Delta-like 4在胰腺癌中的表达及其意义

目的 检测Delta-like 4(DLL4)在胰腺癌中的表达,探讨其临床意义.方法 采用免疫组化法检测60例胰腺癌组织中DLL4的表达,行血管内皮特异性标志物CD34免疫染色,计算微血管密度(MVD);分析它们的相关性及其与胰腺癌临床病理特征、患者预后的关系.结果 DLL4在胰腺癌组织中的表达明显高于正常胰腺组织(68.3％比20.0％,x2=14.239,P＜0.01),其高表达与胰腺癌的肿瘤分化程度、TNM分期、淋巴结转移及累及范围密切相关,与肿瘤大小、部位、病理分型无关.胰腺癌组织MVD明显高于正常胰腺组织(34.9±13.2比18.9 ±2.2,t=3.570,P＜0.01),其与肿瘤分化程度、TNM分期、淋巴结转移及累及范围密切相关,与肿瘤大小、部位及病理分型无关.DLL4阳性表达与预后密切相关.经Cox模型分析,TNM分期、DLL4阳性表达是胰腺癌患者预后不良的独立危险因素.结论 DLL4的高表达在胰腺癌转移、浸润中起重要作用.肿瘤DLL4表达和TNM分期对评估胰腺癌患者的预后有一定价值.     

应用组织芯片技术研究Delta-like 4在胃癌组织中的表达及意义

目的:研究Delta-like 4(DLL4)在胃癌中的表达及其与血管生成的关系.方法:采用免疫组化EnVision法检测胃癌组织芯片中DLL4的表达,用CD34进行微血管内皮细胞染色,计算微血管密度(MVD),分析其相关性.结果:DLL4在胃癌中的表达明显高于正常胃黏膜(85.9% vs 35.3%.P＜0.01).DLL4的高表达与胃癌的转移(r=0.612,P＜0.01)和胃壁浸润深度(r=0.482,P＜0.01)呈正相关,与胃癌的组织病理及Borrmann分型无关.胃癌组织MVD明显高于正常胃黏膜组织(66.5±18.6 vs 34.2±16.4.P＜0.01).MVD值与胃癌的组织病理分型(r=0.506,P＜0.01)和转移有关(r=0.426,P＜0.01),与胃癌胃壁浸润深度和Borrmann分型无明显相关性.DLL4表达阳性组的MVD指数明显高于DLL4表达阴性组(70.5±16.2 vs 32.5±10.4,P7＜0.01),DLL4表达与MVD呈正相关(r=0.521.P＜0.01).结论:DLL4表达促进血管分化,对胃癌的转移、浸润起重要作用.     

Toll样受体4在胰腺癌组织中的表达及其与肿瘤血管生成的关系

目的 探讨Toll样受体4(TLR4)在胰腺癌组织中的表达及其与肿瘤血管生成的关系.方法 采用免疫组化SP法检测62例经病理证实的胰腺癌手术切除标本及35例癌旁正常胰腺组织中TLR4蛋白表达,采用CD31抗体标记微血管内皮细胞,计算微血管密度(MVD).分析TLR4蛋白表达与胰腺癌临床病理特征以及MVD的相关性.结果 胰腺癌组织TLR4蛋白阳性表达率和MVD分别为74.2％ (46/62)和47.3±13.5,均显著高于正常胰腺组织的17.1％ (6/35)和12.6±4.8(P值均＜0.01).有淋巴结转移的胰腺癌组织中TLR4蛋白阳性表达率为83.8％,显著高于无淋巴结转移的60.0％(P=0.036);TNM分期为Ⅲ+Ⅳ期的胰腺癌组织中TLR4蛋白阳性表达率为85.3％,显著高于Ⅰ+Ⅱ期的60.7％(P =0.028).MVD与肿瘤的大小、淋巴结转移及TNM分期密切相关(P值分别为0.008、0.036、0.010).胰腺癌TLR4蛋白表达与MVD呈显著正相关(Υ=0.534,P＜0.01).结论 TLR4参与胰腺癌的发生、发展,其机制可能与促进肿瘤血管生成有关.     

