Development of the utero-placental circulation: the role of carbon monoxide and nitric oxide in trophoblast invasion and spiral artery transformation

It is now well known that in order to establish human hemochorial placentation and to provide a progressive increase in blood supply to the growing fetus, the uterine spiral arteries must undergo considerable alterations. This physiological modification is thought to be brought about by the interaction of invasive cytotrophoblast with the spiral artery vessel wall. Despite intensive research our understanding of the mechanisms that control human trophoblast invasion in normal, let alone abnormal pregnancy, are sill poorly understood. This is partly due to difficulties in obtaining "true" placental bed biopsies and most investigators have relied on in vitro models of trophoblast invasion. This article describes the morphological changes that occur within the placental bed throughout human pregnancy along with a review of the various studies which have attempted to sample the placental bed. Thereafter, follows a review of the evidence that invasive trophoblast can release the vasoactive agents nitric oxide and/or carbon monoxide which, in turn, could contribute to early physiological changes in spiral arteries prior to destruction of the smooth muscle within the vessel wall. Current evidence supports the idea that trophoblast-derived carbon monoxide may contribute to spiral artery modification. In contrast there is no evidence for a similar role by nitric oxide.     

Modification of uterine vasculature during pregnancy in macaques

Embryonic development in macaques includes extensive modification of the uterine vasculature by fetal trophoblast cells. Soon after the onset of blastocyst attachment to the endometrium, syncytial trophoblast cells intrude between endometrial epithelial cells, resulting in focal epithelium loss. Trophoblast cells continue to move into the endometrial stroma and encounter superficial uterine capillaries. These capillaries are penetrated by trophoblast, which permits maternal blood to leave the maternal circulation and enter lacunae formed within the mass of trophoblast cells. Cytotrophoblast cells enter the uterine vessels and attach to the endothelium via cell adhesion molecules prior to migration into confluent spiral arterioles, against the flow of blood. As intra-arterial cytotrophoblast cells migrate, they displace adjacent endothelium, produce matrix metalloproteinases, traverse the tunica intima, and reside in the tunica media as intramural trophoblast. Intramural trophoblast cells disrupt the tunica media and become surrounded by an extensive extracellular matrix. In areas proximal to the placenta, the entire circumferences of spiral arteries are modified in this way. In the same arteries, distal to the placenta and farther "upstream," trophoblast-mediated changes to the arterial wall are less extensive. Uterine veins are modified by trophoblast only in the area immediately next to the trophoblast shell, with no trophoblast migration. The functional consequence of this trophoblast activity may be to ensure an adequate flow of maternal blood to the placenta, thus enhancing the survival of the fetus.     

Confocal laser scanning microscope study of cytokeratin immunofluorescence differences between villous and extravillous trophoblast: cytokeratin downregulation in pre-eclampsia

Pre-eclampsia is a disease characterized by failures in interstitial implantation. One product of the implantation process is the basal plate; a structure whose complexity makes it hard to fully appreciate the pathological changes in significant diseases of pregnancy. This article describes our use of CLSM immunofluorescence to examine the cytokeratin composition of the cells of trophoblastic origin in the term placental basal plate. Large differences in the content of the structural polymeric protein were compared using analysis of digital images. We show that greater pancytokeratin immunofluorescence is observed in extravillous cytotrophoblast cells as compared with villous trophoblast. There is a >30-fold difference in the mean area percent of the most intensely immunofluorescent pixels in the tissue containing these cells. This is a very high, statistically significant difference as defined by the Wilcoxon Signed Ranks Test Asym. Sig. (two-tailed): P < 0.001. The most invasive population of cells of the trophoblast lineage (the extravillous trophoblast) exhibits a significant reduction in cytokeratin immunofluorescence when comparisons of healthy and pre-eclamptic pregnancies are made. This ratio was 2.4:1. It was tested using the Mann-Whitney U-test. From healthy to pre-eclamptic the reduction was from mean rank 83.42((healthy)) to 51.13((pre-eclamptic)). The difference was very highly statistically significant (n = 53 + 75 = 128; U = 984.500; Z = -4.852; P < 0.001). There was also less cytokeratin-related immunofluorescence in villous trophoblast when healthy villi were compared with pre-eclamptic villi. The observed alterations in trophoblastic cytoskeletal components are expected to damage the anchorage and motility of cells. The extravillous trophoblast is known to be necessary for implantation. This leads to a cellular hypothesis of the failure of implantation resulting in reduced depth of uterine invasion and failure to adapt the spiral arterioles for low-pressure perfusion of the intervillus space, two well-known features of pre-eclampsia. The reduction in cytokeratin-related immunofluorescence in the villus trophoblast seen on comparing healthy term placentae with those from pre-eclamptics implies that the trophoblast is a weaker epithelial layer in the hypertensive pregnancy. This could account for the rise in deported trophoblast associated with pre-eclampsia. Deported trophoblast has been invoked as the systemic messenger that leads to generalized maternal hypertension seen in this condition.     

