Objective To observe the effect of a heavy load exercise on the ultrastructure,function and fission of skeletal muscle mitochondria in rats,and to analyze the changes of the phosphorylation expression of mitochondrial fission protein and upstream kinase at different times postexercise,and to explore the effect of acute heavy load exercise on mitochondrial fission in skeletal muscle of rats and its possible mechanism.Methods Forty-eight adult male Sprague-Dawley rats were randomly divided in-to a quiet control group(C,n=8)and an exercise group(E,n=40).Rats in the E group exercised on a treadmill down a 16° decline at 16 m/min for 90 min and were further divided into 0 h,12 h,24 h,48 h,and 72 h postexercise subgroups.Soleus muscle was isolated and mitochondria were ex-tracted at the corresponding time points after exercise.The ultrastructure of mitochondria in the soleus muscle was observed using transmission electron microscopy,and mitochondrial quantity and morphomet-ric analysis were conducted.Moreover,the colocalization and quantity of dynamin-related protein 1(Drp1)and cytochrome C oxidease subunit Ⅳ(COXⅣ)in the soleus muscle were detected using im-munofluorescence double-labeling techniques.Meanwhile,protein levels of soleus musclep-Drp1Ser616,p-Drp1Ser637,p-extracellular regulatory protein kinaseThr202/Tyr204(p-ERKThr202/Tyr204),p-protein kinaseAThr197(p-PKAThr197),and mitochondrial NADH of ubiquinone oxidoreductase subunit B8(NDUFB8)and ubiqui-nol-cytochrome C reductase core protein 2(UQCRC2)were determined by using Western blotting.An-other twenty-four rats were randomly divided into a DMSO group(CD),a U0126 group(CU),an Ex-ercise+DMSO group(ED),and an Exercise+U0126 group(EU).Six mice in each group were giv-en a single intra-bitoneal injection of DMSO or ERK inhibitor U0126 20 min before acute downhill running.Then,their phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 in soleus muscle were de-tected by Western blotting.Results(1)From 0 h to 48 h after exercise,the soleus muscle mitochon-dria showed swelling,rounding,and uneven distribution of mitochondria,among which the degree of mitochondrial damage was the most serious at 12 h and 24 h after exercise.Moreover,the protein ex-pression of NDUFB8 and UQCRC2 in the mitochondria fractions from soleus muscle was significantly lower at 12 h post-exercise(P<0.05).(2)The co-localization of Drp1 and COXⅣ in the skeletal muscle increased significantly at 12 h to 24 h after a heavy load exercise compared with group C and group E0(P<0.01).Moreover,the mitochondrial area,circumference,aspect ratio and Ferret diameter in the skeletal muscle were significantly lower at 12 h to 24 h postexercise(P<0.05).Meanwhile,the number of mitochondria was significantly higher at 24 h after exercise(P<0.01).(3)The phosphoryla-tion of ERKThr202/Tyr204,PKAThr197 and Drp1Ser616 was significantly higher at 24 h after exercise(P<0.01),while that of Drp1Ser637 was significantly lower at 48 h and 72 h post-exercise(P<0.01).However,the phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 were significantly down-regulated by U0126 treatment before exercise.Conclusion A session of heavy load exercise caused mitochondrial structure and function damage and induced mitochondrial fission in the skeletal muscle,and then to maintain the homeostasis of skeletal muscle cells by cleaving damaged mitochondria.The mechanism of promot-ing skeletal muscle repair may be related to the positive and negative regulation of Drp1 activity by the phosphorylation of Drp1Ser616 and Drp1Ser637,respectively.Among them,the activation of ERKThr202/Tyr204 mediates the phosphorylation activation of Drp1Ser616,but PKAThr197 is not an upstream kinase that medi-ates the inactivation of Drp1Ser637 phosphorylation.

