Objective To investigate the effect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ferroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control,low-oxygen intervention,and Jiawei Ditan Decoction intervention groups using the random number table method,with 10 rats per group.The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling,with 8 h of intervention daily.Gavage administration was performed before and after daily intervention.The intervention group received a dosage of 16.38 g/kg Jiawei Ditan Decoction,whereas the other two groups received normal saline.The experimental intervention period was 12 weeks.Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue.Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes.Biochemical detection was used to measure the Fe2+and malondialdehyde(MDA)content in myocardial tissue.Phosphorylated-phosphoinositide 3-kinase(p-PI3K),PI3K,phosphorylated-protein kinase B(p-Akt),Akt,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and acyl-coenzyme A synthetase long-chain family member 4(ACSL4)protein expression in myocardial tissue were measured using western blotting.The rat cardiomyocyte cell line,H9c2,was cultured in high glucose Dulbecco's Modified Eagle Medium,and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction.The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction.The cells were divided into the normoxic,erastin,and erastin+Jiawei Ditan Decoction intervention groups,and p-Akt and GPX4 protein expression was measured using western blotting.p-PI3K and GPX4 protein expression were detected in the normoxic,low-oxygen intervention 12 h,and low-oxygen intervention 12 h+740Y-P groups.The p-PI3K,PI3K,p-Akt,Akt,and GPX4 protein expression was detected in the normoxic,low-oxygen intervention 6 h,low-oxygen intervention 12 h,low-oxygen intervention 12 h+Jiawei Ditan Decoction low-dose,low-oxygen intervention 12 h+Jiawei Ditan Decoction medium-dose,and low-oxygen intervention 12 h+Jiawei Ditan Decoction high-dose groups(drug concentrations of 5,10,and 20 g/L,respectively).Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered,with increased mitochondrial membrane density,ruptured cristae,and vacudar degeneration compared with those in the normal control group.The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater,and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group,and no apparent swelling was observed.Compared with the normal control group,the low-oxygen intervention group showed an increase in the MDA and Fe2+content,a decrease in the p-PI3K/PI3K and p-Akt/Akt values,decreased SLC7A11,GPX4,and Nrf2 expression,and increased ACSL4 expression(P＜0.05).Compared with the low-oxygen intervention group,the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+content,an increase in the p-PI3K/PI3K and p-Akt/Akt values,increased SLC7A11,GPX4,and Nrf2 expression,and decreased ACSL4 expression(P＜0.05).Jiawei Ditan Decoction contained DL-stachydrine,D-(+)-malicacid,adenosine,etc.The cell survival rate of the 10.00 g/L group increased(P＜0.05)compared to that of the Jiawei Ditan Decoction 0,1.25,2.50,5.00,and 20.00 g/L groups.Compared with the normoxic group,p-Akt and GPX4 expression decreased in the erastin group(P＜0.05);compared with the erastin group,the erastin+Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression(P＜0.05).Compared with the normoxic group,p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group(P＜0.01);compared with the low-oxygen intervention 12 h group,the low-oxygen intervention 12 h+740Y-P group showed increased p-PI3K and GPX4 expression(P＜0.05).Compared with the normoxic group,GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups(P＜0.05);compared with the low-oxygen intervention 6 h and 12 h groups,the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h+Jiawei Ditan Decoction low,medium,and high-dose groups(P＜0.05).GPX4 expression was also increased(P＜0.05).Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ferroptosis in rats by regulating the PI3K/Akt signaling pathway,thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats.

