激素性股骨头坏死过程中低氧诱导因子1α与骨细胞凋亡

背景：激素性股骨头缺血坏死发病机制未明,缺血缺氧是其根本原因,缺氧状态下低氧诱导因子1α参与多种信号通路传导。作者的前期研究发现,骨细胞凋亡与激素性股骨头缺血坏死存在关联。 目的：分析低氧诱导因子1α和骨细胞凋亡是否与激素性股骨头缺血坏死存在关联。 方法：选健康5月龄新西兰白兔20只,随机分为空白对照组和实验组,每组10只。实验组兔给予激素联合内毒素制备激素性股骨头缺血坏死模型。最后一次给药后第4周处死所有实验动物,取双侧后肢股骨头,光镜与电子显微镜下观察形态与超微结构变化,计算各组空缺骨陷窝;应用免疫组织化学技术检测低氧诱导因子1α表达,应用TUNEL法检测骨细胞凋亡。 结果与结论：实验组空缺骨陷窝率高于空白对照组(P < 0.01);实验组骨细胞凋亡高于空白对照组(P < 0.01);实验组低氧诱导因子1α低于空白对照组(P < 0.01);实验组中低氧诱导因子1α表达与细胞凋亡率呈负相关(r=-0.675),实验组中空缺骨陷窝率与细胞凋亡率呈正相关(r=0.793)。结果说明,在激素性股骨头缺血坏死早期,低氧诱导因子1α的低表达与骨细胞凋亡存在相关性,二者参与了激素性股骨头缺血坏死的病理变化过程,骨细胞的死亡方式为凋亡。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

激素性股骨头坏死模型：不同构建技术分析

背景：良好的股骨头坏死动物模型的建立,有助于研究股骨头坏死的发病机制,为股骨头坏死的预防和治疗提供理论依据。 目的：研究内毒素脂多糖联合地塞米松注射液诱导兔股骨头坏死的实验效果。 方法：新西兰大白兔36只随机分为模型组21只和对照组15只。模型组连续2 d每日经耳缘静脉注射内毒素脂多糖10 μg/kg,再连续3 d,每日肌肉注射地塞米松注射液25 mg/kg;对照组注射同等剂量的生理盐水。 结果与结论：模型组4周后X射线显示兔关节间隙增宽,密度增大,关节软骨下骨密度增高,股骨头变平,骨小梁模糊,软骨下骨与骨松质界限不清,在股骨头内出现斑块状高密度区域,股骨颈变短粗。双能量X射线骨密度测量仪进行股骨头局部骨密度测量,兔股骨头骨密度检测发现模型组股骨头骨密度、骨矿物质含量均显著低于对照组(P < 0.05)。组织学切片见模型组骨细胞陷窝空疏,脂肪细胞增多,部分血管栓塞,其中存活动物的骨坏死率和骨陷窝率均明显高于对照组。证实地塞米松联合脂多糖可有效建立激素性股骨头坏死模型。     

激素性股骨头缺血性坏死模型兔股骨组织中间隙连接蛋白Cx43的表达

背景：激素性股骨头缺血性坏死的发病机制至今尚未完全阐明,间隙连接蛋白Cx43作为骨组织细胞间的主要间隙连接,通过介导骨细胞间信息、能力的正常传递参与调控骨组织细胞生长、分化,代偿性的骨增加或减少,间隙连接蛋白Cx43与激素性股骨头坏死发生发展的关系国内外尚少见报道。 目的：通过建立兔激素性股骨头坏死模型,初步探讨间隙连接蛋白Cx43在激素性股骨头坏死中的表达变化。 方法：将新西兰大白兔40只随机等分为两组,模型组采用内毒素+激素方法构建激素性股骨头坏死模型,对照组于相同时间点注射等量生理盐水。 结果与结论：建模4周后,苏木精-伊红染色结果显示,模型组股骨头软骨下区骨小梁变细,结构紊乱,空骨陷窝明显增多,脂肪细胞增多,髓腔内造血细胞明显减少;对照组股骨头软骨下区骨小梁排列整齐、很少见空骨陷窝,骨髓造血细胞丰富,脂肪细胞较少;免疫组织化学检测显示：Cx43蛋白阳性表达于骨小梁边缘成骨细胞及骨小梁内骨细胞胞浆上及骨髓细胞间质。Western blot检测显示,碱性磷酸酶和Cx43蛋白的表达在模型组中低于对照组(P < 0.05)。结果证实,在激素性股骨头坏死兔模型组织中Cx43蛋白表达下降,可能是激素性股骨头坏死发生发展的重要环节。 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程全文链接：     