Objective To observe the effect of a heavy load exercise on the ultrastructure,function and fission of skeletal muscle mitochondria in rats,and to analyze the changes of the phosphorylation expression of mitochondrial fission protein and upstream kinase at different times postexercise,and to explore the effect of acute heavy load exercise on mitochondrial fission in skeletal muscle of rats and its possible mechanism.Methods Forty-eight adult male Sprague-Dawley rats were randomly divided in-to a quiet control group(C,n=8)and an exercise group(E,n=40).Rats in the E group exercised on a treadmill down a 16° decline at 16 m/min for 90 min and were further divided into 0 h,12 h,24 h,48 h,and 72 h postexercise subgroups.Soleus muscle was isolated and mitochondria were ex-tracted at the corresponding time points after exercise.The ultrastructure of mitochondria in the soleus muscle was observed using transmission electron microscopy,and mitochondrial quantity and morphomet-ric analysis were conducted.Moreover,the colocalization and quantity of dynamin-related protein 1(Drp1)and cytochrome C oxidease subunit Ⅳ(COXⅣ)in the soleus muscle were detected using im-munofluorescence double-labeling techniques.Meanwhile,protein levels of soleus musclep-Drp1Ser616,p-Drp1Ser637,p-extracellular regulatory protein kinaseThr202/Tyr204(p-ERKThr202/Tyr204),p-protein kinaseAThr197(p-PKAThr197),and mitochondrial NADH of ubiquinone oxidoreductase subunit B8(NDUFB8)and ubiqui-nol-cytochrome C reductase core protein 2(UQCRC2)were determined by using Western blotting.An-other twenty-four rats were randomly divided into a DMSO group(CD),a U0126 group(CU),an Ex-ercise+DMSO group(ED),and an Exercise+U0126 group(EU).Six mice in each group were giv-en a single intra-bitoneal injection of DMSO or ERK inhibitor U0126 20 min before acute downhill running.Then,their phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 in soleus muscle were de-tected by Western blotting.Results(1)From 0 h to 48 h after exercise,the soleus muscle mitochon-dria showed swelling,rounding,and uneven distribution of mitochondria,among which the degree of mitochondrial damage was the most serious at 12 h and 24 h after exercise.Moreover,the protein ex-pression of NDUFB8 and UQCRC2 in the mitochondria fractions from soleus muscle was significantly lower at 12 h post-exercise(P<0.05).(2)The co-localization of Drp1 and COXⅣ in the skeletal muscle increased significantly at 12 h to 24 h after a heavy load exercise compared with group C and group E0(P<0.01).Moreover,the mitochondrial area,circumference,aspect ratio and Ferret diameter in the skeletal muscle were significantly lower at 12 h to 24 h postexercise(P<0.05).Meanwhile,the number of mitochondria was significantly higher at 24 h after exercise(P<0.01).(3)The phosphoryla-tion of ERKThr202/Tyr204,PKAThr197 and Drp1Ser616 was significantly higher at 24 h after exercise(P<0.01),while that of Drp1Ser637 was significantly lower at 48 h and 72 h post-exercise(P<0.01).However,the phosphorylated expressions of ERKThr202/Tyr204 and Drp1Ser616 were significantly down-regulated by U0126 treatment before exercise.Conclusion A session of heavy load exercise caused mitochondrial structure and function damage and induced mitochondrial fission in the skeletal muscle,and then to maintain the homeostasis of skeletal muscle cells by cleaving damaged mitochondria.The mechanism of promot-ing skeletal muscle repair may be related to the positive and negative regulation of Drp1 activity by the phosphorylation of Drp1Ser616 and Drp1Ser637,respectively.Among them,the activation of ERKThr202/Tyr204 mediates the phosphorylation activation of Drp1Ser616,but PKAThr197 is not an upstream kinase that medi-ates the inactivation of Drp1Ser637 phosphorylation.

