BRCA1在子宫内膜癌中的变化与预后的相关性分析

目的:分析乳腺癌易感基因1(Breast cancer susceptibility gene 1,BRCA1)在子宫内膜癌中的变化与预后的相关性.方法:收集本院2017年12月至2020年6月收治的91例子宫内膜癌患者的临床资料作为研究对象的研究组(癌组织),另选择距癌旁3cm处的正常组织作为对照组.比较两组患者子宫内膜组织BRCAl阳性表达率;对患者进行1年随访,分析影响其预后生存的危险因素.结果:研究组BRCAl阳性表达率为31.87％,明显低于对照组的95.60％(P<0.05).临床分期(Ⅲ～Ⅳ期)、淋巴结转移(有)、组织分化(G3)、肌层浸润(≥1/2)及BRCAl(阴性)为影响子宫内膜癌患者预后生存的独立危险因素(P<0.05).结论:BRCAl过度表达可能与子宫内膜癌发生、发展有关,可作为判断子宫内膜癌病情、预后的辅助指标.     

子宫内膜癌中LRP16的表达及临床病理分析

目的 探讨LRP16在子宫内膜癌中的表达及下调LRP16表达对子宫内膜癌增殖和侵袭、转移的影响。方法 采用免疫组化法EliVision检测LRP16蛋白在子宫内膜癌中的表达，分析其与临床病理特征的关系，并复习相关文献。构建LRP16-shRNA表达载体，建立下调LRP16基因表达的子宫内膜癌细胞株(ISK);采用CCK-8和Transwell试验分析转染前、后细胞增殖和迁移、侵袭能力的差异。结果 子宫内膜癌组织中LRP16蛋白的阳性率为86.25%,正常子宫内膜组织中LRP16蛋白阳性率为13.33%,两组相比差异有显著性(P<0.01);LRP16基因表达下调后子宫内膜癌细胞的生长与对照组相比明显减慢。体外观察LRP16基因表达下调后，子宫内膜癌细胞的迁移和侵袭能力与对照组相比显著减弱。结论 LRP16基因在子宫内膜癌组织中表达增高，LRP16表达与临床病理特征相关；下调LRP16基因后，子宫内膜癌细胞的增殖、迁移、侵袭能力受到明显抑制。     

宫腔镜结合C—erbB-2、nm23及ER表达对子宫内膜癌早期诊断意义

目的 探讨宫腔镜结合C—erbB-2、nm23及ER表达在子宫内膜癌中的诊断意义。方法 宫腔镜检查2400例患者，对筛查出的35例子宫内膜癌、10例内膜不典型增生及10例正常内膜，用免疫组化SP法检测C—erbB-2、nm23和ER表达。结果C—erbB-2、nm23、ER阳性表达率依次为74．29％、51．43％、54．29％；50％、30％、60％；30％、10％、90％。三者nm23、ER阳性表达率明显升高，差异有显著性（P〈0．05）；C—erbB-2阳性表达率明显降低，差异有显著性（P〈0．05）。宫腔镜定位活检确诊子宫内膜癌35例（35／2400），占1．46％。结论 宫腔镜直观病灶，结合c—erbB-2、nm23及ER表达对内膜癌早期诊断有意义。     

凋亡抑制蛋白和耐药因子在卵巢癌中的表达及与化疗的关系

目的研究凋亡抑制蛋白Survivin mRNA和P-糖蛋白(P-gp)、谷胱甘肽S转移酶π(GST-π)及肺耐药蛋白(LRP)在卵巢上皮癌中的表达及与化疗疗效的关系。方法应用原位杂交技术检测Survivin mRNA及应用免疫组化方法检测P-gp、GST-π、LRP在70例上皮性卵巢癌的表达。结果①Survivin mRNA、P-gp、GST-π、LRP在卵巢上皮性癌中的阳性表达率分别为68.6%(48/70)、31.4%(22/70)、65.7%(46/70)、58.6%(41/70),明显高于正常卵巢组织和卵巢良性肿瘤中的表达率(P<0.05)。②对首次术后有残余病变的42例患者进行化疗评价,Survivin mRNA阳性组化疗有效率为45.5%低于阴性组100%(P<0.05);P-gp阳性组化疗有效率为40%低于阴性组66.7%(P>0.05);GST-π阳性组化疗的有效率为42.3%低于阴性组81.3%(P<0.05);LRP阳性组化疗有效率为40%低于阴性组82.4%(P<0.05)。③Survivin mRNA与P-gp、GST-π和LRP存在共表达。结论Survivin mRNA、GST-π、LRP阳性表达者化疗疗效比阴性者差。     

