ObjectiveTo verify the protective effect and pharmacological mechanism of Qishen granules against doxorubicin-induced cardiotoxicity， thus providing a basis for developing new drug options for clinical treatment of cardio-oncology disease. MethodsFifty mice were randomly assigned into a normal group （n=10） and a modeling group （n=40）. The model was established by intravenous injection of doxorubicin （5 mg·kg^-1） via the tail vein， once a week for 4 consecutive weeks. The normal group was injected with an equal volume of normal saline during the same period. The modeled mice were further assigned into four groups： doxorubicin （no drug control）， low-dose （3.33 mg·kg^-1） Qishen granules， high-dose （6.67 mg·kg^-1） Qishen granules， and enalapril （15 mg·kg^-1）. Mice were administrated with corresponding drugs by gavage for 4 consecutive weeks. At the end of the experiment， echocardiography， histopathological staining， and live-cell imaging were employed to determine relevant indicators， on the basis of which the protective effect of Qishen granules against doxorubicin-induced cardiotoxicity was evaluated. ResultsCompared with the normal group， doxorubicin treatment reduced the left ventricular ejection fraction （LVEF） （P<0.05） and caused pathological changes including disarrangement of cardiomyocytes， increased cell spacing， cardiomyocyte hypertrophy， and increased apoptosis in the heart tissue. Meanwhile， doxorubicin prolonged the mitochondria-lysosome contact time， downregulated the expression of TBC1 domain family member 15 （TBC1D15） （P<0.01）， upregulated the levels of microtubule-associated protein 1 light chain 3 （LC3） and sequestosome 1 （p62） （P<0.01）， and induced mitochondrial cristae breakage， resulting in mitochondrial dysfunction. Compared with the doxorubicin group， intervention with Qishen granules reversed the above indicators. It not only increased the LVEF （P<0.01） and alleviated pathological damage to the heart， but also upregulated the expression of TBC1D15 （P<0.01）， shortened the mitochondria-lysosome contact time （P<0.05）， and downregulated the protein levels of LC3 and p62. When TBC1D15 in cells was knocked down， the autophagy-activating and mitochondrion-protecting effects of Qishen granules partially disappeared. ConclusionQishen granules upregulate the expression of TBC1D15 to shorten the mitochondria-lysosome contact time， thereby activating autophagy and ultimately exerting a protective effect against doxorubicin-induced cardiotoxicity.

ObjectiveTo verify the protective effect and pharmacological mechanism of Qishen granules against doxorubicin-induced cardiotoxicity， thus providing a basis for developing new drug options for clinical treatment of cardio-oncology disease. MethodsFifty mice were randomly assigned into a normal group （n=10） and a modeling group （n=40）. The model was established by intravenous injection of doxorubicin （5 mg·kg^-1） via the tail vein， once a week for 4 consecutive weeks. The normal group was injected with an equal volume of normal saline during the same period. The modeled mice were further assigned into four groups： doxorubicin （no drug control）， low-dose （3.33 mg·kg^-1） Qishen granules， high-dose （6.67 mg·kg^-1） Qishen granules， and enalapril （15 mg·kg^-1）. Mice were administrated with corresponding drugs by gavage for 4 consecutive weeks. At the end of the experiment， echocardiography， histopathological staining， and live-cell imaging were employed to determine relevant indicators， on the basis of which the protective effect of Qishen granules against doxorubicin-induced cardiotoxicity was evaluated. ResultsCompared with the normal group， doxorubicin treatment reduced the left ventricular ejection fraction （LVEF） （P<0.05） and caused pathological changes including disarrangement of cardiomyocytes， increased cell spacing， cardiomyocyte hypertrophy， and increased apoptosis in the heart tissue. Meanwhile， doxorubicin prolonged the mitochondria-lysosome contact time， downregulated the expression of TBC1 domain family member 15 （TBC1D15） （P<0.01）， upregulated the levels of microtubule-associated protein 1 light chain 3 （LC3） and sequestosome 1 （p62） （P<0.01）， and induced mitochondrial cristae breakage， resulting in mitochondrial dysfunction. Compared with the doxorubicin group， intervention with Qishen granules reversed the above indicators. It not only increased the LVEF （P<0.01） and alleviated pathological damage to the heart， but also upregulated the expression of TBC1D15 （P<0.01）， shortened the mitochondria-lysosome contact time （P<0.05）， and downregulated the protein levels of LC3 and p62. When TBC1D15 in cells was knocked down， the autophagy-activating and mitochondrion-protecting effects of Qishen granules partially disappeared. ConclusionQishen granules upregulate the expression of TBC1D15 to shorten the mitochondria-lysosome contact time， thereby activating autophagy and ultimately exerting a protective effect against doxorubicin-induced cardiotoxicity.

Objective: To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19. Methods: A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg^-1·d^-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results: The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P<0.05). The clinical conditions at hospital admission were different between the two groups (P<0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P>0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P>0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P>0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P>0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group. Conclusions Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.

Objective:To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance in patients with COVID-19.Methods:A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, Zhejiang University School of Medicine were recruited. All patients received oral arbidol and combination of lopinavir/ritonavir or darunavir/cobistitat for antiviral therapy, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg -1·d -1) (glucocorticoid treatment group), and 21 patients did not use glucocorticoid (control group). The time of virologic negative conversion in sputum and the time of radiologic recovery in lung since onset were compared between the two groups. The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups. Results:The median ages of the glucocorticoid group and the control group were 52 (45, 62) and 46 (32, 56) years ( χ2=4.365, P<0.05). The clinical conditions at hospital admission were different between the two groups ( P<0.01). The severe cases accounted for 52.0%, while moderate cases in the control group accounted for 71.4%. The median times from the onset to virologic negative conversion in the two groups were 15 (13, 20) and 14 (12, 20) days ( P>0.05). The median times from onset to radiologic recovery were 13 (11, 15) and 13 (12, 17) days in the two groups ( P>0.05). In moderate cases, the median times from the onset to virologic conversion in sputum were 13 (11, 18) days in the glucocorticoid group and 13 (12, 15) days in the control group ( P>0.05). The median times from onset to radiologic recovery in lung were 12 (10, 15) and 13 (12, 17) days, respectively ( P>0.05). Conclusions:Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19, and also no effect on accelerating radiologic recovery in lung, so it is not recommended.