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OBJECTIVE:To investigate the ru les and characteristics of pembrolizumab-induced immune-related myocarditis , and to provide reference for rational drug use in clinic. METHODS :Using“pembrolizumab/keytruda”“myocarditis”“cardiotoxicity” “Pembrolizumab/Keytruda”“Cardiac toxicity ”“Myocarditis”“Cardiotoxity”“Cardiotoxicity”as Chinese and English retrieval words , CBM,VIP,CNKI,Wanfang database ,PubMed,Wiley Online Library and Embase database were searched on the case reports of pembrolizumab-induced immune-related myocarditis during the inception to Aug. 2020. After eliminating the suspected case literature and repetitive literature ,gender,age,medication cause ,medical history ,drug combination ,drug dosage ,occurrence time of ADR ,clinical manifestation ,intervention measure and outcome of patients in the included literature were analyzed. RESULTS & CONCLUSIONS:A total of 15 literatures were included ,involving 13 English literatures and 2 Chinese literatures. Totally 15 patients were involved ,including 12 males and 3 females,with an average age of 71.35 years. There were 4 cases of non-small cell lung cancer ,4 cases of melanoma ,2 cases of bladder cancer ,1 case of urothelial cancer ,1 case of multiple osteosarcomas,1 case of gastric cancer ,1 case of thymic cancer ,1 case of nasopharyngeal carcinoma. There were 6 patients with previous medical history ,of which 5 had no history of heart disease and 1 had hypertension and hyperlipidemia ;there were 9 patients recorded the combined use of drugs ;the dosage and frequency of pembrolizumab were recorded in 12 patients. Immunological myocarditis of 93.3% patients occurred after the first to second cycle of pembrolizumab administration ,and the average occurrence time was 15.5 days after the last administration. The most common clinical symptoms were dyspnea ,fatigue, dizziness or syncope. 9 patients showed cardiac block on electrocardiogram. All patients were treated with glucocorticoids when they developed immune-associated myocarditis ,and 5 patients died after hospitalization ;another one patient was restarted with pembrolizumab for one cycle after control of immune-related myocarditis ,but developed a recurrence of myocarditis and died of myocarditis ADR. It is suggested that baseline examination and routine monitoring of cardiac function should be done well when patients are treated with pembrolizumab. Once the patient is su spected to have immune-related myocarditis ,they should timely improve the cardiograms and other cardiac function-relatedtests,and start the treatment of high-dose glucocorticoids as 198177) soon as possible ,and are alert to the risk of death due to recurrence of myocarditis after readministration.
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Major allergen ß-lactoglobulin exists in many mammalian types of milk except human breast. Buffalo milk also contains this major allergen but the detailed information on its epitopes is not available. The aim of this work was to map and characterize its conformational antigenic epitopes. Sixty mimotopes of buffalo ß-lactoglobulin were produced by biopanning of phage display peptide library and then 2 mimotopes, specific for sera from rabbit 1 and 2, respectively, were predicted to be conformational epitope candidates by the use of DNAStar and web tool of MIMOX. On the basis of bioinformation analysis, 5 conserved amino acid residues PL-ENK were identified in 2 conformational epitope sequences and 7 conformational epitopes were derived from 2 mimotopes by molecular modeling. The result showed that these conformational epitopes were located in the 2 regions on buffalo ß-lactoglobulin and composed of 5 hydrophilic and 2 hydrophobic amino acids.