Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer

Inflammatory bowel diseases are characterised by inflammation that compromises the integrity of the epithelial barrier. The intestinal epithelium is not only a static barrier but has evolved complex mechanisms to control and regulate bacterial interactions with the mucosal surface. Apical tight junction proteins are critical in the maintenance of epithelial barrier function and control of paracellular permeability. The characterisation of alterations in tight junction proteins as key players in epithelial barrier function in inflammatory bowel diseases is rapidly enhancing our understanding of critical mechanisms in disease pathogenesis as well as novel therapeutic opportunities. Here we give an overview of recent literature focusing on the role of tight junction proteins, in particular claudins, in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer.

Moxibustion down-regulates colonic epithelial cell apoptosis and repairs tight junctions in rats with Crohn's disease

AIM: To investigate the effects of moxibustion on down-regulation of the colonic epithelial cell apoptosis and repair of the tight junctions in rats with Crohn's disease (CD). METHODS: Sixty male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an herbs-partitioned moxibustion (HPM) group, a mild-warm moxibustion (MWM) group and a salicylazosulphapyridine (SASP) group, with 12 rats in each group. The CD model rats were treated with trinitrobenzene sulphonic acid to induce intestinal inflammation. The rats in the HPM and MWM groups were treated at the Tianshu (ST25) and Qihai (CV6) acupoints once daily for 14 d, and the SASP group was fed SASP twice daily for 14 d. No additional treatment was given to the MC and NC groups. Themicrostructure of the colonic epithelium was observed under a transmission electron microscope, the transepithelial resistance was measured using a shortcircuit current, colonic epithelial cell apoptosis was determined by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labelling assay, and the expression of occludin, claudin-1 and zonula occludens-l (ZO-1) in the colonic epithelial junction was determined by Western blotting and immunofluorescence staining. RESULTS: Compared with the MC group, the microstructure of the colonic epithelial barrier was signifi-cantly improved in rats treated with HPM, MWM or SASP, meanwhile, the current flow was reduced signifi-cantly, with values of 168.20 ± 6.14 vs 99.70 ± 3.13, 99.10 ± 4.28 and 120.30 ± 3.65 mA, respectively (P = 0.001). However, the HPM and MWM groups had higher current flow rates than the SASP group (99.70 ± 3.13, 99.10 ± 4.28 vs 120.30 ± 3.65 mA, P = 0.001). The number of the apoptotic colonic epithelial cells in HPM, MWM and SASP groups was largely reduced (61.5 ± 16.91 vs 15.5 ± 8.89, 14.8 ± 6.27 and 24.7 ± 9.68, respectively (P = 0.001); and the expression of occlu- din, claudin-1 and ZO-1 in the MWM and HPM groups was signifi cantly enhanced (0.48 ± 0.10, 0.64 ± 0.09 vs 0.18 ± 0.05 for occludin, 0.12 ± 0.02, 0.17 ± 0.03 vs 0.05 ± 0.01 for claudin-1, and 0.08 ± 0.01, 0.11 ± 0.01 vs 0.02 ± 0.01 for ZO-1). And in SASP group, the expression of occludin and ZO-1 was also signifi cantly increased (0.27 ± 0.04 vs 0.18 ± 0.05 for occludin and 0.05 ± 0.01 vs 0.02 ± 0.01 for ZO-1), but there was no significant difference for claudin-1. The HPM and MWM groups had higher expression of occludin, claudin-1 and ZO-1 than the SASP group. CONCLUSION: HPM and MWM treatment can down-regulate apoptosis of colonic epithelial cells, repair tight junctions and enhance colonic epithelial barrier function in rats with CD.

