ObjectiveTo investigate the effect of icariin （ICA） on steroid-induced ferroptosis in bone microvascular endothelial cells （BMECs）. MethodsRat BMECs were selected and treated with 500 mg·L^-1 hydrocortisone for 1.5 h to establish a ferroptosis model of BMECs. The experimental cells were divided into a blank group， hormone group （500 mg·L^-1 hydrocortisone）， ICA group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA）， and ferroptosis agonist group （500 mg·L^-1 hydrocortisone + 34 mg·L^-1 ICA + 2.7 mg·L^-1 erastin）. Cell viability was detected by CCK-8. The levels of ferrous ion， glutathione （GSH）， malondialdehyde （MDA）， superoxide dismutase （SOD）， and reactive oxygen species （ROS） were detected by related kit species. The ferroptosis-related proteins， such as glutathione peroxidase 4（GPX4）， ferritin light chain （FTL）， and transferrin receptor protein1 （sTfR） were detected by Western blot， as well as autophagy-related proteins including microtubule-associated protein 1 light chain 3B （LC3B）， Beclin1， B-cell lymphoma-2 （Bcl-2）， and Caspase-3. Results500 mg·L^-1 hydrocortisone intervention for 1.5 h could effectively induce ferroptosis in BMECs， and ferroptosis levels could reach a peak as the intervention continued. In terms of cellular antioxidant capacity， compared with those in the blank group， the cell vitality， GSH in the hormone group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions were significantly increased （P<0.01）. Compared with those in the hormone group， the cell viability， GSH were significantly increased， and the levels of ROS， SOD， MDA， and ferrous ions were decreased in the ICA group （P<0.01）. Compared with those in the ICA group， the cell vitality， GSH in the ferroptosis agonist group decreased significantly， and the levels of ROS， SOD， MDA， and ferrous ions increased significantly （P<0.01）. In terms of the relationship between ferroptosis and autophagy， compared with the blank group， the hormone group had significantly increased expression levels of LC3B， sTfR， Beclin1， and FTL and significantly decreased expression levels of GPX4 （P<0.01）. Compared with the hormone group， The ICA group had significantly decreased expression levels of LC3B， sTfR， and FTL and significantly increased expression levels of Beclin 1 and GPX4 （P<0.01）. Compared with those in the ICA group， the expression levels of LC3B， sTfR， and FTL increased in the rapamycin group， and those of Beclin 1 and GPX4 decreased （P<0.01）. In terms of cell ferroptosis and apoptosis，compared with the blank group， the hormone group had significantly increased expression levels of FTL， sTfR and Caspase-3 and significantly decreased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with the hormone group， the ICA group had significantly decreased expression levels of FTL， sTfR and Caspase-3 and significantly increased expression levels of GPX4， and Bcl-2 （P<0.01）. Compared with those in the ICA group， the expression levels of FTL， sTfR and Caspase-3 in the ferroptosis agonist group were increased， and the expression levels of GPX4， and Bcl-2 were decreased （P<0.01）. In terms of cell function，compared with that in the blank group， the ability of cell migration and tube formation was significantly decreased in the hormone group （P<0.01）. Compared with that in the hormone group， the cell migration and tube formation ability in the ICA group were significantly increased （P<0.01）. ConclusionFerroptosis is involved in steroid-induced damage in BMECs. ICA can inhibit steroid-induced ferroptosis in BMECs， and the mechanism may be associated with the inhibition of ferroptosis by regulating autophagy.

Steroid-induced osteonecrosis of the femoral head （SONFH） is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells， necrosis， and trabecular fractures， SONFH is accompanied by pain， femoral head collapse， and joint dysfunction， which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis， bone microvascular endothelial cell （BMEC） apoptosis， oxidative stress， and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation， thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts， promoting angiogenesis in BMECs， and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine （TCM） has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway， as well as its regulatory effects on osteoblasts， mesenchymal stem cells， osteoclasts， BMECs， and other cells. Additionally， the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings， this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM， it is expected to bring safer and more effective treatment options for patients with SONFH.

