Objectives To observe the changes of apoptosis-related proteins during the development of sarcopenia and to explore the effect and mechanism of long-term aerobic exercises and heat shock protein 70 (HSP70) on those changes for the natural aging C57BL/6 mice.Methods After 1 week of acclimatization,50 27-week-old male C57BL/6 mice were randomly divided into a young sedentary control (YS) group,an old sedentary control (OS) group and an old exercises (OE) group.After the gripstrength was measured the mice from group YS were sacrificed at the age of 28 weeks.The mice from group OE exercised on a fiat treadmill at 12rn/minute for 50 min 3 or 4 times a week for 30 weeks with the intensity of 75％ VO2max.At the age of 60 weeks,the mice of group OS and OE were killed after their grip-strength was measured.The gastrocnemius muscle of each group were isolated and weighted,and the sarcopenia index (SI) was measured.Then the total protein of the gastrocnemius muscle was extracted.HSP70 and cleaved caspase-9 expression were examined.The binding rate of HSP70 and Apaf-1 was measured using Co-Immunoprecipitation.TUNEL staining was performed to detect the apoptosis of the gastrocnemius muscle.Results (1) Compared with group YS,SI of group OS decreased significantly by 23.09％,but significant increase was observed in group OE compared to group OS by 30.48％.(2) The grip strength per gram of body weight of group OS decreased significantly by 42.74％ compared to group YS,while that of group OE increased significantly by 21.51％ compared to group OS.(3) The apoptosis index increases by 475.28％ with age.However,the index decreased by 46.41％ in group OE over group OS.(4) Western blotting showed that the expression of cleaved caspase-9 increased significantly by 45.4％ in group OS compared to group YS,while that of group OE decreased significantly by 33.4％ compared to group OS.(5) The binding rate of HSP 70 with Apaf-1 of group OS decreased significantly by 67.11％ compared to group YS,while that of group OE increased significanlty by 306.31％ compared to group OS.Conclusions (1) Gastrocnemius atrophy occurring to mice of 60 weeks can be significanlty delayed through 30-week exercises training.(2) The increasing apoptosis may be involved in the development of age-related sarcopenia and 30-week exercises can significantly attenuate such apoptosis in rodent skeletal muscle.(3) Aerobic exercises increases HSP70/Apaf-1 interaction,which might play an important role in reducing age-related cellular damage and cell death in the skeletal muscle of rats.

Objective To investigate the effect of 6-week high-intensity interval training(HIIT) on the body composition and the autophagy activation in skeletal muscle of C57BL/6 mice,and explore the underlying role of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)α2 in this process.Methods Thirty-six 4-week old male mice with the genotype AMPKα2+/+(n=12),AMPKα2+/-(n=12) and AMPKα2-/-(n=12),were randomly divided into a control(n=6) and an HIIT group(n=6) respectively.The mice from the HIIT group exercised on a motor-driven rodent treadmill for 5 days a week,lasting 6 weeks.The procedure of HIIT included the intensity of 85％ VO2max(20m/min) for 2 min/day and 50％ VO2max(8m/min) for 1 min/day with 12 cycles alternately.The body weight,body mass index(BMI),total body water and fat mass were measured and analyzed after the 6-week exercise.The protein expression of AMPKα2,pAMPK-Thr172,LC3Ⅱ/Ⅰ,Beclin1 and p62 in the skeletal muscle tissue were detected using Western blotting.Results Before exercise,there was no significant difference between the mice of the same genotype in the body weight.However,a significant decrease was observed in the body weight of all the HIIT mice,and BMI of the AMPKα2+/+ and AMPKα2+/-mice undergoing HIIT.There were no significant differences in the total body water between the control and HIIT groups of the same genotype after the intervention.There was significant decrease in the body fat mass in the HIIT group of AMPKα2+/+ and AMPKα2+/-mice after the intervention,while the decrease was not significant in the HIIT AMPKα2-/-mice.The protein expression of pAMPK-Thr172,LC3Ⅱ/Ⅰ and Beclin1 increased significantly,and that of p62 decreased significantly in the skeletal muscle of the AMPK+/+ and AMPK+/-mice after HIIT intervention,but not the AMPK-/-mice.Conclusion HIIT can improve health indicators(i.e,body weight,BMI and fat mass) and enhance autophagy activation in the skeletal muscle through increasing the phosphorylation of AMPKot2.

Objective:To compare the efficacy of the combination of abidol, lopinavir/ritonavir plus recombinant interferon α-2b (rIFNα-2b) and the combination of lopinavir/ritonavir plus rIFNα-2b for patients with COVID-19 in Zhejiang province.Methods:A multicenter prospective study was carried out to compare the efficacy of triple combination antiviral therapy and dual combination antiviral therapy in 15 medical institutions of Zhejiang province during January 22 to February 16, 2020. All patients were treated with rIFNα-2b (5 million U, 2 times/d) aerosol inhalation, in addition 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir/ritonavir (2 tablets, 1 time/12 h) (triple combination group) and 41 patients were treated with lopinavir/ritonavir (2 tablets, 1 time/12 h) (dual combination group). The patients who received triple combination antiviral therapy were further divided into three subgroups: <48 h, 3-5 d and >5 d according the time from the symptom onset to medication starting. The therapeutic efficacy was compared between triple combination group and dual combination group, and compared among 3 subgroups of patients receiving triple combination antiviral therapy. SPSS 17.0 software was used to analyze the data.Results:The virus nucleic acid-negative conversion time in respiratory tract specimens was (12.2±4.7) d in the triple combination group, which was shorter than that in the dual combination group [(15.0±5.0) d] ( t=6.159, P<0.01). The length of hospital stay in the triple combination group [12.0 (9.0, 17.0) d] was also shorter than that in the dual combination group [15.0 (10.0, 18.0) d] ( H=2.073, P<0.05). Compared with the antiviral treatment which was started within after the symptom onset of in the triple combination group, the time from the symptom onset to the viral negative conversion was 13.0 (10.0, 17.0), 17.0 (13.0, 22.0) and 21.0 (18.0, 24.0) d in subgroups of 48 h, 3-5 d and >5 d, respectively ( Z=32.983, P<0.01), while the time from antiviral therapy to viral negative conversion was (11.8±3.9), (13.5±5.1) and (11.2±4.3) d, respectively( Z=6.722, P<0.05). Conclusions:The triple combination antiviral therapy of abidol, lopinavir/litonavir and rIFNα-2b shows shorter viral shedding time and shorter hospitalization time, compared with the dual combination antiviral therapy; and the earlier starting triple combination antiviral therapy will result in better antiviral efficacy.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.