A macroscopic multi-mechanism based constitutive model for the thermo-mechanical cyclic degeneration of shape memory effect of NiTi shape memory alloy

A macroscopic based multi-mechanism constitutive model is constructed in the framework of irreversible thermodynamics to describe the degeneration of shape memory effect occurring in the thermo-mechanical cyclic deformation of NiTi shape memory alloys (SMAs). Three phases, austenite A, twinned martensite and detwinned martensite , as well as the phase transitions occurring between each pair of phases (, , , , and are considered in the proposed model. Meanwhile, two kinds of inelastic deformation mechanisms, martensite transformation-induced plasticity and reorientation-induced plasticity, are used to explain the degeneration of shape memory effects of NiTi SMAs. The evolution equations of internal variables are proposed by attributing the degeneration of shape memory effect to the interaction between the three phases (A, , and and plastic deformation. Finally, the capability of the proposed model is verified by comparing the predictions with the experimental results of NiTi SMAs. It is shown that the degeneration of shape memory effect and its dependence on the loading level can be reasonably described by the proposed model.

A novel rat tail disc degeneration model induced by static bending and compression

Background:A new rat tail intervertebral disc degeneration model was established to observe the morphologic and biologic changes of static bending and compression applied to the discs.Methods:In total,20 Sprague-Dawley rats with similar weight were randomly di-vided into 4 groups.Group 1 served as a control group for a baseline assessment of normal discs.Group 2 underwent a sham surgery,using an external device to bend the vertebrae of coccygeal 8-10.Groups 3 and 4 were the loaded groups,and exter-nal devices were instrumented to bend the spine with a compression level of 1.8 N and 4.5 N,respectively.Magnetic resonance imaging(MRI),histological,and quanti-tative real-time PCR(qRT-PCR)analysis were performed on all animals on day 14 of the experiment.Results:Magnetic resonance imaging and histological results showed that the changes of intervertebral disc degeneration increased with the size of compression load.Some architecture disorganizations in nucleus pulposus and annulus fibro-sus were found on both of the convex and concave side in the groups of 1.8 N and 4.5 N.An upregulation of MM-3,MM-13,and collagen 1-α1 mRNA expression and a downregulation of collagen 2-α1 and aggrecan mRNA expression were observed in the sham and loading groups.Significant changes were found between the loading groups,whereas the sham group showed similar results to the control group.Conclusions:Static bending and compression could induce progressive disc degen-eration,which could be used for biologic study on disc degeneration promoted by static complex loading.

Diffusion tensor imaging as a tool to detect presymptomatic axonal degeneration in a preclinical spinal cord model of amyotrophic lateral sclerosis

The G93A-SOD1 mice model and MRI diffusion as a preclinical tool to study amyotrophic lateral sclerosis （ALS）： ALS is a progressive neurological disease characterized primarily by the development of limb paralysis, which eventually leads to lack of control on muscles under voluntary control and death within 3–5 years. Genetic heterogeneity and environmental factors play a critical role in the rate of disease progression and patients display faster declines once the symptoms have manifested. Since its original discovery, ALS has been associated with pathological alterations in motor neurons located in the spinal cord （SC）, where neuronal loss by a mutation in the protein superoxide dismutase in parenthesis （mSOD1） and impairment in axonal connectivity, have been linked to early functional impairments. In addition,mechanisms of neuroinflammation, apoptosis, necroptosis and autophagy have been also implicated in the development of this disease. Among different animal models developed to study ALS, the transgenic G93A-SOD1 mouse has become recognized as a benchmark model for preclinical screening of ALS therapies. Furthermore, the progressive alterations in the locomotor phenotype expressed in this model closely resemble the progressive lower limb dysfunction of ALS patients. Among other imaging tools, MR diffusion tensor imaging （DTI） has emerged as a crucial, noninvasive and real time neuroimaging tool to gather information in ALS. One of the current concerns with the use of DTI is the lack of biological validation of the microstructural information given by this technique. Although clinical studies using DTI can provide a remarkable insight on the targets of neurodegeneration and disease course,they lack histological correlations. To address these shortcomings, preclinical models can be designed to validate the microstructural information unveiled by this particular MRI technique. Thus, the scope of this review is to describe how MRI diffusion and optical microscopy evaluate axonal structural changes at early stages of the disease in a preclinical model of ALS.

