液基细胞学筛查宫颈癌的临床分析

目的:评价液基薄层细胞学技术对妇科门诊人群子宫颈癌筛查的准确性,探讨宫颈癌患者年轻化的倾向。方法:对妇科门诊18340例宫颈脱落细胞标本,采用薄层细胞学检查(TCT)技术制片和TBS方案进行诊断,阳性者行阴道镜下病理组织学活检并按年龄分组。结果:TCT与病理组织学对照,TCT的阳性符合率:LSIL为29/54(53.70%),HSIL为22/25(88.00%),SCC为1/1(100.00%)。TCT检出的191例ASC经组织学证实143例为炎症或其它,48例为CIN和SCC。31~40岁年龄段是CIN的高发年龄段,几率为40/81(49.38%)。结论:TCT与病理组织学有一定的相关性,TCT作为无创伤检测,是门诊筛查子宫颈癌的有效方法,门诊筛查子宫颈癌要对年轻的妇女特别关注。     

氟康唑粉剂联合托百士滴眼液治疗真菌性角膜溃疡

目的 观察氟康唑粉剂联合托百士滴眼液治疗真菌性角膜溃疡的疗效.方法 将纳入考察范围的患者随机分为观察组和对照组各34例.对照组采用角膜溃疡面清创术及5%碘酊烧灼,后将氟康唑粉刺置于烧灼过的角膜溃疡面上.治疗组在对照组的基础上加用托百士滴眼液.结果 两组治愈率比较统计学差异有显著性（P＜0.05）.治疗组的治愈率显著高于对照组,且未出现不良反应.结论 采用氟康唑粉剂联合托百士滴眼液治疗真菌性角膜溃疡,治疗效果好,安全可靠,值得在基层医院大力推广.     

Anti-VEGF receptor-2 monoclonal antibody prevents portal-systemic collateral vessel formation in portal hypertensive mice

BACKGROUND & AIMS: Portal hypertension is a frequent syndrome that develops in patients with chronic liver diseases, which are one of the most common causes of death in adults worldwide. The most serious clinical consequences of portal hypertension are related to the development of portal-systemic collateral vessels. Those include hepatic encephalopathy and massive bleeding from ruptured gastroesophageal varices. The high relevance of these collateral vessels prompted us to investigate the mechanism underlying its formation in a murine model of portal hypertension. METHODS: To determine whether the development of portal-systemic collateral vessels in portal hypertension is a vascular endothelial growth factor (VEGF)-dependent angiogenic process, we assessed the effects of a monoclonal antibody against VEGF receptor-2 on the formation of these collateral vessels in mice with portal hypertension induced by partial portal vein ligation. We also studied the effects of a selective and specific inhibitor of VEGF receptor-2 autophosphorylation in partial portal vein-ligated rats. RESULTS: A significant and marked inhibition in the formation of portal-systemic collateral vessels was observed in both partial portal vein-ligated mice and rats treated with anti-VEGF receptor-2 monoclonal antibodies or with the inhibitor of VEGF receptor-2 autophosphorylation, respectively, compared with animals receiving control solutions. CONCLUSIONS: Our present study shows that formation of collateral vessels is an angiogenesis-dependent process that can be markedly inhibited by blockade of the VEGF signaling pathway. These findings will make angiogenesis a focal point of research in portal hypertension and may lead to novel approaches for therapy of patients with chronic liver diseases.     

Intracellular signal transduction modulating expression of plasminogen activator inhibitor-1 in adipocytes

