Objective: To analyze the change trends in the body shape indicators and proportions of students in Harbin from 2010 to 2024, and to investigate ergonomic compatibility of functional dimensions of school desks and chairs with current student shape indicators, so as to provide a reference for revising furniture standards of desks and chairs. Methods: Between September and November of both 2010 and 2024, a combination of convenience sampling and stratified cluster random sampling was conducted across three districts in Harbin, yielding samples of 6 590 and 6 252 students, respectively. Anthropometric shape indicators cluding height, sitting height, crus length, and thigh length-and their proportional changes were compared over the 15-year period. The 2024 data were compared with current standard functional dimensions of school furniture. The statistical analysis incorporated t-test and Mann-Whitney U- test. Results: From 2010 to 2024, average height increased by 1.8 cm for boys and 1.5 cm for girls; sitting height increased by 1.5 cm for both genders; crus length increased by 0.3 cm for boys and 0.4 cm for girls; and thigh length increased by 0.5 cm for both genders. The ratios of sitting height to height, and sitting height to leg length increased by less than 0.1 . The difference between desk chair height and 1/3 sitting height ranged from 0.4-0.8 cm. Among students matched with size 0 desks and chairs, 22.0% had a desk to chair height difference less than 0, indicating that the desk to chair height difference might be insufficient for taller students. The differences between seat height and fibular height ranged from -1.4 to 1.1 cm; and the differences between seat depth and buttock popliteal length ranged from -9.8 to 3.4 cm. Among obese students, the differences between seat width and 1/2 hip circumference ranged from -20.5 to -8.7 cm, while it ranged from -12.2 to -3.8 cm among non obese students. Conclusion Current furniture standards basically satisfy hygienic requirements; however, in the case of exceptionally tall and obese students, ergonomic accommodations such as adaptive seating allocation or personalized adjustments are recommended to meet hygienic requirements.

Objective To investigate the role of mitochondrial transcription factor A (TFAM) in platinum-resistant ovarian cancer cells and its effects on metabolic reprogramming and sensitivity to platinum-based drugs Methods The mitochondrial function and metabolic characteristics of platinum-resistant ovarian cancer cells were analyzed. A TFAM-overexpressing cell model was established to assess its effects on platinum sensitivity, mitochondrial function, and aerobic glycolysis; and glycolytic enzyme and drug-resistant protein expression were analyzed. Results Platinum-resistant ovarian cancer cells exhibited considerable mitochondrial dysfunction (reduced oxygen consumption rate) and enhanced aerobic glycolysis (increased extracellular acidification rate, glucose uptake, and lactate production). TFAM was downregulated in resistant cells. Meanwhile, TFAM overexpression significantly enhanced platinum sensitivity (P<0.01), restored mitochondrial function, and inhibited aerobic glycolysis. The expression levels of glycolytic enzymes and drug-resistant proteins were also downregulated (P<0.05). Conclusion TFAM downregulation is associated with suppressed oxidative phosphorylation and enhanced aerobic glycolysis in platinum-resistant ovarian cancer cells. TFAM overexpression can restore cellular dependence on oxidative phosphorylation and increase platinum sensitivity, suggesting that TFAM is a potential therapeutic target for reversing platinum resistance.

AIM: To investigate timing of glucocorticoids use in the treatment of syphilitic uveitis.METHODS: A retrospective study was conducted in 110 patients(134 eyes)with syphilitic uveitis diagnosed from January 2008 to January 2021, of whom 24 were binocular. The time from onset to treatment was 1 d to 3 mo. They were divided into three groups according to the treatment, including 98 eyes with completed clearely fundus lesions and no abnormalities in fundus fluorescein angiography(FFA)+ indocyanine green angiography(ICGA)+ optical coherence tomography(OCT)after treated with antibiotics alone for 1 to 2 wk in single antibiotics group, 26 eyes with in completely cleared fundus lesions and retinal vessels wall staining observed by FFA or choroidal weak fluorescence observed by ICGA after standard antisyphilitic treatments for 1 to 2 wk in first antibiotics followed by hormones group, and 10 eyes treated according to uveitis at other hospital in the absence of a clear cause of disease, that was intravenously dripped with 250 mL of normal saline and 10 mg of dexamethasone once a day for 7 to 10 d in total, then clearly diagnosed as syphilitic uveitis by Treponema pallidum particle agglutination(TPPA)test after receiving treatment for 10 to 14 d in hormones followed by antibiotics group. The best corrected visual acuity, slit-lamp examination, fundus photography, OCT, FFA, ICGA and prognosis of the three groups of patients were compared.RESULTS: There were statistically significant difference in the best corrected visual acuity, optic disc, retinal vasculitis, choroidal weak fluorescence, and RPR titer before and after treatment of the three groups of patients. The prognosis of the hormones followed by antibiotics group was lower than that in the single antibiotics group and antibiotics followed by hormones group, and the proportion of “good” prognosis in the antibiotics followed by hormones group was larger than that in other groups.CONCLUSION: Early diagnosis and regular treatment of syphilitic uveitis has a good overall prognosis, and giving large doses of glucocorticoids before thorough antisyphilitic treatments is not conducive to the recovery of disease. In patients with residual lesions after standard antisyphilitic, the application of small doses of glucocorticoids is helpful for the recovery of the disease.

