溃疡性结肠炎患者外周血Tim-4 mRNA表达水平的变化及意义

目的 探究溃疡性结肠炎患者外周血Tim-4 mRNA的表达变化及临床意义。方法 选取2015年2月~2019年4月我院收治的溃疡性结肠炎患者38例作为观察组,另选取同期来我院体检的健康者30名作为对照组,采用荧光定量PCR测定外周血Tim-4 mRNA表达水平,比较两组Tim-4 mRNA、C反应蛋白（CRP）、红细胞沉降率（ESR）表达水平及观察组Tim-4 mRNA与CRP和ESR的相关性。结果 观察组Tim-4 mRNA、CRP、ESR表达均高于对照组[（0.79±0.37）vs（0.33±0.20）]、[（6.08±3.21）mg/L vs（0.99±0.87）mg/L]、[（19.12±12.13）mm/h vs（5.58±4.10）mm/h],差异有统计学意义（P＜0.05）。观察组外周血单个核细胞Tim-4 mRNA表达水平与CRP呈正相关（r=0.376,P＜0.05）,而与ESR无相关性（r=0.077,P＞0.05）。结论 溃疡性结肠炎患者Tim-4 mRNA异常上调,并与CRP密切相关,可能参与溃疡性结肠炎的致病过程。     

溃疡性结肠炎相关癌的回顾性探讨

目的 通过对565例溃疡性结肠炎患者进行癌变风险分析,为溃疡性结肠炎相关癌（UC-CRC）的早期筛查及预防提供依据.方法 对收治的565例溃疡性结肠炎患者进行分组,其中15例UC-CRC组患者,随机抽取28例溃疡性结肠炎组患者,对两组临床相关资料进行回顾性分析.结果 在565例溃疡性结肠炎患者中,UC-CRC组患者有15例,总体风险为3.77％.两组患者在年龄、病变内镜活检、疾病病程、血清CRP水平等方面差异有统计学意义（P ＜0.05,P＜0.01）.高危风险因素显示：疾病病程、病变范围、血清CRP水平、病理诊断为UC-CRC的高危因素.结论 溃疡性结肠炎患者中有较高的UC-CRC癌变风险,溃疡性结肠炎的疾病病程、血清CRP水平、内镜活检为不典型增生及程度与UC-CRC的发生呈正相关.     

Notch4在溃疡性结肠炎中的表达与分析

目的研究Notch4在溃疡性结肠炎(ulcerative colitis,UC)中的表达、分布及意义。方法收集50例UC患者病变部结肠组织及32例结肠癌患者术后大体标本两端的正常黏膜组织。用免疫组化方法检测Notch4在50例UC及32例对照结肠黏膜组织中的表达情况。结果Notch4在UC患者结肠组织及对照的正常结肠组织中均有表达,两者之间的差异无统计学意义(P>0.05)。Notch4的表达与UC患者的性别、年龄及UC病变程度无统计学意义(P>0.05)。结论Notch4在UC患者结肠黏膜组织与正常结肠黏膜组织中的表达相似,差异无统计学意义。     

溃疡性结肠炎患者CD4+T细胞中PRMT5表达及其作用

为探讨蛋白精氨酸甲基转移酶5(protein arginine methyltransferase 5,PRMT5)在UC中的表达及其作用,采用FCM检测健康对照者和UC患者PRMT5的表达情况,用小干扰RNA和特异性抑制剂处理后观察PRMT5对炎症性T细胞凋亡及炎性因子TNF-α、IL-6表达的影响。结果显示,UC组患者PRMT5表达显著升高(P0.01),干扰PRMT5后CD4~+T细胞凋亡增加, TNF-α和IL-6水平明显降低(P0.01);PRMT5特异性抑制剂EPZ015666显著下调TNF-α和IL-6的水平(P0.01)。提示PRMT5在UC发病中具有重要作用,可能成为治疗UC的潜在靶标。     

MAPK4敲除对DSS诱导小鼠急性溃疡性结肠炎模型的影响

目的:观察MAPK4敲除对葡聚糖硫酸钠(DSS)诱导小鼠急性溃疡性结肠炎模型的影响并探讨其意义.方法:用2％的DSS溶液喂食野生型(WT)小鼠,常规建立小鼠急性溃疡性结肠炎模型,Western blot检测肠组织MAPK4的表达情况;分别建立野生型(WT)和MAPK4基因敲除(KO)小鼠的急性溃疡性结肠炎模型,并观察小...     

