Objective To evaluate the efficacy and safety of rabbit anti-human thymocyte immuneglobulin(rATG)induction therapy in kidney transplant recipients from donation after cardiac death in China.Methods This was a prospective,multicenter,single-arm and interventional study conducted in China(NCT03099122).Adult patients who underwent kidney transplantation from donation after cardiac death and received rATG induction therapy(cumulative dose of 5 mg/kg)were included.Univariate and multivariate logistic regression analyses were used to identify factors associated with acute rejection(AR),delayed graft function(DGF),graft failure and patient death.The occurrence of adverse events was also analyzed.Results A total of 115 adult patients were enrolled in the study,of whom 107 were evaluable for efficacy.The incidence of biopsy-proven acute rejection(BPAR)and acute rejection(AR)was 2.8%(95%confidence interval 0.6%-8.0%)and 4.7%(95%confidence interval 1.5%-10.6%),respectively.The incidence of delayed graft function(DGF)was 13.1%(95%confidence interval 7.3%-21.0%).Graft and patient survival rates were 97.2%(95%confidence interval 92.0%-99.4%)and 99.1%(95%confidence interval 94.9%-100%),respectively.Multivariate logistic regression analysis showed that donor serum creatinine and recipient panel reactive antibodies were risk factors for DGF(both P<0.05).Common treatment-emergent adverse events(incidence>5%)included anemia(8.7%),infectious pneumonia(8.7%),and urinary tract infection(8.7%).Conclusions Standard-dose rATG induction therapy demonstrates low incidences of BPAR,AR,and DGF,and good safety in kidney transplant recipients from donation after cardiac death in China.

Objective:To compare effects of different training modalities on cardiac remodeling(including cardiac hyper-trophy,myocardial fibrosis,fetal gene expression and capillary angiogenesis)in spontaneously hypertensive rats(SHR)and to investigate potential mechanism.Method:Forty-five male SHR were randomly divided into sedentary(SHR-SED)group,continuous endurance training(SHR-CET)group and high-intensity interval training(SHR-HIIT)group,with ten normotensive Wistar-Kyoto rats serving as the normal control(NC)group.The exercise intensity(70%—90%maximal running speed),duration(1-4min)and exercise frequency(3-5d/w)were progressively increased g in SHR-HIIT group,while SHR-CET group consistently exercised at 60%of the maximal running speed.Both groups had equal en-ergy consumption over an intervention period of 12 weeks.After the intervention,caudal artery pressure was assessed by non-invasive blood pressure tester;cardiac structure and function was evaluated by echocardio-gram;histopathological detection was detected by HE and Masson staining;myocardial microvessel density(MVD)was measured by immunohistochemistry;protein expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),hypoxia inducible factor-1α(HIF-1α),endothelial nitric oxide synthase(eNOS)and vascular endothelial growth factor(VEGF)was detected by Western Blot.Result:Compared with NC group,SHR-SED group had elevated blood pressure(P<0.05),concentric hyper-trophy in the left ventricle with decreased cardiac function and myocardial fibrosis,reduced MVD(P<0.05),and increased HIF-1α protein expression(P<0.05).Compared with SHR-SED group,SHR-CET group showed a decrease in blood pressure(P<0.05),left ventricular eccentric hypertrophy with enhanced cardiac function(P<0.05),reduced myocardial fibrosis,increased MVD(P<0.05),decreased HIF-1α expression(P<0.05),and in-creased eNOS expression(P<0.05).The SHR-HIIT group showed worsened left ventricular concentric hypertro-phy and increased BNP expression(P<0.05).Conclusion:Long-term continuous endurance training(CET)alleviated while high-intensity interval training(HI-IT)aggravated cardiac remodeling in hypertensive rats.Traditional CET remains the primary exercise rehabilita-tion method for hypertension,however,the safety and effectiveness of HIIT need to be further confirmed.