Objective To investigate the effect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ferroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control,low-oxygen intervention,and Jiawei Ditan Decoction intervention groups using the random number table method,with 10 rats per group.The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling,with 8 h of intervention daily.Gavage administration was performed before and after daily intervention.The intervention group received a dosage of 16.38 g/kg Jiawei Ditan Decoction,whereas the other two groups received normal saline.The experimental intervention period was 12 weeks.Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue.Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes.Biochemical detection was used to measure the Fe2+and malondialdehyde(MDA)content in myocardial tissue.Phosphorylated-phosphoinositide 3-kinase(p-PI3K),PI3K,phosphorylated-protein kinase B(p-Akt),Akt,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and acyl-coenzyme A synthetase long-chain family member 4(ACSL4)protein expression in myocardial tissue were measured using western blotting.The rat cardiomyocyte cell line,H9c2,was cultured in high glucose Dulbecco's Modified Eagle Medium,and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction.The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction.The cells were divided into the normoxic,erastin,and erastin+Jiawei Ditan Decoction intervention groups,and p-Akt and GPX4 protein expression was measured using western blotting.p-PI3K and GPX4 protein expression were detected in the normoxic,low-oxygen intervention 12 h,and low-oxygen intervention 12 h+740Y-P groups.The p-PI3K,PI3K,p-Akt,Akt,and GPX4 protein expression was detected in the normoxic,low-oxygen intervention 6 h,low-oxygen intervention 12 h,low-oxygen intervention 12 h+Jiawei Ditan Decoction low-dose,low-oxygen intervention 12 h+Jiawei Ditan Decoction medium-dose,and low-oxygen intervention 12 h+Jiawei Ditan Decoction high-dose groups(drug concentrations of 5,10,and 20 g/L,respectively).Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered,with increased mitochondrial membrane density,ruptured cristae,and vacudar degeneration compared with those in the normal control group.The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater,and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group,and no apparent swelling was observed.Compared with the normal control group,the low-oxygen intervention group showed an increase in the MDA and Fe2+content,a decrease in the p-PI3K/PI3K and p-Akt/Akt values,decreased SLC7A11,GPX4,and Nrf2 expression,and increased ACSL4 expression(P＜0.05).Compared with the low-oxygen intervention group,the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+content,an increase in the p-PI3K/PI3K and p-Akt/Akt values,increased SLC7A11,GPX4,and Nrf2 expression,and decreased ACSL4 expression(P＜0.05).Jiawei Ditan Decoction contained DL-stachydrine,D-(+)-malicacid,adenosine,etc.The cell survival rate of the 10.00 g/L group increased(P＜0.05)compared to that of the Jiawei Ditan Decoction 0,1.25,2.50,5.00,and 20.00 g/L groups.Compared with the normoxic group,p-Akt and GPX4 expression decreased in the erastin group(P＜0.05);compared with the erastin group,the erastin+Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression(P＜0.05).Compared with the normoxic group,p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group(P＜0.01);compared with the low-oxygen intervention 12 h group,the low-oxygen intervention 12 h+740Y-P group showed increased p-PI3K and GPX4 expression(P＜0.05).Compared with the normoxic group,GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups(P＜0.05);compared with the low-oxygen intervention 6 h and 12 h groups,the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h+Jiawei Ditan Decoction low,medium,and high-dose groups(P＜0.05).GPX4 expression was also increased(P＜0.05).Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ferroptosis in rats by regulating the PI3K/Akt signaling pathway,thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats.