The concentrations in blood of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis and proteolysis, are elevated in obese and insulin-resistant subjects, predispose them to the risk of thrombosis, and may accelerate atherogenesis. Adipose tissue is a prominent source. Accordingly, intracellular signaling pathways that may influence PAI-1 expression in adipocytes have been the focus of considerable study. Rho, a small GTP binding and GTPase protein, when activated in turn activates its target, Rho-associated coiled-coil forming protein, to yield an active kinase, Rho-kinase, an effector in the Rho pathway. Rho-kinase exerts calcium-sensitizing effects in vascular smooth muscle cells and inhibitory effects on transforming growth factor-beta (TGF-beta) expression in chicken embryonic heart cells. Because TGF-beta is a powerful agonist of PAI-1 expression, we characterized the effects of inhibition of Rho-kinase in 3T3-L1 adipocytes. PAI-1 mRNA was determined by Northern blotting, and PAI-1 protein was determined by Western blotting. The Rho-kinase inhibitor, Y-27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide], increased PAI-1 expression markedly. Although genistein, a flavonoid tyrosine kinase, attenuated the increase of PAI-1 induced by Y-27632, other non-flavonoid tyrosine kinase inhibitors did not. However, another flavonoid, daidzein, which lacks tyrosine kinase activity, decreased basal PAI-1 expression and attenuated the induction of PAI-1 expression by Y-27632. Thus, the Rho/Rho-kinase system inhibits PAI-1 expression by a flavonoid-sensitive mechanism in adipocytes. Therefore, flavonoids may be useful in decreasing elevated PAI-1 expression in adipose tissue and its consequent pathophysiologic sequelae.     

Effect of reduction and alkylation on structure and function of rabbit IgG antibody—I. Effect on ability to activate complement depends on conditions of reduction

Anaerobic reduction of rabbit IgG antibody with either dithiothreitol at pH 8.0 or 2-mercaptoethanol at pH 5.0 results in the production of antibody molecules which lack haemolytic activity yet whose interchain disulfide bonds remain intact. Aerobic reduction with 2-mercaptoethanol results in more haemolytic activity than can be accounted for by the residual amount of Ab with intact interchain bonds. Taken together, these findings suggest that the interheavy chain disulfide bond in rabbit IgG is not essential for interaction with complement but that an intraheavy chain bond is critical.     

Immunolocalization of neurotransmitter-synthesizing enzymes and neuropeptides with associated receptors in the photophores of the hatchetfish, Argyropelecus hemigymnus Cocco, 1829

Anatomical and functional studies of the autonomic innervation of the photophores of luminescent fishes are scarce. The present immunohistochemical study demonstrated the presence of nerve fibers in the luminous epithelium and lens epithelium of the photophores of the hatchet fish, Argyropelecus hemigymnus and identified the immunoreactive elements of this innervation. Phenylethanolanine N-methyltransferase (PNMT) and catecholamine (CA)-synthesizing enzymes were detected in nerve varicosities inside the two epithelia. Neuropeptides were localized in neuropeptide Y (NPY) and substance P (SP)- and its NK11 receptor-immunopositive nerves in the lens epithelium. Neuropeptides were also localized in non-neural cell types such as the lens cells, which displayed immunoreactivities for pituitary adenylate cyclase activating peptide (PACAP) and their receptors R-12 and 93093-3. This reflects the ability of the neuropeptide-containing nerves and lens cells to turn on and off the expression of selected messengers. It appears that the neuropeptide-containing nerves demonstrated in this study may be sensory. Furthermore, neuronal nitric oxide synthase-immunopositive axons associated with photocytes in the luminous epithelium have previously been described in this species. Whereas it is clear that the photophores receive efferent (motor) fibers of spinal sympathetic origin, the origin of the neuropeptide sensory innervation remains to be determined. The functional roles of the above neuropeptides or their effects on the bioluminescence or the chemical nature of the terminals, either sensory or postganglionic neurons innervating the photophores, are still not known.     

Classical and alternative activation of rat hepatic sinusoidal endothelial cells by inflammatory stimuli