Objective To explore the clinical significance of pulse pressure variability(PPV)in early prevention and diagnosis of prostate resection syndrome by observing the changes in PPV during transurethral resection of the prostate.Methods Eighty patients undergoing transurethral resection of the prostate(TURP)under general anesthesia from March to April 2023 were randomly divided into a control group and an observation group,with 40 patients in each group.The control group underwent routine monitoring of invasive blood pressure,while the observation group continued to monitor PPV in addition to invasive blood pressure monitoring.Observe and record the hemodynamic parameters,electrolyte Na+,K+,CL-,Changes in hemoglobin(Hb)and hematocrit(Hct),recording surgical time,intraoperative lavage fluid dosage,and occurrence of dilutive hyponatremia(TURS).Results One patient in the observation group experienced two unexplained drops in blood pressure and heart rate during surgery,and was diagnosed with TURS based on blood gas analysis.Among them,the observation group showed a decreasing trend in PPV with the prolongation of surgery time.PPV gradually decreased at 45～60 minutes after surgery,and at 90 minutes after surgery,PPV decreased significantly compared to preoperative levels.Among them,6 patients had a 50%decrease in PPV compared to preoperative levels.For patients with significantly reduced PPV,immediate treatment was given 10～20 mg of furosemide and 10 mg of dexamethasone.By the end of surgery,PPV had basically recovered to preoperative levels.Both groups of patients showed varying degrees of decrease in Na+,K+,Hct,and Hb levels.Conclusions PPV can reflect the volume status of patients.When PPV decreases by more than 50%compared to preoperative levels and there are unexplained hemodynamic changes and abnormal clinical manifestations during surgery,it is necessary to be vigilant and handle them promptly to reduce and prevent the occurrence of TURS.

Objective To explore the clinical significance of pulse pressure variability(PPV)in early prevention and diagnosis of prostate resection syndrome by observing the changes in PPV during transurethral resection of the prostate.Methods Eighty patients undergoing transurethral resection of the prostate(TURP)under general anesthesia from March to April 2023 were randomly divided into a control group and an observation group,with 40 patients in each group.The control group underwent routine monitoring of invasive blood pressure,while the observation group continued to monitor PPV in addition to invasive blood pressure monitoring.Observe and record the hemodynamic parameters,electrolyte Na+,K+,CL-,Changes in hemoglobin(Hb)and hematocrit(Hct),recording surgical time,intraoperative lavage fluid dosage,and occurrence of dilutive hyponatremia(TURS).Results One patient in the observation group experienced two unexplained drops in blood pressure and heart rate during surgery,and was diagnosed with TURS based on blood gas analysis.Among them,the observation group showed a decreasing trend in PPV with the prolongation of surgery time.PPV gradually decreased at 45～60 minutes after surgery,and at 90 minutes after surgery,PPV decreased significantly compared to preoperative levels.Among them,6 patients had a 50%decrease in PPV compared to preoperative levels.For patients with significantly reduced PPV,immediate treatment was given 10～20 mg of furosemide and 10 mg of dexamethasone.By the end of surgery,PPV had basically recovered to preoperative levels.Both groups of patients showed varying degrees of decrease in Na+,K+,Hct,and Hb levels.Conclusions PPV can reflect the volume status of patients.When PPV decreases by more than 50%compared to preoperative levels and there are unexplained hemodynamic changes and abnormal clinical manifestations during surgery,it is necessary to be vigilant and handle them promptly to reduce and prevent the occurrence of TURS.

Objective:To compare effects of different training modalities on cardiac remodeling(including cardiac hyper-trophy,myocardial fibrosis,fetal gene expression and capillary angiogenesis)in spontaneously hypertensive rats(SHR)and to investigate potential mechanism.Method:Forty-five male SHR were randomly divided into sedentary(SHR-SED)group,continuous endurance training(SHR-CET)group and high-intensity interval training(SHR-HIIT)group,with ten normotensive Wistar-Kyoto rats serving as the normal control(NC)group.The exercise intensity(70%—90%maximal running speed),duration(1-4min)and exercise frequency(3-5d/w)were progressively increased g in SHR-HIIT group,while SHR-CET group consistently exercised at 60%of the maximal running speed.Both groups had equal en-ergy consumption over an intervention period of 12 weeks.After the intervention,caudal artery pressure was assessed by non-invasive blood pressure tester;cardiac structure and function was evaluated by echocardio-gram;histopathological detection was detected by HE and Masson staining;myocardial microvessel density(MVD)was measured by immunohistochemistry;protein expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),hypoxia inducible factor-1α(HIF-1α),endothelial nitric oxide synthase(eNOS)and vascular endothelial growth factor(VEGF)was detected by Western Blot.Result:Compared with NC group,SHR-SED group had elevated blood pressure(P<0.05),concentric hyper-trophy in the left ventricle with decreased cardiac function and myocardial fibrosis,reduced MVD(P<0.05),and increased HIF-1α protein expression(P<0.05).Compared with SHR-SED group,SHR-CET group showed a decrease in blood pressure(P<0.05),left ventricular eccentric hypertrophy with enhanced cardiac function(P<0.05),reduced myocardial fibrosis,increased MVD(P<0.05),decreased HIF-1α expression(P<0.05),and in-creased eNOS expression(P<0.05).The SHR-HIIT group showed worsened left ventricular concentric hypertro-phy and increased BNP expression(P<0.05).Conclusion:Long-term continuous endurance training(CET)alleviated while high-intensity interval training(HI-IT)aggravated cardiac remodeling in hypertensive rats.Traditional CET remains the primary exercise rehabilita-tion method for hypertension,however,the safety and effectiveness of HIIT need to be further confirmed.