Objective To investigate the effect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ferroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control,low-oxygen intervention,and Jiawei Ditan Decoction intervention groups using the random number table method,with 10 rats per group.The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling,with 8 h of intervention daily.Gavage administration was performed before and after daily intervention.The intervention group received a dosage of 16.38 g/kg Jiawei Ditan Decoction,whereas the other two groups received normal saline.The experimental intervention period was 12 weeks.Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue.Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes.Biochemical detection was used to measure the Fe2+and malondialdehyde(MDA)content in myocardial tissue.Phosphorylated-phosphoinositide 3-kinase(p-PI3K),PI3K,phosphorylated-protein kinase B(p-Akt),Akt,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and acyl-coenzyme A synthetase long-chain family member 4(ACSL4)protein expression in myocardial tissue were measured using western blotting.The rat cardiomyocyte cell line,H9c2,was cultured in high glucose Dulbecco's Modified Eagle Medium,and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction.The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction.The cells were divided into the normoxic,erastin,and erastin+Jiawei Ditan Decoction intervention groups,and p-Akt and GPX4 protein expression was measured using western blotting.p-PI3K and GPX4 protein expression were detected in the normoxic,low-oxygen intervention 12 h,and low-oxygen intervention 12 h+740Y-P groups.The p-PI3K,PI3K,p-Akt,Akt,and GPX4 protein expression was detected in the normoxic,low-oxygen intervention 6 h,low-oxygen intervention 12 h,low-oxygen intervention 12 h+Jiawei Ditan Decoction low-dose,low-oxygen intervention 12 h+Jiawei Ditan Decoction medium-dose,and low-oxygen intervention 12 h+Jiawei Ditan Decoction high-dose groups(drug concentrations of 5,10,and 20 g/L,respectively).Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered,with increased mitochondrial membrane density,ruptured cristae,and vacudar degeneration compared with those in the normal control group.The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater,and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group,and no apparent swelling was observed.Compared with the normal control group,the low-oxygen intervention group showed an increase in the MDA and Fe2+content,a decrease in the p-PI3K/PI3K and p-Akt/Akt values,decreased SLC7A11,GPX4,and Nrf2 expression,and increased ACSL4 expression(P＜0.05).Compared with the low-oxygen intervention group,the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+content,an increase in the p-PI3K/PI3K and p-Akt/Akt values,increased SLC7A11,GPX4,and Nrf2 expression,and decreased ACSL4 expression(P＜0.05).Jiawei Ditan Decoction contained DL-stachydrine,D-(+)-malicacid,adenosine,etc.The cell survival rate of the 10.00 g/L group increased(P＜0.05)compared to that of the Jiawei Ditan Decoction 0,1.25,2.50,5.00,and 20.00 g/L groups.Compared with the normoxic group,p-Akt and GPX4 expression decreased in the erastin group(P＜0.05);compared with the erastin group,the erastin+Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression(P＜0.05).Compared with the normoxic group,p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group(P＜0.01);compared with the low-oxygen intervention 12 h group,the low-oxygen intervention 12 h+740Y-P group showed increased p-PI3K and GPX4 expression(P＜0.05).Compared with the normoxic group,GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups(P＜0.05);compared with the low-oxygen intervention 6 h and 12 h groups,the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h+Jiawei Ditan Decoction low,medium,and high-dose groups(P＜0.05).GPX4 expression was also increased(P＜0.05).Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ferroptosis in rats by regulating the PI3K/Akt signaling pathway,thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats.

Objective To investigate the effect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ferroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control,low-oxygen intervention,and Jiawei Ditan Decoction intervention groups using the random number table method,with 10 rats per group.The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling,with 8 h of intervention daily.Gavage administration was performed before and after daily intervention.The intervention group received a dosage of 16.38 g/kg Jiawei Ditan Decoction,whereas the other two groups received normal saline.The experimental intervention period was 12 weeks.Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue.Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes.Biochemical detection was used to measure the Fe2+and malondialdehyde(MDA)content in myocardial tissue.Phosphorylated-phosphoinositide 3-kinase(p-PI3K),PI3K,phosphorylated-protein kinase B(p-Akt),Akt,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and acyl-coenzyme A synthetase long-chain family member 4(ACSL4)protein expression in myocardial tissue were measured using western blotting.The rat cardiomyocyte cell line,H9c2,was cultured in high glucose Dulbecco's Modified Eagle Medium,and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction.The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction.The cells were divided into the normoxic,erastin,and erastin+Jiawei Ditan Decoction intervention groups,and p-Akt and GPX4 protein expression was measured using western blotting.p-PI3K and GPX4 protein expression were detected in the normoxic,low-oxygen intervention 12 h,and low-oxygen intervention 12 h+740Y-P groups.The p-PI3K,PI3K,p-Akt,Akt,and GPX4 protein expression was detected in the normoxic,low-oxygen intervention 6 h,low-oxygen intervention 12 h,low-oxygen intervention 12 h+Jiawei Ditan Decoction low-dose,low-oxygen intervention 12 h+Jiawei Ditan Decoction medium-dose,and low-oxygen intervention 12 h+Jiawei Ditan Decoction high-dose groups(drug concentrations of 5,10,and 20 g/L,respectively).Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered,with increased mitochondrial membrane density,ruptured cristae,and vacudar degeneration compared with those in the normal control group.The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater,and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group,and no apparent swelling was observed.Compared with the normal control group,the low-oxygen intervention group showed an increase in the MDA and Fe2+content,a decrease in the p-PI3K/PI3K and p-Akt/Akt values,decreased SLC7A11,GPX4,and Nrf2 expression,and increased ACSL4 expression(P＜0.05).Compared with the low-oxygen intervention group,the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+content,an increase in the p-PI3K/PI3K and p-Akt/Akt values,increased SLC7A11,GPX4,and Nrf2 expression,and decreased ACSL4 expression(P＜0.05).Jiawei Ditan Decoction contained DL-stachydrine,D-(+)-malicacid,adenosine,etc.The cell survival rate of the 10.00 g/L group increased(P＜0.05)compared to that of the Jiawei Ditan Decoction 0,1.25,2.50,5.00,and 20.00 g/L groups.Compared with the normoxic group,p-Akt and GPX4 expression decreased in the erastin group(P＜0.05);compared with the erastin group,the erastin+Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression(P＜0.05).Compared with the normoxic group,p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group(P＜0.01);compared with the low-oxygen intervention 12 h group,the low-oxygen intervention 12 h+740Y-P group showed increased p-PI3K and GPX4 expression(P＜0.05).Compared with the normoxic group,GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups(P＜0.05);compared with the low-oxygen intervention 6 h and 12 h groups,the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h+Jiawei Ditan Decoction low,medium,and high-dose groups(P＜0.05).GPX4 expression was also increased(P＜0.05).Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ferroptosis in rats by regulating the PI3K/Akt signaling pathway,thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats.

Objective To investigate the effect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ferroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control,low-oxygen intervention,and Jiawei Ditan Decoction intervention groups using the random number table method,with 10 rats per group.The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling,with 8 h of intervention daily.Gavage administration was performed before and after daily intervention.The intervention group received a dosage of 16.38 g/kg Jiawei Ditan Decoction,whereas the other two groups received normal saline.The experimental intervention period was 12 weeks.Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue.Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes.Biochemical detection was used to measure the Fe2+and malondialdehyde(MDA)content in myocardial tissue.Phosphorylated-phosphoinositide 3-kinase(p-PI3K),PI3K,phosphorylated-protein kinase B(p-Akt),Akt,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and acyl-coenzyme A synthetase long-chain family member 4(ACSL4)protein expression in myocardial tissue were measured using western blotting.The rat cardiomyocyte cell line,H9c2,was cultured in high glucose Dulbecco's Modified Eagle Medium,and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction.The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction.The cells were divided into the normoxic,erastin,and erastin+Jiawei Ditan Decoction intervention groups,and p-Akt and GPX4 protein expression was measured using western blotting.p-PI3K and GPX4 protein expression were detected in the normoxic,low-oxygen intervention 12 h,and low-oxygen intervention 12 h+740Y-P groups.The p-PI3K,PI3K,p-Akt,Akt,and GPX4 protein expression was detected in the normoxic,low-oxygen intervention 6 h,low-oxygen intervention 12 h,low-oxygen intervention 12 h+Jiawei Ditan Decoction low-dose,low-oxygen intervention 12 h+Jiawei Ditan Decoction medium-dose,and low-oxygen intervention 12 h+Jiawei Ditan Decoction high-dose groups(drug concentrations of 5,10,and 20 g/L,respectively).Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered,with increased mitochondrial membrane density,ruptured cristae,and vacudar degeneration compared with those in the normal control group.The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater,and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group,and no apparent swelling was observed.Compared with the normal control group,the low-oxygen intervention group showed an increase in the MDA and Fe2+content,a decrease in the p-PI3K/PI3K and p-Akt/Akt values,decreased SLC7A11,GPX4,and Nrf2 expression,and increased ACSL4 expression(P＜0.05).Compared with the low-oxygen intervention group,the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+content,an increase in the p-PI3K/PI3K and p-Akt/Akt values,increased SLC7A11,GPX4,and Nrf2 expression,and decreased ACSL4 expression(P＜0.05).Jiawei Ditan Decoction contained DL-stachydrine,D-(+)-malicacid,adenosine,etc.The cell survival rate of the 10.00 g/L group increased(P＜0.05)compared to that of the Jiawei Ditan Decoction 0,1.25,2.50,5.00,and 20.00 g/L groups.Compared with the normoxic group,p-Akt and GPX4 expression decreased in the erastin group(P＜0.05);compared with the erastin group,the erastin+Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression(P＜0.05).Compared with the normoxic group,p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group(P＜0.01);compared with the low-oxygen intervention 12 h group,the low-oxygen intervention 12 h+740Y-P group showed increased p-PI3K and GPX4 expression(P＜0.05).Compared with the normoxic group,GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups(P＜0.05);compared with the low-oxygen intervention 6 h and 12 h groups,the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h+Jiawei Ditan Decoction low,medium,and high-dose groups(P＜0.05).GPX4 expression was also increased(P＜0.05).Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ferroptosis in rats by regulating the PI3K/Akt signaling pathway,thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats.

Objective To investigate the effect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ferroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control,low-oxygen intervention,and Jiawei Ditan Decoction intervention groups using the random number table method,with 10 rats per group.The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling,with 8 h of intervention daily.Gavage administration was performed before and after daily intervention.The intervention group received a dosage of 16.38 g/kg Jiawei Ditan Decoction,whereas the other two groups received normal saline.The experimental intervention period was 12 weeks.Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue.Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes.Biochemical detection was used to measure the Fe2+and malondialdehyde(MDA)content in myocardial tissue.Phosphorylated-phosphoinositide 3-kinase(p-PI3K),PI3K,phosphorylated-protein kinase B(p-Akt),Akt,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and acyl-coenzyme A synthetase long-chain family member 4(ACSL4)protein expression in myocardial tissue were measured using western blotting.The rat cardiomyocyte cell line,H9c2,was cultured in high glucose Dulbecco's Modified Eagle Medium,and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction.The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction.The cells were divided into the normoxic,erastin,and erastin+Jiawei Ditan Decoction intervention groups,and p-Akt and GPX4 protein expression was measured using western blotting.p-PI3K and GPX4 protein expression were detected in the normoxic,low-oxygen intervention 12 h,and low-oxygen intervention 12 h+740Y-P groups.The p-PI3K,PI3K,p-Akt,Akt,and GPX4 protein expression was detected in the normoxic,low-oxygen intervention 6 h,low-oxygen intervention 12 h,low-oxygen intervention 12 h+Jiawei Ditan Decoction low-dose,low-oxygen intervention 12 h+Jiawei Ditan Decoction medium-dose,and low-oxygen intervention 12 h+Jiawei Ditan Decoction high-dose groups(drug concentrations of 5,10,and 20 g/L,respectively).Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered,with increased mitochondrial membrane density,ruptured cristae,and vacudar degeneration compared with those in the normal control group.The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater,and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group,and no apparent swelling was observed.Compared with the normal control group,the low-oxygen intervention group showed an increase in the MDA and Fe2+content,a decrease in the p-PI3K/PI3K and p-Akt/Akt values,decreased SLC7A11,GPX4,and Nrf2 expression,and increased ACSL4 expression(P＜0.05).Compared with the low-oxygen intervention group,the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+content,an increase in the p-PI3K/PI3K and p-Akt/Akt values,increased SLC7A11,GPX4,and Nrf2 expression,and decreased ACSL4 expression(P＜0.05).Jiawei Ditan Decoction contained DL-stachydrine,D-(+)-malicacid,adenosine,etc.The cell survival rate of the 10.00 g/L group increased(P＜0.05)compared to that of the Jiawei Ditan Decoction 0,1.25,2.50,5.00,and 20.00 g/L groups.Compared with the normoxic group,p-Akt and GPX4 expression decreased in the erastin group(P＜0.05);compared with the erastin group,the erastin+Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression(P＜0.05).Compared with the normoxic group,p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group(P＜0.01);compared with the low-oxygen intervention 12 h group,the low-oxygen intervention 12 h+740Y-P group showed increased p-PI3K and GPX4 expression(P＜0.05).Compared with the normoxic group,GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups(P＜0.05);compared with the low-oxygen intervention 6 h and 12 h groups,the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h+Jiawei Ditan Decoction low,medium,and high-dose groups(P＜0.05).GPX4 expression was also increased(P＜0.05).Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ferroptosis in rats by regulating the PI3K/Akt signaling pathway,thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats.