An animal model to create intervertebral disc degeneration characterized by radiography and molecular biology

Objectives： To develop a rabbit model of intervertebral disc degeneration that more exactly simulates the pathological changes of human intervertebral disc degeneration. Methods： Twelve New Zealand white rabbits were utilized to establish three different disc injury models according to the following protocol; group A： anulus punctures were done with a 18-gauge needle at L2-L3 and L5-L6; Group B： intradiscal injection of interleukin-1 IL-1β with a 23-gauge needle at L3-L4; and Group C： intradiscal injection of phosphate buffer saline（PBS） with a 23-gauge needle at L4-LS. The L1-L2 level was used as a control. Rabbits were killed after 24 weeks. The intervertebral disc height was measured by lateral plain radiographs. After the radiographic measurements were obtained, the intervertebral discs were removed and analyzed for DNA, sulfated glycosaminoglycan（s-GAG） and water contents of nucleus pulposus. Results： The intervertebral disc height, s-GAG, and water contents in anulus needle punctures were significantly decreased in Group A, but the DNA content in the nucleus pulposus was significantly increased when compared to the control. The significant decrease of disc height and water contents were demonstrated, only the s-GAG and DNA contents did not show a significant difference in Group B when compared to the control. The significant decrease of disc height, s-GAG, water, and DNA contents did not show in Group C when compared to the control. Conclusion： The 18-gauge puncture models produced the most consistent disc degeneration in the rabbit lumbar spine.

LDN-73794 Attenuated LRRK2-Induced Degeneration in a <i>Drosophila</i>Parkinson’s Disease Model

Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD and contribute to sporadic PD as well. Disruption of LRRK2 kinase functions has become one of the potential mechanisms underlying disease-linked mutation-induced neuronal degeneration. To further characterize the pharmacological effects of a reported LRRK2 kinase inhibitor, LDN-73794, in vitro cell models and a LRRK2 Drosophila PD model were used. LDN-73794 reduced LRRK2 kinase activity in vitro and in vivo. Moreover, LDN-73794 increased survival, improved locomotor activity, and suppressed DA neuron loss in LRRK2 transgenic flies. These results suggest that inhibition of LRRK2 kinase activity can be a potential therapeutic strategy for PD intervention and LDN-73794 could be a potential lead compound for developing neuroprotective therapeutics.

Degenerate States in Nonlinear Sigma Model with U(1) Symmetry<br/><br/>_{—For Study on Violation of Cluster Property}

Entanglement in quantum theory is a concept that has confused many scientists. This concept implies that the cluster property, which means no relations between sufficiently separated two events, is non-trivial. In the works for some quantum spin systems, which have been recently published by the author, extensive and quantitative examinations were made about the violation of cluster property in the correlation function of the spin operator. The previous study of these quantum antiferromagnets showed that this violation is induced by the degenerate states in the systems where the continuous symmetry spontaneously breaks. Since this breaking is found in many materials such as the high temperature superconductors and the superfluidity, it is an important question whether we can observe the violation of the cluster property in them. As a step to answer this question we study a quantum nonlinear sigma model with U(1) symmetry in this paper. It is well known that this model, which has been derived as an effective model of the quantum spin systems, can also be applied to investigations of many materials. Notifying that the existence of the degenerate states is essential for the violation, we made numerical calculations in addition to theoretical arguments to find these states in the nonlinear sigma model. Then, successfully finding the degenerate states in the model, we came to a conclusion that there is a chance to observe the violation of cluster property in many materials to which the nonlinear sigma model applies.