CXCR4在哮喘小鼠肺组织中的表达及氯喹的干预作用

目的检测哮喘小鼠中趋化因子受体CXCR4的表达及其拮抗剂氯喹(CQ)的干预作用。方法将6~8周SPF级Balb/c小鼠随机分成对照组、哮喘组和氯喹干预组,哮喘组和氯喹干预组用鸡卵清蛋白(OVA)致敏和激发建立哮喘小鼠模型,干预组于激发前30 min给予CQ,连续3 d,对照组用PBS代替。最后1次激发24 h内小鼠肺功能仪检测小鼠气道高反应;最后1次激发48 h内检测支气管肺泡灌洗液(BALF)中细胞总数及细胞分类计数;HE染色光镜下观察肺组织的病理炎症改变,免疫组化染色检测肺组织CXCR4的表达;荧光定量PCR(Q-PCR)测定肺组织中CXCR4 mRNA的表达。结果哮喘组气道高反应及BALF中细胞总数明显高于对照组,干预组小鼠气道高反应及BALF中细胞总数与哮喘组相比显著降低;BALF中哮喘组嗜酸性粒细胞、中性粒细胞和单核细胞数较空白组显著增加,而氯喹干预组较哮喘组显著减低;HE染色结果显示哮喘组肺部炎症细胞浸润明显,干预组与哮喘组相比明显减轻,病理评分降低;免疫组化显示哮喘组CXCR4在气道上皮细胞呈强阳性表达,干预组表达呈弱阳性;哮喘组CXCR4 mRNA的表达较对照组升高,氯喹干预组较哮喘组CXCR4 mRNA表达量降低;CXCR4表达量与BALF细胞总数呈正相关。结论 CXCR4可能参与哮喘小鼠的气道炎症和气道高反应的发生,氯喹能改善哮喘小鼠的气道高反应和气道炎症可能与拮抗CXCR4相关,为氯喹治疗哮喘提供理论和实验依据,为开发治疗哮喘新药提供新的思路。     

丹皮酚对溃疡性结肠炎小鼠的治疗作用及机制

目的 探究丹皮酚对溃疡性结肠炎小鼠结肠损伤的保护作用及可能机制。方法 C57BL/6小鼠40只,随机分为对照组、溃疡性结肠炎组、丹皮酚低剂量组和丹皮酚高剂量组,每组10只。测量结肠长度并计算疾病活动指数评分;HE染色观察结肠组织形态学变化;ELISA方法检测结肠组织炎症因子水平及环腺苷酸（Cyclic adenosine monophosphate, cAMP）含量;TUNEL方法检测结肠组织细胞凋亡;Western blot检测磷酸二酯酶4(phosphodiesterase 4, PDE4)和蛋白激酶A(protein kinase A, PKA)蛋白表达。结果 丹皮酚抑制溃疡性结肠炎小鼠结肠缩短,降低小鼠疾病活动指数评分,改善结肠组织形态,降低结肠组织细胞凋亡,抑制结肠组织炎症因子水平,降低结肠组织PDE4蛋白表达水平,增加结肠组织cAMP含量和PKA蛋白表达水平。结论 丹皮酚减轻溃疡性结肠炎小鼠结肠损伤,其作用机制可能与调控PDE4/cAMP/PKA通路有关。     

SDF-1/CXCR4/CXCR7信号轴在缺血性脑卒中中的作用

基质细胞衍生因子-1（SDF-1）是由骨髓基质细胞产生的CXC类趋化蛋白。CXCR4和CXCR7是已知的两个由SDF-1激活的两个G蛋白偶联受体,在发育和成熟的中枢神经系统中均表达,并参与中枢神经系统中多种病理生理过程,包括脑发育、血管生成、神经变性和神经发生。脑缺血性损伤后,缺血半暗带内SDF-1水平显着增加并诱导神经功能修复,SDF-1/CXCR4/CXCR7信号传导通路可能为卒中的治疗提供新的靶点。本文主要就SDF-1/CXCR4/CXCR7的结构、在中枢神经系统中的表达、相互作用以及其在脑缺血中的作用进行综述,旨在为缺血性脑卒中的治疗提供理论参考。     

