皮肤血管瘤中NOS和VEGF的表达及其与血管增生的关系

目的研究内皮型一氧化氮合酶(eNOS)、诱生型一氧化氮合酶(iNOS)及血管内皮生长因子(VEGF)在增生期皮肤血管瘤组织中的表达及关系,探讨它们在皮肤血管瘤血管生成中的作用。方法应用免疫组化法检测51例增生期皮肤血管瘤标本中eNOS,iNOS和VEGF的表达,第Ⅷ因子相关抗原(FⅧRAg)血管内皮细胞特异性染色计数肿瘤微血管密度(MVD)。结果42例血管瘤组织表达VEGF,32例表达iNOS,37例表达eNOS,血管畸形表达较弱或不表达eNOS,iNOS和VEGF;eNOS表达阳性者MVD与表达阴性者差异无显著性(P>0.05),iNOS表达阳性者MVD与表达阴性者差异有显著性(P<0.05),VEGF表达阳性者MVD与表达阳性者差异有极显著性(P<0.01)。结论iNOS对VEGF的表达和在调节血管生成过程中可能起着重要作用;VEGF和iNOS两者对血管瘤血管生成具有促进作用。     

恶性黑素瘤内皮型一氧化氮合酶和血管内皮生长因子的表达

目的 探讨内皮型一氧化氮合酶(eNOS)和血管内皮生长因子(VEGF)与人恶性黑素瘤血管生成的关系。方法 免疫组化法检测31例人恶性黑素瘤标本eNOS、VEGF和第Ⅷ因子相关抗原(FⅧRAg)血管内皮细胞特异性染色,计数肿瘤微血管密度(MVD)。结果 24例恶性黑素瘤组织表达eNOS,26例表达VEGF,色素痣组织不表达eNOS和VEGF;VEGF与eNOS的表达呈正相关;eNOS、VEGF的表达与恶性黑素瘤MVD呈正相关,恶性黑素瘤MVD明显高于色素痣;eNOS、VEGF表达与淋巴结转移无关。结论 MVD随着eNOS和VEGF表达的增强而增加。     

缺氧诱导因子-1α在黑素瘤中的表达及其与血管生成的关系

目的研究缺氧诱导因子-1α(HIF-1α)及血管内皮生长因子(VEGF)在人黑素瘤组织中表达,探讨HIF-1α在黑素瘤血管生成中的作用。方法应用免疫组织化学方法检测45例人黑素瘤标本HIF-1α,VEGF和第Ⅷ因子相关抗原(FⅧRAg),血管内皮细胞特异性染色计数肿瘤微血管密度(MVD)。结果HIF-1α在黑素瘤和色素痣中均有表达,但在黑素瘤中表达明显高于色素痣(P<0.01),36例(80.00%)黑素瘤组织表达VEGF,色素痣组织不表达VEGF;HIF-1α与VEGF的表达呈正相关(P<0.01),其与淋巴结转移密切相关(P<0.05);HIF-1α,VEGF的表达与黑素瘤MVD呈正相关(P均<0.01)。结论MVD随着HIF-1α和VEGF表达的增强而增加,表明两者可促进黑素瘤血管生成。HIF-1α在VEGF调节肿瘤间质内血管生成中可能具有重要作用。     

血管生成素及其受体Tie2在婴幼儿血管瘤表达的研究

目的研究婴幼儿血管瘤血管内皮细胞血管生成素及其受体Tie2的表达情况,初步探讨婴幼儿血管瘤生长异常的病理生理学机制,为其治疗奠定理论基础。方法以40例血管瘤患儿手术切除的血管瘤组织为研究对象,其中增生期和消退期标本各20例,另取正常皮肤组织（包茎患儿包皮环切术切除的包皮组织）20例作为正常对照。应用半定量PCR技术检测血管生成素-1（Angl）、血管生成素一2（Ang2）及其受体Tie2 mRNA表达情况;应用Western blotting技术检测Ang1、Ang2及其受体Tie2蛋白表达情况。结果Rt—PCR和Westem blotting结果均显示：在增生期和消退期瘤体中,Ang1 mRNA和蛋白的表达量明显低于正常包皮组织,P〈0．05;Ang2和Tie2 mRNA和蛋白的的表达量明显高于正常包皮组织,P〈0．05;三者的表达在增生期和消退期瘤体之间没有统计学差异,P〉0．05。结论婴幼儿血管瘤中存在Ang1、Ang2和Tie2的异常表达,可能参与了血管瘤的发生与发展机制。     

