drugs . In addition ，hemorrhagic cystitis caused by fluconazole，itraconazole and voriconazole were not included in the drug instructions （fluconazole ROR ＝17.73，itraconazole ROR ＝31.43，voriconazole ROR ＝17.06）； netted green spot caused by fluconazole （ROR＝10.50）were not included in the drug instructions . CONCLUSIONS：Clinical staff should pay more attention to the differences in serious ADR related to fluconazole ，ketoconazole，itraconazole and voriconazole ； particularly some ADRs not mentioned in the drug instructions but have high incidence such as hemorrhagic cystitis caused by fluconazole，itraconazole，voriconazole and netted green spot caused by fluconazole ，as well as ADRs mentioned in the drug instructions but have abnormally high signal ，such as Cushing ’s-like syndrome and adrenal suppression caused by itraconazole .
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Objective To evaluate the hemostatic efficacy of complex sponge and drug-loaded complex sponge on hepatic and splenic wounds in rabbits. Methods Complex sponge was prepared by means of cross-linking and lyophilization. Then, the sponge was immersed into the tranexamic acid solution and lyophilized to obtain the drug-loaded sponge. The complex sponge and drug-loaded complex sponge were respectively used on the hepatic and splenic wounds of rabbits to observe the bleeding time and blood loss under normal and liquemine anticoagulation respectively. The gelatin sponge and the chitosan sponge were used as controls. Results Under normal condition, the hemostatic time and blood loss of the complex sponge was decreased obviously compared with the gelatin sponge ( P＜ 0. 01 ) and compared with the chitosan sponge ( P ＜ 0. 05 ). Posterior to liquemine anticoagulation, the hemostatic time was increased obviously in the gelatin sponge but showed no difference for the chitosan sponge and the complex sponge. Compared with complex sponge, the hemostatic efficacy of the tranexamic acid-loaded complex sponge was improved markedly for normal rabbits. While the hemostatic efficacy showed no significant change for rabbits with coagulation disorders, when there was no linear relationship between the hemostatic efficacy and the content of tranexamic acid. Conclusions The hemostatic efficacy of the complex sponge and the drug-loaded complex sponge surpass obviously that of the gelatin sponge, especially for the rabbits with coagulation disorders.