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 To explore the effect of Sanshen Shuxin Decoction combined with Huan-gqi Injection in the treatment of coronary heart disease(CHD)and its impacts on left ventricular function and Rho kinase(ROCK)expression.Methods A total of 120 CHD patients admitted to our hospital from August 2021 to August 2023 were selected as study subjects and randomly divided into three groups,with 40 patients in each group using a random number table method.All three groups received basic treatment.On this basis,control group 1 received Sanshen Shuxin Decoction,control group 2 received Huangqi Injection,and the combined group received both Sanshen Shuxin Decoction and Huangqi Injection.The treatment effects,occurrence of angina pectoris,hemorheo-logical parameters[fibrinogen(FIB),low-shear blood viscosity,erythrocyte aggregation index,high-shear blood viscosity],blood lipid indicators[total cholesterol(TG),triglycerides(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C)],car-diac function[stroke volume(SV),cardiac output(CO),left ventricular ejection fraction(LVEF)],ROCK activity,and occurrence of adverse reactions were compared among the three groups.Results The total effective rate of treatment in the combined group was higher than that in control group 1 and control group 2(P＜0.05).After 14 days of treatment,the frequency of angina pectoris episodes decreased and the duration of episodes shortened in all three groups compared with before treatment,and the combined group had a lower frequency and shorter duration of angina pec-toris episodes than control group 1 and control group 2(P＜0.05).There were no statistically sig-nificant differences in the frequency and duration of angina pectoris episodes between control group 1 and control group 2 after 14 days of treatment(P＞0.05).After 14 days of treatment,FIB level,e-rythrocyte aggregation index,low-shear blood viscosity,and high-shear blood viscosity decreased in all three groups compared with before treatment,and the combined group had lower values than con-trol group 1 and control group 2(P＜0.05).There were no statistically significant differences in these hemorheological parameters between control group 1 and control group 2 after 14 days of treat-ment(P＞0.05).After 14 days of treatment,TG,TC,and LDL-C levels decreased in all three groups compared with before treatment,and the combined group had lower levels than control group 1 and control group 2.HDL-C levels increased in all three groups compared with before treatment,and the combined group had higher HDL-C level than control group 1 and control group 2(P＜0.05).There were no statistically significant differences in TG,TC,LDL-C,and HDL-C levels be-tween control group 1 and control group 2 after 14 days of treatment(P＞0.05).After 14 days of treatment,LVEF,CO,and SV increased in all three groups compared with before treatment,and the combined group had higher values than control group 1 and control group 2(P＜0.05).There were no statistically significant differences in LVEF,CO,and SV between control group 1 and con-trol group 2 after 14 days of treatment(P＞0.05).Before treatment,ROCK activity was(61.28±7.15)％in the combined group,(60.85±5.93)％in control group 1,and(60.61±6.27)％in control group 2,with no statistically significant difference among the three groups(P＞0.05).After 14 days of treatment,ROCK activity decreased in all three groups compared with before treatment,and the combined group had lower ROCK activity than control group 1 and control group 2(P＜0.05).ROCK activity was(40.18±5.03)％in the combined group,(48.24±6.29)％in con-trol group 1,and(47.79±6.12)％in control group 2 after 14 days of treatment.There was no sta-tistically significant difference in ROCK activity between control group 1 and control group 2 after 14 days of treatment(P＞0.05).There was no statistically significant difference in the incidence of adverse reactions among the three groups(P＞0.05).Conclusion Sanshen Shuxin Decoction combined with Huangqi Injection has a significant effect in the treatment of CHD patients.It can im-prove patients'prognosis and ensure treatment safety,demonstrating high clinical value.

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.

OBJECTIVES: To investigate the clinical application of the digital-assisted reconstruction of the mandible and tumors with free fibula transplantation and immediate implantation via the intraoral approach. METHODS: Twelve patients with benign mandibular tumors were collected. Three-dimensional mandibular reconstruction was performed digitally before surgery to simulate mandibular tumor resection, fibula resection and reconstruction, and implant implantation. The intraoperative resection of the mandibular tumor was conducted through the intraoral approach under the guidance of a guide plate, and fibula resection, molding, reconstruction, and oral fixation were immediately performed. Implant implantation was performed during the second phase of implant surgery and denture restoration was performed 1-2 months after surgery. RESULTS: The types of mandibular defects were BrownⅠ (one case), Ⅰc (four cases), Ⅱ (one case), Ⅱc(three cases), and Ⅲ (three cases). The length of the fibular bone was 12-22 cm. The number of fibular molding amputations was as follows: two cases in two segments, six cases in three segments, three cases in four segments, and one case in five segments. All of these cases underwent folding fibular reconstruction of mandibular and alveolar bone defects. A total of 44 implants were implanted, and none failed after operation. CONCLUSIONS The intraoral approach is a reliable method for the resection of mandibular benign tumors, with few postoperative complications and the ability to position and fix accurately the reconstructed folded fibula under digital design. The immediate implantation of the transplanted fibula does not affect the blood supply and has a high success rate. It is an effective and reliable method for the resection and reconstruction of mandibular benign tumors.
Humans ; Fibula/transplantation* ; Mandibular Neoplasms/surgery* ; Mandibular Reconstruction/methods* ; Bone Transplantation/methods* ; Male ; Middle Aged ; Female ; Mandible/surgery* ; Adult ; Free Tissue Flaps ; Surgery, Computer-Assisted

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.

The placenta is a regulator of maternal-fetal circulation，regulating nutrient and waste exchange，endocrine function，and immune response. The placental vascular structure is the basis of the placental exchange function and the key to maternal-fetal circulation. Placental vascular changes may affect fetal growth and cardiovascular development，and even the origin of postnatal health and disease. The placenta is crucial in fetal growth and development and future health，but our understanding of placental vascular structure is still insufficient. This article reviews the imaging methods and progress of placental imaging，focusing on the placental microvascular imaging technology，which aims to provide a method reference for prenatal evaluation and monitoring of placental vascular structure by realizing the visualization of placental vascular structure. Based on this new technology，it is expected to provide new ideas for the study of the hemodynamic mechanisms of fetal growth and cardiovascular development in the future.

Metagenomic next-generation sequencing, as an unbiased detection technology, demonstrates higher diagnostic efficacy than traditional methods. Gut microorganisms are important flora for safeguarding health and have become a hot research topic. Modeling and analyzing the genomic data of intestinal flora using machine learning is very important in disease prediction and diagnosis. This paper briefly introduces the characteristics of metagenomic next-generation sequencing, key algorithms and evaluation indexes of machine learning, outlines the main steps of combining machine learning with metagenomic next-generation sequencing, and summarizes the application of the combination of machine learning and metagenomic next-generation sequencing technology in the study of intestinal flora, which will provide a more accurate method for diagnosis and prediction of the related diseases, and give more ideas for the future research and clinical practice.

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.