Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

BACKGROUND:The lower-limb muscle strength shows a significant physiological decline with aging.There may be a certain correlation between sedentary behavior,fear of falling,age and lower-limb muscle strength,but the influence path and effect relationship among them are not yet clear.OBJECTIVE:To examine the relationship between sedentary behavior and lower-limb muscle strength,and to explore the influences of fear of falling and age in such an association among community-dwelling older adults.METHODS:This cross-sectional study recruited 331 community-dwelling older adults(aged≥60 years)in Shanghai.A questionnaire survey was conducted to collect basic information,demographic data,etc.The Short Form of the International Physical Activity Questionnaire was applied to measure sedentary time.Lower-limb muscle strength was assessed by the 30-second chair-stand test.Fear of falling was measured by the Chinese version of Fall Efficacy Scale-International.Descriptive statistics analysis,correlation analysis,regression-based path analysis and mediation analyses were performed on the data.RESULTS AND CONCLUSION:Valid data from 318 community-dwelling older adults[78.9%females,mean age(67.8±5.5)years old]were finally included in the analysis.There were 185 with sedentary time≥3 hours and 133 with sedentary time<3 hours.(1)There was a positive correlation between sedentary behavior and fear of falling(P<0.01),and there were negative correlations between lower-limb muscle strength and sedentary behavior(P<0.01)and between lower-limb muscle strength and fear of falling(P<0.001).(2)Sedentary behavior negatively predicted lower-limb muscle strength(β=-0.125,P<0.05),and positively predicted fear of falling(β=0.182,P<0.01).Fear of falling negatively predicted lower-limb muscle strength(β=-0.293,P<0.001).(3)Fear of falling mediated the relationship between sedentary behavior and lower-limb muscle strength(β=-0.053,95%confidence interval:-0.100 to-0.018).(4)Sedentary behavior had a statistically significant predictive effect on fear of falling(β=0.164,P<0.01),indicating that age moderates the effect of sedentary behavior on fear of falling.

Objective To investigate the effects and mechanisms of combined prescriptions of essential oils from five traditional Chinese medicinal herbs,namely peppermint,turmeric,ginger,Tibetan fennel,and cumin,on symptoms related to functional abdominal pain syndrome(FAPS).Methods Gas chromatography-mass spectrometry(GC-MS)was employed to analyze the chemical constituents of five essential oils,while network pharmacology was utilized to predict the key targets and signaling pathways associated with these essential oils in alleviating functional abdominal pain syndrome.A formula design methodology centered on these core targets and signaling pathways was developed for creating new prescriptions.Molecular docking technology was conducted to predict its the underlying mechanisms.Subsequently,animal experiments were performed to assess pharmacological activity,including hot plate tests and acetic acid-induced writhing assays to validate the analgesic effects of the newly formulated prescription,as well as xylene-induced ear swelling tests to evaluate its anti-inflammatory properties.The impact of the essential oil formulation on intestinal peristaltic function was examined through intestinal propulsion experiments.Additionally,enzyme-linked immunosorbent assay(ELISA)methods were employed to measure levels of serotonin(5-HT),prostaglandin E2(PGE2),and gamma-aminobutyric acid(GABA)in brain tissue.Western blot analysis was conducted to determine protein expression levels of TPH1 and SERT in the intestine,along with TPH2 and SERT in the brain.Results The main chemical components in five essential oils were identified and screened(peppermint:12,turmeric:8,ginger:14,cumin:2,fennel:6).Based on the network pharmacology analysis,four new essential oil prescriptions were successfully designed according to the complementary relationship between the five essential oils in improving functional abdominal pain syndrome at the target level,including 4 new prescription named Prescription A,B,C and D,these four prescriptions were all based on ginger and turmeric essential oils,with other essential oils serving as supplements or enhancements.The results of animal experiments showed that Prescription D could significantly reduce the writhe frequency of mice(P<0.05),all the four groups could significantly prolong the pain threshold of mice(P<0.05),and Prescription C had a significant effect on reducing the degree of ear swelling(P<0.05).The prescription of essential oil did not significantly affect the function of peristalsis and the speed of propulsion.The levels of 5-HT and PGE2 in the brain tissue were significantly inhibited(P<0.05),and the level of GABA was significantly increased(P<0.05).Prescription C could reduce the expression of TPH1 in the intestinal tissue(P<0.05),Prescription A,C and D could reduce the expression of TPH2,and all groups had a tendency to increase the expression of SERT in the brain tissue.Conclusion In summary,the therapeutic effects of the four novel prescriptions composed of the five essential oils demonstrated potential in improving symptoms related to FAPS,the mechanism might be through modulating abnormalities in the brain-gut axis system.