子宫内膜癌组织中cyclin E和p27表达的相关性及其与临床预后的关系

目的 :探讨子宫内膜癌组织中cyclinE与 p2 7表达的相关性及其与临床预后的关系。方法 :用免疫组化方法检测 40例子宫内膜癌、10例子宫内膜不典型增生、2 0例正常子宫内膜组织中cyclinE和p2 7的表达 ,并用Log Rank检验p2 7蛋白和cyclinE蛋白表达与子宫内膜癌患者生存率的关系。结果 :cyclinE表达的阳性率 ,子宫内膜癌组显著高于内膜不典型增生组和正常子宫内膜组 (P <0 .0 5 )。p2 7表达与子宫内膜癌的组织学分级、手术分期及肌层浸润深度有关 (P <0 .0 5 )。cyclinE与p2 7的表达呈负相关。cyclinE蛋白表达阳性患者生存率低于阴性患者 ,p2 7蛋白表达阳性患者生存率高于阴性患者 ,但无统计学意义 (P >0 .0 5 )。结论 :cyclinE对子宫内膜癌的发生可能起一定作用 ,p2 7则与抑制子宫内膜癌的进展有关 ,并可能成为判断预后的有用指标     

子宫内膜癌组织中COX-2、YKL-40、NF-κB的表达及临床意义

目的探究子宫内膜癌组织中环氧合酶-2(COX-2)、甲壳质酶蛋白40(YKL-40)、核转录因子κB(NF-κB)的表达及临床意义。方法选择2014年2月至2018年12月我院妇科收集的80例子宫内膜癌组织及同期行子宫切除的40例正常子宫内膜组织标本作为研究样本,采用免疫组化方法测定组织中COX-2、YKL-40、NF-κB蛋白表达情况,分析子宫内膜癌组织蛋白表达与患者临床参数、预后的相关性。结果子宫内膜癌组织COX-2、YKL-40、NF-κB蛋白阳性表达率显著高于正常内膜组织(P<0.05);子宫内膜癌患者COX-2水平与患者FIGO分期、淋巴结转移相关(P<0.05);YKL-40、NF-κB水平与FIGO分期、分化程度、肌层浸润、淋巴结转移相关(P<0.05);Kaplan-Meier生存曲线显示,COX-2、YKL-40、NF-κB阳性表达患者总体生存率均显著低于阴性表达患者;COX多因素分析示,在矫正其他临床资料后,YKL-40、NF-κB蛋白阳性表达是子宫内膜癌患者预后不良的独立危险因素(P<0.05)。结论子宫内膜癌组织存在COX-2、YKL-40、NF-κB等阳性表达率的升高,与肿瘤侵袭性及预后相关,可作为病情判断及预后预测的参考指标。     

子宫内膜癌中S100A4和Snail的表达及临床意义

目的分析正常子宫内膜、内膜不典型增生及子宫内膜癌组织中S100A4和Snail的表达及与子宫内膜癌临床病理特征及患者预后的关系。方法采用免疫组化SP法检测S100A4和Snail蛋白的表达,分析两者表达与子宫内膜癌临床病理特征的关系;采用Spearman等级相关分析两者表达的相关性;采用Kaplan-Meier法绘制生存曲线及Log-rank检验进行生存分析。结果正常子宫内膜、内膜不典型增生和子宫内膜癌组织中S100A4和Snail蛋白的阳性率均呈升高趋势,分别为3.33%和3.33%、30.00%和23.33%、54.55%和49.09%。S100A4表达与子宫内膜癌组织学分级、FIGO分期、肌层浸润深度和淋巴结转移相关(P均0.05);Snail表达与子宫内膜癌FIGO分期和淋巴结转移相关(P均0.05)。子宫内膜癌中S100A4和Snail的表达呈正相关(r=0.531,P0.001)。生存分析发现,S100A4和Snail阳性子宫内膜癌患者的术后生存时间明显短于阴性组(P均0.05)。结论 S100A4和Snail在子宫内膜癌发生、发展中异常表达,S100A4/Snail阳性子宫内膜癌更易发生淋巴结转移,并且与内膜癌患者的不良预后有关,S100A4和Snail有望成为子宫内膜癌靶向治疗和预后评估的指标。     