Objective The morphological and data characteristics of premature ventricular contraction(PVC)were obtained through dynamic electrocardiogram(DCG),and its correlation with new-onset major adverse cardiovascular events(MACE)was analyzed.Methods A total of 115 patients with PVC admitted to Huzhou First People's Hospital from January 2022 to January 2024 were retrospectively selected and divided into MACE group(n=31)and non-MACE group(n=84)according to the new-onset MACE.Collect the baseline data of patients,as well as DCG data such as the morphological and data characteristics of PVC.Collect the baseline data of patients,as well as DCG data such as the morphological and data characteristics of PVC.Multivariate Logistic regression was used to analyze the influencing factors of new-onset MACE in patients with PVC.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of influencing factors for the risk of new-onset MACE in patients with PVC.Results There were statistically significant differences in gender,disease duration,QRS wave duration,PVC origin,PVC load,and Lown classification between two groups of patients(P＜0.05).Multivariate Logistic regression analysis showed that QRS wave duration(OR=1.070),PVC origin(OR=6.840)and PVC load(OR=2.583)were independent risk factors for new-onset MACE in PVC patients(P＜0.05).The ROC curve showed that the area under the curve for predicting new-onset MACE in PVC patients with QRS wave duration,PVC origin,and PVC load were 0.791,0.750,and 0.917 respectively.The predictive value of PVC load was the highest.Conclusion QRS wave duration,PVC origin and PVC load are related to new-onset MACE in PVC patients,and PVC load has a good predictive effect on the risk of new-onset MACE in PVC patients.

Objective:To investigate the differential effects of proton FLASH irradiation and conventional dose rate (CONV) irradiation on human normal liver cells WRL68 and human hepatocellular carcinoma cells HepG2.Methods:Using a 100 MeV high-current proton cyclotron accelerator, WRL68 and HepG2 cells were subjected to CONV (0.8 Gy/min) and FLASH (40 Gy/s) irradiation with 4 Gy protons. After irradiation, changes in cell proliferation, apoptosis, and cell cycle arrest were detected at different time points. Additionally, transcriptome sequencing was employed to analyze alterations in the gene expression profiles of the two cell lines.Results:For WRL68 cells, compared with CONV irradiation, proton FLASH irradiation enhanced cell proliferative activity ( t=10.18-16.67, P<0.05), reduced the apoptotic rate ( t=3.21-8.30, P<0.05), and decreased the proportion of cells arrested in the G 2 phase at the same time points ( t=34.08-65.16, P<0.05). In contrast, for HepG2 cells, proton FLASH irradiation significantly inhibited cell proliferation ( t=2.57-9.39, P<0.05), increased the apoptotic rate ( t=3.25-66.70, P<0.05), and similarly induced cell cycle arrest predominantly in the G 2 phase ( t=10.87-27.47, P<0.05). Transcriptome sequencing identified 906 differentially expressed genes (DEGs) between the FLASH group and the CONV group in WRL68 cells, and 1 243 DEGs were detected in HepG2 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs suggested that cellular adhesion and oxygen effect may serve as crucial microscopic mechanisms underlying FLASH radiotherapy. Conclusions:Under proton FLASH irradiation, the radiation-induced damage to human normal liver cells was significantly alleviated, whereas the damage to hepatocellular carcinoma cells was aggravated. The identified DEGs are involved in multiple radiobiological functional pathways.