Objective To explore the regulatory effect of moderate intensity aerobic exercise on glu-cose and lipid metabolism disordersafter immune stimulation in high-fat diet induced insulin resistance(IR)mice by inducing tolerance of trained immunity.Methods Eighteen of 70 male C57BL/6 male mice were randomly selected as the control group(CON group),while the remaining mice were subjected to high-fat diet intervention(HFD group)for 8 weeks.After modeling,six of the CON group and HFD group were measured their glucose and lipid metabolism and inflammation levels.The remaining mice in the HFD group were randomly divided into HFD sedentary group(HS group)and HFD exer-cise group(HE group),each of 16.The HE groups underwent a daily 60-minute running on a hori-zontal treadmill at 12 m/min,5 days a week for 8 weeks.After that,the CON,HS and HE groups were randomly divided into an immune stimulation group(lipopolysaccharides,LPS group)and a con-trol group(phosphate buffered saline,PBS group),with 6 in CON-PBS and CON-LPS groups,and 8 in HS-PBS,HS-LPS,HE-PBS and HE-LPS groups.The LPS group received intraperitoneal injec-tion of LPS as an immune stimulus,and were taken samples 24 hours after intervention.During the intervention period,the body weight,food intake,fasting blood glucose(FBG),glucose tolerance,and insulin tolerance were tested for all groups.Then,the serum blood lipid level was tested.More-over,the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and interleukin-10(IL-10)in serum were detected by using the enzyme-linked immunosorbent assay,while the protein expression of IL-1β,IL-10,induciblenitricoxidesynthase(iNOS)andarginase-1(Arg-1)were measured by using Western Blot.Results(1)After 8 weeks of high-fat diet intervention,compared with the CON group,there was a significant increase in the body weight,food intake,and FBG,the level of TNF-α and IL-1β in serum and expressions of IL-1β and iNOS in liver,skeletal muscle and adipose tissue,but a significant decrease in glucose and insulin tolerance,the level of anti-in-flammatory factor IL-10,as well as IL-10 and Arg-1 in liver and Arg-1 in adipose tissues in group HFD(P<0.01,P<0.05).(2)After 8 weeks of diet intervention,the body weight of group HS-PBS was still significantly higher than group CON-PBS(P<0.01).However,no significant differences were found between group CON-PBS and HS-PBS in other indicators(P>0.05).After LPS intervention,the food intake of both CON-LPS and HS-LPS groups was significantly lower than the corresponding PBS group(P<0.05).However,the levels of FBG,TG,TC,LDL-C,TNF-α and IL-1β in serum,IL-1β and iNOS in liver and adipose tissues,and iNOS in skeletal muscles of group HS-LPS were signif-icantly higher compared with group HS-PBS and CON-LPS(P<0.05).Meanwhile,the levels of IL-10 in serum,skeletal muscles and adipose tissues,and Arg-1 in skeletal muscles and adipose tissues of group HS-LPS decreased significantly compared with group HS-PBS and CON-LPS(P<0.05).(3)Af-ter simultaneous aerobic exercise intervention,there were no significant differences between group HE-LPS and HE-PBS in FBG,TC,LDL-C,TNF-α,IL-1β and IL-10 in serum,as well as IL-1β,iN-OS and IL-10 in the liver,skeletal muscles and adipose tissues(P>0.05).Moreover,thelevels of FBG,TG,TC,TNF-α,IL-1β in serum,and IL-1β and iNOS in the liver,skeletal muscle and adi-pose tissue decreased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Howev-er,the levels of IL-10 in the serum and liver,and IL-10 and Arg-1 in skeletal muscles and adi-pose tissues increased significantly in group HE-LPS compared with group HS-LPS(P<0.05).Conclu-sion Eight-week aerobic exercise can effectively relieve the glucose and lipid metabolism disorder after immune stimulation in IR mice,which may be related to the stimulation of immunologic tolerance in innate immune cells,thereby reducing the excessive inflammatory response caused by secondary im-mune stimulation.

