胰岛素样生长因子-2在宫颈癌组织中的表达及其临床意义

目的 探讨宫颈癌组织中胰岛素样生长因子-2(IGF-2)的表达及其与临床病理特征的关系.方法 采用免疫组织化学链霉亲和素-生物素过氧化物酶法检测15例正常宫颈(NCE组)、30例宫颈上皮内瘤变(CIN 组)和50例宫颈癌(SCC 组)中IGF-2的表达.结果 NCE、CIN及SCC组IGF-2阳性表达率分别为0.00%(0/15)、43.33%(13/30)和74.00%(37/50),从NCE、CIN到SCC组,IGF-2 阳性表达率显著升高(P均<0.05).IGF-2 的表达率在盆腔淋巴结转移、组织学分级、间质浸润程度中差异有统计学意义(χ~2分别为8.698,5.162,4.278,P均<0.05),且与癌组织对宫颈间质的浸润程度、淋巴结转移呈正相关(r值分别为0.361、0.723,P均<0.01).在年龄、国际妇产科联盟(FIGO)临床分期中差异无统计学意义(χ~2值分别为0.435,0.631,P均>0.05).结论 IGF-2的高表达与宫颈癌的发生、发展及侵袭转移有关,可能是有价值的肿瘤生物学行为标记物.     

巨噬细胞移动抑制因子及相关因子在宫颈鳞癌组织中的表达及意义

目的探讨宫颈鳞癌（SCC）中巨噬细胞移动抑制因子（MIF）、金属蛋白酶‐9（MMP‐9）和血管内皮生长因子（VEGF）的表达及意义。方法选择SCC组织标本51份（SCC组）、宫颈上皮内瘤样病变（CIN）标本41份（CIN组）,正常宫颈组织（NCE）标本32份（NCE组）,采用免疫组化SP法检测各组MIF 、MMP‐9和VEGF的表达并比较分析。结果 NCE组、CIN组、SCC组MIF、MMP‐9、VEGF阳性率及微血管密度（MVD）值依次升高,组间比较有统计学差异（ P ＜0．05）,且SCC组显著高于CIN组、NCE组;MIF、MMP‐9和VEGF在SCC组织中的阳性表达均与组织分化程度、有无淋巴结转移、临床分期有关（ P ＜0．05）;MIF、MMP‐9和VEGF阳性表达的M VD值与SCC临床分期、分化程度、淋巴结转移显著相关（ P ＜0．05）;在SCC中M IF和M M P‐9的表达呈显著正相关（ P ＜0．05）,而VEGF和MIF、MMP‐9的表达无相关性（ P ＞0．05）。结论 MIF、MMP‐9和 VEGF在SCC的发生、发展、浸润及转移中起重要作用;SCC组织学分化越差,MIF、MMP‐9和VEGF阳性表达率及MVD值越高,提示三者联合检测可为评估SCC严重程度。     

转录因子Twist、Snail在宫颈鳞癌中的表达及其与血管生成的关系

目的探讨Twist、Snail蛋白在宫颈鳞癌组织中的表达情况及其与微血管密度的关系。方法采用免疫组织化学方法对60例宫颈鳞癌组织Twist及Snail蛋白的表达进行检测,分析其与临床病理特征的关系。CD34抗体标记癌组织内血管内皮细胞数量,计算微血管密度(MVD)。结果宫颈鳞癌组织中Twist及Snail的阳性表达均与患者的组织学分级及临床分期无关(P0.05),与淋巴结转移有关(P0.05)。Twist及Snail阳性表达组MVD显著高于Twist、Snail阴性组。在宫颈鳞癌组织中Twist及Snail蛋白的表达之间存在显著正相关(r=0.529,P0.05)。结论宫颈鳞癌组织中存在Twist及Snail蛋白的高表达,两者的联合表达可能增加肿瘤细胞的侵袭力,并且可以通过微血管生成在宫颈鳞癌的浸润、转移过程中发挥促进作用。     