Objective To observe the clinical and echocardiographic manifestations of Williams syndrome(WS).Methods Two children with WS were retrospectively enrolled,and 21 cases of WS in literature were reviewed,and clinical and echocardiographic manifestations of WS were observed.Results Clinical manifestations of 23 cases including 21 cases of"elf"face,8 cases of intellectual disability,7 cases of developmental delay,7 cases of inguinal hernia,6 cases of hypothyroidism,4 cases of hypercalcemia,3 cases of urinary system abnormalities(1 case of hydrocele,1 case of ureteral dilation and tortuosity,and 1 case of kidney stones),2 cases of behavioral abnormalities,2 cases of feeding difficulties,1 case of congenital hypertrophic pyloric stenosis,1 case of binocular esotropia,1 case of hyperbilirubinemia,and 1 case of corpus callosum dysplasia.Echocardiography showed cardiovascular malformations in all 23 cases,including 20 cases of supravalvular aortic stenosis(SVAS),18 cases of pulmonary artery stenosis(PAS)and 10 cases of other cardiovascular malformations.Conclusion WS presented multiple system abnormalities in clinic,and cardiovascular malformations,especially SVAS and PAS could often be detected with echocardiography.

Objective To investigate the expression and clinical significance of serum cystatin SA(Cystatin SA)and long non-coding RNA(lncRNA)promoter of CDKN1A antisense DNA damage activated RNA(PANDAR)in patients with type 2 dia-betic kidney disease(T2DN).Method A total of 142 patients with type 2 diabetes mellitus(T2DM)admitted to Shanghai Jiao Tong University School of Medicine Suzhou Jiulong Hospital from February 2021 to October 2023 were selected.According to whether they had nephropathy,they were divided into T2DN group(n=82)and non-T2DN group(n=60).60 healthy people who underwent physical examination during the same period were used as the control group.Serum Cystatin SA levels were detected by enzyme-linked immunosorbent assay(ELISA).Serum lncRNA PANDAR level was detected by real-time fluorescence quanti-tative PCR.Pearson correlation analysis was used to analyze the correlation between serum Cystatin SA,lncRNA PANDAR and clinical parameters in T2DN patients.Logistic regression analysis was used to analyze the influencing factors of T2 DN.The re-ceiver operating characteristic(ROC)curve was used to analyze the value of serum Cystatin SA and lncRNA PANDAR in the evaluation of T2DN.Results Serum Cystatin SA(236.28±44.63 ng/L)and serum lncRNA PANDAR(3.21±0.34)in the T2DM group were higher than those in the control group(91.25±22.33 ng/L,1.06±0.23),and the differences were statistically significant(t=23.127,42.379,all P<0.001).Serum Cystatin SA(275.08±46.83 ng/L)and lncRNA PANDAR(3.64±0.38)in T2DN group were higher than those in non-T2DN group(183.25±40.88 ng/L,2.62±0.30),and the differences were statistically significant(t=12.169,17.226,all P<0.001).Serum Cystatin SA and lncRNA PANDAR in T2DN patients were positively correlat-ed with diabetes duration,serum creatinine(sCr),blood urea nitrogen(BUN)and UACR(r=0.562～0.750,all P<0.001),and neg-atively correlated with eGFR(r=-0.656,-0.634,all P<0.001).Serum Cystatin SA,lncRNA PANDAR,duration of diabetes,UACR,sCr were risk factors for T2DN,eGFR was a protective factor(Wald χ2=4.257～12.360,all P<0.001).The area under the curve(AUC)of serum Cystatin SA combined with lncRNA PANDAR in predicting T2DN was 0.920(0.899～0.960),which was greater than that of single index[0.847(0.791～0.887),0.851(0.803～0.896)],and the differences were statistically significant(Z=4.522,4.319,all P<0.05).Conclusion Serum Cystatin SA and lncRNA PANDAR are elevated in patients with T2DN,which are related to renal function indexes and are risk factors affecting the occurrence of T2DN.The combination of the two can effec-tively evaluate the occurrence of T2DN.