UCK2 promotes the proliferation,migration, and invasion of trophoblast cells in preeclampsia by activating the STAT3 pathway

Background: Preeclampsia (PE), characterized by hypertension and proteinuria, leads to serious maternal and infant complications. Uridine-cytidine kinase 2 (UCK2) belongs to the UCK family, a class of enzymes that catalyzes the conversion of uridine and cytidine to monophosphate form. However, the role of UCK2 in PE has not been reported. Methods: The expression of UCK2 was detected in the placenta of PE patients and N(ω)-nitro-L-arginine methyl esterinduced PE mouse model. Through forced up-regulation or down-regulation of UCK2 in vitro, we examined the effects of UCK2 on the proliferation, apoptosis, migration, and invasion of trophoblast cells. Stattic, the inhibitor of STAT3 pathway, was used to investigate whether the STAT3 pathway mediates the biological function of UCK2 in trophoblast cells. Results: The present study found that UCK2 showed low expression in the placenta of PE patients and PE mouse model. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and flow cytometry assays verified that up-regulation of UCK2 promoted the proliferation of trophoblast cells, while the silence of UCK2 suppressed cell proliferation. Besides, flow cytometry and TdT-mediated dUTP Nick-End Labeling assays demonstrated that knockdown of UCK2 resulted in apoptosis of trophoblast cells. The wound healing and transwell assays showed that the migration and invasion activities of the trophoblast cells were facilitated by the overexpression of UCK2 and were blocked by the silence of UCK2. Furthermore, the expression of phosphorylated STAT3 was increased with the upregulation of UCK2 and decreased with the inhibition of UCK2. When the STAT3 pathway was blocked by its inhibitor stattic, the promotion effects of UCK2 on trophoblast cells were suppressed. Conclusion: UCK2 promotes the proliferation, migration, and invasion of trophoblast cells, and these effects may be partly mediated by the activation of the STAT3 pathway.     

Immunohistochemical distribution of heat shock protein 70 and proliferating cell nuclear antigen in mouse placenta at different gestational stages

The aim of the present study was to investigate immunohistochemical distribution of heat shock protein 70 (Hsp70) and proliferating cell nuclear antigen (PCNA) in the mouse placenta at different gestational stages. For this purpose a total of 18 Swiss albino female mice at 12–14 weeks of age were used. Females were sacrificed on days 3 (early), 10 (mid‐), and 17 (late) of pregnancy and the implantation sites of the pregnant uterus were sampled. The sections were made transversely through the central region of the implantation site and stained with hematoxylin and eosin for histological examination. PCNA and Hsp70 was stained immunohistochemically. Since the definitive placenta was not still formed on day 3 of pregnancy, Hsp70 and PCNA positivity were evaluated in only luminal epithelium and decidual‐stromal cells. On days 10 and 17 of pregnancy, Hsp70 and PCNA positivity were evaluated in labyrinth zone, junctional zone and decidual layer of placenta. Hsp70 expression was observed trophoblast cells and decidual cells and was relatively constant throughout the pregnancy. This protein was strongly labeled in the trophoblast cells; while decidual cells were displayed moderate staining. In early pregnant mouse uteri, PCNA was mainly localized in decidual‐stromal cells. The trophoblast cells and decidual cells displayed highly proliferative activity at the midgestational period. However there was a significant decrease in the percentage of PCNA positive cells in late gestation. Microsc. Res. Tech. 79:251–257, 2016. © 2016 Wiley Periodicals, Inc.     

Healthy and pre-eclamptic placental basal plate lining cells: quantitative comparisons based on confocal laser scanning microscopy

Immunocytochemical confocal laser scanning microscope images of the monolayer of cells lining the intervillus space at the basal plate of term placentae were analysed using stereology. Immunoreactively-distinct regions of this mosaic layer were measured. In basal plate from healthy pregnancies, trophoblast epithelium occupied 18.91% of the surface area and endothelium 60.81%. In pre-eclampsia the equivalent areas were 15.57% and 67.63%. Acellular fibrinoid covers the remaining area and this component decreases in area in pre-eclampsia. The statistically significant increase in the cellular endothelial compartment may be relevant to the hypertensive pathology of pre-eclampsia as endothelial signalling plays a major role in regulation of blood pressure.     