Objective To investigate the effect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ferroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control,low-oxygen intervention,and Jiawei Ditan Decoction intervention groups using the random number table method,with 10 rats per group.The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling,with 8 h of intervention daily.Gavage administration was performed before and after daily intervention.The intervention group received a dosage of 16.38 g/kg Jiawei Ditan Decoction,whereas the other two groups received normal saline.The experimental intervention period was 12 weeks.Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue.Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes.Biochemical detection was used to measure the Fe2+and malondialdehyde(MDA)content in myocardial tissue.Phosphorylated-phosphoinositide 3-kinase(p-PI3K),PI3K,phosphorylated-protein kinase B(p-Akt),Akt,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and acyl-coenzyme A synthetase long-chain family member 4(ACSL4)protein expression in myocardial tissue were measured using western blotting.The rat cardiomyocyte cell line,H9c2,was cultured in high glucose Dulbecco's Modified Eagle Medium,and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction.The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction.The cells were divided into the normoxic,erastin,and erastin+Jiawei Ditan Decoction intervention groups,and p-Akt and GPX4 protein expression was measured using western blotting.p-PI3K and GPX4 protein expression were detected in the normoxic,low-oxygen intervention 12 h,and low-oxygen intervention 12 h+740Y-P groups.The p-PI3K,PI3K,p-Akt,Akt,and GPX4 protein expression was detected in the normoxic,low-oxygen intervention 6 h,low-oxygen intervention 12 h,low-oxygen intervention 12 h+Jiawei Ditan Decoction low-dose,low-oxygen intervention 12 h+Jiawei Ditan Decoction medium-dose,and low-oxygen intervention 12 h+Jiawei Ditan Decoction high-dose groups(drug concentrations of 5,10,and 20 g/L,respectively).Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered,with increased mitochondrial membrane density,ruptured cristae,and vacudar degeneration compared with those in the normal control group.The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater,and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group,and no apparent swelling was observed.Compared with the normal control group,the low-oxygen intervention group showed an increase in the MDA and Fe2+content,a decrease in the p-PI3K/PI3K and p-Akt/Akt values,decreased SLC7A11,GPX4,and Nrf2 expression,and increased ACSL4 expression(P＜0.05).Compared with the low-oxygen intervention group,the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+content,an increase in the p-PI3K/PI3K and p-Akt/Akt values,increased SLC7A11,GPX4,and Nrf2 expression,and decreased ACSL4 expression(P＜0.05).Jiawei Ditan Decoction contained DL-stachydrine,D-(+)-malicacid,adenosine,etc.The cell survival rate of the 10.00 g/L group increased(P＜0.05)compared to that of the Jiawei Ditan Decoction 0,1.25,2.50,5.00,and 20.00 g/L groups.Compared with the normoxic group,p-Akt and GPX4 expression decreased in the erastin group(P＜0.05);compared with the erastin group,the erastin+Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression(P＜0.05).Compared with the normoxic group,p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group(P＜0.01);compared with the low-oxygen intervention 12 h group,the low-oxygen intervention 12 h+740Y-P group showed increased p-PI3K and GPX4 expression(P＜0.05).Compared with the normoxic group,GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups(P＜0.05);compared with the low-oxygen intervention 6 h and 12 h groups,the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h+Jiawei Ditan Decoction low,medium,and high-dose groups(P＜0.05).GPX4 expression was also increased(P＜0.05).Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ferroptosis in rats by regulating the PI3K/Akt signaling pathway,thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats.