Carcinoma of the gastroesophageal junction in Chinese patients

Carcinoma of the gastroesophageal junction(GEJ) is defined as carcinoma that crosses the GEJ line,irrespective of where the tumor epicenter is located.This group of cancer is rare but controversial.Based on study results from the majority of epidemiologic and clinicopathologic investigations carried out in Western countries,this cancer is believed to arise from Barrett's esophagus(BE) and includes both distal esophageal and proximal gastric carcinomas because of similar characteristics in epidemiology,clinicopathology,and molecular pathobiology in relation to BE.As such,the most recent American Joint Committee on Cancer staging manual requires staging all GEJ carcinomas with the rule for esophageal adenocarcinoma(EA).This mandate has been challenged recently by the data from several studies carried out mainly in Chinese patients.The emerging evidence derivedfrom those studies suggests:(1) both BE and EA are uncommon in the Chinese population;(2) almost all GEJ cancers in Chinese arise in the proximal stomach and show the features of proximal gastric cancer,not those of EA;(3) application of the new cancer staging rule to GEJ cancer of Chinese patients cannot stratify patients' prognosis effectively;and(4) prognostic factors of GEJ cancer in Chinese are similar,but not identical,to those of EA.In conclusion,the recent evidence suggests that GEJ cancer in Chinese shows distinct clinicopathologic characteristics that are different from EA.Further investigations in molecular pathology may help illustrate the underlying pathogenesis mechanisms of this cancer in Chinese patients and better manage patients with this fatal disease.

Use of volumetric laser endomicroscopy for dysplasia detection at the gastroesophageal junction and gastric cardia

To determine specific volumetric laser endomicroscopy (VLE) imaging features associated with neoplasia at the gastroesophageal junction (GEJ) and gastric cardia. METHODSDuring esophagogastroduodenoscopy for patients with known or suspected Barrett’s esophagus, VLE was performed before biopsies were taken at endoscopists’ discretion. The gastric cardia was examined on VLE scan from the GEJ (marked by top of gastric folds) to 1 cm distal from the GEJ. The NinePoints VLE console was used to analyze scan segments for characteristics previously found to correlate with normal or abnormal mucosa. Glands were counted individually. Imaging features identified on VLE scan were correlated with biopsy results from the GEJ and cardia region. RESULTSThis study included 34 cases. Features characteristic of the gastric cardia (gastric rugae, gastric pit architecture, poor penetration) were observed in all (100%) scans. Loss of classic gastric pit architecture was common and there was no difference between those with neoplasia and without (100% vs 74%, P = NS). The abnormal VLE feature of irregular surface was more often seen in patients with neoplasia than those without (100% vs 18%, P < 0.0001), as was heterogeneous scattering (86% vs 41%, P < 0.005) and presence of anomalous glands (100% vs 59%, P < 0.05). The number of anomalous glands did not differ between individual histologic subgroups (ANOVA, P = NS). CONCLUSIONThe transition from esophagus to gastric cardia is reliably identified on VLE. Histologically abnormal cardia mucosa produces abnormal VLE features. Optical coherence tomography algorithms can be expanded for use at the GEJ/cardia.

Modeling of Unsteady Flow through Junction in Rectangular Channels: Impact of Model Junction in the Downstream Channel Hydrograph

Open channel junctions are encountered in urban water treatment plants, irrigation and drainage canals, and natural river systems. Junctions are very important in municipal sewerage systems and river engineering. Adequate theoretical description of flow through an open channel junction is difficult because numerous variables are to be considered. Equations of junction models are based on mass and momentum or mass and energy conservation. The objective of this study is to compare two junction models for subcritical flows. In channel branches, we solve numerically the Saint-Venant hyperbolic system by combining Preissmann scheme and double sweep method. We validate our results with HEC-RAS using Nash and Sutcliffe efficiency. In junction models, equality of water stage and complete energy conservation equation from HEC-RAS are compared. Outcome of the research clearly indicates that the complete conservation energy model is more suitable in flow through junction than equality of water stage model in serious situations.

Josephson Current in f-Wave Superconductor/f-Wave Superconductor Junctions

We study the temperature T and the phase of the Josephson critical current I（Ф） by taking into account the roughness scattering effect at inerface in an f-wave superconductor （S）/Insulator layer （I）/f-wave superconductor （S） junction. It is found that the Josephson critical currents in f-wave Sir-wave S, the barrier strength and the roughness strength at inerface always suppress the Andreev reflection. When α=β, the phase dependence of the Josephson current I（Ф） between two f-wave S is predicted to be sin Ф; particularly, when a α≠ β, the phase dependence of the Josephson current I（Ф） between two f-wave superconductors is not predicted to be sin Ф and with the barrier strength increasing, the period of the I（Ф） turns decrease.