Chronic cough is one of the common complications after pulmonary nodule surgery. Its etiology and pathogenesis are complex， and syndrome differentiation and treatment in traditional Chinese medicine （TCM） require comprehensive consideration of the distinct characteristics across the preoperative， intraoperative， and postoperative phases. Prior to surgery， there may be healthy qi depletion with lingering pathogens in the lungs； during surgery， metal instruments may injure the body， leading to qi and blood damage； after surgery， the depletion of healthy qi worsens， with dual deficiency of lung and spleen qi and yin as the root condition， often complicated by pathogens such as wind， phlegm， stagnation， and stasis. Treatment should follow the principle of comprehensively considering all three phases with a focus on the postoperative phase. Replenishing deficiency is the primary， particularly by tonifying qi and nourishing yin， as well as supplementing the lung and fortifying the spleen. For different accompanying syndromes， therapeutic methods such as dispelling wind， resolving phlegm， relieving stagnation， and unblocking stasis should be applied accordingly， while aggressive purgative herbs should be used with caution to avoid depletion of qi and blood injury.

Cells and exosomes derived from them are extensively used as biological carrier systems. Cells demonstrate superior targeting specificity and prolonged circulation facilitated by their rich array of surface proteins, while exosomes, due to their small size, cross barriers and penetrate tumors efficiently. However, challenges remain, cells' large size restricts tissue penetration, and exosomes have limited targeting accuracy and short circulation times. To address these challenges, we developed a novel concept termed exosomal spheres. This approach involved incorporating platelet-derived exosomes shielded with phosphatidylserine (PS) and linked via pH-sensitive bonds for drug delivery applications. The study demonstrated that, compared with exosomes, the exosomal spheres improved blood circulation through the upregulation of CD47 expression and shielding of phosphatidylserine, thereby minimizing immune clearance. Moreover, the increased expression of P-selectin promoted adhesion to circulating tumor cells, thereby enhancing targeting efficiency. Upon reaching the tumor site, the hydrazone bonds of exosome spheres were protonated in the acidic tumor microenvironment, leading to disintegration into uniform-sized exosomes capable of deeper tumor penetration compared to platelets. These findings suggested that exosome spheres addressed the challenges and offered significant potential for efficient and precise drug delivery.

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 of Huangqi-Ezhu-Chonglou combination on macrophage polarization and its mechanism of inhibiting colorectal cancer(CRC)cells proliferation and migration.METHODS THP-1 cells were stimulated with phorbol 12-myristate 13-acetate(PMA)and interleukin-4(IL-4)to establish M2 macrophage polarization model.The experiment was divided into M0 group(PMA treatment),M2 group(PMA+IL-4 treatment),and M2+ Huangqi-Ezhu-Chonglou combination group(PMA+IL-4+Huangqi-Ezhu-Chonglou combination treatment).The effect of Huangqi-Ezhu-Chonglou combination freeze-dried powder on the viability of macrophage was detected by CCK-8 method.The expression of macrophage polarization markers,glu-taminase(GLS)mRNA and protein was detected by qPCR and Western blot.The levels of interleukin-10(IL-10),transforming growth factor-β(TGF-β)and tumor necrosis factor-α(TNF-α)in cell supernatant were detected by ELISA.CCK-8 method and Tr-answell assays were used to detect the proliferation and migration of HCT116 cells intervened by the supernatant of macrophage culture treated with Huangqi-Ezhu-Chonglou combination,namely conditioned medium(CM).RESULTS Compared with the M0 group,the expression levels of IL-10,mannose receptor(CD206),arginase 1(ARG1),and GLS mRNA and protein in the M2 group were significantly increased(P<0.01,P<0.001),the levels of IL-10 and TGF-β secreted by macrophages were significantly increased(P<0.01,P<0.001);compared with the M2 group,the M2+ Huangqi-Ezhu-Chonglou combination group had significantly reduced IL-10,CD206,ARG1,and GLS mRNA and protein expression(P<0.05,P<0.01),the mRNA and protein levels of TNF-α and in-ducible nitric oxide synthase(iNOS)were significantly increased(P<0.05,P<0.01,P<0.001),the interleukin-1β(Interleukin-1β,IL-1β)mRNA expression significantly increased(P<0.01),and the contents of IL-10 and TGF-β in the cell supernatant sig-nificantly decreased(P<0.05,P<0.01),while TNF-α content significantly increased(P<0.01).CCK-8 and Transwell results showed that compared with the M0-CM group,the M2-CM promoted the proliferation and migration of HCT116 cells(P<0.01,P<0.001),the M2+ Huangqi-Ezhu-Chonglou-CM group significantly inhibited HCT116 cell proliferation and reduced cell migration compared to the M2-CM group(P<0.01,P<0.001).CONCLUSION Huangqi-Ezhu-Chonglou combination can inhibit colorectal cancer cells proliferation and migration by regulating macrophage polarization,and its mechanism may be related to the changes in the expression of GLS,a key enzyme in glutamine metabolism.

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.