Degenerate States in Nonlinear Sigma Model with SU(2) Symmetry

Entanglement in quantum theory is a peculiar concept to scientists. With this concept we are forced to re-consider the cluster property which means that one event is irrelevant to another event when they are fully far away. In the recent works we showed that the quasi-degenerate states induce the violation of cluster property in antiferromagnets when the continuous symmetry breaks spontaneously. We expect that the violation of cluster property will be observed in other materials too, because the spontaneous symmetry breaking is found in many systems such as the high temperature superconductors and the superfluidity. In order to examine the cluster property for these materials, we studied a quantum nonlinear sigma model with U(1) symmetry in the previous work. There we showed that the model does have quasi-degenerate states. In this paper we study the quantum nonlinear sigma model with SU(2) symmetry. In our approach we first define the quantum system on the lattice and then adopt the representation where the kinetic term is diagonalized. Since we have no definition on the conjugate variable to the angle variable, we use the angular momentum operators instead for the kinetic term. In this representation we introduce the states with the fixed quantum numbers and carry out numerical calculations using quantum Monte Carlo methods and other methods. Through analytical and numerical studies, we conclude that the energy of the quasi-degenerate state is proportional to the squared total angular momentum as well as to the inverse of the lattice size.

Age related macular degeneration: from evidence based-care to experimental models

To describe the current aging population in China and globally,especially as it applies to age-related macular degeneration(AMD).To review the current standards of care for treating both wet(exudative)eAMD and dry(atrophic)aAMD.And to introduce a model for experimentation that is based on the Age-Related Eye Disease Study(AREDS)using eye bank tissue.A literature search that outlines current aging populations,standards of clinical treatment as defined by large,multicenter,randomized clinical trials that present level-I data with a low risk for bias.An experimental model system of AMD is presented that enables scientific analysis of AMD pathogenesis by applying grading criteria from the AREDS to human eye bank eyes.Analysis includes proteomic,cellular,and functional genomics.The standard of care for the treatment of eAMD is currently defined by the use of several anti-vascular endothelial growth(anti-VEGF)agents alone or in combination with photodynamic therapy.Monotherapy treatment intervals may be monthly,as needed,or by using a treat-and-extend(TAE)protocol.There are no proven therapies for aAMD.AMD that is phenotypically defined at AREDS level 3,should be managed with the use of anti-oxidant vitamins,lutein/zeaxanthin and zinc(AREDS-2 formulation).By understanding the multiple etiologies in the pathogenesis of AMD(i.e.,oxidative stress,inflammation,and genetics),the use of human eye bank tissues graded according to the Minnesota Grading System(MGS)will enable future insights into the pathogenesis of AMD.Initial AMD management is with lifestyle modification such as avoiding smoking,eating a healthy diet and using appropriate vitamin supplements(AREDS-2).For eAMD,anti-VEGF therapies using either pro re nata(PRN)or TAE protocols are recommended,with photodynamic therapy in appropriate cases.New cellular information will direct future,potential therapies and these will originate from experimental models,such as the proposed eye bank model using the MGS,that leverages the prospective AREDS database.

The complexities underlying age-related macular degeneration： could amyloid beta play an important role？

e-related macular degeneration （AMD） causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognized, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarize the literature describing how the Alzheimer＇s-linked amyloid beta （Aβ） group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer＇s disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that Aβ fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of Aβ were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of Aβ accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of Aβ-mediated retinopathy. Furthermore, we discuss our findings revealing how Aβ behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose Aβ as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for latestage AMD.