Objective To explore the effect of 4-week repetitive downhill treadmill running on the mi-tochondrial structure,function,and autophagy in skeletal muscle of rats,so as to analyze the role of FKBP8-mediated mitophagy in exercise-induced mitochondrial damage in their skeletal muscles.Meth-ods Thirty-two male adult Sprague-Dawley rats were randomly divided into a 2-week quiet control group(2C group,n=8),a 4-week quiet control group(4C group,n=8),a 2-week exercise group(2E group,n=8)and a 4-week exercise group(4E group,n=8).Rats in 2E and 4E groups performed dai-ly 90-minute downhill treadmill running(-16°,16 m/min)5 days a week for two and four weeks,re-spectively.Then,they rested for 24 hours and received an exhaustive exercise test.Running distance and blood lactate were measured prior to and at the time of exercise cessation.Moreover,mitochondri-al ultrastructural changes in soleus muscles were observed by using a transmission electron microscope.The protein expression of mitochondrial succinate dehydrogenase subunit B(SDHB),cytochrome C oxi-dase subunit 1(MTCO1),FK506 binding protein 8(FKBP8)and microtubule associated protein 1 light chain 3(LC3)in the soleus muscle were measured using Western blotting.Meanwhile,the co-localiza-tion of FKBP8 with LC3 and cytochrome C oxidase subunit Ⅳ(COXⅣ)with LC3,lysosomal associat-ed membrane protein 2(LAMP2)were detected by the immunofluorescence double labeling technique.Results(1)The running distance of one exhaustive exercise and the blood lactate before and after the test in 2E group were significantly higher than 2C and 4E groups(P<0.05 or P<0.01),and the run-ning distance of 4E group was significantly higher than 4C group(P<0.01).However,there was no sig-nificant difference between 4E and 4C groups in the blood lactate before and after the exhaustive exer-cise test(P>0.05).(2)In both 2E and 4E groups,significant mitochondrial swelling and accumulation under cell membrane,as well as a number of mitophagosomes and mitophagolysosomes were observed,together with a significant reduce in the number of mitochondria(P<0.05),which was more severe in 2E group than 4E group.(3)The protein expression of mitochondrial SDHB and MTCO1 in 2E and 4E groups were lower than 2C and 4C groups,respectively,with significantly greater changes of these proteins in 4E group than 2E group(P<0.05 or P<0.01).(4)The protein expression of mitochondrial FKBP8 and LC3,as well as the co-localization of FKBP8 with LC3 and COXⅣ with LC3,LAMP2 in 2E and 4E groups were higher than 2C and 4C groups,respectively,with significantly greater changes in 4E group than 2E group(P<0.05 or P<0.01).Conclusion After 4-week downhill treadmill running,the structure,quantity and function of mitochondria in skeletal muscle are impaired.FKBP8-mediated mitophagy is activated,but is insufficient to degrade the damaged mitochondria,leading to muscular damage,as well as the increasing and falling down of running capacity.

The Chinese Pharmacopoeia 2020 edition was reviewed and approved by the National Medical Products Administration and the National Health Commission of the People's Republic of China in July 2020.The current edition was officially implemented on December 30,2020.The general chapters of the Chinese Pharmacopoeia discuss the general testing methods and guidelines,which are the common re-quirements and basis for the implementation of drug standards in the Chinese Pharmacopoeia.Owing to adherence to the principles of scientificity,versatility,operability,and sustainable development,there is an improvement in the general chapters of the 2020 edition over those of the previous editions.Further,the application of advanced and mature analytical techniques has expanded,the development of testing methods for exogenous pollutants in traditional Chinese medicines has been strengthened,and technical requirements are now better harmonized with international standards.The updated edition provides technical and methodological support to ensure safety,effectiveness,and control of pharmaceuticals in China and will play an important and active role in encouraging the application of advanced technolo-gies,improving the quality control of medicines,and strengthening the means of drug regulation in China.This review provides a comprehensive introduction of the main features of and changes to the general chapters in the Chinese Pharmacopoeia 2020 edition and aims to provide reference for its correct understanding and accurate implementation.