E-钙黏附蛋白、骨桥蛋白在宫颈鳞癌中的表达及其与预后的关系

目的探讨E-钙黏附蛋白(E-cadherin)、骨桥蛋白(OPN)在宫颈鳞癌中的表达及其与预后的关系。方法采用免疫组化SP法检测78例宫颈鳞癌、30例正常宫颈组织中E-cadherin、OPN的表达,评价二者与宫颈鳞癌临床病理参数及预后的关系。结果正常宫颈组织、宫颈鳞癌中E-cadherin的阳性表达呈明显下降(P0.05),E-cadherin阳性表达率与临床分期、组织学分级、淋巴结转移有关(P0.05)。正常宫颈组织、宫颈鳞癌中OPN的阳性表达呈显著上升(P0.05),OPN阳性表达率与组织学分级、淋巴结转移有关(P0.05)。E-cadherin表达阴性、OPN表达阳性的患者的总生存率显著低于E-cadherin表达阳性、OPN表达阴性的患者(P0.05)。多因素分析表明,淋巴结转移、E-cadherin和OPN的表达与预后不良有关(P0.05)。E-cadherin、OPN的表达呈负相关(r=0.321,P0.01)。结论 E-cadherin表达降低或缺失和OPN高度表达与宫颈鳞癌的发生、进展及转移密切相关。     

基质金属蛋白酶组织抑制物-1在宫颈癌的表达与临床意义

目的 :探讨基质金属蛋白酶组织抑制物 - 1(TIMP- 1)在早期宫颈癌的表达和临床意义。方法 :采用免疫组织化学 SP法检测 75例早期宫颈浸润癌 (宫颈癌组 )、18例宫颈上皮内瘤样病变 (CIN组 )和 15例癌旁正常宫颈上皮 (对照组 )中 TIMP- 1的表达情况 ,并检测其中微血管密度 (CD34 标记 )和癌细胞增殖标记指数 (Ki- 6 7标记 )。结果 :TIMP- 1主要表达于宫颈癌细胞膜和 (或 )细胞浆 ,Ki- 6 7主要表达于癌细胞核 ,CD34 主要表达于癌巢间质血管内皮细胞。从对照组到 CIN组再到宫颈癌组 ,TIMP- 1的阳性表达率未见显著升高 (P>0 .0 5 )。 TIMP- 1在宫颈癌中表达与 FIGO分期、组织学分级、盆腔淋巴结转移和间质浸润深度有关 (P<0 .0 5 ) ;而与年龄、组织学类型、脉管浸润、Ki- 6 7表达及微血管密度无关 (P>0 .0 5 )。 FIGO分期为 期、组织学分级为 级、有盆腔淋巴结转移及突破深肌层间质浸润者 ,其 TIMP- 1阳性表达率分别显著低于 FIGO分期为 期、组织学分级在 级以内、无盆腔淋巴结转移和浸润深度在浅肌层间质以内者 (P<0 .0 5 )。结论 :宫颈癌 TIMP- 1表达降低可能在侵袭转移中起一定作用。检测宫颈癌 TIMP- 1表达对进一步了解宫颈癌生物学行为和判断预后有一定价值。     