Animal models of amyotrophic lateral sclerosis： a comparison of model validity

Animal models are necessary to investigate the pathogenic features underlying motor neuron degeneration and for therapeutic development in amyotrophic lateral sclerosis（ALS）. Measures of model validity allow for a critical interpretation of results from each model and caution from over-interpretation of experimental models. Face and construct validity refer to the similarity in phenotype and the proposed causal factor to the human disease, respectively. More recently developed models are restricted by limited phenotype characterization, yet new models hold promise for novel disease insights, thus highlighting their importance. In this article, we evaluate the features of face and construct validity of our new zebrafish model of environmentally-induced motor neuron degeneration and discuss this in the context of current environmental and genetic ALS models, including C9 orf72, mutant Cu/Zn superoxide dismutase 1 and TAR DNA-binding protein 43 mouse and zebrafish models. In this mini-review, we discuss the pros and cons to validity criteria in each model. Our zebrafish model of environmentally-induced motor neuron degeneration displays convincing features of face validity with many hallmarks of ALS-like features, and weakness in construct validity. However, the value of this model may lie in its potential to be more representative of the pathogenic features underlying sporadic ALS cases, where environmental factors may be more likely to be involved in disease etiology than single dominant gene mutations. It may be necessary to compare findings between different strains and species modeling specific genes or environmental factors to confirm findings from ALS animal models and tease out arbitrary strain-and overexpression-specific effects.

GLOBAL EXISTENCE AND ASYMPTOTIC BEHAVIOR FOR AN 1-D COMPRESSIBLE ENERGY TRANSPORT MODEL

In this article, the global existence and the large time behavior of smooth solutions to the initial boundary value problem for a degenerate compressible energy transport model are established.

Changes in proteins related to early nerve repair in a rat model of sciatic nerve injury

Peripheral nerves have a limited capacity for self-repair and those that are severely damaged or have significant defects are challenging to repair. Investigating the pathophysiology of peripheral nerve repair is important for the clinical treatment of peripheral nerve repair and regeneration. In this study, rat models of right sciatic nerve injury were established by a clamping method. Protein chip assay was performed to quantify the levels of neurotrophic, inflammation-related, chemotaxis-related and cell generation-related factors in the sciatic nerve within 7 days after injury. The results revealed that the expression levels of neurotrophic factors(ciliary neurotrophic factor) and inflammationrelated factors(intercellular cell adhesion molecule-1, interferon γ, interleukin-1α, interleukin-2, interleukin-4, interleukin-6, monocyte chemoattractant protein-1, prolactin R, receptor of advanced glycation end products and tumor necrosis factor-α), chemotaxis-related factors(cytokine-induced neutrophil chemoattractant-1, L-selectin and platelet-derived growth factor-AA) and cell generation-related factors(granulocyte-macrophage colony-stimulating factor) followed different trajectories. These findings will help clarify the pathophysiology of sciatic nerve injury repair and develop clinical treatments of peripheral nerve injury. This study was approved by the Ethics Committee of Peking University People's Hospital of China(approval No. 2015-50) on December 9, 2015.

Modeling subcortical ischemic white matter injury in rodents:unmet need for a breakthrough in translational research

Subcortical ischemic white matter injury(SIWMI),pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging,is a common cause of cognitive decline in elderly.Despite its high prevalence,it remains unknown how various components of the white matter degenerate in response to chronic ischemia.This incomplete knowledge is in part due to a lack of adequate animal model.The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components.The SIWMI animal models are categorized into 1)chemically induced SIWMI models,2)vascular occlusive SIWMI models,and 3)SIWMI models with comorbid vascular risk factors.Chemically induced models display consistent lesions in predetermined areas of the white matter,but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities.Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified.When combined with comorbid vascular risk factors(specifically hypertension),however,they can produce progressive and definitive white matter lesions including diffuse rarefaction,demyelination,loss of oligodendrocytes,and glial activation,which are by far the closest to those found in human white matter hyperintensities lesions.However,considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models.In the meantime,in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury.Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities.

