Ischemic stroke is a common cerebrovascular disease， characterized by hypoxia and nutritional deficiency in local brain tissue due to insufficient blood supply. Angiogenesis， the formation of new vascular networks on the basis of existing blood vessels， is of great significance for increasing blood flow in the ischemic area of brain tissue， restoring blood and oxygen supply， and improving disease prognosis. This complex process is regulated by various factors， including cytokines， growth factors， and signaling pathways. Among these， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is considered a key regulatory pathway. It not only plays an important role in anti-apoptosis and promoting cell survival， but also regulates cell growth， differentiation， migration， and survival， while deeply participating in the regulation of angiogenesis. Chinese medicine offers unique advantages with its multi-component， multi-target， and multi-pathway approach in the treatment of stroke， showing significant potential in treating ischemic stroke. In recent years， it has been found that Chinese medicine can promote angiogenesis after ischemic stroke through the PI3K/Akt signaling pathway. This paper focuses on the PI3K/Akt signaling pathway as the research entry point， and explores in-depth the mechanisms by which Chinese medicine monomers， active components， extracts， derivatives， drug pairs， and Chinese medicine compounds promote angiogenesis after ischemic stroke. The research discusses the regulation of microRNAs （miRNA）， endothelial progenitor cells （EPCs）， apoptosis， upstream pro-angiogenic factors， and downstream target molecules. The paper also elaborates on related research progress， aiming to reveal how Chinese medicine can exert its potential utility in ischemic stroke treatment through this key signaling pathway， providing a theoretical basis for clinical treatment.

Ischemic stroke is a common cerebrovascular disease， characterized by hypoxia and nutritional deficiency in local brain tissue due to insufficient blood supply. Angiogenesis， the formation of new vascular networks on the basis of existing blood vessels， is of great significance for increasing blood flow in the ischemic area of brain tissue， restoring blood and oxygen supply， and improving disease prognosis. This complex process is regulated by various factors， including cytokines， growth factors， and signaling pathways. Among these， the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is considered a key regulatory pathway. It not only plays an important role in anti-apoptosis and promoting cell survival， but also regulates cell growth， differentiation， migration， and survival， while deeply participating in the regulation of angiogenesis. Chinese medicine offers unique advantages with its multi-component， multi-target， and multi-pathway approach in the treatment of stroke， showing significant potential in treating ischemic stroke. In recent years， it has been found that Chinese medicine can promote angiogenesis after ischemic stroke through the PI3K/Akt signaling pathway. This paper focuses on the PI3K/Akt signaling pathway as the research entry point， and explores in-depth the mechanisms by which Chinese medicine monomers， active components， extracts， derivatives， drug pairs， and Chinese medicine compounds promote angiogenesis after ischemic stroke. The research discusses the regulation of microRNAs （miRNA）， endothelial progenitor cells （EPCs）， apoptosis， upstream pro-angiogenic factors， and downstream target molecules. The paper also elaborates on related research progress， aiming to reveal how Chinese medicine can exert its potential utility in ischemic stroke treatment through this key signaling pathway， providing a theoretical basis for clinical treatment.

Objective With considerion of aortic wall hyperelasticity and residual stress,to propose a numerical simulation method for predicting aortic blood pressure based on vascular compliance.Methods The residual stress solution method based on the closing opening angle was used to realize the analytical solution for the pressure-radius relationship of the idealized double-layered aortic wall model.The vascular compliance was calculated,and the pressure-radius relationship was applied to the moving boundary representing the motion of the aortic wall for numerical simulation,to obtain the relationship between vascular compliance and pulse pressure.The effects of with or without residual stress,hyperelasticity or linear elasticity constitutive relationships,as well as different ages on vascular compliance and aortic blood pressure were compared.The function of the stent graft was incorporated,by considering the stented region as a rigid wall,and the effects of different stent numbers and stent positions on aortic blood pressure were simulated.Results Vascular compliance with residual stress was higher than that without residual stress;correspondingly,when residual stress was considered,aortic pulse pressure was slightly lower than that without residual stress.Compared to the linear elastic model,the hyperelastic model predicted a smaller aortic pulse pressure value.The vascular compliance for different age groups showed 40-49 year-old＞60-69 year-old＞70 year-old and above;correspondingly,the pulse pressure for different age groups showed 40-49 year-old＜60-69 year-old＜70 year-old and above.When a stent with 60 mm length was implanted in the aorta,as the number of stents increasing,the aortic pulse pressure continued to rise,indicating that the wider the range of stent implantation,the higher the pulse pressure.The closer the stent implantation site was to the heart,the higher the pulse pressure.Conclusions The proposed simulation method in this study can accurately predict blood pressure and evaluate aortic compliance,providing theoretical and technical support for stent design and surgical plan optimization.