BACKGROUND:The lower-limb muscle strength shows a significant physiological decline with aging.There may be a certain correlation between sedentary behavior,fear of falling,age and lower-limb muscle strength,but the influence path and effect relationship among them are not yet clear.OBJECTIVE:To examine the relationship between sedentary behavior and lower-limb muscle strength,and to explore the influences of fear of falling and age in such an association among community-dwelling older adults.METHODS:This cross-sectional study recruited 331 community-dwelling older adults(aged≥60 years)in Shanghai.A questionnaire survey was conducted to collect basic information,demographic data,etc.The Short Form of the International Physical Activity Questionnaire was applied to measure sedentary time.Lower-limb muscle strength was assessed by the 30-second chair-stand test.Fear of falling was measured by the Chinese version of Fall Efficacy Scale-International.Descriptive statistics analysis,correlation analysis,regression-based path analysis and mediation analyses were performed on the data.RESULTS AND CONCLUSION:Valid data from 318 community-dwelling older adults[78.9%females,mean age(67.8±5.5)years old]were finally included in the analysis.There were 185 with sedentary time≥3 hours and 133 with sedentary time<3 hours.(1)There was a positive correlation between sedentary behavior and fear of falling(P<0.01),and there were negative correlations between lower-limb muscle strength and sedentary behavior(P<0.01)and between lower-limb muscle strength and fear of falling(P<0.001).(2)Sedentary behavior negatively predicted lower-limb muscle strength(β=-0.125,P<0.05),and positively predicted fear of falling(β=0.182,P<0.01).Fear of falling negatively predicted lower-limb muscle strength(β=-0.293,P<0.001).(3)Fear of falling mediated the relationship between sedentary behavior and lower-limb muscle strength(β=-0.053,95%confidence interval:-0.100 to-0.018).(4)Sedentary behavior had a statistically significant predictive effect on fear of falling(β=0.164,P<0.01),indicating that age moderates the effect of sedentary behavior on fear of falling.

Objective:To investigate the effects of melatonin(Mel)on inflammatory damage in the retina of rats with oxygen-induced retinopathy(OIR)and the molecular mechanisms.Methods:Healthy neonatal SD rats were di-vided into the sham group(Sham),the model group(OIR),and the melatonin treatment group(OIR+Mel).The OIR model was induced by alternating 50%/10%oxygen concentration exposure for 14 d.The OIR+Mel group was in-jected intraperitoneally with 10 mg-kg-1 melatonin.Hematoxylin-eosin(HE)staining was used to observe the morpho-logical changes in the retinal tissue;immunohistochemical staining was used to detect the expression of retinal cleaved-caspase-1 and IL-1β proteins;and immunofluorescence staining was used to detect the expression of cGAS-STING-NL-RP3 signaling molecules and gasdermin(GSDMD)in the microglia of the retina.Results:HE staining results showed that compared with the Sham group,the retinal cells in the OIR group were disorganized and the thickness of the inner retina was significantly thinner,and the retinal cells in the OIR+Mel group were more neatly arranged compared with those in the OIR group(P<0.05).Immunohistochemical staining results showed that the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cleaved-caspase-1+and IL-1β+cells in the retina of rats in the OIR+Mel group decreased signifi-cantly compared with that of the OIR group(P<0.05).Immunofluorescence staining results showed that the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR group increased significantly compared with that in the Sham group,and the number of cGAS+,STING+and NLRP3+cells in the retina of rats in the OIR+Mel group de-creased significantly compared with that in the OIR group(P<0.05);The number of Iba-1+/N-GSDMD+cells in-creased significantly in the OIR group compared with the Sham group,whereas the number of Iba-1+/N-GSDMD+cells in the OIR+Mel group was significantly less than that in the OIR group,but still more than that in the Sham group(P<0.05).Conclusion:Mel inhibits the pyroptosis of retinal microglia,thus attenuates retinal inflammatory injury in OIR rats,and its mechanism may be related to the cGAS-STING-NLRP3 signaling pathway.