A modified laser-induced choroidal neovascularization animal model with intravitreal oxidized low-density lipoprotein

AIM: To investigate whether intravitreal injection of oxidized low-density lipoprotein(OxLDL) can promote laserinduced choroidal neovascularization(CNV) formation in mice and the mechanism involved, thereby to develop a better animal model.METHODS: C57BL6/J mice were randomized into three groups. Immediately after CNV induction with 532 nm laser photocoagulation, 1.0 μL of OxLDL [100 μg/m L in phosphate-buffered saline(PBS)] was intravitreally injected, whereas PBS and the same volume low-density lipoprotein(LDL;100 μg/m L in PBS) were injected into the vitreous as controls. Angiogenic and inflammatory cytokines were measured by quantitative real-time polymerase chain reaction(q RT-PCR) and Western blotting(WB) after 5 d, and CNV severity was analyzed by choroid flat mount and immunofluorescence staining after 1wk. In vitro, retinal pigment epithelial(RPE) cell line(ARPE19) were treated with OxLDL(LDL as control) for 8 h. Angiogenic and inflammatory cytokine levels were measured. A specific inhibitor of lectin-like oxidized low-density lipoprotein receptor 1(LOX1) was used to evaluate the role of LOX1 in this process.RESULTS: At 7 d after intravitreal injection of 1 μL(100 μg/mL) OxLDL, T15-labeled OxLDL was mainly deposited around the CNV area, and the F4/80-labeled macrophages, the CD31-labeled vascular endothelial cells number and CNV area were increased. Meanwhile, WB and qR T-PCR results showed that vascular endothelial growth factor(VEGF), CC chemokine receptor 2(CCR2), interleukin-6(IL-6), IL-1β, and matrix metalloproteinase 9(MMP9) expressions were increased, which was supported by in vitro experiments in RPE cells. LOX1 inhibitors significantly reduced expressions of inflammatory factors IL-1β and VEGF. CONCLUSION: A modified laser-induced CNV animal model is established with intravitreal injection of 1 μL(100 μg/mL) of OxLDL at 7 d, which at least partially through LOX1. This animal model can be used as a simple model for studying the role of OxLDL in age-related macular degeneration.

MicroRNA expression in animal models of amyotrophic lateral sclerosis and potential therapeutic approaches

A review of recent animal models of amyotrophic lateral sclerosis showed a large number of mi RNAs had altered levels of expression in the brain and spinal cord,motor neurons of spinal cord and brainstem,and hypoglossal,facial,and red motor nuclei and were mostly upregulated.Among the mi RNAs found to be upregulated in two of the studies were mi R-21,mi R-155,mi R-125 b,mi R-146 a,mi R-124,mi R-9,and mi R-19 b,while those downregulated in two of the studies included mi R-146 a,mi R-29,mi R-9,and mi R-125 b.A change of direction in mi RNA expression occurred in some tissues when compared(e.g.,mi R-29 b-3 p in cerebellum and spinal cord of wobbler mice at 40 days),or at different disease stages(e.g.,mi R-200 a in spinal cord of SOD1(G93 A)mice at 95 days vs.108 and 112 days).In the animal models,suppression of mi R-129-5 p resulted in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and tended to improve motor neuron survival in the SOD1(G93 A)mouse model.Suppression of mi R-155 was also associated with increased lifespan,while lowering of mi R-29 a tended to improve lifespan in males and increase muscle strength in SOD1(G93 A)mice.Overexpression of members of mi R-17~92 cluster improved motor neuron survival in SOD1(G93 A)mice.Treatment with an artificial mi RNA designed to target h SOD1 increased lifespan and improved muscle strength in SOD1(G93 A)animals.Further studies with animal models of amyotrophic lateral sclerosis are warranted to validate these findings and identify specific mi RNAs whose suppression or directed against h SOD1 results in increased lifespan,improved muscle strength,reduced neuromuscular junction degeneration,and improved motor neuron survival in SOD1(G93 A)animals.

EXISTENCE OF WEAK SOLUTIONS TO A DEGENERATE STEAD-STATE SEMICONDUCTOR EQUATIONS

In this paper, we consider a degenerate steady-state drift-diffusion model for semiconductors. The pressure function used in this paper is （）（s） = s~α（α 〉 1）. We present existence results for general nonlinear diffhsivities for the degenerate Dirichlet-Neumann mixed boundary value problem.