银屑病患者皮损中血管内皮生长因子和基质金属蛋白酶2的表达

目的探讨血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP-2)在寻常性银屑病皮损血管生成中的作用。方法采用免疫组化法检测30例寻常性银屑病皮损、12例非皮损和12例正常人皮肤中VEGF、MMP-2的表达水平与分布特征。结果①VEGF在银屑病皮损组织中阳性表达明显高于非皮损组织和正常人皮肤(P<0.05)。②MMP-2在银屑病皮损组织中的阳性表达明显高于非皮损组织和正常人皮肤(P<0.05)。③VEGF、MMP-2在银屑病皮损中表达呈正相关(P<0.05)。结论VEGF、MMP-2在寻常性银屑病发病的血管生成中可能起协同作用。     

银屑病皮损中Survivin、VEGF和Ang—2的表达

目的：检测存活素（Survivin）、血管内皮生长因子（VEGF）及血管生成素-2（Ang-2）等因子在寻常型银屑病（PV）皮损中的表达。方法：用免疫组化方法检测30例PV皮损及30例正常皮肤组织中Survivin、VEGF及Ang-2的表达。结果：PV皮损中Survivin、VEGF及Ang-2的表达明显强于正常皮肤组织。Survivin，VEGF和Ang-2之间的表达呈正相关。结论：Survivin、VEGF及Ang-2共同参与了银屑病新生血管的生成过程。     

血管瘤及血管畸形中聚集素和Bcl-2的表达

目的:检测聚集素(clusterin)和B细胞淋巴瘤/白血病-2基因(Bcl-2)在血管瘤和血管畸形中的表达,探讨他们在血管瘤自发消退过程中的作用。方法:采用免疫组化SP法检测30例增殖期、22例消退期血管瘤、27例血管畸形及5例正常皮肤组织中clusterin和Bcl-2的表达;用TUNEL法测定内皮细胞凋亡率。结果:clusterin在血管瘤消退期的表达明显高于增殖期、血管畸形和正常皮肤(P<0.01);Bcl-2在血管畸形中表达高于正常,血管瘤消退期低于正常(P<0.01);内皮细胞凋亡率在血管瘤消退期明显高于增殖期、血管畸形和正常皮肤(P<0.01)。在血管瘤中,内皮细胞凋亡率与clusterin的阳性率呈正相关而与Bcl-2呈负相关。结论:clusterin在血管瘤中发挥促凋亡作用,血管瘤的自然消退与其有关;Bcl-2发挥抗凋亡作用。     

黑素瘤细胞生长因子表达及微血管密度研究

目的:探讨血管内皮细胞生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)在人黑素瘤中的表达和微血管密度(MVD)的关系。方法:采用免疫组化方法检测42例黑素瘤组织中的VEGF、bFGF的表达;利用第Ⅷ因子相关抗原(FⅧ-RAg)血管内皮细胞特异性染色,对肿瘤MVD进行计数和分析。结果:42例黑素瘤组织中,表达VEGF32例,bFGF29例,两指标均表达25例,VEGF与bFGF的表达呈正相关,VEGF、bFGF表达与淋巴结转移有关;色素痣组织不表达VEGF、bFGF;黑素瘤MVD明显高于色素痣。结论:MVD随着VEGF、bFGF表达的增强而增加,VEGF和bFGF在促进黑素瘤血管形成和促进肿瘤转移方面起协同作用。     