宫颈癌组织P16 INK4A、端粒酶、人宫颈癌癌基因表达及其与临床病理的相关性研究

目的观察宫颈癌(SCC)组织P16INK4A、端粒酶及人宫颈癌基因(HCCR)蛋白表达水平及其与临床病理的相关性。方法选取2017年1月至2019年3月该院妇科门诊110例疑诊为宫颈病变患者的病理组织,其中正常宫颈组织、宫颈上皮内瘤变(CIN)Ⅰ级组织、CINⅡ级组织、CINⅢ级组织各20例,SCC组织30例。检测各组织P16INK4A、HCCR蛋白表达及端粒酶活性,并进行统计学分析。结果 P16INK4A蛋白阳性表达率正常宫颈组织组CINⅠ级组CINⅡ级组CINⅢ级组和SCC组,HCCR蛋白阳性表达率正常宫颈组织组和CINⅠ级组CINⅡ级组CINⅢ级组SCC组,端粒酶活性水平正常宫颈组织组CINⅠ级组CINⅡ级组CINⅢ级组SCC组,差异均有统计学意义(P0.05)。不同病理类型的SCC组织P16INK4A蛋白阳性率差异无统计学意义(P0.05),但低、中分化及有淋巴结转移的SCC组织P16INK4A蛋白阳性率均为100.00%;不同分化程度、有无淋巴结转移SCC组织中HCCR蛋白阳性表达率及端粒酶活性水平差异有统计学意义(P0.05);且不同宫颈癌国际妇产科联盟分期SCC组织中端粒酶活性水平差异有统计学意义(P0.05)。结论 SCC组织P16INK4A、HCCR蛋白表达及端粒酶活性明显异常,且与病理特征有一定相关性,均可作为预测CIN晋级趋势及诊断SCC的参考指标。     

宫颈癌血管生成与癌细胞增殖及浸润转移的关系

目的　探讨早期宫颈癌血管生成与癌细胞增殖及浸润转移的关系。方法　采用免疫组织化学 SP法检测75例早期宫颈癌、18例宫颈上皮内瘤样病变 (CIN)和 15例癌旁正常宫颈上皮中微血管密度 (MVD,CD34 标记 )及 Ki- 6 7抗原的表达情况 ,探讨宫颈癌血管生成与癌细胞增殖及浸润转移的关系。结果　 CD34 主要表达于宫颈癌巢间质血管内皮细胞 ,而 Ki- 6 7主要表达于宫颈癌细胞核。从正常宫颈上皮→ CIN→宫颈浸润癌 ,MVD和 Ki- 6 7表达均显著升高 (P<0 .0 5 )。宫颈癌 MVD与盆腔淋巴结转移、脉管浸润、间质浸润和 Ki- 6 7表达有关 (P<0 .0 5 ) ;而与年龄、FIGO分期、组织学分级和组织学类型无关 (P>0 .0 5 )。有盆腔淋巴结转移、脉管浸润、≥深层间质浸润及 Ki- 6 7呈高度表达者 ,其 MVD分别显著高于无盆腔淋巴结转移、无脉管浸润、<深层间质浸润及 Ki- 6 7<高度表达者 (P<0 .0 5 )。结论　肿瘤血管生成可能在宫颈癌发生发展、癌细胞增殖和浸润转移中起重要作用。宫颈癌伴 MVD显著升高者 ,其癌细胞增殖活跃 ,易发生浸润转移 ,但并非唯一决定因素。检测宫颈癌 MVD对进一步了解宫颈癌生物学行为具有一定的临床应用价值。     

食管鳞癌组织中 PI3K 和 caspase-3的表达及其临床意义

目的：研究 PI3K 和 caspase-3在食管鳞癌组织(esophageal squamous cell carcinoma,ESCC)中的表达及其与食管肿瘤发生、发展与转移的关系。方法应用免疫组织化学链霉菌抗生物素蛋白过氧化物酶链结(SP)法检测24例正常食管黏膜、94例食管鳞癌组织中 PI3K 和 caspase-3的表达情况,并分析其与临床病理特征之间的关系。结果 PI3K 在食管鳞癌中的表达高于正常食管黏膜(P <0.01);PI3K 蛋白在高中分化鳞癌中表达低于低分化鳞癌,随着浸润深度和临床分期的增加,其表达阳性率增高,在淋巴结转移阳性组的表达高于阴性组(92.0% vs 47.7%, P <0.01);而 caspase-3阳性表达与 PI3K 相反,高中分化鳞癌中表达高于低分化鳞癌,随着浸润深度和临床分期的增加,其表达阳性率降低,在淋巴结转移阳性组的表达低于阴性组(38.0% vs 68.2%,P <0.01);PI3K 与 caspase-3表达有关联(r =-0.230,P <0.05)。结论 PI3K 高表达和 caspase-3低表达与食管鳞癌发生发展及侵袭转移存在协同作用,是反映食管鳞癌生物学行为的重要指标。     

