大鼠门静脉分支残端置管模型构建及细胞移植途径的评价

目的：大鼠肝部分切除模型被广泛的应用于肝脏疾病的研究,随着干细胞治疗肝损伤及护肝药物研究的发展,对大鼠肝损伤模型也提出了很多新的要求。本实验拟在大鼠肝部分切除术的基础上改进以建立大鼠肝断面门静脉分支残端的静脉置管模型,并进行细胞移植实验,对比分析新模型的优劣。方法：60只F344大鼠分为三组。A、B组行行85％肝切除术;C组行85％肝切除术＋肝断面门静脉分支残端置管术。术中B组经门静脉注入4×105个表达GFP（greenfluorescenceprotein,GFP）的胎肝干细胞（fetalliverstern／progenitorcells,FLSPCs）。c组经留置导管注射入同等量的FLSPCs,A组注射同等剂量的培养液。72小时取血清,测定肝功能ALT、AST,统计死亡率;取肝脏组织切片观察其修复情况。统计学采用方差分析和LSD—t检验。结果：B、C组F344大鼠72小时肝功指标（ALT、AST）均明显优于A组;B组、C组肝脏组织学的病理损伤的恢复分别较A组快。B、C组间肝功指标无统计学意义。结论：经门静脉分支残端置管途径移植FLSPCs效果等同于经门静脉穿刺途径,且该模型具有可反复、可选时、减少创伤等优点。     

骨髓间充质干细胞移植治疗大鼠肝损伤的实验研究

目的:了解肝损伤大鼠在输注骨髓间充质干细胞后肝功能生化指标和肝脏组织病理变化情况,为临床应用提供实验依据。方法:将大鼠随机分为正常组和造模组。造模组采用腹腔注射四氯化碳的方法构建,然后将造模组随机分为干细胞移植治疗组、模型对照组。干细胞移植组经门静脉输注标记的骨髓间充质干细胞。3周后处死大鼠。然后检测大鼠肝功能、肝脏病理改变分析干细胞移植治疗肝损伤效果。结果:干细胞移植治疗3周后,大鼠的肝脏与对照组比较,明显恢复,但是并没有恢复到正常水平。结论:骨髓间充质干细胞对肝损伤的大鼠有治疗作用。     

声触诊组织量化技术（VTQ）测量肝硬度与血清AST/ALT比值评价肝硬化患者严重程度及预后分析

摘要 目的：探讨VTQ测量肝硬度与血清AST/ALT比值对肝硬化患者严重程度及预后的评价价值。方法：回顾性选择2018年1月至2022年10月来我院诊治的肝硬化患者80例,根据Child-Pugh分级将80例患者分为Child-Push A级30例、B级25例、C级25级,根据是否存在并发症将80例患者分为并发症组（45例）与非并发症组（35例）,80例患者均用VTQ法检测VTQ值,检测所有患者的血清ALT、AST水平,计算ALT/AST比值。对比不同Child-Push分级患者不同部位的VTQ值,对比不同Child-Push分级患者的AST、ALT水平及AST/ALT比值,对比有无并发症组的不同部位VTQ值,对比有无并发症组患者的AST、ALT水平及AST/ALT比值,分析80例患者不同部位VTQ值与AST、ALT、AST/ALT比值的相关性。结果：C组患者不同肝脏部位的VTQ值明显较A组及B组高,B组患者不同肝脏部位的VTQ值较A组高（P<0.05）。C组的AST水平、AST/ALT值明显较A组、B组高,B组的AST水平、AST/ALT值明显较A组高（P<0.05）,C组的ALT水平较A组、B组高,B组的ALT水平较A组高,但组间对比无统计学意义（P>0.05）。并发症组不同肝脏部位的VTQ值明显较无并发症组高（P<0.05）。并发症组的AST、AST/ALT比值明显较无并发症组高（P<0.05）,并发症组的ALT较无并发症组高,但组间对比无统计学意义（P>0.05）。80例肝硬化患者的AST、AST/ALT比值与不同部位的VTQ值正相关（P<0.05）,ALT水平与不同部位的VTQ值无相关性（P>0.05）。结论：VTQ测量肝硬度与血清AST/ALT比值可用于评价肝硬化严重程度及预后。     