Objective To investigate the effect and mechanism of Jiawei Ditan Decoction on cardiomyocyte ferroptosis in rats with chronic intermittent hypoxia based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)signaling pathway.Methods Thirty 8-week-old male Sprague-Dawley rats were randomly divided into normal control,low-oxygen intervention,and Jiawei Ditan Decoction intervention groups using the random number table method,with 10 rats per group.The low-oxygen and Jiawei Ditan Decoction intervention groups were treated with intermittent hypoxia chamber for modeling,with 8 h of intervention daily.Gavage administration was performed before and after daily intervention.The intervention group received a dosage of 16.38 g/kg Jiawei Ditan Decoction,whereas the other two groups received normal saline.The experimental intervention period was 12 weeks.Hematoxylin and eosin staining was used to observe the morphology of myocardial tissue.Transmission electron microscope was used to observe the mitochondrial ultrastructure in cardiomyocytes.Biochemical detection was used to measure the Fe2+and malondialdehyde(MDA)content in myocardial tissue.Phosphorylated-phosphoinositide 3-kinase(p-PI3K),PI3K,phosphorylated-protein kinase B(p-Akt),Akt,solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),nuclear factor erythroid 2-related factor 2(Nrf2),and acyl-coenzyme A synthetase long-chain family member 4(ACSL4)protein expression in myocardial tissue were measured using western blotting.The rat cardiomyocyte cell line,H9c2,was cultured in high glucose Dulbecco's Modified Eagle Medium,and the ultra-high-performance liquid chromatography was used to detect drug components in Jiawei Ditan Decoction.The CCK-8 assay was used to detect the cell survival rate of cells treated with different concentrations of Jiawei Ditan Decoction.The cells were divided into the normoxic,erastin,and erastin+Jiawei Ditan Decoction intervention groups,and p-Akt and GPX4 protein expression was measured using western blotting.p-PI3K and GPX4 protein expression were detected in the normoxic,low-oxygen intervention 12 h,and low-oxygen intervention 12 h+740Y-P groups.The p-PI3K,PI3K,p-Akt,Akt,and GPX4 protein expression was detected in the normoxic,low-oxygen intervention 6 h,low-oxygen intervention 12 h,low-oxygen intervention 12 h+Jiawei Ditan Decoction low-dose,low-oxygen intervention 12 h+Jiawei Ditan Decoction medium-dose,and low-oxygen intervention 12 h+Jiawei Ditan Decoction high-dose groups(drug concentrations of 5,10,and 20 g/L,respectively).Results The myocardial cells in the low-oxygen intervention group were disordered and swollen and the mitochondrial arrangement of myocardial cells was disordered,with increased mitochondrial membrane density,ruptured cristae,and vacudar degeneration compared with those in the normal control group.The myocardial cells in the Jiawei Ditan Decoction intervention group were arranged neater,and the morphology of mitochondria was relatively regular than those in the low-oxygen intervention group,and no apparent swelling was observed.Compared with the normal control group,the low-oxygen intervention group showed an increase in the MDA and Fe2+content,a decrease in the p-PI3K/PI3K and p-Akt/Akt values,decreased SLC7A11,GPX4,and Nrf2 expression,and increased ACSL4 expression(P＜0.05).Compared with the low-oxygen intervention group,the Jiawei Ditan Decoction intervention group showed a decrease in MDA and Fe2+content,an increase in the p-PI3K/PI3K and p-Akt/Akt values,increased SLC7A11,GPX4,and Nrf2 expression,and decreased ACSL4 expression(P＜0.05).Jiawei Ditan Decoction contained DL-stachydrine,D-(+)-malicacid,adenosine,etc.The cell survival rate of the 10.00 g/L group increased(P＜0.05)compared to that of the Jiawei Ditan Decoction 0,1.25,2.50,5.00,and 20.00 g/L groups.Compared with the normoxic group,p-Akt and GPX4 expression decreased in the erastin group(P＜0.05);compared with the erastin