组蛋白去乙酰化酶抑制剂与5-FU合用对肝癌细胞HepG2的影响

目的：探讨MS-275和5-Fu联用对HepG2细胞周期和凋亡的影响，并对其机制进行初步探讨。方法：将细胞分成对照组、MS-275组、5-FU组和联合用药组。流式细胞仪检测各组细胞凋亡和周期变化；Westernblot分析各组Bcl-2、Bax、CyclinD1、P21蛋白表达。结果：MS-275和5-Fu联用能抑制肝癌细胞生长，诱导G0—G1期阻滞，促进细胞凋亡。上述效应具有时间和剂量依赖性。二者联用可以使P21蛋白上调，Bcl-2、CyclinD1蛋白下调，Bax蛋白无明显变化。结论：5-Fu和MS-275联用能提高HepG2细胞凋亡率和周期阻滞，其机制与下调CyclinD1、Bcl-2蛋白的表达、上调P21蛋白表达有关。     

Presynaptic opioid kappa-receptor and regulation of the release of Met-enkephalin in the rat brainstem

Opioid kappa-agonists had much more potent inhibitory effects on the high K+-evoked Met-enkephalin release from rat brain slices than did the mu- or delta-agonists. The opioid kappa- antagonist, MR2266 enhanced the evoked release of Met-enkephalin to a greater extent than did mu- or delta-antagonists in vitro and had a potent analgesia in mice in vivo. These findings suggest that the release of Met-enkephalin may be regulated in vitro and in vivo, mainly by presynaptic kappa-receptor-mediated mechanisms.     

Brachydactyly type A3 is caused by a novel 13 bp HOXD13 frameshift deletion in a Chinese family

Brachydactyly type A (BDA) is defined as short middle phalanges of the affected digits and is subdivided into four types (BDA1‐4). To date, the molecular cause is unknown. However, there is some evidence that pathogenic variants of HOXD13 could be associated with BDA3 and BDA4. Here, we report a Chinese autosomal dominant BDA3 pedigree with a novel HOXD13 mutation. The affected individuals presented with an obviously shorter fifth middle phalanx. The radial side of the middle phalanx was shorter than the ulnar side, and the terminal phalanx of the fifth finger inclined radially and formed classical clinodactyly. Interestingly, the index finger was normal. The initial diagnosis was BDA3. However, the distal third and fourth middle phalanges were also slightly affected, resulting in mild radial clinodactyly. Both feet showed shortening of the middle phalanges, which were fused to the distal phalanges of the second to the fifth toes, as reported in BDA4. Therefore, this pedigree had combined BDA3 and atypical BDA4. By direct sequencing, a 13 bp deletion within exon 1 of HOXD13 (NM_000523.4: c.708_720del13; NP_000514.2: p.Gly237fs) was identified. The 13 bp deletion resulted in a frameshift and premature termination of HOXD13. This study provides further evidences that variants in HOXD13 cause BDA3‐BDA4 phenotypes.     

Cortical dendritic pathology in human immunodeficiency virus encephalitis.

Previous neuropathological and morphometric studies of the cerebral cortex of patients with human immunodeficiency virus encephalitis (HIVE) have shown a decrease in the population of large neurons, moderate loss in synaptophysin immunoreactivity, and pathological changes in dendrites. To further characterize and quantify alterations in the dendritic tree of neocortical pyramidal neurons, we performed a modified Golgi impregnation technique on Formalin fixed blocks from the frontal cortex of 5 HIVE cases, 5 human immunodeficiency virus seropositive control cases without encephalitis, and 5 human immunodeficiency virus seronegative controls. Apical dendrites of HIVE cases were dilated, vacuolated, and tortuous with decreased length and branching. Basal and oblique dendrites also showed these alterations, but to a lesser extent. Some dendrites presented lacunae and filopodia consistent with remodeling. Computer aided quantification of HIVE cases showed a 40-60% decrease in spine density throughout the entire length of dendrites. Laser confocal imaging of Golgi impregnated sections displayed aberrant spines in regions of abnormal second order dendritic branches. These observations support the role of primary dendritic damage in HIVE in contrast to other neurodegenerative disorders where the primary pathology is presynaptic.     

正常人周围神经内膜中的纤维性长间距体及神经束膜细胞的超微结构

本文报道在电镜下观察了正常人腹壁神经小分支的神经束膜细胞的超微结构,并在神经内膜间质中发现了纤维性长间距体(FLS)。 1.2～5层神经束膜细胞紧密地包绕着神经束。束膜细胞呈扁平样排列,胞质内有丰富的微丝和吞饮小泡,基膜明显而连续。紧贴其外的和神经内膜中的成纤维细胞均无基膜。两相贴的束膜细胞之间可见缝管连接和丰富的桥粒,也可见胶原纤维。神经内膜间质中胶原原纤维细,有FLS体存在;而束膜外侧的胶原原纤维较粗,未见FLS体。 2.多数FLS体与无髓神经纤维的Schwann细胞基膜相连,个别处周围为一般胶原原纤维,未见基膜;有髓神经纤维的Schwann细胞处未见FLS体。纵切面上,多数FLS体呈纺锤状,大小不等,其长轴与相邻胶原原纤维的长轴平行,有时可见两者相互延续移行。偶见FLS体呈桥样架于两Schwann细胞之间,FLS体的暗带与两侧Schwann细胞的基膜相延续。还见2～3个FLS体并为一体,但横纹错开。FLS体的斜断面近似长方形,也呈横纹样结构,与纵断面没有很大区别。FLS体的横纹周期长约133nm,暗带约53nm,主要由电子较密的颗粒状物构成;明带约80nm,由方向大致相同的微丝网构成;横纹周期中无细横纹存在。本文并对神经束膜细胞可能的作用、FLS体与基膜的关系、FLS体的横纹周期问题进行了讨论。     