Objective To analyze the procurement data of lipid-lowering drugs in hospitals at different levels in Jiangsu Province from October 2019 to September 2023,to evaluate the impact of the volume-based procurement(VBP)policy,and to provide references for clinical rational drug use and healthcare policy optimization.Methods Based on procurement data from the Jiangsu Provincial Health Information Center,statistical analyses of procurement expenditures,defined daily doses(DDDs),and defined daily cost(DDC)were conducted.Mixed-effects models were applied to assess changes in procurement expenditures,DDDs,and DDC before and after VBP implementation.Results From 2019 to 2023,statins dominated the market in Jiangsu Province,with rosuvastatin recording the highest DDDs(748 million).Statins,traditional Chinese medicines,and cholesterol absorption inhibitors ranked highest in procurement expenditures.Tertiary hospitals accounted for the largest share of usage(47.6%)and expenditures(55.8%),while secondary hospitals had the lowest DDC(1.22 yuan)and tertiary hospitals the highest(1.89 yuan).Post-VBP,procurement expenditures and DDC decreased by 53.9%and 35.4%,respectively.Primary hospitals showed the largest expenditure reduction(61.6%),and secondary hospitals exhibited the greatest DDC decline(53.9%).DDDs increased significantly in primary care settings(e.g.,pitavastatin surged by 239.79%in secondary hospitals),while tertiary hospitals saw reduced usage of some drugs(e.g.,amlodipine/atorvastatin decreased by 7.34%).Mixed-effects models confirmed that VBP significantly reduced expenditures(OR=-1.07,P<0.01)and DDC(OR=-2.70,P<0.01)while indirectly lowering prices of non-VBP drugs.After covariate adjustment,expenditure reductions for rosuvastatin and atorvastatin narrowed,ezetimibe expenditures increased(OR=0.13,P<0.01),and pitavastatin usage declined(OR=-0.10,P<0.01).Changes in amlodipine/atorvastatin and ezetimibe lacked statistical significance due to short VBP implementation periods.Tertiary hospitals demonstrated the strictest policy adherence,with the largest expenditure and DDC reductions(P<0.01).Subgroup analysis revealed that the policy did not significantly affect clinical demand(DDDs)in hospitals at different levels,though it was considered to have triggered adjustments in medication structure.Conclusion Jiangsu's lipid-lowering drug structure aligns with guidelines(statin-based,moderate-intensity preference).VBP effectively reduced costs,with tertiary hospitals prioritizing originator-to-generic substitution and primary hospitals reflecting cost-control and demand variations.Confounding factors influenced policy evaluation.The study recommends continuous monitoring and policy optimization to enhance procurement efficiency,ensure rational clinical use,and sustain cost savings,providing insights for further healthcare reform.

Objective To investigate the effect of Scutellarin(Scu)regulating miR-26a-3p/Survivin molecular axis on myocardial ischemia/reperfusion injury(MIRI)in rats and its mechanism.Methods Fifty SD rats were randomly divided into sham group,model group,scutellarin group(Scu),miR-26a-3p agomir group(agomir)and scutellarin+miR-26a-3p agomir group(Scu+agomir)with 10 rats in each group.The animal model of MIRI was established by ligating the anterior descending coronary artery.The rats in each group were given 20 mg/kg Scu or 10 nmol agomir before and during operation,respectively,and the rats in sham group and model group were given the same amount of solvent.At 48 h after operation,the cardiac function of rats was examined by echocardiography.The pathological changes of myocardial tissue were detected by HE staining.The levels of myocardial injury markers creatine kinase isoenzyme MB(CK-MB),lactate dehydrogenase(LDH)and cardiac troponin I(cTnI)in serum and the contents of oxidative markers Malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in myocardial tissue were detected by biochemical kit.The apoptosis of rat cardiomyocytes was detected by TUNEL staining.The mRNA expression levels of miR-26a-3p and Survivin in rat myocardium were detected by qRT-PCR.Expression levels of Survivin,cyclin-dependent kinase inhibitor(p21)and cleaved-caspase 3 were detected by Western blot.Results Compared with sham group,the