Objective To explore the mechanism of the thioredoxin-interacting protein(TXNIP)/thioredoxin-1(Trx-1)pathway in regulating the polarization of retinal microglia in rats after retinal ischemia-reperfusion(RIR)in rats,and to provide new ideas for the prevention and treatment of retinal ischemia reperfusion injury(RIRI).Methods For-ty-two healthy adult male Sprague-Dawley rats were randomly divided into a Sham group,a RIRI group and a TXNIP siRNA group.The right eye of the rats was experimented.For RIRI and TXNIP siRNA groups,RIRI models were established using the anterior chamber high intraocular pressure method.Rats in the TXNIP siRNA group were given the intravitreal injection of TXNIP siRNA 3 d before modeling.Hematoxylin-eosin(HE)staining was used to analyze retinal histopathologic changes of rats in all groups 24 h after modeling.Immunohistochemical staining of brain-specific homeobox/POU domain proteins 3A(Brn-3a)was made to count the number of retinal ganglion cells(RGCs).The dynamical changes in the number of TXNIP+cells 6 h,24 h,72 h and 7 d after modelling were analyzed through immunohistochemical staining in the RIRI group.The retinal microglia polarization and changes in the expression of TXNIP and Trx-1 proteins in each group were de-tected by double immunofluorescence staining and Western blot 24 h after modeling.Results HE staining results showed that 24 h after modelling,the retinal cells were disordered and the inner retinal layer was thickened and swelled in RIRI and TXNIP siRNA groups,compared with those in the Sham group(all P＜0.05).Immunohistochemical staining results of Brn-3a showed that 24 h after modeling,the number of Brn-3a+cells in RIRI and TXNIP siRNA groups significantly decreased,compared with that in the Sham group(both P＜0.05).The number of Brn-3a+cells in the TXNIP siRNA group was signifi-cantly higher than that in the RIRI group(P＜0.05).Immunohistochemical staining results of TXNIP at different time points after modeling showed that the expression of TXNIP+proteins started to increase 6 h after modeling.The TXNIP+protein level reached a peak at 24 h and then decreased gradually.Western blot results revealed that 24 h after modeling,RIRI and TXNIP siRNA groups had significantly higher TXNIP levels and significantly lower Trx-1 levels than the Sham group(all P＜0.05).Compared with those in the RIRI group,the expression of TXNIP proteins was significantly lower and the expression of Trx-1 proteins was significantly higher in the TXNIP siRNA group(both P＜0.05).Double immunofluores-cence staining showed that 24 h after modeling,Iba1+/CD206+cells were significantly more and Iba1+/CD16+cells were significantly less in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).RIRI and TXNIP siRNA groups had significantly more Ibal+/TXNIP+cells and significantly less Iba1+/Trx-1+cells than the Sham group(both P＜0.05).The number of Iba1+/TXNIP+cells was significantly lower and the number of Iba1+/Trx-1+cells was significantly higher in the TXNIP siRNA group than those in the RIRI group(both P＜0.05).Conclusion RIR activates the TXNIP/Trx-1 path-way to induce the activation of retinal microglia and regulate the polarization of microglia,thereby resulting in RIRI in rats.