子宫内膜癌组织中生长抑素受体、VEGF的表达及其与血管形成的关系

目的 探讨生长抑素受体(somatostatin receptor,SSTR)、血管内皮生长因子(vascular endothelial growth factor,VEGF)在子宫内膜癌组织中的表达及其与肿瘤血管形成的关系.方法 应用免疫组织化学方法检测60例子宫内膜癌组织中SSTR各亚型、VEGF及CD34标记的微血管密度(microvessel denisity,MVD)的表达情况,探讨其与子宫内膜癌临床病理学特征及肿瘤血管形成的关系.结果 在60例子宫内膜癌组织中,SSTR各亚型(SSTR1、SSTR2、SSTR3、SSTR4及SSTR5)的阳性表达率分别为70.0 %,15.0 %,21.7 %,23.3 %及18.3 %;SSTR3、SSTR4在中高分化组表达阳性率明显高于低分化组(P＜0.05).VEGF的阳性表达率为83.3 %,VEGF在低分化组表达阳性率明显高于中高分化组、深肌层浸润组表达阳性率明显高于浅肌层浸润组、FIGO分期≥Ⅱ期组表达阳性率明显高于Ⅰ期组(P＜0.05).子宫内膜癌组MVD(44.85±15.78)明显高于正常子宫内膜组MVD(18.96±4.30)(P＜0.01).SSTR5的表达与VEGF呈负相关,VEGF阳性表达组子宫内膜癌组织MVD高于VEGF阴性组.结论 联合检测SSTR和VEGF对子宫内膜癌预后的评估有一定临床意义.生长抑素类似物(somatostatin analogs,SSTA)可能为子宫内膜癌的诊治提供新的靶点.     

STAT3在子宫内膜癌中的表达及其临床病理意义

目的 检测信号转导与转录激活因子3(STAT3)在子宫内膜癌组织中的表达,探讨其与常见临床病理参数的关系。方法 选择45例子宫内膜癌患者,癌组织为观察组,癌旁内膜组织为对照组进行研究。采用免疫组织化学染色法检测STAT3的表达,分析其表达水平与各项临床病理参数的关系。结果 子宫内膜癌组织中STAT3的阳性表达率明显高于癌旁内膜组织,差异具有统计学意义(P<0.001)。组织学分级为G_2-3级、肌层侵袭>1/2的内膜癌组织中STAT3的阳性表达率高于组织学分级为G₁、肌层侵袭≤1/2的癌组织,差异具有统计学意义(P<0.05)。结论 子宫内膜癌组织中STAT3的表达显著升高,其高表达与子宫内膜癌组织学分级和肌层侵袭有关,对子宫内膜癌的靶向治疗和预后评估具有一定的意义。     

PTEN缺失型子宫内膜癌中ER、PR的表达及意义

目的：探讨ER、PR在PTEN缺失型子宫内膜癌中的表达及PTEN、ER和PR表达特征与子宫内膜癌组织临床病理特征的关系。方法采用免疫组化EnVision法检测100例子宫内膜癌组织中PTEN、ER和PR表达。结果 PTEN在子宫内膜癌患者的缺失率为52．0%(52/100);PTEN缺失型子宫内膜癌组织中ER和PR阳性率分别为15．4%(8/52)和19．2%(10/52), PTEN高表达子宫内膜癌组织中ER和PR阳性率分别为72．7%(8/11)和63．6%(7/11);子宫内膜癌患者中PTEN-ER-PR-的比率为42．0%(42/100),均明显高于其它类型(P<0．05)。不同PTEN、ER和PR表达特征与子宫内膜癌患者组织学分级和病理分期有关(P<0．05),与肌层浸润无关。结论 PTEN、ER、PR三者联合检测可能对子宫内膜癌患者预后及治疗具有重要参考价值。     

Schizophrenia in a North Swedish geographical isolate, 1900–1977. Epidemiology, genetics and biochemistry