肠道干细胞在溃疡性结肠炎中的作用

肠道黏膜屏障损伤是溃疡性结肠炎（UC）发生发展的重要因素。肠道干细胞在维护肠道黏膜屏障完整中发挥巨大的作用。关于肠道干细胞在维护屏障的作用机制已成为研究者们关注的热点问题。因此,笔者首先描述UC、肠道黏膜屏障和肠道干细胞的基本概况,简要阐述肠道黏膜屏障与UC、肠道干细胞的联系,并总结对肠道干细胞的调控运行机制的探讨,为临床研究干细胞治疗UC提供一些参考。如何逆转该因素或是研究治疗UC的一大方向。肠道干细胞在正常肠道中担负着肠上皮细胞的更新迭代,是维持肠道黏膜屏障完整的重要条件,因此研究能够干预该干细胞的因素具有相当重要的意义。但尚未深入探讨每一种途径的具体构成和运行机制。     

血沉在溃疡性结肠炎分期及治疗中的价值

目的通过观察溃疡性结肠炎患者的血沉变化,评价血沉在活动性溃疡性结肠炎病情分期及治疗中的应用价值。方法采集72例活动性溃疡性结肠炎患者的血清,检测治疗前后血清中血沉变化水平,评估其在溃疡性结肠炎患者病情分期及临床疗效中的价值。结果活动性溃疡性结肠炎病情越重,血沉水平越高。活动性溃疡性结肠炎患者经过使用药物美沙拉秦和糖皮质激素有效治疗后,大多可以控制病情,检测血沉水平明显下降(P<0.05)。结论血沉可以作为一种评价和判断活动性UC患者严重程度及疗效的有价值指标。     

Two novel mutations responsible for hereditary type I protein C deficiency: characterization by denaturing gradient gel electrophoresis.

Hereditary protein C (PC) deficiency is usually associated with a high risk of thrombosis. We report the results of a study undertaken to screen for molecular defects in families with hereditary quantitative PC deficiency. Using a strategy combining polymerase chain reaction amplification of selected gene fragments, denaturing gradient gel electrophoresis of the amplification products, and direct sequencing of fragments with altered melting behavior, we studied the PC gene exons and exon/intron junctions of subjects with hereditary type I PC deficiency. Computer simulation of DNA melting was used to design several sets of primers, each containing a GC-clamp, permitting the complete analysis of each amplified exon sequence. Using this procedure, we identified two previously undescribed mutations located in exon VII: a C-to-T substitution generating a nonsense codon in place of Arg 157 in the mature PC and a G-to-A substitution converting Arg 178 to GIn. The two mutations were detected in, respectively, 3 and 2 apparently independent families. This strategy is therefore a valuable tool for screening patients, and the results emphasize its advantages over plasma assays in individuals with a family history of thrombosis.     

Protein C Mangel — Risikofaktor für venöse Thrombosen

Summary Protein C is a vitamin K-dependent protein which is produced in the liver. Activated protein C has an anticoagulant effect by inactivating the clotting factors V and VIII. We report on a young female patient who suffered from recurrent thrombosis of the deep calf and pelvic veins with pulmonary embolism. Superficial thrombophlebitis also occurred repeatedly. In the plasma of this patient we found reduced levels of protein C antigen (0.62 U/ml) and activity (0.42 U/ml). Investigation of other family members revealed a protein C deficiency in her father, sister, and son. During the anticoagulant treatment with Marcumar the patient developed a coumarin-induced skin necrosis, to which complication a protein C deficiency is evidently predisposed. Thsi complication could only be prevented if heparin was given simultaneously during the adjustment period.