BACKGROUND:Acute myocardial infarction can cause cardiac remodeling and heart failure,as well as skeletal myopathy,affecting patients'quality of life.Exercise therapy is an important rehabilitation method for patients with heart failure;however,the optimal exercise prescription has not been clarified. OBJECTIVE:To compare the effects of different exercise modes(aerobic exercise,resistance exercise)on skeletal muscle remodeling in rats with acute myocardial infarction induced heart failure and to explore the possible mechanism,so as to provide a basis for optimizing the exercise rehabilitation program. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham operation group,myocardial infarction group,aerobic exercise group and resistance exercise group.Coronary artery ligation was used to create model of heart failure.After 3 months,animals in the aerobic exercise group and resistance exercise group underwent 12 weeks of corresponding exercise mode interventions,while those in the sham operation group and myocardial infarction group were kept quietly in mouse cages.After the experiment,maximal running speed and maximal weight-bearing load were measured by graded treadmill exercise test and ladder-climbing test respectively,and heart structure and function were evaluated by echocardiography.The heart was isolated,and hematoxylin-eosin staining and Sirius red staining were performed to detect cardiac remodeling.For the gstrocnemius muscle,ATPase staining was performed to observe changes in muscle fiber type and cell cross-sectional area,dihydroethidium method was used to evaluate reactive oxygen species levels,enzyme-linked immunosorbent method was used to determine malondialdehyde content and antioxidant enzyme activity,western blot was used to determine the expression of ubiquitin-proteasome system proteins,and the number of activated satellite cells(Pax7+/MyoD+)were detected by double immunofluorescence staining. RESULTS AND CONCLUSION:(1)Exercise performance:Compared with the sham operation group,maximal running speed and maximal weight-bearing load in the myocardial infarction group decreased(P<0.05);compared with the myocardial infarction group,the maximal running speed of the aerobic exercise group and the maximal weight-bearing load of the resistance exercise group increased(P<0.05).(2)Cardiac remodeling:Compared with the sham operation group,infarction area,myocardial cell cross-sectional area,and collagen content in the myocardial infarction group increased(P<0.05),while leftventricular ejection fraction and shortening fraction decreased(P<0.05);compared with the myocardial infarction group,there was no statistical difference in the above parameters in both aerobic exercise resistance exercise groups(P>0.05).(3)Skeletal muscle remodeling:Compared with the sham operation group,gastrocnemius muscle mass,gastrocnemius muscle mass index,cell cross-sectional area,superoxide dismutase activity,glutathione peroxidase activity,and the number of activated satellite cells decreased in myocardial infarction group(P<0.05),while reactive oxygen species content,malondialdehyde content,and the protein expression of ubiquitin,MuRF1 and MAFbx increased(P<0.05);compared with the myocardial infarction group,gastrocnemius muscle mass index,superoxide dismutase activity,the number of activated satellite cells increased in both aerobic exercise and resistance exercise groups(P<0.05),while reactive oxygen species content and the protein expression of ubiquitin,MuRF1,and MAFbx decreased(P<0.05);compared with the aerobic exercise group,gastrocnemius muscle mass,gastrocnemius muscle mass index,cell cross-sectional area,reactive oxygen species content,malondialdehyde content,the number of activated satellite cells increased in resistance exercise group(P<0.05),while superoxide dismutase activity,glutathione peroxidase activity down-regulated(P<0.05).To conclude,aerobic exercise and resistance exercise can both improve exercise performance of rats with heart failure,and the mechanism is related to reducing oxidative stress,inhibiting ubiquitin-proteasome system activity and activating satellite cells to improve skeletal muscle remodeling.Aerobic exercise has a better effect on improving skeletal muscle oxidative stress,while resistance exercise has a more significant effect on promoting skeletal muscle regeneration.