Over 200 schizophrenic patients belonging to three major and interrelated pedigree complexes have been investigated over the past 30 years in a North Swedish geographically isolated population, presently numbering about 6,000. An intensive investigation of a number of biochemical correlates and genetic markers in a few selected families belonging to one of the major pedigrees has indicated new strategies for the current research program.
Schizophrenia, as defined operationally, is significantly associated with decreased activities of two enzymes (1) blood platelet monoamine oxidase, (2) plasma dopamine-β-hydroxylase, and (3) with the genetic marker Gc² (group specific antigen). Both enzymes are subject to genetic variation. A positive score for linkage between schizophrenia and low plasma DBH activity has been calculated, but, so far, available data are insufficient for discrimination between linkage and partial contribution of genetically controlled low plasma DBH to the pathogenesis of the disease. Alternatively, both mechanisms could be involved.
As a model for continued research, schizophrenia is explained as based on a double dominant-recessive genotype (Aabb), representing a vulnerability which in about 50 % of cases develops into clinical schizophrenia. It is suggested that the dominant mutation (A) operates on or affects MAO activity, and that the recessive genotype (bb) is instrumental in low variates of DBH activity and very likely such variates within the normal range of physiological variation. Moreover, it is suggested that the combined effects of MAO- and DBH-reduced efficiency on the metabolism of e.g. dopamine could be an essential pathogenic mechanism for the schizophrenic illness which is segregating in this population.     

Renal dysplasia and asplenia in two sibs

A family is reported in which two sibs, one male and the other female, both died within 24 hours of birth with enlarged polycystic kidneys. Postmortem histology in the second child showed gross renal dysplasia. In both children the pancreas was enlarged, nodular and cystic but the liver appeared macroscopically normal. In the second child, histological examination confirmed pancreatic fibrosis with cystic dilation of ducts, but showed portal fibrosis with bile duct proliferation in the liver.
This combination of findings is very reminiscent of those in a girl and her brother reported by Ivemark et al. (1959). The children reported here also showed absence or hypoplasia of the spleen, cardiac anomalies and other features of the Ivemark syndrome (Ivemark 1955), a quite different, usually sporadic, congenital disorder. It is suggested that the children described here have a distinct lethal congenital disorder, probably inherited in an autosomal recessive manner.     

The dominant diseases of modernized societies as omega-3 essential fatty acid deficiency syndrome: Substrate beriberi

About 1900, modern food selection and processing caused widespread $\text{epidemics}$ of the B vitamin deficiency diseases of beriberi and pellagra which, for genetic reasons, often expressed as different diseases ranging from bowel and heart disease to dermatoses and psychoses. But the B vitamins merely help convert essential fatty acids (EFA) into the prostaglandin (PG) tissue regulators and it now turns out that, through hydrogenation, milling and selection of w3-poor southern foods, we have also been systematically depleting, by as much as 90%, a newly discovered trace Nordic EFA (w3) of special importance to primates and sole precursor of the PG3(4) series, even as a concurrent fiber deficiency increases body demand for EFA. Since substrate EFA is processed by many B vitamin catalysts, an EFA deficiency will mimic a $\text{panh}$ypovitaminosis B, i.e., a mixture of $\text{substrate}$ beriberi and $\text{substrate}$ pellagra resembling vitamin beriberi and pellagra but exhibiting as even more diverse $\text{endemic}$ disease. This would consitute a second stage of the Modern Malnutrition and explain why some workers now hold the dominant diseases of modermized societies to be new, nutritionally based, pellagraform yet lipid-related and to range, once again, from heart disease to psychosis. It is an assumption that our dominant diseases are unrelated to each other or are merely revealed by our diagnostic acumen and therapeutic success; and that hydrogenating millions of tons of food oils annually, to destroy the rancidity producing w3-EFA, is safe for $\text{primates}$. Extensive beriberiform disease is reported here in 32 typical cases taken from medical practice which responds strikingly to linseed oil supplements (60% w3-EFA) in confirmation of identical results in Capuchins.     

'Very sore nights and days': the child's experience of illness in early modern England, c.1580-1720

Sick children were ubiquitous in early modern England, and yet they have received very little attention from historians. Taking the elusive perspective of the child, this article explores the physical, emotional, and spiritual experience of illness in England between approximately 1580 and 1720. What was it like being ill and suffering pain? How did the young respond emotionally to the anticipation of death? It is argued that children’s experiences were characterised by profound ambivalence: illness could be terrifying and distressing, but also a source of emotional and spiritual fulfilment and joy. This interpretation challenges the common assumption amongst medical historians that the experiences of early modern patients were utterly miserable. It also sheds light on children’s emotional feelings for their parents, a subject often overlooked in the historiography of childhood. The primary sources used in this article include diaries, autobiographies, letters, the biographies of pious children, printed possession cases, doctors’ casebooks, and theological treatises concerning the afterlife.     