Advanced glycation end-products change placental barrier function and tight junction in rats with gestational diabetes mellitus via the receptor for advanced glycation end products/nuclear factor-κB pathway

The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo. Gestational diabetes mellitus (GDM), the most common complication during pregnancy, highly affects placental function in late gestation. Advanced glycation end-products (AGEs), a complex and heterogeneous group of compounds engaged by the receptor for AGEs (RAGE), are closely associated with diabetes-related complications. In this study, AGEs induced a decrease in the expression of tight junction (TJ) proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB. Sprague-Dawley (SD) rats injected with 100 mg/kg AGEs-rat serum albumin (RSA) via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group (n = 10). The effect of AGEs on placental permeability was determined using the EvansBlue dye extravasation method. The ultrastructure of the placenta samples was observed by transmission electron microscopy. The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE (sRAGE). AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta, but has no effect on blood glucose. The expression of TJ-related proteins, including ZO-1, Occludin, and Claudin 5, were downregulated after AGEs treatment. Further, AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor. The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE. This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.     

人体脊柱T12-L2活动节段三维重建及扭转特性研究

研究人体脊柱T12-L2活动节段的三维重建方法以明确脊柱该节段扭转特性对人体脊柱胸腰段诊断具有重要的意义。本文探讨了基于mimics模型,利用SolidWorks实体编辑方法,对人体脊柱T12-L2活动段进行三维实体重建,并对重建后的人体脊柱胸腰段模型,利用有限元方法进行扭转特性分析。分析结果认为:建立精确的人体脊柱三维实体模型和研究人体脊柱的扭转特性,是进行胸腰段疾病诊断和腰部手法治疗的关键因素。本文研究内容为人体脊柱胸腰段疾病诊断和腰部手法治疗提供一定借鉴作用。     

油气长输管道系统中人的可靠性因素体系分析

管道系统中人为因素的影响是管道可靠性分析不可避免的一部分,分析引起管道事故的人为因素,防止或减少人为因素的影响,为保证安全运行提供依据.本文针对油气管道事故和安全问题,对引发事故的人为因素的分类和重要的因素进行了详细的讨论,建立了人的可靠性因素体系,给出了人为因素与人为差错的关系,并根据对人为因素的分析提出了预防和减少人为因素影响的措施.     

可穿戴式下肢助力机器人运动学分析与仿真

可穿戴下肢助力机器人是将人和机器人机构结合在一起,通过获取人体下肢运动行为信息来控制机器人机构与人体协调、同步行走,并实时为人体下肢提供助力的一种装置。可穿戴下肢助力机器人机械系统不仅符合以往的拟人机器人行走机构的设计要求,又要与人体下肢系统相匹配,为人体提供助力时,与人体下肢相协调、互不产生运动干涉。基于人体下肢各关节运动参数,对助力机器人机械系统进行了运动学分析并建立了模型,通过对人体下肢运动仿真,验证了所建立的运动学模型的可行性。     

人体运动学模型的研究

人体运动学模型对研究人体空间运动的位姿与人的最佳出力、最佳受力有重要意义。研究人体运动学模型对开展人机工程的研究也有重要意义。提出人体机械化的概念，把人体等效为机构，应用机构学的基本理论建立了人体的运动学模型，再运用坐标变换的数学方法解决了人体运动位姿的计算问题，对操作机械设备及科学培训体育运动员等人因工程有很大的应用价值。     

运动人体图像分割算法研究

许多监视系统要求能对运动人体的行为进行监视,如监狱、仓库、保密室、办公室、会场等场景,对运动人体的识别特点是区分运动人体与其他运动目标,而非判别人的个体间差别.以帧间差分法分割运动目标图像为基础,通过人的外形模式匹配、肤色匹配和姿态匹配的融合构造了一种识别运动目标中人体运动目标的算法(AMHBR),该算法的特点是简洁高效、适合嵌入式系统等资源受限的监视系统.通过试验证明,该算法能在不同的场景中分割出运动人体图像,具有很好的鲁棒性和准确度,达到了实用的程度.该算法对于监视系统中自动控制镜头对准运动人体具有实际意义.     