pathological damage of myocardial tissue in the model group was serious,the levels of cardiac function LVEDP and serum CK-MB,LDH and cTnI significantly increased(P<0.01),and the levels of LVESP,LVEF and LVFS significantly decreased(P<0.01).The apoptosis level and MDA level of myocardial tissue significantly increased(P<0.01),while the SOD and GSH-Px levels significantly decreased(P<0.01).Meanwhile,the expression levels of miR-26a-3p and cleaved-caspase 3 protein significantly increased(P<0.01),the p21 protein and Survivin mRNA and protein expression levels significantly decreased(P<0.01).Compared with model group,the pathological injury of myocardium in Scu group was significantly improved,the levels of cardiac function LVEDP and serum CK-MB,LDH and cTnI significantly decreased(P<0.01),and the levels of LVESP,LVEF and LVFS significantly increased(P<0.01).The apoptosis level and MDA level of myocardial tissue significantly decreased(P<0.01),while the SOD and GSH-Px levels significantly increased(P<0.01).Meanwhile,the expression levels of miR-26a-3p and cleaved-caspase 3 protein significantly decreased(P<0.01),the p21 protein and Survivin mRNA and protein expression levels significantly increased(P<0.01).However,intervention with miR-26a-3p agomir could significantly reverse the improvement effect of Scu on MIRI in rats.Conclusion Scu can improve cardiac function and myocardial injury and inhibit myocardial cell apoptosis in MIRI rats,and its mechanism may be related to the regulation of miR-26a-3p/Survivin molecular axis.

Objective To investigate the therapeutic efficacy of Zhi Long Huoxue Tongyu Capsules combined with Edaravone in the treatment of patients with ischemic cerebrovascular disease(ICVD)of qi deficiency and blood stasis syndrome,and to explore their effect on serum levels of soluble cluster of differentiation 40 ligand(sCD40L),lipoprotein phospholipase A2(Lp-PLA2),and glycated albumin(GA).Methods A total of 117 patients with ICVD of qi deficiency and blood stasis syndrome were randomly divided into control group 1,control group 2,and study group,with 39 patients in each group.The three groups were all given basic treatment with agents of diuretic,lipid regulation,antiplatelet,and antihypertensive,and additionally,control group 1 was given Edaravone,control group 2 was given Zhi Long Huoxue Tongyu Capsules,and the study group was given Zhi Long Huoxue Tongyu Capsules combined with Edaravone.The course of treatment for the three groups covered 14 days.Before and after treatment,the three groups were observed in the changes of National Institutes of Health Stroke Scale(NIHSS)scores for neurological function,modified Barthel Index(MBI)scores for activities of daily living(ADL),cerebral hemodynamics indicators[peak systolic velocity(PSV),end-diastolic velocity(EDV),mean velocity(Vm),pulsatility index(PI),and resistance index(RI)],neurofactors[neuron-specific enolase(NSE),S100β protein(S100β),and myelin basic protein(MBP)],vascular endothelial function indicators[von Willebrand factor(VWF),endothelin 1(ET-1),and nitric oxide(NO)],and levels of serum sCD40L,Lp-PLA2,and GA.After treatment,the clinical efficacy and the incidence of adverse reactions among the three groups of patients were compared.Results(1)After 14 days of treatment,the total effective rate of the study group was 94.87%(37/39),which was significantly higher than that of control group 1[71.79%(28/39)]and control group 2[76.92%(30/39)],the differences being statistically significant(P<0.05).No statistically significant difference was shown between control group 1 and control group 2(P>0.05).(2)After treatment,the cerebral hemodynamics indicators of PSV,EDV,Vm,and PI of the middle cerebral artery(MCA)in the three groups were increased compared with those before treatment(P<0.05),and the RI was decreased compared with that before treatment(P<0.05).The increase of PSV,EDV,Vm,and PI of the MCA and the decrease of RI in the study group were significantly superior to those in control group 1 and control group 2(P<0.05).No statistically significant differences in PSV,EDV,Vm,PI,and RI of MCA were shown between control group 1 and control group 2 after treatment(P>0.05).