Application of molybdenum target X-ray photography in imaging analysis of caudal intervertebral disc degeneration in rats

BACKGROUND Conventional plain X-ray images of rats,the most common animals used as degeneration models,exhibit unclear vertebral structure and blurry intervertebral disc spaces due to their small size,slender vertebral bodies.AIM To apply molybdenum target X-ray photography in the evaluation of caudal intervertebral disc(IVD)degeneration in rat models.METHODS Two types of rat caudal IVD degeneration models(needle-punctured model and endplate-destructed model)were established,and their effectiveness was verified using nuclear magnetic resonance imaging.Molybdenum target inspection and routine plain X-ray were then performed on these models.Additionally,four observers were assigned to measure the intervertebral height of degenerated segments on molybdenum target plain X-ray images and routine plain X-ray images,respectively.The degeneration was evaluated and statistical analysis was subsequently conducted.RESULTS Nine rats in the needle-punctured model and 10 rats in the endplate-destructed model were effective.Compared with routine plain X-ray images,molybdenum target plain X-ray images showed higher clarity,stronger contrast,as well as clearer and more accurate structural development.The McNemar test confirmed that the difference was statistically significant(P=0.031).In the two models,the reliability of the intervertebral height measured by the four observers on routine plain X-ray images was poor(ICC<0.4),while the data obtained from the molybdenum target plain X-ray images were more reliable.CONCLUSIONMolybdenum target inspection can obtain clearer images and display fine calcification in the imaging evaluation of caudal IVD degeneration in rats,thus ensuring a more accurate evaluation of degeneration.

Characterization and validation of a chronic retinal neovascularization rabbit model by evaluating the efficacy of anti-angiogenic and anti-inflammatory drugs

AIM:To establish a rabbit model with chronic condition of retinal neovascularization(RNV)induced by intravitreal(IVT)injection of DL-2-aminoadipic acid(DL-AAA),a retinal glial(Mül er)cell toxin,extensive characterization of DL-AAA induced angiographic features and the suitability of the model to evaluate anti-angiogenic and anti-inflammatory therapies for ocular vascular diseases.METHODS:DL-AAA(80 mmol/L)was administered IVT into both eyes of Dutch Belted rabbit.Post DL-AAA delivery,clinical ophthalmic examinations were performed weekly following modified Mc Donald-Shadduck Scoring System.Color fundus photography,fluorescein angiography(FA),and optical coherence tomography(OCT)procedures were performed every 2 or 4 wk until stable retinal vascular leakage was observed.Once stable retinal leakage(12 wk post DL-AAA administration)was established,anti-vascular endothelial growth factor(VEGF)(bevacizumab,ranibizumab and aflibercept)and anti-inflammatory(triamcinolone,TAA)drugs were tested for their efficacy after IVT administration.Fluorescein angiograms were scored before and after treatment following a novel grading system,developed for the DL-AAA rabbit model.RESULTS:Post DL-AAA administration,eyes were presented with moderate to severe retinal/choroidal inflammation which was accompanied by intense vitreous flare and presence of inflammatory cells in the vitreous humor.Retinal hemorrhage was restricted to the tips of neo-retinal vessels.FA revealed maximum retinal vascular leakage at 2 wk after DL-AAA injection and then persisted as evidenced by stable mean FA scores in weeks 8 and 12.Retinal vascular angiographic and tomographic features were stable and consistent up to 36 mo among two different staggers induced for RNV at two different occasions.Day 7,mean FA scores showed that 1μg/eye of bevacizumab,ranibizumab,aflibercept and 2μg/eye of TAA suppress 65%,90%,100%and 50%retinal vascular leakage,respectively.Day 30,bevacizumab and TAA continued to show 66%and 44%suppression while ranibizumab effect was becoming less effective(68%).In contrast,aflibercept was still able to fully(100%)suppress vascular leakage on day 30.On day 60,bevacizumab,ranibizumab and TAA showed suppression of 7%,12%,and 9%retinal vascular leakage,respectively,however,aflibercept continued to be more effective showing 50%suppression of vascular leakage.CONCLUSION:The DL-AAA rabbit model mimics RNV angiographic features like RNV and chronic retinal leakage.Based on these features the DL-AAA rabbit model provides an invaluable tool that could be used to test the therapeutic efficacy and duration of action of novel anti-angiogenic formulations,alone or in combination with anti-inflammatory compounds.