Type 1 diabetes mellitus ( T1DM) is mostly an autoimmune disease. The combined effects of genetic and environmental factors lead to progressive islet beta cell functional failure and lifelong dependence on exogenous insulin therapy. Numerous studies have shown that regular physical exercise may reduce the daily insulin dose in patients with T1DM and patients need to be clear how to safely increase their physical activity, and incorporate more independent physical activity into daily life. At the same time, they should master the contraindications in order to avoid the risks of movement. Currently a recommendation for all T1DM patients is engaging in at least 150 min/week of moderate to vigorous intensity aerobic exercise, sustainability or high-intensity interval training, combined with resistance training such as resistance machines and bands, as well as other stretching and balance exercises such as yoga, tai chi, for 3 to 7 times per week, which is depended on the physical condition of patients and the exercise intensity, besides resistance training can be performed on nonconsecutive days.

Objective To establish an improved model of exercise-induced glycometabolism in type II diabetic rats,and to provide a theoretical reference for the establishment of exercise prescription for type II diabetes.Methods Forty-five 8-week old SPF male Wistar rats were used in this study.Of which 32 were fed with high-fat diet for 7 weeks,and intraperitoneal injection of 30 mg/kg STZ was given to establish the rat model of type II diabetes.The normal rats and successful model rats were divided into four groups:The normal control group (C group),normal exercise group (CE group),diabetic group (DM group) and diabetic exercise group (DME group).The exercise group was assigned by the Ploug training protocol,6 days/week,60 min/day,for a total of 8 weeks.After the high fat diet fed for 7 weeks,blood sample was taken from the tail vein,FBG and serum insulin were detected after baseline and 8 weeks exercise,and blood sample was collected from the tail vein to determine the FBG.Serum insulin (FINS) was detected by orbital blood sampling at the end of 8 weeks of exercise,and HOMA-IR was calculated.Results 1.After 7 weeks of high fat diet,compared with the groups C and CE,the levels of FBG,FINS and HOMA-IR were significantly higher in the DM and DME groups.2.After 8 weeks of exercise intervention,compared with the groups C and CE,FINS was significantly lower in the groups DM and DME,but the FBG and HOMA-IR were higher.Compared with the DM group,the level of FINS was significantly higher in the DME group,and the levels of FBG and HOMA-IR were significantly lower.The body weights of DM and DME groups were significantly lower than those of the groups Cand CE,the body weight had no significant difference between the DME and DM groups,and similar result was between the groups CE and C.Conclusions 1.The rat model of type II diabetes is successfully established with high fat diet for 7 weeks plus STZ injection(30 mg/mL).2.Aerobic exercise 60 min/day for a total of 8 weeks can improve the glycometabolism in type 2 diabetic rats,to be an ideal animal model for study of the mechanism of prevention and amelioration of type II diabetes.

AIM:To explore the influence of long-term swimming on peripheral neuropathy in type 2 diabetic rats.METHODS:Male Wistar rats were fed with a high-fat and high-fructose diet, and injected with streptozocin to estab-lish a model of type 2 diabetes mellitus.The rats were randomly divided into 4 groups:blank control group (C group), ex-ercise control group ( CE group ) , diabetes mellitus group ( DM group ) and diabetes mellitus +exercise group ( DME group).The rats in CE group and DME group received 8-week swimming training (6 d/week).The training time was 20, 30 and 45 min in the first 3 d,respectively, and then it increased to 60 min a day.Eight weeks later, the motor nerve conduc-tion velocity ( MNCV ) and the levels of tumor necrosis factor α( TNF-α) , interleukin 6 ( IL-6 ) and C-reactive protein ( CRP) in sciatic nerve tissues of the rats were measured .The morphological changes of the sciatic nerve were also observed under light microscope .RESULTS:Compared with DM group , 8-week swimming obviously accelerated the MNCV ( P<0.05), decreased the levels of TNF-α, IL-6 and CRP in DME group (but no significant difference, P>0.05).The obvi-ous nerve injury in DM group was observed .However , the pathological change of the sciatic nerve in DME group was re-lieved.CONCLUSION:Eight-week swimming training significantly accelerates the MNCV , attenuates the nerve injury in diabetic rats and has protective effect on peripheral nerve , which may be correlated with relieving the inflammatory reaction .