宫颈鳞状细胞癌中DLC-1和cyclinD1的表达及其临床意义

目的 观察肝癌缺失基因1(deleted in liver cancer-1,DLC-1)和细胞周期蛋白D1(cyclinD1)在正常宫颈组织、宫颈上皮内瘤变(CIN)及宫颈鳞状细胞癌(CSCC)中的表达,并探讨两者与CSCC临床病理因素之间的关系.方法 应用免疫组化SP法检测DLC-1和cyclinD1在正常宫颈组织、CIN及CSCC中的表达.结果 ①DLC-1在正常宫颈组织、CIN和CSCC中的阳性表达率依次降低,与CSCC的肿瘤分级、FIGO分期及淋巴结转移有关,且差异显著(P＜0.05).②cyclinD1在正常宫颈组织、CIN和CSCC中的阳性率依次升高,其表达与CSCC的肿瘤分级、FIGO分期及淋巴结转移有关,且差异显著(P＜0.05).③DLC-1和cyclinD1在CSCC中的表达呈负相关.结论 DLC-1低表达和cyclinD1高表达与CSCC的发生、发展、侵袭、转移相关,二者有望成为CSCC辅助诊断、治疗的新靶点.     

髓样分化因子88在宫颈鳞癌组织中的表达及临床意义

目的探讨髓样分化因子88(My D88)在正常宫颈组织、宫颈上皮内瘤变(CIN)组织和宫颈鳞癌组织中的表达及临床意义。方法采用免疫组化SP法检测30例正常宫颈组织、45例CIN组织及55例宫颈鳞癌组织中Toll样因子受体4(TLR4)及My D88蛋白的表达,并研究其与宫颈癌患者临床病理特征之间的相关性。采用Western Blot法检测正常宫颈组织及宫颈鳞癌组织中TLR4及My D88蛋白的表达。结果免疫组化结果显示,TLR4及My D88在正常宫颈组织、CIN及宫颈鳞癌组织中阳性表达逐渐增强,组间相比差异有统计学意义(P0.05)。Western Blot结果提示,与正常宫颈组织相比,TLR4及My D88在宫颈鳞癌组织中的蛋白表达水平明显上调,宫颈鳞癌组织中TLR4蛋白表达水平增加了284.89%(P0.05),My D88蛋白表达水平增加了45%(P0.05)。且TLR 4蛋白表达异常增高与肿瘤浸润程度及有无淋巴结转移相关(P0.05),与不同临床分期及肿瘤分化均无显著差异(P0.05);My D88的表达与组织学类型和病理分级无关(P0.05),与患者有无淋巴结转移及临床分期也无显著相关性(P0.05)。结论 My D88可能参与宫颈鳞状上皮的恶性转变过程,TLR 4可能通过My D88信号通路来参与宫颈癌的发生、发展。     

NO and HNO donors,nitrones, and nitroxides: Past,present, and future

The biological effects attributed to nitric oxide (^?NO) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age‐related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N‐O bond enabled the development of several classes of compounds with potential clinical interest, among which ^?NO and HNO donors, nitrones, and nitroxides are of particular importance. Although primarily studied for their application as cardioprotective agents and/or molecular probes for radical detection, continuous efforts have unveiled a wide range of pharmacological activities and, ultimately, therapeutic applications. These efforts are of particular significance for diseases in which oxidative stress plays a key pathogenic role, as shown by a growing volume of in vitro and in vivo preclinical data. Although in its early stages, these efforts may provide valuable guidelines for the development of new and effective N‐O‐based drugs for age‐related disorders. In this report, we review recent advances in the chemistry of NO and HNO donors, nitrones, and nitroxides and discuss its pharmacological significance and potential therapeutic application.     