缺氧诱导因子-1α表达与胰腺癌病理学特征及新生血管生成的关系

目的研究胰腺癌组织中缺氧诱导因子-1α(HIF-1α)的表达与胰腺癌病理学特征的关系,以及HIF-1α表达与血管内皮生长因子(VEGF)和肿瘤微血管密度(MVD)之间的相互关系.方法应用免疫组织化学方法检测47例胰腺癌和10例正常胰腺组织中HIF-1α和VEGF蛋白的表达.同时用CD34单克隆抗体标记胰腺癌和正常胰腺组织中的微血管.结果HIF-1α和VEGF蛋白在47例胰腺癌组织中的阳性表达率分别为55.3%(26/47)和61.7%(29/47),而在10例正常胰腺组织中均未见表达.胰腺癌组织MVD为37.61±14.3,正常胰腺组织为7.55±2.4,二者间有显著性差别(t'=13.51,P＜0.001).HIF-1α和VEGF蛋白阳性表达率及MVD均与胰腺癌的浸润和转移密切相关(χ2=4.32,6.01,4.75,4.62;t=2.38,3.92;P＜0.05),而与胰腺肿块大小、组织学分级和患者术后1年生存率无关(P＞0.05).HIF-1α与VEGF(r=0.329,x2=5.71;P＜0.05)、HIF-1α与MVD(r=0.594,t=4.96;P＜0.001)及VEGF与MVD(r=0.366,t=2.64;P＜0.05)间在胰腺癌组织中的表达均呈显著的正相关性.结论在缺氧状态下,胰腺癌组织中HTF-1α基因被激活,过量表达HIF-1α蛋白,并通过诱导VEGF的生成而刺激肿瘤新生血管的生成,促进癌细胞的浸润和转移.     

血管内皮生长因子的表达与胰腺癌转移及预后关系的研究

目的 探讨血管内皮生长因子(VEGF)对胰腺癌转移、预后的影响.方法 收集74例胰腺癌组织和6例正常胰腺组织、4例CP组织、6例癌旁正常胰腺组织,采用免疫组化方法检测VEGF的表达,分析VEGF表达与胰腺癌病理指标及患者预后的关系.结果 胰腺癌组织VEGF表达率为71.6%(53/74),其他组织为12.5%(2/16),差异显著(P＜0.05).肿瘤组织VEGF阳性表达与淋巴结转移、神经浸润明显相关(P＜0.05或P＜0.01).Kaplan-Meier方法和log-rank检验显示,VEGF表达、淋巴结转移、神经浸润、肿瘤分期与患者预后相关(P＜0.05或P＜0.01).多变量COX风险模型分析显示,神经浸润、淋巴结转移与患者预后有直接相关性,而VEGF表达不是直接相关因素.结论 VEGF可以作为判断胰腺癌转移与预后的指标,有一定临床价值.     

转录因子Twist及其相关因子N-cadherin在胰腺癌中的表达及意义

目的 探讨转录因子Twist及其下游相关因子N-cadherin在人胰腺癌组织中的表达及与肿瘤临床病理特征、患者预后的关系.方法 采用免疫组化MaxVision两步法分别检测62例胰腺癌组织和10例正常胰腺组织中Twist及N-cadherin的表达,分析二者表达与临床病理特征及患者预后的相关性.结果 Twist在胰腺癌组织的阳性表达率明显高于正常胰腺组织(96.8％比30.0％,P＜0.01),N-cadherin在胰腺癌组织的阳性表达率也明显高于正常胰腺组织(75.8％比0,P＜0.01),但两者的表达无明显相关性(r=0.100,P=0.441).Twist及N-cadherin表达与胰腺癌TNM分期、淋巴结转移、门静脉或神经浸润、肿瘤部位均密切相关(P值均＜0.05),与患者年龄、性别及肿瘤分化程度均无明显相关性(P值均＞0.05).胰腺癌患者术后生存期随Twist表达的增强而缩短,但与N-cadherin表达强度无明显相关性.TNM分期、Twist表达强度是影响胰腺癌患者预后的独立因素.结论 胰腺癌组织Twist及N-cadherin均高表达,其表达与胰腺癌的恶性生物学行为相关,Twist的异常表达可能是评估胰腺癌患者预后的潜在指标.     

类肝素酶在胰腺癌组织中的表达意义

目的 探讨胰腺癌组织中类肝素酶(heparanase 1,Hpal)表达与胰腺癌侵袭性、临床病理等因素之间的关系.方法 采用逆转录-聚合酶链反应(RT-PCR)、免疫组化(SP)法检测37例胰腺癌患者痛组织、癌旁组织及正常胰腺组织中Hpal表达,并统计分析Hpal表达与胰腺癌侵袭性、临床病理等因素之间的相关性.结果 Hpal在胰腺癌组织、癌旁组织、正常胰腺组织中的表达阳性率分别为64.9%(24/37)、56.8%(21/37)和10.8%(4/37).胰腺癌组织中Hpal表达与胰腺癌TNM分期、侵及神经和血管情况、包膜完整情况以及淋巴转移明显相关(P＜0.05),但与患者年龄、性别、组织学分化程度、肿瘤大小无关(P＞0.05).结论 Hpal与胰腺癌发生、发展密切相关,Hpal表达与胰腺癌的侵袭性、局部浸润、临床分期以及区域淋巴结转移有密切关系,胰腺癌Hpal过表达可促进胰腺癌浸润生长与转移,其表达对评价胰腺癌预后亦有一定的价值.     