Physics-Driven CFD Modeling of Complex Anatomical Cardiovascular Flows—A TCPC Case Study

Recent developments in medical image acquisition combined with the latest advancements in numerical methods for solving the Navier-Stokes equations have created unprecedented opportunities for developing simple and reliable computational fluid dynamics (CFD) tools for meeting patient-specific surgical planning objectives. However, for CFD to reach its full potential and gain the trust and confidence of medical practitioners, physics-driven numerical modeling is required. This study reports on the experience gained from an ongoing integrated CFD modeling effort aimed at developing an advanced numerical simulation tool capable of accurately predicting flow characteristics in an anatomically correct total cavopulmonary connection (TCPC). An anatomical intra-atrial TCPC model is reconstructed from a stack of magnetic resonance (MR) images acquired in vivo. An exact replica of the computational geometry was built using transparent rapid prototyping. Following the same approach as in earlier studies on idealized models, flow structures, pressure drops, and energy losses were assessed both numerically and experimentally, then compared. Numerical studies were performed with both a first-order accurate commercial software and a recently developed, second-order accurate, in-house flow solver. The commercial CFD model could, with reasonable accuracy, capture global flow quantities of interest such as control volume power losses and pressure drops and time-averaged flow patterns. However, for steady inflow conditions, both flow visualization experiments and particle image velocimetry (PIV) measurements revealed unsteady, complex, and highly 3D flow structures, which could not be captured by this numerical model with the available computational resources and additional modeling efforts that are described. Preliminary time-accurate computations with the in-house flow solver were shown to capture for the first time these complex flow features and yielded solutions in good agreement with the experimental observations. Flow fields obtained were similar for the studied total cardiac output range (1–3 l/min); however hydrodynamic power loss increased dramatically with increasing cardiac output, suggesting significant energy demand at exercise conditions. The simulation of cardiovascular flows poses a formidable challenge to even the most advanced CFD tools currently available. A successful prediction requires a two-pronged, physics-based approach, which integrates high-resolution CFD tools and high-resolution laboratory measurements.     

中国健康人两项血液流变学参考值与海拔高度的关系

为制定中国健康成年男性血沉参考值(温氏法)和中老年女性红细胞压积参考值(温氏法)的统一标准提供科学依据,本文研究了中国226个单位测定的22707例健康成年男性的血沉参考值(温氏法)和312个单位测定的15608例健康中老年女性的红细胞压积参考值(温氏法),并对其与海拔高度的关系进行了研究,发现随着海拔高度的逐渐增大,健康成年男性血沉参考值(温氏法)在逐渐的减小,而健康中老年女性红细胞压积参考值(温氏法)在逐渐的增大,相关性都很显著。用回归分析的方法推导出了二个一元回归方程。如果知道了中国某地的海拔高度,就可以用这二个回归方程,估算这个地区的健康成年男性血沉参考值(温氏法)和健康中老年女性红细胞压积参考值(温氏法)。     

焦虑敏感问卷中文版的信度和效度

目的:翻译和修订焦虑敏感问卷,测试中文版的信效度。方法:翻译焦虑敏感量表,通过对中学生的三次测试,对量表的因素结构、信度和效度进行了检验。结果:修编的焦虑敏感问卷中文版通过探索性因素分析将原量表由36题缩减为15题,共包括三个因素:对生理唤醒的恐惧;对认知失控的恐惧;对社会评价的恐惧;三个因素的累积贡献率为52．29％,项目的因素负荷率在0．63～0．98之间;因素彼此之间的相关在0.37～0．53之间,因素与问卷总分之问的相关在0．72～0．84之间,因素内部的相关在0．68～0．78之间。问卷在各个因素上的内部一致性系数在0.73～0．78之间．分半信度在0．71～0．76之间,重测信度在0．70～0．78之间。结论:问卷的中文简化版在中学生中具有良好的信度和效度。     

G蛋白β3亚单位基因C825T多态性与PTCA支架内再狭窄

目的 探讨G蛋白β3亚单位基因C825T多态性与PTCA支架植入后再狭窄之间的相关性。方法 采用多聚酶联反应结合限制性内切酶片断长度多态性分析方法(PCR-RFLP)检测50例经PTCA支架植入术后半年内发生再狭窄的患者和85例经PTCA支架植入在半年内未发生再狭窄的患者之间G蛋白β3亚单位基因C825T多态性。结果 再狭窄组G蛋白β3亚单位基因型频率(CC 14％、CT 54％、TT 32％),等位基因频率(C 41％、T 59％)与未狭窄组G蛋白β3亚单位基因型频率(CC31.8％、CT 44.7％、TT 23.5％),等位基因频率(C 54.2％、T 45.8％)比较统计学上有差异。结论 G蛋白β3亚单位基因C825T多态性可能与PTCA支架内再狭窄有关。