(3)After treatment,the serum sCD40L,Lp-PLA2,and GA levels in the three groups were decreased compared with those before treatment(P<0.05),and the decrease in the study group was significantly superior to that in control group 1 and control group 2(P<0.05).However,the differences of the serum levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(4)After treatment,the serum levels of neurofactors of NSE,S100β,and MBP in the three groups were all decreased compared with those before treatment(P<0.05),and the decrease of the serum levels in the study group was significantly superior to that in control group 1 and control group 2,while the differences of the serum levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(5)After treatment,the vascular endothelial function indicators of serum vWF and ET-1 levels in the three groups were decreased compared with those before treatment(P<0.05),and the serum NO level was increased compared with that before treatment(P<0.05).The decrease of serum vWF and ET-1 levels and the increase of serum NO level in the study group were significantly superior to those in control group-1 and control group-2(P<0.05),while the difference of serum vWF,ET-1 and NO levels after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(6)After treatment,the NIHSS scores for neurological function in the three groups were decreased(P<0.05)and the MBI scores for ADL were increased(P<0.05)compared with those before treatment,and the decrease of the NIHSS scores and the increase of the MBI scores in the study group was significantly superior to those in control group 1 and control group 2(P<0.05),while and the differences of NIHSS and MBI scores after treatment between control group 1 and control group 2 were not statistically significant(P>0.05).(7)The incidence rate of adverse reactions was 15.38%(6/39)in the study group,7.69%(3/39)in the control group 1,and 12.82%(5/39)in the control group 2,and the pairwise comparison between groups showed that the difference was not statistically significant(P>0.05).Conclusion Zhi Long Huoxue Tongyu Capsules combined with Edaravone exert certain efficacy in the treatment of patients with ICVD of qi deficiency and blood stasis syndrome,and the combined therapy is effective on improving blood circulation,restoring neurological function,enhancing the ADL,with higher safety.Its therapeutic mechanism may be related to the improvement of the vascular endothelial function,and the down-regulation of serum levels of neurofactors of NSE,S100 β,MBP,and serum expression levels of sCD40L,Lp-PLA2,and GA.

Objective The morphological and data characteristics of premature ventricular contraction(PVC)were obtained through dynamic electrocardiogram(DCG),and its correlation with new-onset major adverse cardiovascular events(MACE)was analyzed.Methods A total of 115 patients with PVC admitted to Huzhou First People's Hospital from January 2022 to January 2024 were retrospectively selected and divided into MACE group(n=31)and non-MACE group(n=84)according to the new-onset MACE.Collect the baseline data of patients,as well as DCG data such as the morphological and data characteristics of PVC.Collect the baseline data of patients,as well as DCG data such as the morphological and data characteristics of PVC.Multivariate Logistic regression was used to analyze the influencing factors of new-onset MACE in patients with PVC.The receiver operating characteristic(ROC)curve was drawn to analyze the predictive value of influencing factors for the risk of new-onset MACE in patients with PVC.Results There were statistically significant differences in gender,disease duration,QRS wave duration,PVC origin,PVC load,and Lown classification between two groups of patients(P＜0.05).Multivariate Logistic regression analysis showed that QRS wave duration(OR=1.070),PVC origin(OR=6.840)and PVC load(OR=2.583)were independent risk factors for new-onset MACE in PVC patients(P＜0.05).The ROC curve showed that the area under the curve for predicting new-onset MACE in PVC patients with QRS wave duration,PVC origin,and PVC load were 0.791,0.750,and 0.917 respectively.The predictive value of PVC load was the highest.Conclusion QRS wave duration,PVC origin and PVC load are related to new-onset MACE in PVC patients,and PVC load has a good predictive effect on the risk of new-onset MACE in PVC patients.