BACKGROUND & AIMS: The present study was designed to elucidate the neurotransmitters involved in activation of the noradrenergic nucleus, locus coeruleus, by distention of the distal colon. Locus coeruleus spontaneous discharge rate was recorded from halothane-anesthetized rats before, during and after distention of the colon produced by inflation of a balloon catheter with varying volumes of water. Locus coeruleus activation by colon distention was volume-dependent and reversible. Activation of cortical electroencephalographic activity was temporally correlated with locus coeruleus activation during colon distention and prolonged distention (greater than 2 min) resulted in tachyphalaxis to both locus coeruleus and cortical electroencephalographic activation. The corticotropin-releasing factor antagonist, DPheCRF(12-41), administered intracerebroventricularly (3 microg) or microinfused into the locus coeruleus (10 ng) significantly attenuated locus coeruleus activation produced by lower, but not higher magnitudes of colon distention, implicating corticotropin-releasing factor afferents to the locus coeruleus in this response. Consistent with this, prior exposure to 30 min of footshock stress, which desensitizes locus coeruleus neurons to corticotropin-releasing factor, produced a similar attenuation of locus coeruleus activation by low, but not high magnitudes of distention. Kynurenic acid, administered intracerebroventricularly (5 micromol), significantly antagonized locus coeruleus activation by all magnitudes of colon distention. However, this excitatory amino acid antagonist was ineffective when administered directly into the locus coeruleus (0.3 nmol). Together, these findings suggest that low magnitudes of colon distention activate the locus coeruleus-noradrenergic system via corticotropin-releasing factor release within the locus coeruleus and that excitatory amino acid neurotransmission at a site distal to the locus coeruleus is necessary for this response. Activation of the locus coeruleus-noradrenergic system during colon distention may serve as a cognitive limb of the peripheral parasympathetic response. This activation may also play a role in disorders characterized by comorbidity of colonic and psychiatric symptoms, such as irritable bowel syndrome.

背景与目标： 本研究旨在阐明远端结肠扩张引起的去甲肾上腺素能核激活的神经递质。记录了氟烷麻醉大鼠在用不同体积的水充胀球囊导管充盈结肠之前，期间和之后自发排出蓝藻的频率。结肠扩张引起的蓝斑轨迹激活是体积依赖性的和可逆的。皮质脑电图活动的激活在时间上与结肠扩张期间脑蓝素的激活相关，而长期扩张（大于2分钟）会导致脑脊髓蓝素和皮质脑电图的速动性。皮质激素释放因子拮抗剂DPheCRF（12-41），经脑室内（3微克）或微输注到蓝斑（10 ng）时，可显着减弱由较低但不是较高程度的结肠扩张产生的蓝斑激活，这暗示促肾上腺皮质激素-在这种反应中，释放因子传入蓝斑。与此相一致，事先暴露于30分钟的足底震荡中，使蓝斑蓝皮病的神经元对促肾上腺皮质激素释放因子不敏感，通过低但不高的扩张程度，蓝斑蓝皮病的激活也有类似的减弱。脑室内（5微摩尔）施用的犬尿酸通过各种程度的结肠扩张显着拮抗蓝斑轨迹激活。但是，这种兴奋性氨基酸拮抗剂当直接施用于蓝斑（0.3 nmol）时无效。总之，这些发现表明低水平的结肠扩张通过蓝藻中的促肾上腺皮质激素释放因子释放来激活蓝藻-去甲肾上腺素能系统，并且在蓝藻远侧的部位，兴奋性氨基酸神经传递对于该反应是必需的。结肠扩张期间蓝斑-去甲肾上腺素能系统的激活可能充当外周副交感反应的认知肢体。这种活化作用还可能在以结肠和精神症状合并症为特征的疾病中起作用，例如肠易激综合症。

BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： ：据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了低氧刺激是否影响基质以及胰腺癌细胞。我们的发现表明，低氧显着提高了胰腺癌（PK8）和成纤维细胞（MRC5）中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用由低氧MRC5细胞制备的条件培养基（低氧条件培养基）培养低氧PK8细胞时，侵袭性进一步加快。在缺氧条件下，PK8细胞中的MMP-2，MMP-7，MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子（HGF）分泌，从而导致PK8细胞中c-Met磷酸化的升高。相反，通过从低氧条件培养基中去除HGF，可以降低PK8细胞的癌浸润，MMP活性和c-Met磷酸化水平的升高。在免疫组织化学研究中，在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达，因此表明在癌细胞和基质细胞中均存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统，从而促进了胰腺癌的侵袭性侵袭性。