OBJECTIVE To study the therapeutic effect of Hongqi Shenmai Drink on heart failure(HF)after acute myocardial in-farction(AMI)with qi-yin deficiency and blood stasis,and its regulatory effect on serum secretory phosphoprotein 1(SPP1)in AMI-HF patients.METHODS Seventy-six patients with AMI-HF of qi-yin deficiency and blood stasis type were enrolled in this study from three centers:Affiliated Hospital of Integrated Traditional and Western Medicine,Nanjing University of Chinese Medicine;Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine;and Changzhou Hospital of Traditional Chinese Medicine.They were randomly di-vided into a traditional Chinese medicine(TCM)group and a control group,with 38 patients in each group.During the treatment period,4 patients in the TCM group and 3 patients in the control group dropped out.The control group received conventional Guideline-directed medical therapy(GDMT),while the TCM group received GDMT plus Hongqi Shenmai Drink.The treatment course for both groups was 12 weeks.The TCM syndrome scores of the two groups of patients were compared before and after treatment,and the clini-cal efficacy and readmission rate were assessed.Echocardiography was used to assess cardiac structure and function.ELISA was used to detect changes in serum SPP1,N-terminal pro-brain natriuretic peptide(NT-proBNP),interleukin-1β(IL-1β),type Ⅰ collagen α1(COL1α1),and matrix metalloproteinase 9(MMP9)levels.The 6-minute walk test(6MWT)was used to assess exercise tolerance,and the Minnesota living with heart failure questionnaire(MLHFQ)was used to assess patients'quality of life.Adverse reactions were monitored in both groups during treatment.RESULTS After treatment,the TCM syndrome scores of both groups decreased signifi-cantly(P<0.01),with the TCM group showing a significantly lower score than the control group(P<0.01).The total effective rate of TCM clinical efficacy in the TCM group was superior to that in the control group(P<0.05),and the readmission rate in the TCM group was significantly lower than that in the control group(P<0.01).Left ventricular end diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),6MWT,and MLHFQ scores improved in both groups(P<0.01),with the TCM group showing superior improvement compared to the control group(P<0.05,P<0.01).Serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 decreased in both groups(P<0.05,P<0.01).Serum SPP1 levels were significantly decreased in the TCM group(P<0.01),and serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 in the TCM group were significantly lower than those in the con-trol group(P<0.01).The change in SPP1(ΔSPP1)showed a negative correlation with the change in the cardiac function ΔLVEF(r=-0.42,P<0.01),and a positive correlation with the myocardial fibrosis marker ΔCOL1α1(r=0.58,P<0.01)and the matrix degradation marker ΔMMP9(r=0.51,P<0.01).There was no significant difference in adverse reaction rates between the two groups during treat-ment(P>0.05).CONCLUSION Hongqi Shenmai Drink combined with GDMT can effectively improve clinical symptoms and cardiac function in patients with AMI-HF of qi-yin deficiency and blood stasis type,with good safety.Its mechanism may be related to the in-hibition of SPP1-mediated inflammation-fibrosis pathway and the downregulation of IL-1β,COL1α1,and MMP9 expression.

OBJECTIVE To study the therapeutic effect of Hongqi Shenmai Drink on heart failure(HF)after acute myocardial in-farction(AMI)with qi-yin deficiency and blood stasis,and its regulatory effect on serum secretory phosphoprotein 1(SPP1)in AMI-HF patients.METHODS Seventy-six patients with AMI-HF of qi-yin deficiency and blood stasis type were enrolled in this study from three centers:Affiliated Hospital of Integrated Traditional and Western Medicine,Nanjing University of Chinese Medicine;Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine;and Changzhou Hospital of Traditional Chinese Medicine.They were randomly di-vided into a traditional Chinese medicine(TCM)group and a control group,with 38 patients in each group.During the treatment period,4 patients in the TCM group and 3 patients in the control group dropped out.The control group received conventional Guideline-directed medical therapy(GDMT),while the TCM group received GDMT plus Hongqi Shenmai Drink.The treatment course for both groups was 12 weeks.The TCM syndrome scores of the two groups of patients were compared before and after treatment,and the clini-cal