激素性股骨头缺血性坏死兔模型的构建

背景:成人股骨头缺血性坏死可导致股骨头塌陷和髋关节破坏,但其真正的病因和发病机制尚未完全明了。因此建立实验性动物模型是目前研究激素性股骨头缺血性坏死的重要手段之一。目的:建立兔激素性股骨头缺血性坏死模型,探讨其可能的发病机制。方法:将健康成年新西兰白兔以抽签法随机分成4组。对照组,注射生理盐水;激素组,注射甲基泼尼松龙3次;单次内毒素组,静脉注射大肠杆菌内毒素24h后,立即注射甲基泼尼松龙3次;双次内毒素组,大肠杆菌内毒素注射24h后重复给药1次,随后注射甲基泼尼松龙3次。造模前及造模后行X射线片、MRI检查及组织学检查、透射电镜观察,并计算空骨陷窝率。结果与结论:造模第8周时激素组、单次内毒素组、双次内毒素组空骨陷窝率较对照组明显增高(P0.01),并且双次内毒素组空骨陷窝率明显高于激素组和单次内毒素组(P0.01)。双次内毒素组较激素组及单次内毒素组股骨头出现坏死的时间更早、坏死的效果更显著,并且随着时间的推移股骨头坏死的效果越来越明显。说明在相同的实验条件下,实施双次内毒素与激素联合诱发股骨头坏死出现最早、坏死效果最明显,且骨陷窝空虚率随时间的延长而增加。     

激素性股骨头坏死模型兔骨组织病理及功能变化

背景：目前对激素性股骨头坏死的研究均未涉及成骨细胞、破骨细胞变化所引起的细胞功能改变。 目的：观察激素性股骨头坏死模型兔骨代谢指标及骨组织病理学变化。 方法：将32只新西兰大白兔随机等分为正常组和模型组。模型组臀肌注射醋酸氢化可的松注射液8.0 mg/kg,每周2次,持续8周,建立激素性股骨头坏死兔模型;正常组注射等量的生理盐水。 结果与结论：与正常组比较,模型组从第2周开始血清钙、磷显著降低(P < 0.05),而抗酒石酸酸性磷酸酶活性显著升高 (P < 0.05);从第4周开始,模型组骨特异性碱性磷酸酶水平升高,骨钙素水平降低(P < 0.05);模型组骨特异性碱性磷酸酶水平至第8周有所下降。与正常组比较,模型组股骨转子骨密度从第2周开始降低(P < 0.05),股骨头骨密度从第4周开始降低(P < 0.05);成骨细胞数从第4周开始明显降低,破骨细胞数从第4周开始明显升高(P < 0.05)。提示激素可通过损伤骨组织细胞引起骨塑形及骨重建的破坏,造成骨矿物盐的丢失,引起激素性股骨头坏死的发生。     