     

Macroamylasemia associated with ulcerative colitis

We describe a very rare case in which macroamylasemia was associated with ulcerative colitis of total colitis type. The patient's serum amylase isozyme pattern by electrophoresis showed a broad abnormal peak toward the side of the positive pole compared with regular salivary and pancreatic fractions. Sephadex G-200 column chromatography showed a sedimentation coefficient of 6.6 S. Amylase activity was bound to IgG. Double diffusion experiments demonstrated that amylase activity could be precipitated in gel by an antibody to the chain. Although inflammatory bowel disease is occasionally associated with hyperamylasemia due to pancreatitis, we emphasize that, when hyperamylasemia is recognized in patients with inflammatory bowel disease, macroamylasemia also should be considered.Abbreviations MA Macroamylasemia - UC Ulcerative colitis - IBD Inflammatory bowel disease     

Endovascular management of iliofemoral deep venous thrombosis due to iliac vein compression syndrome in patients with protein C and/or S deficiency

The purpose of this study was to evaluate the early outcome of endovascular management in patients with iliofemoral deep venous thrombosis (DVT) due to iliac vein compression syndrome (IVCS) and protein C and/or S deficiency. Between September 2000 and January 2003, catheter-directed thrombolysis was performed in 11 patients with a diagnosis of acute iliofemoral DVT: 7 with protein C and/or S deficiency and 4 without protein C and/or S deficiency. After thrombolysis, the diagnosis of IVCS was confirmed in 6 patients: 4 with protein C and/or S deficiency and 2 without protein C and/or S deficiency. Further intervention consisted of angioplasty and stent placement was performed. Four patients with IVCS and protein C and/or S deficiency were included in this study. The immediate technical and clinical success rates were 100% in all 4 patients. There were no complications or clinically detectable pulmonary emboli. This initial experience suggests that endovascular management of iliofemoral DVT due to IVCS in patients with protein C and/or S deficiency is safe and effective.     

Neutrophil extracellular traps-associated protein peptidyl arginine deaminase 4 immunohistochemical expression in ulcerative colitis and its association with the prognostic predictors

Neutrophil extracellular traps (NETs) are incriminated in several immune and inflammatory diseases including ulcerative colitis (UC). Analysis of colonic tissues for NETs-related markers in UC carries prognostic and therapeutic implications. This work aims to evaluate the immunohistochemical (IHC) expression of NETs-associated-protein arginine deaminase 4 (PAD4) in colonic biopsies from UC patients in comparison to normal colon (NC). Association between PAD4 expression level and histopathologic grade, patient’s therapeutic response and other clinicopathological prognostic predictors in UC are determined. This cohort study included biopsies from 42 UC patients and 11 NC controls. Clinicopathological data including patient's age at diagnosis, gender, presenting symptoms, anatomical disease extent, extra-intestinal manifestations, type and response to therapy and surgical interventions were recorded and tabulated. Histopathological grading of disease activity and associated epithelial changes were assessed. PAD4 immunostaining was conducted using Horseradish Peroxidase technique and scored semiquantitatively considering intensity and percentage of nuclear staining of lamina propria inflammatory cells. Appropriate statistical tests were applied. Anti-PAD4 was localized mainly in the nuclei of lamina propria infiltrating neutrophils. It was expressed more significantly in UC (95.2 %) compared to NC (p 0.001). Increased PAD4 expression level was significantly associated with increasing histopathologic grade, anatomical disease extent, lacking response to therapy and subjection to radical surgery (p:0.001, = 0.038, 0.046, 0.046 respectively). Age, gender, presenting symptoms, extra-intestinal manifestations and epithelial changes showed insignificant associations. This study characterizes a subset of UC patients with high histopathological grade of activity, pancolonic involvement, strong/moderate PAD4 expression levels and who are unresponsive to routine medical therapeutic regimens rendering them candidates for radical surgery. In conjunction with histopathological grading, IHC evaluation of PAD4 in UC is recommended to guide patient’s selection for targeted therapy using the novel-discovered selective PAD4 inhibitors.     