group,the erastin+Jiawei Ditan Decoction intervention group showed increased p-Akt and GPX4 expression(P＜0.05).Compared with the normoxic group,p-PI3K and GPX4 expression decreased in the low-oxygen intervention 12 h group(P＜0.01);compared with the low-oxygen intervention 12 h group,the low-oxygen intervention 12 h+740Y-P group showed increased p-PI3K and GPX4 expression(P＜0.05).Compared with the normoxic group,GPX4 expression and the p-Akt/Akt and p-PI3K/PI3K were reduced in the low-oxygen intervention 6 and 12 h groups(P＜0.05);compared with the low-oxygen intervention 6 h and 12 h groups,the p-PI3K/PI3K and p-Akt/Akt values increased in the low-oxygen intervention 12 h+Jiawei Ditan Decoction low,medium,and high-dose groups(P＜0.05).GPX4 expression was also increased(P＜0.05).Conclusion Jiawei Ditan Decoction may improve cardiomyocyte ferroptosis in rats by regulating the PI3K/Akt signaling pathway,thereby playing a protective role against chronic intermittent hypoxia-induced cardiac injury in rats.

Objective To investigate the effects and mechanism of modified Ditan Decoction in regulating miR-149 on liver injury in rats with chronic intermittent hypoxia.Methods Totally 18 male SD rats were randomly divided into control group,model group,and modified Ditan Decoction,with 6 rats in each group.The model group and the modified Ditan Decoction group were modeled in a low oxygen chamber.During the modeling period,the modified Ditan Decoction group was given gavage of the modified Ditan Decoction for 12 consecutive weeks.HE staining was used to observe the pathological changes of liver tissue;the ultrastructural changes of liver tissue were observed by transmission electron microscopy,TUNEL staining was used to observe hepatocyte apoptosis,the contents of ALT,AST,SOD and MDA in liver tissue were detected,the mRNA and protein expression of miR-149,ATF6,GRP78 and CHOP in liver tissue were detected by RT-qPCR and Western blot.The correlation between the mRNA transcription levels of miR-149 and ATF6 was analyzed.Results Compared with the control group,a small amount of inflammatory cell infiltration in liver tissue of the model group,with irregular arrangement of liver cells,varying degrees of edema,expansion of endoplasmic reticulum,ribosome shedding,mitochondrial membrane rupture,and apoptosis rate of liver cells increased(P<0.05),the contents of ALT,AST and MDA significantly increased(P<0.05),while the content of SOD significantly decreased(P<0.05),the expression of miR-149 mRNA in liver tissue decreased(P<0.05),while the mRNA and protein expression of ATF6,GRP78 and CHOP increased(P<0.05).Compared with the model group,no obvious edema or inflammatory cell infiltration was observed in liver tissue of rats in the modified Ditan Decoction group,the liver cells were arranged in a regular manner,with slightly expanded endoplasmic reticulum and more uniform distribution of ribosomes,the mitochondrial membrane was relatively intact,and the apoptosis rate of liver cells decreased(P<0.05),the contents of ALT,AST and MDA decreased(P<0.05),while the content of SOD increased(P<0.05),the expression of miR-149 mRNA in liver tissue significantly increased(P<0.05),while the mRNA and protein expression of ATF6,GRP78 and CHOP significantly decreased(P<0.05).The level of miR-149 mRNA was significantly negatively correlated with that of ATF6 mRNA(r=-0.766).Conclusion Modified Ditan Decoction may inhibit liver oxidative stress response in chronic intermittent hypoxia rats and improve liver injury by regulating the miR-149/ATF6 pathway.

Objective:To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin′s lymphoma (R/R cHL).Methods:Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children′s Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded.Results:In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment.Conclusion:Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin′s lymphoma in children.