BACKGROUND:Stem cell transplantation is a novel therapy for myocardial infarction,but the extremely hostile microenvironment in the infarct area results in low survival rate of stem cells and little long-term effect.Exercise preconditioning is a way to induce endogenous protective effects through exercise,which can be used as a new strategy for prevention and treatment of cardiac rehabilitation. OBJECTIVE:To evaluate whether exercise preconditioning potentiates the cardioprotective effects of adipose-derived stem cell transplantation following myocardial infarction in rats and to explore the mechanism of angiogenesis. METHODS:Six-week-old male SD rats were randomly divided into control group,modeling group,stem cell group,and stem cell plus exercise group.Acute myocardial infarction model was made by coronary artery occlusion,and sham operation was performed in control group.The stem cell plus exercise group underwent aerobic exercise for 8 weeks before modeling,and adipose-derived stem cell transplantation was performed 30 minutes after modeling.The stem cell group performed only adipose-derived stem cell transplantation.One and seven days after stem cell transplantation,the expression levels of myocardial total Akt(t-Akt),phosphorylated Akt(p-Akt),vascular endothelial growth factor(VEGF),total endothelial nitric oxide synthase(t-eNOS),and phosphorylated endothelial nitric oxide synthase(p-eNOS)protein were measured by western blotting,and the ratios of p-Akt/t-Akt and p-eNOS/t-eNOS were calculated.At 4 weeks after stem cell transplantation,the heart structure and function as well as myocardial blood flow were detected by color Doppler ultrasound diagnostic system.Myocardial infarction area was measured by TTC staining.Myocardial interstitial collagen deposition was examined by Masson staining.Myocardial capillary density was detected by immunofluorescence staining,and myocardial apoptosis was measured by TUNEL staining. RESULTS AND CONCLUSION:(1)Four weeks after stem cell transplantation:Compared with control group,left ventricular shortening fraction,left ventricular ejection fraction,myocardial capillary density,and myocardial blood flow decreased(P<0.05),myocardial infarction area,collagen volume fraction,and apoptosis increased(P<0.05)in the modeling group.Compared with the modeling group,the above indexes(except for left ventricular fractional shortening and left ventricular ejection fraction)in the stem cell group improved(P<0.05).Compared with the stem cell group,the above parameters were further improved in the stem cell plus exercise group(P<0.05).(2)One day after stem cell transplantation:Compared with the control group,the protein expression of t-Akt,p-Akt,VEGF,t-eNOS,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS had no significant changes in the modeling group(P>0.05).Compared with the modeling group,there were no significant changes in the above indexes in the stem cell group(P>0.05),and p-Akt protein expression and the ratio of p-Akt/t-Akt were up-regulated in the stem cell plus exercise group(P<0.05).(3)Seven days after stem cell transplantation:Compared with the control group,the protein expression of p-Akt,VEGF,p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were decreased in the modeling group(P<0.05).Compared with the modeling group,there were no significant changes in all parameters in the stem cell group(P>0.05),and the protein expression of p-Akt,VEGF p-eNOS and the ratio of p-Akt/t-Akt and p-eNOS/t-eNOS were increased in the stem cell plus exercise group(P<0.05).These findings confirm that exercise preconditioning can potentiate the therapeutic effect of adipose-derived stem cells on cardiac remodeling in rats with myocardial infarction,and its mechanism is associated with the promotion of myocardial angiogenesis and blood perfusion.

