Objective To investigate the improvement effect and related mechanism of roxadustat on myocardial ischemia-reperfusion(I/R)injury in mice.Methods Twenty four male C57BL/6N mice were randomly divided into the sham operation group,the control group and the roxadustat group,with eight mice in each group.A mouse myocardial I/R model was established.The control group was given 100 μL saline injection containing 5%dimethyl sulfoxide by gavage.The roxadustat group was given 25 mg/kg roxadustat by gavage.The left anterior descending coronary artery of mice in both groups was ligated for 40 minutes,and then reperfusion for 24 hours to establish the myocardial I/R model.In the sham operation group,only the left anterior coronary artery was pierced without ligation.The area of myocardial infarction in mice was detected by triphenyltetrazolium chloride(TTC)staining.The apoptosis of mouse cardiomyocytes was detected by TdT-mediated dUTP nick and labeling(TUNEL)staining.The expression of apoptosis-related proteins bcl-2 associated X protein(Bax),Caspase3 and inflammatory cell markers F4/80 and myeloperoxidase(MPO)were detected by immunohistochemistry staining.The damage of myocardial cells was observed by hematoxylin-eosin(HE)staining.Results The area of myocardial infarction after myocardial I/R was reduced in the roxadustat group compared to the control group and the sham operation group(P＜0.05).The number of apoptotic cells was higher in the control group and the roxadustat group than that in the sham operation group,and the number of apoptotic cells was lower in the roxadustat group than that in the control group(P＜0.05).The expression levels of Bax and Caspase3 proteins in myocardial tissue were higher in the control group and the roxadustat group than those in the sham operation group,while those of the roxadustat group was lower than those of the control group(P＜0.05).The expression levels of F4/80 and MPO proteins in myocardial tissue were lower in the roxadustat group than those in the control group(P＜0.05).In the control group,the myocardial tissue arrangement was disordered,and there was an increase in interstitial vacuoles.Compared with the control group,the myocardial cells were arranged more neatly in the roxadustat group,and the interstitial vacuoles were reduced.Conclusion Roxadustat can reduce the myocardial infarction area after I/R injury,inhibit myocardial cell apoptosis,alleviate myocardial injury,reduce infiltration of myocardial macrophages and neutrophils,and reduce inflammatory injury.

OBJECTIVE：To explore the regularity and characteristics of adverse drug reactions （ADR）induced by alectinib ， and to provide reference for rational drug use in clinic. METHODS ：Retrieved from CNKI ，Wanfang database ，VIP，PubMed， Web of Science and Embase database during the inception to Mar. 1st，2021，case reports of alectinib-induced ADR were collected ， summarized and analyzed with descriptive statistical analysis method in terms of general information ，occurrence time of ADR ， involved organ/system ，clinical manifestations ，treatment and outcome ，etc. RESULTS ：A total of 17 literatures were included ， involving 17 patients. Among them ，4 cases（23.53％）were males ，and 13 cases（76.47％）were females. The mean age of the patients was （61.82±14.18）years old. The patients were from 5 countries/regions，among which America took the largest ratio （41.18％）. Most ADR occurred within 30 days（52.94％）after therapy. ADR mainly involved skin and its appendants （35.29％）， followed by respiratory system （23.53％），urinary system （11.76％），cardiovascular system （11.76％），gastrointestinal system （11.76％）and blood system （5.87％）；hair loss ，pancreatitis and duodenal perforation belonged to ADRs not recorded in the drug instructions. After 17 patients suffered from ADR ，2 patients still continued to use aletinib ，while 15 patients withdrew aletinib and some patients received symptomatic and supportive treatment ，and their symptoms improved. Among them ，10 patients restarted aletinib treatment after their symptoms improved ，and 8 patients did not suffered from ADR again. CONCLUSIONS ：Female patients and patients over 50 years old are more likely to suffer from ADR after using aletinib ，and most of ADR occur within 1 month after treatment. ADR involves many organs/systems ，mainly skin and its appendants. Special attention should be paid to ADR such as hair loss ，pancreatitis and duodenal perforation.