VEGF和DLL4在婴幼儿血管瘤组织中的表达及相关性

目的探讨VEGF及DLL4在婴幼儿血管瘤发生、发展过程中的作用机制。方法应用免疫组织化学SP法检测50例婴幼儿血管瘤(增生期26例,消退期24例)组织中VEGF,DLL4和FⅧRAg的表达水平。采用HPIAS-1000图文报告管理系统对VEGF和DLL4的表达进行定量分析。结果增生期组VEGF的表达明显高于消退期组和正常皮肤组(P0.05),而后两组比较差异无统计学意义(P0.05)。增生期组DLL4的表达明显高于消退期组和正常皮肤组(P0.05),而后两组比较差异无统计学意义(P0.05)。结论 VEGF和DLL4在增生期血管瘤组织中高表达,两者的表达具有明显的一致性,共同促进血管瘤内皮细胞的增殖,在血管瘤的发生、发展过程中起了重要的促进作用。     

HIF-1α与VEGF在银屑病皮损中的表达及其与血管生成的关系

目的探讨缺氧诱导因子-1α(HIF-1α)与血管内皮生长因子(VEGF)在银屑病皮损中的表达,并分析两者的相关性,同时研究两者在银屑病血管形成中所起的作用。方法采用免疫组织化学SABC法及Western blotting检测32例进展期寻常型银屑病和20例正常人皮肤组织HIF-1α与VEGF蛋白的表达,同时用CD34标记血管内皮细胞,计算微血管密度(MVD)。结果 20例正常对照组皮肤组织中HIF-1α,VEGF在表皮表达弱或几乎无表达,但在皮脂腺、毛囊、汗腺可见强表达,32例银屑病患者皮损中HIF-1α,VEGF均在表皮全层表达;与正常对照组相比,银屑病患者皮损中HIF-1α,VEGF表达均显著上调(P0.05);并均与MVD值呈显著正相关(r=0.743,P0.01;r=0.759,P0.01);银屑病皮损中VEGF的表达与HIF-1α的表达呈明显正相关(r=0.681,P0.01);结论银屑病皮损组织存在HIF-1α与VEGF蛋白的过表达,两者在促进银屑病新生血管生成中具有协同作用,可能在银屑病的发生、发展过程中起到重要作用。     

Lumps and bumps in neonates and infants

There are many developmental abnormalities that may appear in the neonate and in infants when critical steps in embryogenesis fail. These steps are often not fatal but can lead to significant morbidity for those patients affected. A logical approach is needed in addressing both the diagnostic and therapeutic issues that arise when caring for these patients, as various lesions will warrant an observational approach, and others may require imaging studies or definitive surgical intervention. Additionally, there are other "lumps and bumps" that are seen in the neonatal and infantile age groups that include malignancies and cutaneous neoplasms with associated systemic sequelae.     

Understanding and Evaluating Systematic Reviews and Meta-analyses

A systematic review is a summary of existing evidence that answers a specific clinical question, contains a thorough, unbiased search of the relevant literature, explicit criteria for assessing studies and structured presentation of the results. A systematic review that incorporates quantitative pooling of similar studies to produce an overall summary of treatment effects is a meta-analysis. A systematic review should have clear, focused clinical objectives containing four elements expressed through the acronym PICO (Patient, group of patients, or problem, an Intervention, a Comparison intervention and specific Outcomes). Explicit and thorough search of the literature is a pre-requisite of any good systematic review. Reviews should have pre-defined explicit criteria for what studies would be included and the analysis should include only those studies that fit the inclusion criteria. The quality (risk of bias) of the primary studies should be critically appraised. Particularly the role of publication and language bias should be acknowledged and addressed by the review, whenever possible. Structured reporting of the results with quantitative pooling of the data must be attempted, whenever appropriate. The review should include interpretation of the data, including implications for clinical practice and further research. Overall, the current quality of reporting of systematic reviews remains highly variable.     