Genomics, Nutrition, Obesity, and Diabetes

PURPOSE: To present evidence of genetic and environmental interactions as they relate to nutrition, diabetes, and obesity. METHODS: A review of seminal literature related to genetics, obesity, and diabetes. FINDINGS: Multifactorial interactions are important in the development of nutrition-related disorders, but the challenge remains to explain how these interactions are expressed. Treating subpopulations of people might be important and useful to some extent at present, but in the future treating people of given genetic predispositions and other personal and environmental factors will have greater effects on quality-of-life indicators and life expectancies. CONCLUSIONS: Individualization coupled with multifactorial interactions will lead to new and more effective preventive and treatment modalities of nutrition-related disorders. With obesity and diabetes, genomics will bridge the traditional use of diet, exercise, and weight reduction with other environmental factors, ultimately leading to healthier lives.     

Platelets,thrombosis, coagulation,and atherosclerosis

When I first got the invitation to join a medical delegation going to Moldova, I thought for a moment that our destination was the fictional country in the old Marx Brothers movie Duck Soup. On further checking, it turns out that entertaining place was called Freedonia. I now know that Moldova is indeed a real country, bordered on the west by Romania and on the other three sides by the Ukraine. It is a proud country, rich with traditions, and its people are warm, giving, eager to learn ways to improve their healthcare system, and deeply appreciative of our attempts to help them in the task.     

Vomiting, diarrhea, constipation, and gastroenteritis

Diseases that cause vomiting, diarrhea, constipation, and gastroenteritis are major problems for populations worldwide. Patients, particularly infants, elderly, and immunocompromised individuals, may present at any point in a wide spectrum of disease states, underscoring the need for the clinician to treat these ailments aggressively. Several promising new treatment modalities, from oral rehydration solutions to antiemetic therapies, have been introduced over the past decade. Future directions include the use of probiotic agents and better tolerated rehydration solutions. Gastrointestinal disease will continue to be a focus worldwide in the search for better ways to cure illnesses associated with vomiting and diarrhea.     

Thoughts,images, worry,and anxiety

Recent models suggest that worry is primarily a verbal-linguistic process that enables images to be avoided and reduces somatic activation. Five-hundred and two subjects completed a questionnaire that assessed variables related to generalized anxiety disorder (GAD) criteria and also asked subjects to indicate the percentage of thoughts and images while worrying. Subjects were divided into excessive worriers (worry excessively about two or more topics more days than not for at least the last 6 months) and ordinary worriers (those who did not meet the previous criteria). As predicted, worry was reported as being composed predominantly of thoughts rather than images, and excessive worriers reported a significantly higher percentage of thoughts compared to ordinary worriers. The number of somatic symptoms was positively correlated with the percentage of images. This relationship was stronger among excessive worriers than ordinary worriers, specifically for autonomic hyperactivity symptoms. Further, in the excessive worry group only there was a significant negative correlation between the number of autonomic hyperactivity symptoms and the percentage of thoughts.This research was partially supported by grants from les Fonds de Recherche en Santé de Québec and the Medical Research Council of Canada. The study was completed while the first author was supported by the Medical Research Council of Canada.The authors gratefully acknowledge the assistance of France Blais for recruiting subjects, administering questionnaires, and entering data.     

Lipid messenger, diacylglycerol, and its regulator, diacylglycerol kinase, in cells, organs, and animals: history and perspective

Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid containing two acyl chains, to convert phosphatidic acid. DG is produced through phosphoinositide turnover within the membrane and is well known to act as a second messenger that modulates the activity of protein kinase C in the cellular signal transduction. Recent studies have revealed that DG also activates several proteins, including Ras guanine-nucleotide releasing protein and ion channels such as transient receptor potential proteins. Therefore, DGK is thought to participate in a number of signaling cascades by modulating levels of DG. Previous studies have disclosed that DGK is composed of a family of the isozymes, which differ in the structure, enzymological property, gene expression and localization, subcellular localization, and binding molecules. The present review focuses on the stories of phosphoinositide turnover and DG, including historical views, structural features, metabolism, and relevant cellular phenomena, together with the characteristics of DGK isozymes and the pathophysiological findings on animal studies using knockout mice and models for human diseases. Now it is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.