海参胶原低聚肽对抗结核药物性肝损伤改善效果

目的：探讨海参胶原低聚肽（SCCOPs）对利福平和异烟肼联用所致大鼠肝损伤的保护作用。方法：72只Wistar雄性大鼠随机分为正常对照组（A）、模型组（B）、阳性对照组（C）、海参肽低剂量组（D）、海参肽中剂量组（E）和海参肽高剂量组（F）6组。除A组给予0.9%生理盐水（20mg/kg）外,其余5组大鼠分别给予异烟肼+利福平各50 mg/kg·BW,2h后,A、B组给予灌胃等体积生理盐水,C组给予水飞蓟宾22.1mg/kg·BW,D组给予SCCOPs 346 mg/kg·BW、E组给予SCCOPs 692 mg/kg·BW、F组给予SCCOPs 1 038 mg/kg·BW;实验周期为4w。HE染色观察肝脏组织形态结构及组织病理学评分;测定丙氨酸氨基转氨酶（ALT）、天冬氨酸氨基转氨酶（AST）、碱性磷酸酶（ALP）;测定大鼠肝脏指数;测定大鼠肝匀浆氧化应激指标。结果：模型组大鼠肝脏组织呈现大部分肝细胞浊肿变性,分界不清;肝小叶排列不齐,肝窦道受压变窄;脂肪变性广泛,伴有炎性细胞浸润,给予水飞蓟宾和海参低聚肽干预后得到显著改善。与正常对照组相比,模型组血清谷氨酸氨基转氨酶（ALT）和碱性磷酸酶（ALP）水平分别升高了6.46%和17.70%（P＜0.05）。与模型组相比,水飞蓟宾组的ALT和ALP水平分别降低了25.36%和29.65%（P＜0.05）,而海参低聚肽低、中和高剂量组ALT水平分别降低了28.89%、27.77%和18.56%（P＜0.05）;ALP水平分别降低了14.84%、24.78%和21.08%（P＜0.05）。结论：海参胶原低聚肽可明显改善抗结核药物性肝损伤。     

80％门静脉结扎后肝脏组织中MMP-9的表达与肝再生作用的相关性研究

目的：探讨基质金属蛋白酶-9（MMP-9）在大鼠80％门静脉分支结扎模型中大鼠增生肝脏组织中的表达及其与肝再生作用的关系。方法：健康SD雄性大鼠48只,随机平均分成假手术对照组（Sham）和门静脉结扎实验组（PVL）。观察术后1、3、7和14d保留侧肝叶重量／体重比值;下腔静脉采血后检测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）值的变化;光镜下观察保留侧肝脏组织的病理形态变化;用免疫组化法检测增殖细胞核抗原（Proliferating cell nuclear antigen,PCNA）的表达,用免疫印记法检测MMP-9的表达,并进行统计分析。结果：80％门静脉分支结扎后,结扎侧肝叶呈进行性萎缩,保留侧肝叶重量／体重比值逐渐增加,7d达“平台期”;与对照纽明显不同,PVL组的ALT、AST的值在1h达到高峰,7d后回到正常水平;保留侧肝脏组织中PCNA阳性细胞计数与对照组比较,3d开始表述增强（P〈0．05）,7d以后逐渐恢复至正常水平（P〉0．05）;保留侧肝叶MMP-9蛋白的表达在术后3d开始增加,术后7d达到高峰。结论：MMP-9蛋白的表达在80％门静脉结扎后大鼠肝再生过程中发挥重要作用。     

移植途径对大鼠骨髓间充质干细胞归巢及肝功能恢复的影响

目的 探讨移植途径对骨髓间充质干细胞(MSCs)归巢及促进肝切除大鼠肝再生的影响.方法 建立肝切除大鼠模型,随机分为3 组,即肝切除对照组、尾静脉移植组和门静脉移植组.移植组分别经尾静脉和门静脉注射DAPI 标记的MSCs 约1.5×106/ 只,分别于第3 天和第9 天后采血清检测肝功能,第9 天处死大鼠取肝脏标本,...     