Objective To develop a quantitative method ology for assessing the aortic media damage induced by the stent-graft,and study the influence of various stent oversizing ratios(ORs)on damage of the aortic media.Methods Based on experimetal data from uniaxial tensile test on human aortic dissection,the material parameters of aortic wall's constitutive equation were determined,including damage parameters.A finite element model was constructed to simulate the deployment process of the stent-graft in blood vessel.Damage factor was determined to analyze the stress distribution and the result ant damage within aortic media at different ORs of the stent-graft.Results The distribution of damage factor and von Mises stress was basically consistent,with both peaking at the large curvature side near the aortic arch.Additionally,stress concentration was observed in distal anchoring region of the aortic wall.An increment in OR was correlated with a proportional increase in both peak values.At ORs of 10％,15％and 20％,the maimum von Mises stresses were 469,480 and 580 kPa,respectively,with increments of 2.3％and 20.8％.Correspondingly,the maximum damage factors were 0.01,0.011 and 0.014,with an elevation of 10％and 27.3％.Conclusions An increment in OR is associated with a pronounced increase in peak value of the damage factor and the rate of increase,indicating a more severe impact on the aortic media.The distribution of the damage factor aligns closely with that of the von Mises stress,with both exhibiting peak values at the large curvature side of aortic arch.This correlation underscores the damage factor's efficacy as a reliable indicator of the aortic media's integrity and can accurately reflect the degree of medial layer injury in the aortic wall,thereby providing a theoretical basis for the subsequent assessment of endovascular interventional treatment risks through damage factor analysis.

Objective To develop a quantitative method ology for assessing the aortic media damage induced by the stent-graft,and study the influence of various stent oversizing ratios(ORs)on damage of the aortic media.Methods Based on experimetal data from uniaxial tensile test on human aortic dissection,the material parameters of aortic wall's constitutive equation were determined,including damage parameters.A finite element model was constructed to simulate the deployment process of the stent-graft in blood vessel.Damage factor was determined to analyze the stress distribution and the result ant damage within aortic media at different ORs of the stent-graft.Results The distribution of damage factor and von Mises stress was basically consistent,with both peaking at the large curvature side near the aortic arch.Additionally,stress concentration was observed in distal anchoring region of the aortic wall.An increment in OR was correlated with a proportional increase in both peak values.At ORs of 10％,15％and 20％,the maimum von Mises stresses were 469,480 and 580 kPa,respectively,with increments of 2.3％and 20.8％.Correspondingly,the maximum damage factors were 0.01,0.011 and 0.014,with an elevation of 10％and 27.3％.Conclusions An increment in OR is associated with a pronounced increase in peak value of the damage factor and the rate of increase,indicating a more severe impact on the aortic media.The distribution of the damage factor aligns closely with that of the von Mises stress,with both exhibiting peak values at the large curvature side of aortic arch.This correlation underscores the damage factor's efficacy as a reliable indicator of the aortic media's integrity and can accurately reflect the degree of medial layer injury in the aortic wall,thereby providing a theoretical basis for the subsequent assessment of endovascular interventional treatment risks through damage factor analysis.

Objective With considerion of aortic wall hyperelasticity and residual stress,to propose a numerical simulation method for predicting aortic blood pressure based on vascular compliance.Methods The residual stress solution method based on the closing opening angle was used to realize the analytical solution for the pressure-radius relationship of the idealized double-layered aortic wall model.The vascular compliance was calculated,and the pressure-radius relationship was applied to the moving boundary representing the motion of the aortic wall for numerical simulation,to obtain the relationship between vascular compliance and pulse pressure.The effects of with or without residual stress,hyperelasticity or linear elasticity constitutive relationships,as well as different ages on vascular compliance and aortic blood pressure were compared.The function of the stent graft was incorporated,by considering the stented region as a rigid wall,and the effects of different stent numbers and stent positions on aortic blood pressure were simulated.Results Vascular compliance with residual stress was higher than that without residual stress;correspondingly,when residual stress was considered,aortic pulse pressure was slightly lower than that without residual stress.Compared to the linear elastic model,the hyperelastic model predicted a smaller aortic pulse pressure value.The vascular compliance for different age groups showed 40-49 year-old＞60-69 year-old＞70 year-old and above;correspondingly,the pulse pressure for different age groups showed 40-49 year-old＜60-69 year-old＜70 year-old and above.When a stent with 60 mm length was implanted in the aorta,as the number of stents increasing,the aortic pulse pressure continued to rise,indicating that the wider the range of stent implantation,the higher the pulse pressure.The closer the stent implantation site was to the heart,the higher the pulse pressure.Conclusions The proposed simulation method in this study can accurately predict blood pressure and evaluate aortic compliance,providing theoretical and technical support for stent design and surgical plan optimization.

Microglia efferocytosis,the process by which microglia phagocytose damaged and dead cells,has anti-inflammatory and pro-damage repair effects.Recent studies have shown that microglia efferocytosis plays a crucial role in the pathogenesis of Alzheimer's disease(AD)and may be a novel therapeutic target for AD.This paper reviews the relationship between microglia efferocytosis and AD pathogenesis and the potential of using efferocytosis-related molecules as therapeutic targets for AD.The aim of this review is to provide new ideas and approaches for the treatment of AD.