地塞米松联合脂多糖诱导股骨头坏死模型的构建

背景：对于研究股骨头坏死的发病机制及治疗方法,建立与股骨头坏死病程相似的动物模型是非常重要的。 目的：观察地塞米松联合脂多糖诱导兔股骨头坏死的实验效果。 方法：健康雄性新西兰大白兔30只,随机分为模型组(n=20)和对照组(n=10)。模型组经耳缘静脉注射2次10 μg/kg的脂多糖,再肌肉注射3次地塞米松25 mg/kg,对照组注射同等剂量的生理盐水。 结果与结论：4周后,CT扫描显示模型组兔股骨头不同程度的骨密度不均匀。显微CT观察发现,模型组骨体积分数、骨矿物质密度、骨矿物质含量和骨小梁厚度均显著低于对照组,而骨小梁间隙高于对照组(P < 0.05)。组织学切片见模型组骨细胞陷窝空疏,脂肪细胞增多,部分血管栓塞,其中存活动物的骨坏死率和骨陷窝空虚率均明显低于对照组。说明地塞米松联合脂多糖可有效建立骨坏死模型。     

Bcl—2在激素性股骨头坏死过程中表达的实验研究

目的探讨激素性股骨头坏死的发病机制。方法24只新西兰大白兔随机分为实验组（冲击注射地塞米松）和对照组。实验8周处死动物，取股骨头作骨细胞组织病理学、超微结构观察，并用TUNEL及免疫组化技术分别检测骨细胞凋亡和Bcl-2表达情况。结果光镜下实验组较对照组股骨头骨小梁变细、稀疏、空骨陷窝明显增多，脂肪细胞增大。电镜下实验组骨细胞体积缩小，核固缩，线粒体及高尔基体肿胀，染色质边聚较多见。实验组凋亡骨细胞增多，Bcl-2表达骨细胞轻度增加。结论激素性股骨头坏死是骨细胞凋亡和坏死共同作用的结果。     

普伐他汀干预激素性股骨头坏死兔模型的组织学变化:大体和光镜下比较和印证

背景:研究表明普伐他汀可通过上调内源性骨形成蛋白2、核心结合因子α1和血管内皮生长因子等基因的表达从而产生促进激素性股骨头坏死兔模型坏死股骨头修复的作用。目的:验证性观察普伐他汀干预激素性股骨头坏死兔模型大体和光镜下的组织学改变,并进行相互比较和印证。方法:将80只新西兰白兔按随机数字表法分为对照组18只,实验组62只。向实验组耳缘静脉注射大肠杆菌内毒素(10μg/kg)2次,注射间隔24h。并于第2次注射大肠杆菌内毒素后,臀肌注射甲强龙(20mg/kg)3次,注射间隔24h,制备兔激素性股骨头缺血坏死模型。造模第5周,将造模成功的39只新西兰白兔以随机数字表法分配其中的36只至模型组和他汀组,每组18只。他汀组以普伐他汀(1.2mg/kg)灌胃,1次/d;模型组和对照组以等体积的蒸馏水灌胃。造模后8,12,16周,取股骨头,分别进行大体和光镜观察。结果与结论:大体观察及光镜观察显示模型组出现明显的骨坏死灶,骨髓腔内可见大量脂肪细胞增生;与模型组比较,他汀组骨细胞受损程度较轻,骨小梁密度较高,空骨陷窝比率较少,骨坏死面积和髓腔内脂肪细胞数量明显减少,骨坏死修复迹象明显。说明普伐他汀可有效促进早期激素性股骨头坏死兔模型坏死股骨头的修复。     