移植途径对大鼠骨髓间充质干细胞归巢及肝功能恢复的影响

目的 探讨移植途径对骨髓间充质干细胞（MSCs）归巢及促进肝切除大鼠肝再生的影响.方法 建立肝切除大鼠模型,随机分为3 组,即肝切除对照组、尾静脉移植组和门静脉移植组.移植组分别经尾静脉和门静脉注射DAPI 标记的MSCs 约1.5×106/ 只,分别于第3 天和第9 天后采血清检测肝功能,第9 天处死大鼠取肝脏标本,并通过荧光显微镜观察两种移植途径对MSCs 向肝脏迁移的影响.结果 门静脉移植组（18.1 ± 3.4）个细胞/100 倍视野到肝脏归巢及定植的 MSCs 多于尾静脉移植组（7.6 ± 2.0）个细胞/100 倍视野,差异有统计学意义（P 〈 0.01）.术后第9 天各组大鼠肝功能均有好转,丙氨酸氨基转移酶（ALT）及天冬氨酸氨基转移酶（AST）3 组之间对比差异无统计学意义（F = 2.822,1.046,P = 0.057,0.365,P 〉 0.05）;但两移植组与单纯肝切除组比较血浆白蛋白（ALB）均有明显升高,差异具有统计学意义（F = 6.259,P = 0.006）;尾静脉移植组与门静脉移植组两移植组之间相比,差异无统计学意义（P 〉 0.05）.结论 移植途径对 MSCs 归巢、定植到肝脏有一定影响,门静脉途径优于外周静脉,MSCs 移植对肝大部切除大鼠肝功能恢复具有促进作用.     

制备低剂量四氯化碳诱导小鼠慢性肝损伤模型的探讨

目的：通过注射低剂量四氯化碳（ carbon tetrachloride ,CC14）建立B/C小鼠肝损伤模型。方法正常B/C小鼠随机分为正常对照组、油对照组、CCl4模型组。正常对照组常规饲养;油对照组腹腔注射鲁花花生油（10μL/g,1次/3天,连续6周）;CC14模型组腹腔注射0.5％CC14（10μL/g,1次/3天,连续6周）。第6周,各组小鼠检测血清AST、ALT浓度,HE及Masson染色后观察小鼠肝脏结构、细胞形态及纤维化程度。结果第6周CCl4模型组小鼠血清ALT（P＝0.00）、AST（P＝0.00）浓度极显著性增高,HE及Masson染色显示CCl4模型组小鼠肝上皮细胞呈广泛性空泡样变及大量坏死,肝小叶内出现明显的条索样纤维增生,其纤维化程度评分显著性升高（P ＝0.00）,纤维显色积分光密度值极显著性增高（P ＝0.00）。结论注射低剂量CCl4可以诱导B/C小鼠肝损伤模型,实验模型具备肝损伤和肝纤维化病理特征。     

海兔素对刀豆蛋白A诱导的化学性肝损伤保护作用

目的:探讨海兔素对刀豆蛋白A诱导的化学性肝损伤保护作用。方法:雄性Wistar大鼠随机分为4组。模型组与海兔素组给予15 mg/kg刀豆蛋白A尾静脉注射每周一次,制作化学性肝损伤模型,模型制作成功后,正常对照组、模型组每日给予大豆油灌胃,海兔素低、高剂量组给予100、150 mg/kg·d海兔素+大豆油灌胃。实验持续8周后,禁食12 h,处死大鼠。HE染色观察肝组织形态学改变;Masson Trichrome及天狼星红染色观察肝组织纤维化状况;全自动生化分析仪检测血清ALT、AST及LDH水平;ELISA实验测定血清TNF-α和TGF-β1水平。结果:与正常对照组相比,模型组大鼠肝小叶结构模糊紊乱,纤维组织增生明显,可见灶状坏死及炎性细胞浸润,胶原纤维明显增多,胶原指数明显升高。血清中ALT、AST、LDH及TNF-α和TGF-β1水平显著升高(P0.05)。海兔素干预后,肝小叶病变程度较模型组明显减轻,染色胶原显著减少,纤维增生明显改善,血清中ALT、AST、LDH及TNF-α和TGF-β1水平较模型组显著降低(P0.05),海兔素高剂量组与低剂量组相比,肝脏病变改善程度更为明显(P0.05)。结论:海兔素对刀豆蛋白A诱导的化学性肝损伤具有一定保护作用,其机制可能与下调TNF-α、TGF-β1水平有关。     