均匀磁场下二维拓扑绝缘体边缘态的多重Andreev反射研究

研究均匀磁场下的二维拓扑绝缘体在超导隧道结中的电压偏置约瑟夫森结的输运性质,电流-电压特性显示了马约拉纳束缚态的存在。在亚谐隙结构中,也可以观察到磁场对超导能隙的影响。研究结果表明,在S波超导体/正常金属/S波超导结的隧道谱中存在亚谐隙结构。透明度只影响超导结的零偏压电导值的大小,而不影响亚谐隙结构的位置。但是在磁场作用下,亚谐隙结构会发生变化,不再固定出现在特定位置。这一结果对应于拓扑螺旋态中超导和铁磁序之间的相互作用。

S-亚硝基谷胱甘肽对小鼠肠急性缺血再灌注损伤后肠屏障功能的影响

目的探讨S-亚硝基谷胱甘肽（GSNO）预处理对小鼠肠急性缺血再灌注（I/R）所致的肠黏膜屏障损伤的影响。方法6~8周龄雄性C57BL/6小鼠24只,分为Sham组、I/R组、I/R＋GSNO组,每组8只。采用夹闭肠系膜上动脉30min,再灌注6h作为小鼠肠I/R模型。苏木素-伊红（HE）染色观察小肠组织形态学的变化;免疫组织化学观察肠上皮细胞间紧密连接蛋白claudin-1的表达情况;Western blot检测claudin-1蛋白水平变化。结果 HE染色显示,与Sham组比较,I/R组肠黏膜明显肿胀,绒毛部分脱落、变粗,绒毛倒伏、断裂,而I/R＋GSNO组肠黏膜无明显肿胀,绒毛完整,形态接近正常;免疫组织化学观察显示I/R刺激可造成肠上皮表面claudin-1连续性明显破坏,阳性表达率明显降低,I/R＋GSNO组肠上皮claudin-1连续性明显恢复,阳性染色显著增加;肠上皮claudin-1蛋白定量分析显示：与Sham组比较,I/R组及I/R＋GSNO小肠上皮紧密连接蛋白claudin-1表达分别下降32.5%,13.8%（P〈0.05）;与I/R组比较,I/R＋GSNO组小鼠肠上皮紧密连接蛋白claudin-1表达上调27.8%（P〈0.05）。结论小肠急性I/R刺激可造成明显的肠黏膜损伤及肠上皮间紧密连接的显著破坏;GSNO预处理可通过上调claudin-1表达,有效缓解I/R对肠黏膜结构与肠上皮屏障功能的损伤。

S形弯曲河段低水头闸坝枢纽口门区通航水流条件研究

以老口枢纽为例,分析S形弯曲河段上低水头闸坝枢纽引航道上、下游口门区水流特点,通过整体物理模型试验及自航船模验证试验,提出改善水流条件的具体措施。研究结果表明:通过修改上下引航道隔墙形式、局部地形开挖、岸坡回填、增设潜丁坝,以及调整凸岸岸线等措施,调整了引航道中心线位置并缩小引航道中心线与河道主流流向交角,减弱及消除了上下游引航道及口门区存在的回流、挑流及隔墙堤头的绕流等不利流态,有效改善了老口枢纽的通航水流条件,为S形弯曲河段低水头闸坝枢纽设计提供参考。

旁栅电压下MESFET沟道电流的低频振荡

通过测试不同旁栅电压条件下的 MESFET沟道电流的低频振荡现象 ,发现旁栅偏压无论朝正向还是负向变化都存在一个阈值可消除此低频振荡 .并从理论上探讨了出现这种现象的原因 ,初步认为这与沟道 -衬底 (C- S)结的特性和高场下衬底深能级 EL2