葡萄籽原花青素拮抗激素性股骨头坏死骨细胞凋亡的作用

文题释义： 原花青素：广泛存在于蔓蓦、松树皮、越桔、绿茶等植物中,特别是葡萄籽中含有大量的原花青素。自从1961年德国科学家KARL首次在葡萄籽中分离出了2种多酚化合物开始,很多学者对各种花青素进行了广泛深入的研究。大量实验数据证实原花青素具有强力的抗氧化、减少细胞酶抑制以及血管保护等活性,体外实验显示葡萄籽原花青素提取物还具有较强的抗细胞凋亡作用。 含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)：是一类蛋白酶家族,成员较多,在人类已经鉴定了11种不同的Caspase,根据其蛋白酶序列的同源性可分为3个亚族：Caspase-1亚族包括 Caspase-1、4、5、11;Caspase-2亚族包括Caspase-2、9;Caspase-3亚族包括Caspase-3、6、7、8、10。 背景：激素性股骨头缺血坏死具有复杂的生物学过程,其发病机制至今未明,临床上缺乏行之有效的治疗手段。因此,探明激素性股骨头缺血坏死的病因学机制,仍然是该领域研究的重要内容。 目的：观察葡萄籽原花青素提取物对激素性股骨头坏死骨细胞凋亡的影响。 方法：日本大耳白兔27只,随机分为3组：模型组静脉注射大肠杆菌内毒素,共2次,每次100 μg/kg,间隔24 h,在第2次注射完成后随即肌肉注射甲基强的松龙20 mg/kg,共注射3次,每次间隔24 h;治疗组进行相同造模,在甲基强的松龙注射同时肌肉注射葡萄籽原花青素提取物200 μg/kg,共注射3次,每次间隔24 h;对照组采用相同剂量注射生理盐水;最后一次注射后第4周空气栓塞法处死动物,取双侧股骨头常规固定脱钙、包埋,切片、苏木精-伊红染色,光镜下计数空缺骨陷窝,Hoechst染色法观察细胞凋亡情况,免疫组织化学染色法观察股骨头组织Caspase-9、Bcl-2的表达。 结果与结论：①模型组空缺骨陷窝率显著高于对照组(P < 0.01);治疗组空缺骨陷窝率显著低于模型组(P < 0.05),但仍高于对照组(P < 0.01);②对照组股骨头组织凋亡细胞较少;模型组股骨头组织中存在大量凋亡细胞,细胞核呈致密浓染;治疗组中凋亡细胞数有所减少,但仍高于对照组水平;③模型组Caspase-9的平均吸光度显著高于对照组(P < 0.01),治疗组Caspase-9的平均吸光度显著低于模型组(P < 0.01),与对照组相比无显著差异;模型组Bcl-2的平均吸光度值显著低于对照组(P < 0.05),治疗组Bcl-2的平均吸光度显著高于模型组(P < 0.01);④结果表明,骨细胞凋亡参与了激素性股骨头坏死的发生发展,葡萄籽原花青素可能通过促进Bcl-2的表达和抑制Caspase-9的表达来减少骨细胞凋亡的发生。 ORCID: 0000-0002-5431-8717(张志峰) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

兔激素性股骨头坏死模型的建立

目的： 建立兔激素性股骨头坏死的模型。方法: 新西兰大白兔24只,分为正常对照组（N）、模型2周（M2)组和模型4周(M4)组。使用内毒素+激素建立股骨头坏死的动物模型。给药后2周和4周取双侧股骨头观察骨小梁和髓腔的组织形态学变化。结果: 模型组骨小梁内骨细胞核固缩,空骨陷窝增加,小梁间脂肪细胞增多、增大;髓腔内脂肪细胞增多、增大,造血组织明显减少。结论: 小剂量内毒素+激素成功诱导兔股骨头坏死模型,这种动物模型操作简单,稳定可靠,重复性好,为研究激素性股骨头坏死的发病机制和治疗方法提供了帮助。     

CyclinE-CDK2分子活性调节机制

Cyc linE-CDK2是细胞周期G1/S期的转折中的关键调控因子,其分子活性受各种细胞因子、磷酸化/去磷酸化修饰、泛素介导的蛋白降解途径及细胞周期依赖性蛋白激酶抑制物(cyc lin-dependent k inase in-h ib itor,CK Is)等多种方式构成的精细调控网络调节。其活性失调将导致细胞增殖紊乱甚至肿瘤的发生。认识Cyc linE-CDK2分子活性调节机制有助于理解它在肿瘤形成中的作用。     