黄芪多糖预防2 型糖尿病大鼠肝损伤的实验研究

目的:研究分析黄芪多糖(Astragalus polysaecharides,APS)在预防2型糖尿病大鼠肝损伤的作用。方法:Wistar大鼠72只,其中48只以小剂量链脲佐菌素(Streptozotocin,STZ)建立2型糖尿病大鼠模型,并随机分为模型对照组(B组)和APS组(C组),余24只大鼠为正常对照组(A组)。C组大鼠给予APS 400 mg/kg/d灌胃,A、B组分别给予等量生理盐水。分别于第0、2、4、6周检测3组大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)以及丙二醛(MDA)水平,透射电镜下观察3组大鼠肝细胞超微结构变化。结果:第0、2周时B、C组大鼠ALT、AST、SOD以及MDA水平比较无显著差异(P0.05)。第4、6周时,C组大鼠ALT、AST以及MDA水平均高于A组,但低于B组;而SOD水平低于A组,但高于B组;差异均有统计学意义(P0.05)。电镜下观察,A组肝细胞内大量线粒体、内质网,结构完好,未见损伤;B组细胞器数量减少,线粒体及内质网形态异常,膜结构破损,细胞空化;C组细胞器也存在损伤,但较B组明显减轻。结论:APS可增加肝细胞抗氧化酶的活性,促进氧自由基的清除,减少肝细胞损伤,对预防2型糖尿病引起的肝功能损害有一定的价值。     

Some inequalities for the expectation of a product of functions of a random variable and for the multivariate distribution function at a random point

Under certain assumptions the expectation of a product of functions of a random variable is greater (smaller) than the product of expectations. The multivariate distribution function of m independent random variables at a random point is greater than the product of the distribution functions of the m variables.     

Empirical regression as a conditional expected value of a special distribution-mixture for a modelfree quantitative recording of stochastical relations

An “empirical” distribution function F?(x, y) is estimated from measured points (xi, yi), i =1(1)n, of a continuous two-dimensional random variable (X, Y) with unknown continuous density function f(x, y). The density function F?(x, y) of F?(x, y) is a mixture of n two-dimensional normal densities. The first order moments of F?(x, y) are the sample means x and y, whilst the second order moments are only proportional to the sample variances and the sample covariance. This “empirical” distribution F?(x, y) is used for evaluation of an empirical regression curve where a free parameter has to be fixed by an optimality criterion. The procedure is demonstrated by an example from morphometrical research.     

《生物信息学》课程教学模式探讨

在教学实践的基础上,结合生物信息学课程的学科特点,以及现代教育技术,就开设生物信息学课程的必要性及构建最合适的复合型教育模式展开了初步的探讨,为我国生物信息学课程的教学实施提供指导。随着时代的不断进步和发展,生物信息学的内涵也在不断扩大,包括生物信息学所涉及到的计算机基础知识、生物学基础知识、生物信息学研究领域、生物信息学应用领域等等。在生物信息学的教学实施过程中,将多个基础学科交叉融合是必备的,这不仅有助于增强学生对生物信息学科的了解,也对于学生在后续的生物信息学研究中起到了基石的作用。因此,如何将这些涉及范围广、涉及内容深的生物信息学基础课程恰当的传授给学生是教师们最需要考虑的问题,从而形成一套独特的教学体系,使生物信息学的教学工作更顺利,完整的进行下去。     

Estimation of the Number of Classes in a Population

The problem of estimating M, the number of classes in a population, is formulated as an occupancy problem in which N items are drawn from M urns. Under the assumption of a uniform distribution for the number of classes in the population, the sufficient statistic for M, which is the number of distinct classes observed, does not depend upon the number of repetitions in the sample. Point and interval estimates of M are developed using maximum likelihood and the method of moments. Both techniques give rise to the same basic equation which requires a simple iterative solution. These same techniques are used in the more general situation in which the classes can be further subdivided according to type.     