Objective To calculate the pre-stretching of the microscopic components of the aortic wall under physiological homeostasis by considering a three-dimensional(3D)residual stress field.Methods The aortic wall was simplified into a double-layer ideal circular tube,and the 3D residual stress field of the vascular wall was calculated based on a 3D expansion angle experiment.Then,the in vivo stress distribution characteristics under mean blood pressure and the pre-stretching of each microscopic constituent of the vascular wall under a physiologically steady state were obtained.The inverse problem was constructed according to the internal pressure-radius relationship measured in vivo.Physiological homeostasis of the aorta was considered the reference state,and inversion identification of the material parameters of the aorta in vivo was realized while integrating the three residual stress fields.Results When residual stress was not considered,the mean stress of the middle membrane was greater than that of the outer membrane.When residual stress was considered,the outer membrane bore more stress than the middle membrane,and the outer membrane protected the middle membrane.The pre-stretching of the middle film with residual stress was lower than that without residual stress,whereas the pre-stretching of the outer film was higher than that without residual stress.Moreover,the pre-stretching of the outer membrane collagen fibers was greater than that of the middle membrane collagen fibers.The in vivo calculations of the material parameters of the aorta were performed using physiological homeostasis as the reference configuration,and the proportion of each component was consistent with the experimental results.However,the proportion of elastin in the outer membrane was significantly overestimated when the non-stress configuration was used as the initial configuration,which was inconsistent with the experimental results.Conclusions Residual stress significantly influences the pre-stretching and physiologically steady mechanical states of the microscopic components of the aortic wall.Therefore,it is necessary to fully consider the influence of residual stress to establish the physiologically steady state of the aortic wall accurately.Furthermore,it is also necessary to fully consider the 3D characteristics and layer specificity of residual stress in the in vivo identification of material parameters.

Effectiveness of tumor immunotherapy is largely evaluated based on mouse models.Due to species differences,traditional mouse models cannot mirror condition of immune response in human body,resulting in vast majority of mouse-based achievements are not applicable to humans.In recent years,with emergence of immunodeficient mice and its improvement,humanized immune system mouse models based on immunodeficient mice are expected to help us overcome this barrier.We highlight the latest advances and barriers in generation of immunodeficient mice and humanized mouse models,as well as application of humanized mouse models on tumor immune,with aim of providing a guide for their application to tumor immunotherapy studies with potential for clinical translation.

Objective To investigate the effect of electroacupuncture preconditioning on microglia polarization in rats after cerebral ischemia reperfusion(IR)injury and explore the role of tyrosine kinase 2(J AK2)/signal transducer and activator of transcription 3(STAT3)pathway in the process.Methods Forty-five clean-grade healthy male Sprague-Dawley rats were randomly and equally divided into sham operation group,IR group and electroacupuncture preconditioning group.Rat model of IR injury was induced with thread occlusion of the internal carotid artery.Before modeling,electroacupuncture preconditioning was applied to Baihui acupoint for 5 consec-utive days in the preconditioning group,and exposure of the cervical blood vessels were inflicted in the sham-operation group.At 24 h after reperfusion,the severity of neurological deficit was observed by modified neurological deficit score(mNSS),and the cerebral infarct volume was observed by TTC staining.Western blotting was used to detect the protein levels of classical acti-vated type(M1)marker inducible nitric oxide synthase(iNOS),alternative activated type(M2)marker arginase 1(Arg-1),JAK2 and p-JAK2,and STAT3 and p-STAT3,and q-PCR was applied to detect the mRNA expression of iNOS and Arg-1.The expression of TNF-α and IL-10 was measured by ELISA.Results Compared with the sham operation group,the mNSS,infarct vol-ume,protein levels of p-JAK2/JAK2,p-STAT3/STAT3,protein and mRNA levels of iNOS and Arg-1,and expression of TNF-α and IL-10 were significantly increased in the IR and electroacu-puncture preconditioning groups(P＜0.01).The preconditioning group had obviously lower mNSS,smaller infarct volume,decreased protein levels of p-JAK2/JAK2,p-STAT3/STAT3,re-duced protein and mRNA levels of iNOS,and declined TNF-α expression,but elevated expression of Arg-1 at protein(2.0±0.2 vs 1.5±0.1)and mRNA(4.2±0.8 vs 3.1±0.3)levels and increased IL-10 expression(49.1±7.1 pg/mg vs 27.9±5.9 pg/mg)when compared with the IR group(P＜0.01).Conclusion Electroacupuncture preconditioning can promote the polarization of microglia to M2 and inhibit the polarization of microglia to M1 after cerebral IR injury,which may be relat-ed to the inhibition of JAK2/STAT3 pathway.