Inhaled furosemide: a whole new mechanism of action

The use of aerosolized furosemide has been increasing throughout Mexico, primarily because of its mechanism and site of action as well as its local and systemic effect. We hypothesize that its effect on the respiratory system is totally independent from its diuretic activity and that it is primarily caused by its interaction with the chlorine channels. Furthermore, there is also evidence that furosemide induces prostaglandin synthesis, blocks the sodium-calcium pump, producing relaxation of the smooth muscle that narrows the airway and causes reduced nerve responsiveness to the Neurokinin A produced in acute asthma attacks.     

‘Arc’-hitecture of normal cognitive aging

Arc is an effector immediate-early gene that is critical for forming long-term memories. Since its discovery 25 years ago, it has repeatedly surprised us with a number of intriguing properties, including the transport of its mRNA to recently-activated synapses, its master role in bidirectionally regulating synaptic strength, its evolutionary retroviral origins, its ability to mediate intercellular transfer between neurons via extracellular vesicles (EVs), and its exceptional regulation—both temporally and spatially. The current review discusses how Arc has been used as a tool to identify the neural networks involved in cognitive aging and how Arc itself may contribute to cognitive outcome in aging. In addition, we raise several outstanding questions, including whether Arc-containing EVs in peripheral blood might provide a noninvasive biomarker for memory-related synaptic failure in aging, and whether rectifying Arc dysregulation is likely to be an effective strategy for bending the arc of aging toward successful cognitive outcomes.     

蛋白质组学及其在疾病研究中的应用

生命的表现形式最终是由蛋白质决定的。因此 ,对蛋白质组的研究具有很现实的意义。从研究之初至今 ,研究技术不断提高 ,涉及面日益广泛 ,其应用价值越来越大。本文着重从技术及应用的角度 ,追踪最新的研究进展 ,对蛋白质组学及其在疾病研究中的应用作一的概述     

Animal models of human pituitary tumors

Three animal models of pituitary tumors were compared: the spontaneous prolactinoma in Wistar/Furth (W/Fu) rats, an estrogen-induced transplantable tumor in the Fischer rat (MtTF4), and a spontaneous prolactin transplantable tumor in the W/Fu rat (SMtTW1). The spontaneous prolactinoma in W/Fu rats is interesting in that it resembles the human prolactinoma by its morphological characteristics, its benign nature, and its secretion of prolactin alone. It may be useful to study the initial factors of tumorigenesis but it is very expensive and the variability of tumor growth makes it difficult to plan experiments. The MtTF4 tumor is an easy model to study because it is transplantable but this tumor differs from most human pituitary tumors by its induction by estrogen, its malignancy, its undifferentiated aspect and its secretion of ACTH, GH, and prolactin. The SMtTW1 tumor, a new model of transplantable tumor, is close to the human pituitary tumor because the initial tumor is spontaneous, the transplanted tumors are benign and well differentiated. They secrete prolactin only. These transplantable tumors are valuable for studying the factors of growth. Since no single tumor system is a perfect model, researchers have to work on different models each of which is appropriate for investigating specific problems.     

Structure-activity relationships of an exotoxin of Pseudomonas aeruginosa.

The relation of the structure of Pseudomonas aeruginosa exotoxin A (PA toxin) to its enzymatic activity (adenosine 5'-diphosphate-ribosyl transferase) in vitro and to its toxicity in vivo was examined. PA toxin is produced as a single polypeptide chain with a molecular weight of about 71,500. PA toxin is produced by Pseudomonas as a toxic proenzyme that lacks enzymatic activity. Adenosine 5'-diphosphate-ribosyl transferase activity is expressed when the molecule is denatured and reduced or when its is cleaved by Pseudomonas proteases to yield an enzymatically active 27,000-dalton fragment (fragment a). A 45,000-dalton protein is tentatively identified as the enzymatically inactive fragment b of PA toxin. Enzymatically active forms of the toxin lack toxicity for mouse L-cells or mouse lethality. Thus, it is concluded that the native toxin proenzyme is required for toxicity and that a structural rearrangement must precede its intracellular activity.     