Superposition of modes in a caricature of a model for morphogenesis

In a model proposed for cell pattern formation by Nagorcka et al. (J. Theor. Biol. 1987) linear analysis revealed the possibility of an initially spatially uniform cell density going unstable to perturbations of two distinct spatial modes. Here we examine a simple one-dimensional caricature of their model which exhibits similar linear behaviour and present a nonlinear analysis which shows the possibility of superposition of modes subject to appropriate parameter values and initial conditions.     

Nano-intentionality: a defense of intrinsic intentionality

I suggest that most discussions of intentional systems have overlooked an important aspect of living organisms: the intrinsic goal-directedness inherent in the behaviour of living eukaryotic cells. This goal directedness is nicely displayed by a normal cell’s ability to rearrange its own local material structure in response to damage, nutrient distribution or other aspects of its individual experience. While at a vastly simpler level than intentionality at the human cognitive level, I propose that this basic capacity of living things provides a necessary building block for cognition and high-order intentionality, because the neurons that make up vertebrate brains, like most cells in our body, embody such capacities. I provisionally dub the capacities in question “nano-intentionality”: a microscopic form of “aboutness”. The form of intrinsic intentionality I propose is thoroughly materialistic, fully compatible with known biological facts, and derived non-mysteriously through evolution. Crucially, these capacities are not shared by any existing computers or computer components, and thus provide a clear, empirically-based distinction between brains and currently existing artificial information processing systems. I suggest that an appreciation of this aspect of living matter provides a potential route out of what may otherwise appear to be a hopeless philosophical quagmire confronting information-processing models of the mind.

A Comparison Between a Parametric and a Non-Parametric Method of Estimating the Percentiles of a Difference

A parametric and a nonparametric method of estimating the percentiles of a difference are compared. The parametric method assumes an underlying normal distribution and the nonparametric method estimates the distribution from the residuals. Applications to immunology are discussed.     

Persistent propensities: Portrait of a familiar controversy

Susan Mills and John Beatty's propensity interpretation of fitness encountered very different philosophical criticisms by Alexander Rosenberg and Kenneth Waters. These criticisms and the rejoinders to them are both predictable and important. They are predictable as raisingkinds of issues typically associated with disposition concepts (this is established through a systematic review of the problems generated by Carnap's dispositional interpretation of all scientific terms). They are important as referring the resolution of these issues to the development of evolutionary biology. This historical approach to the propensity interpretation of fitness draws attention to the precarious relation between philosophical clarification of scientific concepts and any given state of the empirical arts.     

Asymmetry of Motor Behavior of the Goldfish in a Narrow Channel

We studied swimming of goldfish fries about 3 cm long in a narrow channel by calculating the numbers of spontaneous turns on different sides. The ratio of fishes preferring to turn to the right vs to the left was 1.5:1.0, respectively; two-thirds of the fishes demonstrated an ambilateral behavior. Experiments with compulsory 10-min-long rotation of the fishes (clockwise around the longitudinal body axis for fishes preferring right-side turns and anticlockwise for fishes preferring left-side turns) showed that the behavioral asymmetry smoothed somewhat after such a procedure, and a greater number of the fishes became ambilateral in their preference to turn to one side or another. After a one- or two-day-long test, the initial asymmetry of motor behavior completely recovered. Compulsory rotation of similar fishes in the opposite direction exerted no influence on the asymmetry in the choice of the turning direction. Adaptation-induced training of the fishes (using fatiguing long-lasting vestibular stimulation) resulted in some smoothing of motor asymmetry but did not change its general pattern. Thus, our findings allow us to believe that a noticeable proportion of the goldfish individuals (similarly to other animals and humans) is characterized by an innate asymmetry of the motor function with a clear preference for either right- or left-side turnings. These relations can be smoothed under experimental influences but are recovered later on, i.e., they are stable and are not fundamentally transformed. We assume that the asymmetry of motor behavior of fishes in a narrow channel can be an adequate pre-requisite for further examination of the asymmetry of the brain and motor centers controlling changes in locomotion (body turnings)Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 52–60, January–February, 2005.