Objective To evaluate the efficacy and safety of rabbit anti-human thymocyte immuneglobulin(rATG)induction therapy in kidney transplant recipients from donation after cardiac death in China.Methods This was a prospective,multicenter,single-arm and interventional study conducted in China(NCT03099122).Adult patients who underwent kidney transplantation from donation after cardiac death and received rATG induction therapy(cumulative dose of 5 mg/kg)were included.Univariate and multivariate logistic regression analyses were used to identify factors associated with acute rejection(AR),delayed graft function(DGF),graft failure and patient death.The occurrence of adverse events was also analyzed.Results A total of 115 adult patients were enrolled in the study,of whom 107 were evaluable for efficacy.The incidence of biopsy-proven acute rejection(BPAR)and acute rejection(AR)was 2.8%(95%confidence interval 0.6%-8.0%)and 4.7%(95%confidence interval 1.5%-10.6%),respectively.The incidence of delayed graft function(DGF)was 13.1%(95%confidence interval 7.3%-21.0%).Graft and patient survival rates were 97.2%(95%confidence interval 92.0%-99.4%)and 99.1%(95%confidence interval 94.9%-100%),respectively.Multivariate logistic regression analysis showed that donor serum creatinine and recipient panel reactive antibodies were risk factors for DGF(both P<0.05).Common treatment-emergent adverse events(incidence>5%)included anemia(8.7%),infectious pneumonia(8.7%),and urinary tract infection(8.7%).Conclusions Standard-dose rATG induction therapy demonstrates low incidences of BPAR,AR,and DGF,and good safety in kidney transplant recipients from donation after cardiac death in China.

BACKGROUND:Exercise is an effective strategy to prevent and treat various cardiovascular diseases and protect the heart from ischemia-reperfusion injury.Its mechanism of action needs to be studied in depth. OBJECTIVE:To observe the effect of aerobic exercise preconditioning on myocardial ischemia-reperfusion injury and to explore the effect of endothelial nitric oxide synthase(eNOS)activation(including coupling and phosphorylation). METHODS:Eighty adult Wistar rats were randomly divided into sedentary(n=40)and exercise(n=40)groups.The rats in the exercise group were subjected to aerobic exercise for 8 weeks while those in the sedentary group were quietly fed and caged.After 8 weeks of intervention,three experiments were performed.(1)Experiment 1:After the last training,cardiac function,cardiac nitric oxide metabolite content and cardiac eNOS,phosphorylated eNOS-S1177,eNOS dimer and eNOS monomer protein expression levels were detected.(2)Experiment 2:Rats were divided into sedentary control group,exercise control group,sedentary+eNOS inhibitor group,exercise+eNOS inhibitor group,all of which were subjected to an in vitro myocardial ischemia-reperfusion injury experiment.eNOS inhibitor was continuously infused into the sedentary+eNOS inhibitor group and exercise+eNOS inhibitor group 10 minutes before reperfusion,and cardiac function and myocardial infarction area were detected 3 hours after reperfusion.(3)Experiment 3:Rats were divided into sedentary control group,exercise control group,sedentary+eNOS coupler group and exercise+eNOS coupler group,all of which were subjected to an in vitro myocardial ischemia-reperfusion injury experiment.The rats in the sedentary+eNOS coupler group and exercise+eNOS coupler group were treated with eNOS coupler.Myocardial infarct area,cardiac nitric oxide metabolite content,cardiac protein expression of eNOS,phosphorylated eNOS-S1177,eNOS dimer,eNOS monomer and 3-nitrotyrosine were detected 3 hours after reperfusion.The phosphorylated eNOS-S1177/eNOS ratio reflected the phosphorylated/dephosphorylated level of eNOS and eNOS dimer/monomer ratio reflected eNOS coupling/uncoupling level. RESULTS AND CONCLUSION:Experiment 1:Compared with the sedentary group,the exercise group had increased cardiac output and left ventricular ejection fraction(P<0.05),increased nitrite and S-nitrosothiol contents(P<0.05),upregulated phosphorylated eNOS-S1177,eNOS protein expression and phosphorylated eNOS-S1177/eNOS ratio(P<0.05),eNOS dimer protein expression and eNOS dimer/monomer ratios were elevated(P<0.05).Experiment 2:Compared with the sedentary control group,left ventricular development pressure increased(P<0.05)and myocardial infarct area decreased(P<0.05)in the exercise control group.Compared with the exercise control group,left ventricular development pressure decreased(P<0.05)and myocardial infarct area increased(P<0.05)in the exercise+eNOS inhibitor group.Experiment 3:Compared with the sedentary control group,the exercise control group had increased left ventricular developmental pressure(P<0.05),decreased myocardial infarct area(P<0.05),decreased phosphorylated eNOS-S1177/eNOS ratio(P<0.05),decreased eNOS dimer/monomer ratio(P<0.05),increased S-nitrosothiol content(P<0.05),and decreased 3-nitrotyrosine protein expression(P<0.05).Compared with the exercise control group,the exercise+eNOS coupler group had decreased left ventricular developmental pressure(P<0.05),increased myocardial infarct area(P<0.05),increased phosphorylated eNOS-S1177/eNOS ratio(P<0.05),increased eNOS dimer/monomer ratio(P<0.05),and elevated 3-nitro tyrosine protein expression(P<0.05).To conclude,aerobic exercise preconditioning could induce cardioprotection,which is related to uncoupling and dephosphorylation of eNOS during cardiac ischemia-reperfusion,thereby inhibiting the excessive production of nitric oxide and reducing nitro-oxidative stress.