Evidence that CD4+, but not CD8+ T cells are responsible for murine interleukin-2-deficient colitis

Mice deficient in interleukin-2 production (IL-2^null mice) develop colonic inflammation closely resembling ulcerative colitis in humans. Although this disease is marked by substantial infiltration of the colon by CD8⁺ and CD4⁺ T lymphocytes, no function has yet been assigned to these T cell subsets in the development of colitis in the IL-2^null mouse. For the present study, we investigated the involvement of T lymphocytes in the onset of colitis in IL-2^null mice, and examined the possible role played by cytotoxic T cells. Both lamina propria lymphocytes (LPL) and intraepithelial lymphocytes (IEL) of the colon of IL-2^null mice were potently cytotoxic ex vivo in short-term redirected cytotoxic lymphocyte (CTL) assays. In contrast, colonic T cells of wild-type animals showed little or no constitutive cytotoxic T cell activity. Colonic CTL were detectable prior to the appearance of disease in IL-2^null animals and CTL activity was confined to the TcRαβ, rather than to the TcRγδ IEL subset. IL-2^null animals crossed with major histocompatibility complex class I-deficient mice [IL-2^null × β₂ microglobulin (β₂m^null] mice also developed colitis, which appeared even earlier than in most IL-2^null mice. These findings suggest that neither CD8⁺ IEL nor LPL were causal in the onset of colitis in IL-2^null animals. In IL-2^null × β₂m^null mice, an ulcerative colitis-like disease was evident from histological studies and immunohistological staining which showed very large numbers of CD4⁺ lymphocytes within the intestinal mucosa. Significant ex vivo killing by CD4⁺ T cells was observed in IL-2^null × β₂m^null animals, although this required an extended incubation time compared to colonic CD8⁺ T cells. Peripheral as well as colonic CD4⁺ T cells in IL-2^null and IL-2^null × β₂m^null animals, were activated as judged by their cell surface phenotype (CD45RB^lo, L-selectin^lo and CD69⁺). In light of these findings, we propose that infiltrating CD4⁺, but not CD8⁺ T cells are central to the inflammation observed in the intestinal mucosa in IL-2^null colitis.     

溃疡性结肠炎患者外周血淋巴细胞亚群检测的临床价值

目的 探究外周血淋巴细胞亚群检测在溃疡性结肠炎（ulcerative colitis,UC）诊断中的临床价值.方法 随机选择解放军总医院第一附属医院2011年1月至2013年12月溃疡性结肠炎确诊患者70例,健康体检人群39人,检测其外周血CD3、CD4、CD8、CD4/CD8四项免疫学指标.以SPSS16.0进行独立样本t检验,分析各项指标的诊断价值.结果 溃疡性结肠炎患者与健康人群相比,CD3、CD8差别不明显,CD4、CD4/CD8具有明显差别（P＜0.05）.结论 淋巴细胞亚群的检测对溃疡性结肠炎实验室诊断具有重要临床价值.     

趋化因子及其受体CXCL12/CXCR4在人前列腺癌转移机制中的作用

目的 探讨趋化因子及其受体CXCL12/CXCR4在人前列腺癌转移机制中的作用.方法 免疫组织化学技术分析CXCL12/CXCR4蛋白在18例前列腺癌组织中的表达;免疫细胞化学技术分析CXCL12/CXCR4蛋白在人前列腺癌细胞株PC3、DU145和LNCap中的表达;迁移、侵袭试验分析外源性CXCL12对PC3、DU145和LNCap体外侵袭能力的调节作用.结果 18例人前列腺癌组织中,17例不同强度表达CXCR4蛋白,1例阴性表达,同时除1例标本弱表达CXCL12蛋白外,其余不表达CXCL12蛋白.3种前列腺癌细胞株均表达CXCR4蛋白,不表达CXCL12蛋白.外源性CXCLl2可明显促进PC3、DU145及LNCap的体外迁移、侵袭,以抗CXCL12或CXCR4抗体预处理PC3、LNCap细胞可以拮抗CXCL12对它们的促迁移、侵袭作用.结论 人前列腺癌组织表达CXCR4蛋白,CXCL12/CXCR4信号通路可能参与前列腺癌的侵袭、转移.