efficacy and readmission rate were assessed.Echocardiography was used to assess cardiac structure and function.ELISA was used to detect changes in serum SPP1,N-terminal pro-brain natriuretic peptide(NT-proBNP),interleukin-1β(IL-1β),type Ⅰ collagen α1(COL1α1),and matrix metalloproteinase 9(MMP9)levels.The 6-minute walk test(6MWT)was used to assess exercise tolerance,and the Minnesota living with heart failure questionnaire(MLHFQ)was used to assess patients'quality of life.Adverse reactions were monitored in both groups during treatment.RESULTS After treatment,the TCM syndrome scores of both groups decreased signifi-cantly(P<0.01),with the TCM group showing a significantly lower score than the control group(P<0.01).The total effective rate of TCM clinical efficacy in the TCM group was superior to that in the control group(P<0.05),and the readmission rate in the TCM group was significantly lower than that in the control group(P<0.01).Left ventricular end diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF),6MWT,and MLHFQ scores improved in both groups(P<0.01),with the TCM group showing superior improvement compared to the control group(P<0.05,P<0.01).Serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 decreased in both groups(P<0.05,P<0.01).Serum SPP1 levels were significantly decreased in the TCM group(P<0.01),and serum levels of NT-proBNP,IL-1β,COL1α1,and MMP9 in the TCM group were significantly lower than those in the con-trol group(P<0.01).The change in SPP1(ΔSPP1)showed a negative correlation with the change in the cardiac function ΔLVEF(r=-0.42,P<0.01),and a positive correlation with the myocardial fibrosis marker ΔCOL1α1(r=0.58,P<0.01)and the matrix degradation marker ΔMMP9(r=0.51,P<0.01).There was no significant difference in adverse reaction rates between the two groups during treat-ment(P>0.05).CONCLUSION Hongqi Shenmai Drink combined with GDMT can effectively improve clinical symptoms and cardiac function in patients with AMI-HF of qi-yin deficiency and blood stasis type,with good safety.Its mechanism may be related to the in-hibition of SPP1-mediated inflammation-fibrosis pathway and the downregulation of IL-1β,COL1α1,and MMP9 expression.

Objective To explore the role of icariin on diabetic osteoporosis(DOP)in rats by regulating estrogen reoeptor 1(ER1).Methods Fifty SD rats were randomly divided into five groups:control,diabetes(STZ),low-dose icariin[four weeks after successful establishment of diabetic model rats,50 mg/(kg·d)icariin was administered by gavage for eight weeks],high-dose icariin[100 mg/(kg·d)icariin administered by gavage for eight weeks],and high-dose icariin+ER1-siRNA group[icariin 100 mg/(kg·d)administered by gavage for eight weeks.A total of 10 μL ER1-siRNA was injected via the tail vein once every four weeks,two times in total],with 10 rats in each group.HE staining was used to detect the pathological morphology of the femoral tissue.Enzyme-linked immunosorbent assay(ELISA)was used to measure serum ALP,TRAP,and blood calcium concentrations.Protein-protein interaction(PPI)network analysis predicted icariin core targets and validated molecular docking.ER1,PDE5A,Wnt,and β-cantenin expression levels in rat femoral tissue were detected using Western blotting.Results In the STZ group,the number of empty lacunae in the subchondral region increased,ALP expression and blood calcium concentration decreased(P＜0.01),and TRAP expression increased(P＜0.01),compared with the control group.In the low-and high-dose icariin groups,blood glucose levels decreased(P＜0.01),the number of empty bone lacunae in the subchondral region decreased,ALP expression and blood calcium concentration increased(P＜0.01),and TRAP expression decreased(P＜0.01),compared with the STZ group.PPI network analysis and molecular docking showed that icariin stably bound to the ER1 protein structure.Com-pared with the control group,expression of ER1,Wnt,and β-cantenin decreased in STZ group(P＜0.01).The expression of ER1,Wnt,and β-cantenin in the high-dose icariin group increased compared with the STZ group(P＜0.01).Moreover,expression of ER 1,Wnt,andβ-cantenin decreased in the high-dose icariin+ER1-siRNA group,compared with the high-dose icariin group(P＜0.01).The protective effects of icariin were reversed by ER1-siRNA administration.Conclusion Icariin could significantly improve osteoporosis in diabetes rats,which may be relevant to the activation of the ER 1-mediated Wnt/β-cantenin pathway.