The limitations of the paracrystalline model of disorder

The basic concept of the paracrystalline disorder model is revised and its applicability to disordered structures, notably liquids and amorphous materials, is examined. The concept of the ideal paracrystal can be considered useful provided its application is restricted to a semi-quantitative interpretation of anisotropic disorder structures; its applicability to liquid structures and amorphous structures with homogenous density fluctuations is very limited. The concept of the real paracrystal does not appear to be an improvement over that of the ideal paracrystal.     

A systematic review of the morphology and function of the sacrotuberous ligament

The sacrotuberous ligament (STL) has been linked to conditions such as pelvic girdle pain and pudendal nerve entrapment, yet its contribution to pelvic stability is debated. The purpose of this review was to explore the current understanding of the STL and highlight any gaps in knowledge regarding its anatomy and function. A systematic search of the literature was conducted, focussing on the morphology and attachments of the STL, the relationship of the STL with surrounding structures, and its neurovascular supply and function. A total of 67 papers and four textbooks were obtained. The attachment sites of the STL are largely consistent; however, the extent of its connections with the long head of biceps femoris, gluteus maximus, piriformis, the posterior layer of the thoracolumbar fascia, and sacrospinous ligament are unclear. Morphometric parameters, such as mean STL length (6.4–9.4 cm), depth (0.3–0.4 cm), and width (1.8–3.5 cm, at its mid‐point) are variable within and between studies, and little is known about potential side‐, age‐, or sex‐related differences. The STL is pierced in several sites by the inferior and superior gluteal arteries, but information on its innervation pattern is sparse. Functionally, the STL may limit sacral nutation but it appears to have a limited contribution to pelvic stability. Some morphological aspects of the STL warrant further investigation, particularly its connections with surrounding structures, innervation pattern and function. Knowledge of the detailed anatomy and function of this ligament is important to better understanding its role in clinical conditions. Clin. Anat. 32:396–407, 2019. © 2018 Wiley Periodicals, Inc.     

On the inadequacy of the concept of disease

A framework for a critical examniation of the disease concept is presented. The human organism is regarded as a complex system upon which certain hierarchies are imposed. The cell is regarded in this framework as the lowest hierarchy. Cells are aggregated into tissues and tissues into organs. Organs are assembled into organ systems constituting the human organism. The elementary indivisible unit in each hierarchy is called the HOLON. When viewed from the hierarchy below it encompasses a continuum. The holon is defined by its attributes. Its STATE represents the magnitudes of its attributes. The state of the organism is defined by the states of its holons. For each attribute a criterion level (or state) defines its ILLNESS STATE. ILLNESS is defined by the set of attributes crossing the criterion level. These attributes are divided into two two sets: Attributes requiring treatment by the physician and those not requiring intervention by him. The first is defined as DISEASE, while the second as the VIS MEDICATRIX NATURAE. THERAPY is the restoration of “ill” attributes below their criterion levels. The process of selecting the DISEASE attribute set from all organismic attributes is called DIAGNOSIS. The correctness of a diagnosis is testable by treatment results. A successful treatment corroborates the diagnosis and vice versa. Since an intractable disease is also untreatable, its diagnosis is not testable (or falsifiable) in Popper's sense. The framework provides also means to test the relevancy of cancer theories to human cancer.     

微型轴流式血泵材料表面处理技术分析

由于微型轴流式血泵置入心内的特殊部位，既要保证其血液相容性，又要保证组织相客性，与血液接触的材料表面，可选择r-水蛭素处理，以提高材料的血液相容性；与各种生物组织材料接触的表面一可选择纤连蛋白处理，使材料表面内皮化。以提高材料的组织相容性。