Human T lymphocytes and mast cells differentially express and regulate extra- and intracellular CXCR1 and CXCR2

CXCL8 plays a major role in cell recruitment to sites of inflammation. Apart from neutrophils, little is known, however, about the cellular distribution and regulation of CXCL8 receptors in cells involved in acquired and adaptive immune responses. In previous studies, we have demonstrated the extracellular expression and function of CXCR1/2 on mast cells and also detected an intracellular pool of CXCR1/2. Here, we have addressed the question of receptor regulation during stimulation of human mast cells (HMC-1 cell line) and have studied T cells in comparison. Cell permeabilization was performed to detect both surface and possible intracellular receptor pools. HMC-1 cells stained positive for both receptors on the cell surface (CXCR1, 50%; CXCR2, 51%) and also after cell permeabilization (CXCR1, 86%; CXCR2, 74%). Similarly, T cells exhibited both cell-surface receptor expression (CXCR1, 30%; CXCR2, 23%) and higher total receptor expression (CXCR1, 50%; CXCR2, 36%), although overall values were lower than that in HMC-1 cells. On immunoblot, molecular weights of extra- and intracellular receptors on mast cells were the same, excluding altered receptor glycosylation. On stimulation with phorbol 12-myristate 13-acetate plus calcium ionophore, a time-dependent decrease of surface-membrane receptors was observed in both cell types, while total receptor remained the same, suggesting that receptor shedding is not involved. The kinetics of membrane receptor internalization and replenishment differed for the two cell types. Furthermore, receptor internalization was associated with decreased F-actin polymerization, a basic prerequisite for cell migration. These findings demonstrate for the first time the expression of extra- and intracellular CXCR1/2 receptors on T cells and delineate the dynamics of CXCR1/2 receptors on mast cells and T cells. Furthermore, they suggest a cell-type-specific and finely tuned regulation of chemokine responses at the receptor level in the context of inflammation.     

噬菌体疗法及其在皮肤和泌尿生殖道感染中的应用与展望

【摘要】 随着耐药菌的大量出现,给临床抗感染治疗带来严峻挑战。噬菌体疗法被认为是能够应对这种困境非常有希望的方法,已在很多学科得到探索和应用,在清除皮肤黏膜感染方面的疗效也得到证实,成为目前国际研究的热点。应用多种噬菌体混合的鸡尾酒疗法、噬菌体内溶酶以及噬菌体蛋白治疗耐药的金黄色葡萄球菌、铜绿假单胞菌、大肠杆菌、克雷伯菌、变形杆菌等获得良好的效果。本文综述噬菌体疗法的背景、特征、发展特点及其在皮肤和泌尿生殖道感染中的应用和前景。     

BRAF、NRAS癌基因与恶性黑素瘤的研究

近年来,世界范围内黑素瘤的发生率正逐渐升高,发病年龄也愈来愈早,其死亡率也随之增加.环境因素和遗传易感因素是恶性黑素瘤发病的主要机制.遗传易感性的研究发现,与散发性恶性黑素瘤发病密切相关的两个遗传易感基因是位于RAS-RAF-MEK-ERK途径的BRAF、NRAS基因.其中BRAF基因是黑素瘤中突变率最高的基因,也是目前黑素瘤特异性靶向治疗研究的热点基因.概述BRAF、NRAS基因突变在恶性黑素瘤形成、发生、发展中所起的重要作用,并评述BRAF基因突变在黑素瘤临床诊治上的应用价值.     

血管瘤与脉管畸形诊疗现状与展望

【摘要】 随着血管瘤和脉管畸形分类的不断更新,其诊断和治疗也逐步发展。婴儿血管瘤预后良好,但治疗时机和方法选择对预后至关重要,β受体阻滞剂是一线药物。而脉管畸形尤其一些发病率较低的脉管畸形相关综合征的正确诊断及鉴别诊断仍是现代医学领域面临的挑战。近年研究显示,脉管畸形致病与相关基因突变相关,这些发现为靶向药物治疗提供了理论依据。本文阐述常见的血管瘤及脉管畸形的诊断和治疗现状、存在问题及未来研究方向。