人与其他动物椎间盘解剖和组织学结构的比较医学研究进展

《2023年中国退行性脊柱健康报告》提到35岁以下患者的腰椎手术比例近年来显著增加,颈、腰椎病有年轻化的趋势。腰椎间盘突出症成为最困扰大众的疾病之一,研究椎间盘退变的发病机制和治疗方法有着重要的临床意义。目前人类椎间盘相关疾病多采用影像学诊断,由于脊柱的组织样本不易得到,实验动物以成本低、周期短、易获取的优点,成为替代性研究对象。人与其他动物的椎间盘有着结构和生理上的差异,比较人与其他动物的椎间盘结构和病理生理特点是研究的基础和关键。本文综述了不同动物椎间盘解剖与组织学结构相关研究文献并进行比较分析,分别从椎间盘的高度、椎间盘的几何形状、腰椎间盘软骨终板特征、椎间盘内细胞外基质组分4个角度比较了不同动物的椎间盘特点。分析结果表明:人类、袋鼠、绵羊、猪、大鼠在第六颈椎至第七颈椎处的椎间盘相对高度数值最接近;与人类腰部椎间盘几何形状最为相似的是小鼠腰椎间盘;与其他动物相比,人类的软骨终板最厚,细胞密度最小;猪纤维环内部的胶原蛋白与人类的差异最大,但猪、绵羊、兔、大鼠的髓核含水量与人类相比无差异性。在此基础上,本文还阐述了人与其他动物之间椎间盘退变的共性和差异表现,也对不同实验动物椎间盘退变的造模方法进行了总结,旨在为椎间盘退变研究选择合适的实验动物模型提供基础数据。

寒湿阻滞型腰痛大鼠模型构建及独活寄生汤干预效果的实验研究

目的构建大鼠寒湿阻滞型腰痛动物模型,评估独活寄生汤对该模型的干预效果。方法24只雄性SD大鼠适应性喂养7 d后,随机分为空白组、模型组和独活寄生汤组。空白组仅腹腔注射戊巴比妥钠麻醉,模型组、独活寄生汤组在腹腔注射戊巴比妥钠麻醉下行“腰椎后柱结构部分切除术”,并在寒湿环境下饲养6周。造模2周后,空白组、模型组予等体积蒸馏水灌胃,独活寄生汤组予独活寄生汤18.6 g/(kg·d)灌胃,均连续灌胃4周。比较各组大鼠一般情况、自发性疼痛行为学评分和神经功能评分,CT三维成像评估脊柱生理曲度形态改变情况,椎间盘组织病理切片评估椎间盘髓核病变程度。结果造模后1周,与空白组比较,模型组、独活寄生汤组开始出现少动、皮毛无光泽、嗜睡蜷缩、反应迟钝、大便稀溏表现,体质量减轻(P<0.05),自发性疼痛行为学评分和神经功能评分升高(P<0.05);给药后3周,与模型组比较,独活寄生汤组疼痛行为学评分和神经功能评分降低(P<0.05)。给药后4周,与模型组比较,独活寄生汤组大鼠脊柱CT三维成像形态退变不明显,椎间盘组织病理切片显示,独活寄生汤组椎间盘髓核病变不明显。结论“腰椎后柱结构部分切除术+寒湿环境饲养”可成功构建SD大鼠寒湿阻滞型腰痛动物模型,独活寄生汤对该模型有较好的干预效果。