An investigation on the integrated human driver model for closed-loop simulation of intelligent safety systems

This paper presents an integrated human driver model for a closed-loop simulation of the intelligent safety system. A lateral human driver model was developed to represent the steering behavior of a human driver using the finite preview optimal control method. A longitudinal human driver model represents a human driver’s throttle and brake control behavior relative to the preceding vehicle motion. It computes the desired acceleration and generates throttle/brake inputs to maintain vehicle-to-vehicle clearance at a desired level or to control vehicle speed. An integrated driver model was been developed using the longitudinal and lateral driver models to represent the behavior of a human driver in alternative driving situations, that is, vehicle following, lane following, emergency braking, and so on. Simulation studies were conducted using “Carsim” model which is validated using vehicle test data. Results showed that a human driver’s behaviors could be well represented by the integrated human driver model presented in this paper. Closed-loop simulations of a unified chassis control system with the integrated human driver model were conducted.     

对大学学者自由本质的哲学解读

自由是人的本质规定,因而自由是一切社会活动的价值合理性依据.自由是大学学者从事学术活动的普遍性条件,它是一种工具价值;同时,促进人类自由,把对人类的限制减低到最低程度是大学学者学术活动追寻的终极价值,因而大学学者的学术活动不仅是一个实践自由的过程,也是追寻人类自由的价值过程.从这个意义上说,学者的应然本质是自由.     

人体坐姿尺寸虚拟测量系统的开发

针对目前我国国民体型原始数据缺乏、与坐姿相关的产品(坐姿产品)设计不良的问题,研究了人体坐姿尺寸的测量方法和人体坐姿特征点提取算法,运用机器视觉和虚拟仪器相结合的手段,设计开发了人体坐姿尺寸虚拟测量系统,为人体坐姿尺寸数据的不断更新提供了有效的测量工具,对保证坐姿产品的设计能遵循人机工程学原理具有现实意义。     

人的固有性、可能性和现实性——兼论教育目的

因有意识而获得自由，是人区别于动物的固有性；人更重要更独特的方面，在于人有可能性。教育是让人越来越远离动物的一种活动，在一定的意义上就是让人发展、创造可能性，及避免某些可能性。事实上，教育提供可能性也就是提供获得种种现实结果的可能性，可能性让我们对现实可以有更多的期待。但教育并不需要过于介意一些似乎更现实的口号，教育越富于理想才越能表现属于它自己的现实。     

载人离心机平衡调节系统设计

为了实现载人离心机精确的配平,减小运转过程中的不平衡力,设计了由手轮、丝杠-螺母、导轨-滑块、活动配重块、固定配重块等组成的平衡调节系统。根据测力传感器获得的数据计算不平衡量,移动活动配重块,实现平衡调节。计算了载人离心机静止时,实现活动配重块移动所需在手轮上施加的力和载人离心机运转时丝杠所承受的离心力。分析了固定配重块在载人离心机满载荷运转时的应力、应变。分析结果表明,平衡调节系统可以满足载人离心机的配平要求。     

人体骨盆位姿模拟机构的运动学分析及仿真

根据人体骨盆的运动规律,设计了一种4自由度人体骨盆位姿模拟机构.建立了人体骨盆位姿模拟机构的正运动学模型和逆运动学模型,并推导出了机构的雅可比矩阵.基于机构的运动学模型建立了仿真模型,并采用MATLAB/Simulink对人体骨盆位姿模拟机构进行了仿真分析.仿真结果表明:该机构方案是可行的,能够模拟人体骨盆的运动规律.同时仿真结果也验证了运动学模型的正确性.     

人机智能协同在医疗康复机器人领域的应用

生物智能(人类智能)和人工智能(机器智能)各有所长,具有很强的互补性。借助各种人—机接口技术和方法,将生物智能和人工智能结合起来,使它们优势互补、协同工作,从而产生更强大的智能形态,并将孕育出重大的理论创新和技术方法突破。首先介绍了人机智能协同的主要研究方向、关键科学问题和主要研究内容,之后对人机智能协同在服务、医疗和康复机器人领域的应用及推动作用做了进一步介绍,最后分析了应用存在的可能问题和挑战并做出总结。     

Human following of a mobile service robot with single laser range finder

The human following becomes one of the significant procedure in human-friendly navigation of mobile robots.Many potential applications of human-following technology are developed lately.This paper sugg...