BACKGROUND:Postmenopausal osteoporosis significantly increases the risk of fracture,which seriously affects the quality of life of patients.Exercise therapy is an important non-drug means and prevention and treatment strategy for patients with osteoporosis,in which strength training is the best mode,but its specific biological mechanism has not been determined. OBJECTIVE:To investigate the effects of strength training on bone morphology,materials and biomechanics in ovariectomized rats and to explore the mechanism of extracellular matrix remodeling. METHODS:Forty-eight female Sprague-Dawley rats were divided into sham operation group,sham operation exercise group,ovariectomized group and ovariectomized exercise group according to the random number table method.The menopausal animal model was established by bilateral ovariectomy in the ovariectomized group and ovariectomized exercise group,while sham operation was performed in the sham operation group and sham operation exercise group.Four weeks after operation,the sham operation exercise group and the ovariectomized exercise group underwent 12-week tail weight-bearing ladder training,and the sham operation group and the ovariectomized group were raised quietly in the cage.The bilateral femur and tibia were separated after training.The right tibia was used for dual-energy X-ray densitometry and biomechanical,biophysical and biochemical analyses,the left tibia was detected using micro-computed tomography for bone microstructural examination,the right femur was subjected to hematoxylin-eosin staining for histological observation,and the left femur was used for western blot and gelatin zymography detection of protein expression and enzyme activity of extracellular matrix metabolism-related factors,respectively. RESULTS AND CONCLUSION:Compared with the sham operation group,the maximal load and stiffness decreased(P＜0.05),bone density,bone mineral density,bone inorganic matter content,bone calcium content decreased(P＜0.05),bone water content increased(P＜0.05),trabecular bone volume fraction,trabecular connectivity density,and trabecular number decreased(P＜0.05),trabecular separation,structural model index increased(P＜0.05),bone adipocyte number and cross-sectional area increased(P＜0.05),matrix metalloproteinase-2 activity decreased(P＜0.05),and protein expression of tissue inhibitor of metalloproteinase-1 and osteoprotegerin increased(P＜0.05)in the ovariectomized group.Compared with the ovariectomized group,the maximal load,stiffness,fracture load and resilience increased(P＜0.05),bone mineral density,bone mineral content,bone mineral density,bone inorganic matter content,and bone calcium content increased(P＜0.05),bone water content decreased(P＜0.05),trabecular separation and bone marrow area decreased(P＜0.05),trabecular bone thickness,cortical bone volume fraction,cortical bone area fraction,cortical bone thickness,and cortical bone porosity increased(P＜0.05),bone adipocyte number and cross-sectional area reduced(P＜0.05),matrix metalloproteinase-2 activity increased(P＜0.05),and protein expression of tissue inhibitor of metalloproteinase-1,Runt-related transcription factor 2 and osteoprotegerin decreased(P＜0.05)in the ovariectomized exercise group.To conclude,strength training can protect against bone injury caused by estrogen deficiency,which is characterized by improvement of bone biomechanical properties,bone tissue composition and bone microstructure,and its mechanism is related to the regulation of extracellular matrix remodeling.