BACKGROUND & AIMS: :Although the considerable progress against gastric cancer, it remains a complex lethal disease defined by peculiar histological and molecular features. The purpose of the present study was to investigate pRb2/p130, VEGF, EZH2, p53, p16(INK4A), p27(KIP1), p21(WAF1), Ki-67 expressions, and analyze their possible correlations with clinicopathological factors. The expression patterns were examined by immunohistochemistry in 47 patients, 27 evaluated of intestinal-type, and 20 of diffuse-type, with a mean follow up of 56 months and by Western blot in AGS, N87, KATO-III, and YCC-2, -3, -16 gastric cell lines. Overall, stomach cancer showed EZH2 correlated with high levels of p53, Ki-67, and cytoplasmic pRb2/p130 (P < 0.05, and P < 0.01, respectively). Increased expression of EZH2 was found in the intestinal-type and correlated with the risk of distant metastasis (P < 0.05 and P < 0.01, respectively), demonstrating that this protein may have a prognostic value in this type of cancer. Interestingly, a strong inverse correlation was observed between p27(KIP1) expression levels and the risk of advanced disease and metastasis (P < 0.05), and a positive correlation between the expression levels of p21(WAF1) and low-grade (G1) gastric tumors (P < 0.05), confirming the traditionally accepted role for these tumor-suppressor genes in gastric cancer. Finally, a direct correlation was found between the expression levels of nuclear pRb2/p130 and low-grade (G1) gastric tumors that was statistically significant (P < 0.05). Altogether, these data may help shed some additional light on the pathogenetic mechanisms related to the two main gastric cancer histotypes and their invasive potentials.

背景与目标： ：尽管在对抗胃癌方面取得了长足的进步，但它仍然是由特殊的组织学和分子特征定义的复杂致死性疾病。本研究的目的是研究pRb2 / p130，VEGF，EZH2，p53，p16（INK4A），p27（KIP1），p21（WAF1），Ki-67的表达，并分析其与临床病理因素的可能关系。通过免疫组织化学方法对47例患者的表达模式进行了检查，其中27例为肠型，20例为弥漫型，平均随访56个月，并通过Western blot检测AGS，N87，KATO-III和YCC-2 ，-3，-16个胃细胞系。总体而言，胃癌显示EZH2与高水平的p53，Ki-67和细胞质pRb2 / p130相关（分别为P <0.05和P <0.01）。在肠型中发现EZH2表达增加，并且与远处转移的风险相关（分别为P <0.05和P <0.01），表明该蛋白可能在这种类型的癌症中具有预后价值。有趣的是，观察到p27（KIP1）表达水平与晚期疾病和转移的风险之间存在强烈的负相关（P <0.05），而p21（WAF1）和低度胃癌（G1）的表达水平之间呈正相关。肿瘤（P <0.05），证实了这些肿瘤抑制基因在胃癌中的传统接受作用。最后，在核pRb2 / p130的表达水平与低度（G1）胃肿瘤的表达水平之间发现了直接相关性，具有统计学意义（P <0.05）。总之，这些数据可能有助于进一步阐明与两种主要胃癌组织学类型及其侵袭潜能有关的致病机制。

BACKGROUND & AIMS: BACKGROUND:Several studies described the benefits of the heparin-surface-modified intraocular tens (HSM IOL) with regard to the reduced inflammation in routine extracapsular cataract extractions. However, limited information is available about the advantages of the HSM IOL in patients with an intraocular inflammation. AIM:To assess the eventual benefits of the HSM IOL compared to the regular polymethylmethacrylate intraocular lens (PMMA IOL) in patients with uveitis. METHODS:A retrospective study of 43 patients with uveitis of various origins who underwent an extracapsular cataract extraction (24 with HSM, 19 with PMMA IOL). The activity of intraocular inflammation, visual acuity, eventual complications, and medications were examined. Standardized follow-up dates were used (before surgery, one and fourteen days, five and eleven months after surgery.) RESULTS:No difference in the inflammatory, activity was noted between HSM and PMMA groups; neither at short term clinical evaluation, nor at five months after surgery. Despite a slightly better visual acuity in the HSM group before surgery, no long term differences were observed. After surgery the increase in visual acuity was similar for both groups, as well as the frequency of cystoid macular oedema (CMO) and synechiae. Fewer patients in HSM group required Nd:YAG posterior capsulotomy, but the difference was not significant. CONCLUSION:No clinical advantage was found when the HSM IOL was compared with the regular PMMA IOL in 43 patients with uveitis.

背景与目标： 背景：多项研究描述了肝素表面修饰眼内张力（HSM IOL）在常规囊外白内障摘除术中减少炎症方面的益处。但是，关于眼内炎症患者中HSM IOL的优势的信息很少。
目的：评估与常规聚甲基丙烯酸甲酯人工晶状体（PMMA IOL）相比，HSM IOL在葡萄膜炎患者中的最终益处。
方法：回顾性研究43例不同来源葡萄膜炎患者的囊外白内障摘除术（HSM 24例，PMMA IOL 19例）。检查眼内炎症，视力，最终并发症和药物的活动。使用标准化的随访日期（手术前，手术后的第1天，第14天，手术后的第5个月和第11个月）。
结果：HSM和PMMA组之间在炎症，活性方面没有差异；既不进行短期临床评估，也不在术后五个月进行评估。尽管术前HSM组的视敏度稍好，但未观察到长期差异。手术后，两组的视敏度增加，囊状黄斑水肿（CMO）和粘连的发生率相似。 HSM组需要Nd：YAG后囊切开术的患者较少，但差异无统计学意义。
结论：将HSM IOL与常规PMMA IOL相比较在43例葡萄膜炎患者中未发现临床优势。