The ability of rat hepatic sinusoidal endothelial cells (HSEC) to become activated in response to diverse inflammatory stimuli was analyzed. Whereas the classical macrophage activators, IFNγ and/or LPS upregulated expression of iNOS in HSEC, the alternative macrophage activators, IL-10 or IL-4 + IL-13 upregulated arginase-1 and mannose receptor. Similar upregulation of iNOS and arginase-1 was observed in classically and alternatively activated Kupffer cells, respectively. Removal of inducing stimuli from the cells had no effect on expression of these markers, demonstrating that activation is persistent. Washing and incubation of IFNγ treated cells with IL-4 + IL-13 resulted in decreased iNOS and increased arginase-1 expression, while washing and incubation of IL-4 + IL-13 treated cells with IFNγ resulted in decreased arginase-1 and increased iNOS, indicating that classical and alternative activation of the cells is reversible. HSEC were more sensitive to phenotypic switching than Kupffer cells, suggesting greater functional plasticity. Hepatocyte viability and expression of PCNA, β-catenin and MMP-9 increased in the presence of alternatively activated HSEC. In contrast, the viability of hepatocytes pretreated for 2 h with 5 mM acetaminophen decreased in the presence of classically activated HSEC. These data demonstrate that activated HSEC can modulate hepatocyte responses following injury. The ability of hepatocytes to activate HSEC was also investigated. Co-culture of HSEC with acetaminophen-injured hepatocytes, but not control hepatocytes, increased the sensitivity of HSEC to classical and alternative activating stimuli. The capacity of HSEC to respond to phenotypic activators may represent an important mechanism by which they participate in inflammatory responses associated with hepatotoxicity.     

Inhibitory transcranial magnetic theta burst stimulation attenuates prefrontal cortex oxygenation

Recent studies highlighted the great potential of newly established theta burst stimulation (TBS) protocols for non‐invasive human brain stimulation studies using transcranial magnetic stimulation (TMS). While intermittent TBS over the primary motor cortex was found to potentiate motor evoked potentials, continuous TBS led to profound attenuations. Although numerous studies investigated the impact of TBS on motor cortex function, yet, only few imaging studies focused on its effects in other brain areas. Particularly for the prefrontal cortex, it is unclear whether TBS has similar effects compared to application over motor areas. In the current study continuous TBS was applied to either the left or right dorsolateral prefrontal cortex in a sample of healthy subjects. Changes in prefrontal oxygenation were measured during an emotional Stroop task by means of functional multi‐channel near‐infrared spectroscopy (fNIRS) before and after stimulation. Results showed bilaterally decreased prefrontal oxygenation following inhibitory stimulation of the left prefrontal cortex but no behavioral effect. No such alterations were observed following right‐hemispheric or sham stimulation. The results of the current study are in line with earlier findings and additionally demonstrate that also prefrontal oxygenation can be impaired by continuous TBS. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Dissociation and re-association studies on the interaction domains of mannan-binding lectin (MBL)-associated serine proteases,MASP-1 and MASP-2, provide evidence for heterodimer formation

Activation of the lectin pathway of complement begins with the activation of mannan-binding lectin (MBL)-associated serine proteases, MASP-1 and MASP-2, which are bound to the recognition molecules, MBL and ficolins. MASPs are Ca²⁺-dependent dimers. Dimerization and Ca²⁺-dependent association with the recognition molecules occurs via the first 3 domains, the CUB1-EGF-CUB2 region. The CUB1-EGF-CUB2 (D1-3) regions of MASP-1 and MASP-2, and also their tagged versions, were expressed in E. coli, refolded and purified. The first three domains of MASP-1 are identical with the respective regions of MASP-3 and MAp44, which are also associated with MBL and ficolins. The functionality of the fragments was checked by inhibition of C3 deposition from human serum. Time-course of the dissociation and re-association was examined by size exclusion chromatography. Both refolded proteins are tight Ca²⁺-dependent dimers, as expected. In buffer containing EDTA MASP-1_D1-3 dissociated to monomers, however it took about 1 h to reach an equilibrium. Upon re-calcification dimers were re-formed, but this process was even slower; only after overnight incubation was the dimerization completed. MASP-2_D1-3 showed a somewhat different behavior: dissociation by EDTA was even slower, less complete, and higher MW aggregates also appeared. Heterodimer formation was detected by native PAGE. As modeled by the D1-3 fragments, MASP-1 and MASP-2 can readily form heterodimers after dissociation and re-association, however, in the presence of Ca²⁺ exchange of subunits is slow between the homodimers. MASP-1:MASP-3 heterodimer formation was modeled by the tagged and untagged D1-3 fragments, and data indicate that subunits of these proteins are readily exchanged even in the presence of Ca²⁺. The existence of heterodimers influences the current view on the composition of lectin pathway complexes and their activation.