胃腺癌中缺氧诱导因子-1αmRNA表达和血管生成的关系

目的:探讨胃腺癌中缺氧诱导因子-1α(HIF-1α)mRNA、血管内皮生长因子(VEGF)和MVD的表达,探讨其间的相互关系及临床意义. 方法:应用原位杂交和免疫组化方法检测HIF-1αmRNA、VEGF蛋白的表达,用CD-34单克隆抗体标记肿瘤微血管密度. 结果:胃腺癌组HIF-1αmRNA、VEGF的阳性表达率分别为76.7%和66.7%,明显高于正常对照组的20%和0%,胃腺癌组的MVD为34±10,高于正常对照组的15±5,(P＜0.01),.MVD表达与肿瘤的分化情况,即病理分型密切相关,(P＜0.01);而与TNM分期、淋巴结转移和远处转移情况无明显相关性.VEGF阳性表达率与TNM分期表现出一定的相关性,而与病理分型无关,发生远处转移者的VEGF阳性表达率81.9%,高于无远处转移者52.6%(P＜0.05).HIF-1mRNA表达与MVD呈正相关(r=0.37,P＜0.05);与VEGF表达也表现出正相关性(r=0.42,P＜0.05);而VEGF表达与MVD并无相关(r=0.19,P＞0.05). 结论:胃腺癌HIF-1αHIF-1αmRNA过度表达与肿瘤中血管生成密切相关,HIF-1α可以通过诱导VEGF生成而刺激肿瘤血管生成,但这一路径并不是HIF-1α影响肿瘤的血管生成的唯一路径.     

TMPRSS4在胰腺癌组织中的表达及其临床意义

目的 检测Ⅱ型跨膜丝氨酸蛋白酶4( TMPRSS4)在胰腺癌组织中的表达及其与临床病理特征的关系.方法 采用实时PCR法和蛋白质印迹法检测16例胰腺癌和配对癌旁组织TMPRSS4 mRNA和蛋白表达;采用免疫组织化学法检测61例胰腺癌标本、26例配对癌旁组织、4例正常胰腺组织TMPRSS4蛋白的表达,分析其与临床病理特征的相关性.结果 胰腺癌组织TMPRSS4mRNA和蛋白表达明显高于配对癌旁组织(9.09±7.01比1.27±0.72;1.223±0.125比0.667 ±0.106,P值均＜0.01),胰腺癌组织TMPRSS4蛋白阳性表达率为67.2％ (41/61),显著高于癌旁组织3.8％ (1/26)的阳性表达率(P＜0.01).正常胰腺组织未见TMPRSS4蛋白表达.胰腺癌TMPRSS4表达与患者年龄、性别及肿瘤部位、肿瘤大小无关,而与肿瘤分化程度、淋巴结转移、临床分期密切相关(P值均＜0.05).结论 胰腺癌组织高表达TMPRSS4,其表达与肿瘤的恶性程度相关.     

畸胎瘤细胞源性生长因子和血管内皮生长因子在食管鳞癌中的表达及临床意义

目的 探讨食管鳞癌(ESCC)中畸胎瘤细胞源性生长因子(PCDGF)、血管内皮生长因子(VEGF)的表达与肿瘤临床病理参数之间的关系,明确PCDGF和VEGF在血管生成中的作用.方法 以免疫组化方法检测郑州大学第一附属医院2005年7月至2006年5 月收治的50例食管鳞癌患者手术切除标本PCDGF与VEGF的表达,并以CD105抗体标记肿瘤组织血管内皮细胞,计算肿瘤间质微血管密度(MVD).结果 食管鳞癌中PCDGF、VEGF的表达较正常食管上皮明显增加(P＜0.01);PCDGF和VEGF与肿瘤的浸润深度、TNM分期和淋巴结转移呈正相关(P均＜0.05);PCDGF、VEGF的表达与MVD值呈显著正相关(P＜0.01);PCDGF的表达与VEGF的表达呈正相关(P＜0.05).结论 PCDGF标记癌组织的敏感性较高,有望成为一种新的食管鳞癌肿瘤标志物.食管鳞癌中PCDGF、VEGF的表达与血管生成关系密切,可能通过促进肿瘤新生血管生成参与肿瘤的生长、浸润和转移.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.