非霍奇金淋巴瘤中MCM2、Cx43、Skp2蛋白的表达

目的:研究非霍奇金淋巴瘤(non-hodgkin's lymphoma,NHL)中微小染色体维持蛋白2(Minichromosome maintenance protein 2,MCM2)与细胞间隙连接蛋白43(Connexin 43,Cx43)以及S期激酶相关蛋白2(S phase kinase-associated protein 2,Skp2)在非霍奇金淋巴瘤中的表达及临床意义,以期为临床诊治非霍奇金淋巴瘤提供一定的参考。方法:选取2013年1月至2015年1月间入院诊治的非霍奇金淋巴瘤36例作为实验组,并选取同期入院诊治的淋巴结反应性增生18例作为对照组,应用免疫组化法检测MCM2、Cx43、Skp2的表达情况,同时分析MCM2、Cx43、Skp2的表达与非霍奇金淋巴瘤恶性程度、临床分期等的相关性。结果:实验组NHL患者MCM2阳性表达率为83.33%、Skp2阳性表达率为86.11%,显著高于对照组22.22%与27.78%的阳性表达率(P<0.01);NHL患者Cx43阳性表达率为22.22%,显著低于对照组61.11%阳性表达率(P<0.01)。NHL患者MCM2阳性表达与肿瘤恶性程度、临床分期及Ki67水平密切相关(P<0.05);NHL患者Cx43阳性表达与肿瘤恶性程度呈负相关(P<0.01);NHL患者Skp2阳性表达与肿瘤恶性程度及临床分期密切相关(P<0.05)。结论:MCM2、Cx43、Skp2的异常表达与非霍奇金淋巴瘤的恶性程度密切相关,联合检测MCM2、Cx43、Skp2可为非霍奇金淋巴瘤的诊治提供一定的参考。

SiewertⅡ、Ⅲ型胃食管结合部癌的临床特点及HER2、SKP2表达

目的：探讨 Siewert Ⅱ、Ⅲ型胃食管结合部癌（AEG）的临床特点及人表皮生长因子受体2（HER2）、细胞S 期激酶相关蛋白2（SKP2）表达变化。方法选取 SiewertⅡ及Ⅲ型 AEG 患者206例，比较二者的临床特点；应用免疫组化方法检测其 HER2、SKP2表达情况，分析 SiewertⅡ、Ⅲ型 AEG 患者 HER2、SKP2阳性表达与临床病理参数的关系。结果两型 AEG 患者肿瘤大小、淋巴结转移、肿瘤分化程度和 TNM分期比较有统计学差异（P 均＜0．05）。SiewertⅡ型 AEG 患者 HER2、SKP2阳性表达率分别为32．9％、41．2％，SiewertⅢ型 AEG 患者 HER2、SKP2阳性表达率分别为36．3％、55．4％；两组 SKP2阳性表达率差异有统计学意义（P ＜0．05）。SiewertⅡ或Ⅲ型 AEG 患者中，肿瘤直径＜5 cm 与≥5 cm、浸润深度 T1～T2与 T3～T4、高～中分化与低分化、淋巴结转移 N0～N1与 N2～N3之间 HER2阳性表达率有统计学差异（P 均＜0．05）。结论 HER2、SKP2异常表达可促进 AEG 的发生发展， HER2、SKP2表达检测对 AEG 早期诊断及疗效判断有重要作用。

一维Ginzburg-LandauS-N-S超导方程组解的收敛性

讨论导体材料在中间、超导材料在两边的一维Ginzburg-Landau超导方程组的渐近性态,并证明了当 Ginzburg-Landau参数趋于无穷大时方程组的解趋向于一个非线性常微分方程组的解.

s/FI/d超导结的直流Josephson电流

在 s波超导体 /铁磁绝缘层 / d波超导体 Josephson结 (s/ FI/ d)中 ,考虑结界面铁磁绝缘层的磁散射和粗糙散射情况下 ,运用 Bd G方程和 FT的电流公式计算准粒子的输运系数及 s/ FI/ d结的直流 Josephson电流与温度 T、结两侧的相位差之间的关系。研究表明 :结界面的磁散射和粗造散射均抑制结中准粒子的 Andreev反射 ,降低了流过 s/ FI/ d结的直流 Josephson电流 ,直流Josephson电流 I随温度 T、相位差φ的变化曲线强烈地依赖于

选择离子注入GaAs MESFET的旁栅特性研究

主要研究了平面选择离子注入隔离工艺条件下的GaAs MESFET的旁栅效应,分别设计了不同的测试方法来分析旁栅效应的多种特性,并从理论上对测试结果进行了解释.认为这些特性都与沟道-衬底(C-S)结的特性和高场下衬底深能级EL2的碰撞电离有关.

基于BCD工艺的局部电荷补偿超结LDMOS

针对功率集成电路中的高压器件应用,提出一种局部电荷补偿超结横向双扩散金属氧化物半导体(LDMOS)器件结构。利用常规LDMOS工艺,通过调整n阱的版图尺寸,在漏区形成局部的电荷补偿,可以缓解横向超结器件中存在的衬底辅助耗尽效应,促进超结的电荷平衡。n型电荷补偿区与p型衬底在超结下方形成pn结,可以同时优化横向和纵向电场分布,提高超结器件的耐压。此器件结构可以通过BCD工艺实现,适用于功率集成电路。三维器件仿真结果表明,新结构的器件耐压达到490 V,较常规的电荷补偿超结器件提高了53%。

不对称s波超导体/绝缘层/s波超导体结的直流Josephson电流

在不对称s波超导体/绝缘层/s波超导体Josephson结(s/I/s)中,考虑结界面粗糙散射情况下,运用Bogoliubov deGennes(BdG)方程和Furusaki Tsukada(FT)的电流公式计算准粒子的输运系数及s/I/s结的直流Josephson电流.研究表明,结界面的通常势垒和粗糙散射均抑制结中准粒子的Andreev反射,降低了流过s/I/s结的直流Josephson电流,直流Josephson电流I随温度T的变化关系与结两侧的对称性有关.

Role of the intestinal barrier in inflammatory bowel disease

A critical function of the intestinal mucosa is to form a barrier that separates luminal contents from the interstitium. The single layer of intestinal epithelial cells (IECs) serves as a dynamic interface between the host and its environment. Cell polarity and structural properties of the epithelium is complex and is important in the development of epithelial barrier function. Epithelial cells associate with each other via a series of intercellular junctions. The apical most intercellular junctional complex referred to as the Apical Junction Complex (AJC) is important in not only cell-cell recognition, but also in the regulation of paracellular movement of fluid and solutes. Defects in the intestinal epithelial barrier function have been observed in a number of intestinal disorders such as inflammatory bowel disease (IBD). It is now becoming evident that an aberrant epithelial barrier function plays a central role in the pathophysiology of IBD. Thus, a better understanding of the intestinal epithelial barrier structure and function in healthy and disease states such as IBD will foster new ideas for the development of therapies for such chronic disorders.

Intestinal epithelial cells in inflammatory bowel diseases

The pathogenesis of inflammatory bowel diseases (IBDs) seems to involve a primary defect in one or more of the elements responsible for the maintenance of intestinal homeostasis and oral tolerance. The most important element is represented by the intestinal barrier, a complex system formed mostly by intestinal epithelial cells (IECs). IECs have an active role in producing mucus and regulating its composition; they provide a physical barrier capable of controlling antigen traff ic through the intestinal mucosa. At the same time, they are able to play the role of non-professional antigen presenting cells, by processing and presenting antigens directly to the cells of the intestinal immune system. On the other hand, immune cells regulate epithelial growth and differentiation, producing a continuous bi-directional cross-talk within the barrier. Several alterations of the barrier function have been identif ied in IBD, starting from mucus features up to its components, from epithelial junctions up to the Toll-like receptors, and altered immune responses. It remains to be understood whether these defects are primary causes of epithelial damage or secondary effects. We review the possible role of the epithelial barrier and particularly describe the role of IECs in the pathogenesis of IBD.

阿帕明对IJP和NO－Cys、SNP所致大鼠胃底环形肌细胞超极化的影响

采用常规微电极技术，研究数种钾通道阻断剂对电刺激（ＥＦＳ）所致的抑制性接头部电位（ＩＪＰ）以及Ｓ－亚硝基半胱氨酸（ＮＯ－Ｃｙｓ）、硝普钠（ＳＮＰ）所致的大鼠胃底环形肌细胞超极化的影响。结果表明，大鼠胃底平滑肌的非肾上腺素能、非胆碱能神经元的递质可能是释放ＮＯ的物质而不是ＮＯ本身；ＥＦＳ和ＮＯ－Ｃｙｓ是通过激活阿帕明敏感的和不敏感的钾通道而致超极化，而ＳＮＰ仅是通过激活阿帕明不敏感的钾通道而致超极化。此外，ＮＯ－Ｃｙｓ和ＳＮＰ可能通过激活颗粒性鸟苷酸环化酶而增加ｃＧＭＰ的合成，进而激活阿帕明不敏感的钾通道而致超极化。