Guidelines for the Validation and Use of Immunoassays for Determination of Introduced Proteins in Biotechnology Enhanced Crops and Derived Food Ingredients

Recent advancements in agricultural biotechnology have created a need for analytical techniques to determine introduced proteins in crops enhanced through modern biotechnology techniques. These proteins are expressed in plant tissues and may be present in food ingredients. Immunoassays are ideally suited for protein detection and may be used as both quantitative and threshold methods. Microplate ELISA and lateral flow devices are two of the most commonly used immunoassay formats for agricultural biotechnology applications. This paper provides general background information and a discussion of criteria for the validation and application of immunochemical methods to the analysis of proteins introduced into plants and food ingredients using biotechnology methods. It is the result of a collaborative effort of members of the Analytical Environmental Immunochemical Consortium. This collaborative effort represents the combined expertise of several organizations to reach consensus on establishing guidelines for the validation and use of immunoassays. Further, the paper offers developers and users a consistent approach to adopting the technology as well as aid in producing accurate and meaningful results.     

HLA in North Colombia Chimila Amerindians

HLA-A,-B,-C,-DRB1 and -DQB1 alleles have been studied in Chimila Amerindians from Sabana de San Angel (North Colombian Coast) by using high resolution molecular typing. A frequent extended haplotype was found:HLA-A*24:02-B*51:10-C*15:02-BRB1*04:07-DQB1*03:02 (28.7%) which has also been described in Amerinndian Mayos Mexican population (Mexico, California Gulf, Pacific Ocean). Other haplotypes had already been found in Amerindians from Mexico (Pacific and Atlantic Coast), Peru (highlands and Amazon Basin), Bolivia and North USA. A geographic pattern according to HLA allele or haplotype frequencies is lacking in Amerindians, as already known. Also, five new extended haplotypes were found in Chimila Amerindians. Their HLA-A*24:02 high frequencies characteristic is shared with aboriginal populations of Taiwan; also, HLA-C*01:02 high frequencies are found in New Zealand Maoris, New Caledonians and Kimberly Aborigines from Australia. Finally, this study may show a model of evolutionary factors acting and rising one HLA allele frequency (-A*24:02), but not in others that belong to the same or different HLA loci.     

Ultracryotomy: development and application (with examples from the yeast cytology) (author's transl)

The preparation steps usually necessary for obtaining ultrathin frozen sections of biological material (chemical prefixation, enclosing, cryoprotective treatment, freezing, sectioning, and post-staining the sections for transmission electron microscopy) are submitted to a critical analysis. The application of cryo-ultramicrotomy, in particularly for cytochemical purposes, is reviewed. Fundamental considerations of chemical prefixation and poststaining are supported by examples from yeast cytology. Furthermore, the efficiency of the cryo-ultramicrotomy (electron optical resolution of ultrastructural details) is demonstrated on yeast cells and protoplasts.     

The universal muscular chamber. A basic unit of the genitourinary, cardiovascular, gastro-intestinal, skeletal, cutaneous, respiratory and other systems, endocameral hypertension; and spasm, the key to their idiopathic diseases and arthropathies

Starting with the integument, we see many organs are contractile sacs or multiples thereof, which tubes or bags constitute the major part of the entire body. Recognition of this basic unit and its characteristics sheds new light, individually and collectively, on many disorders previously considered unrelated. Muscular tears and perforations develop in the walls of these chambers, being no way peculiar to those organs, wherein, hydrochloric acid occurs. So, it is not necessary to explain the absence of excessive acid from patients who exhibit holes in the gastric, uterine, aortic, duodenal, rectal, pulmonary, retina, and other walls. Muscle, not acid is the great common factor relating idiopathic disorders in the gastrointestinal tract to each other and to similar diseases in other systems. When the units are linked together, the lesions tend to appear as arthropathies, i.e. at the joints. Rephrasing common-place observations, frees us from conventional, conceptual cul-de-sacs. An observation is only as good as its interpretation, so all possibilities must be considered, otherwise, we will remain blinded by our misconceptions.     

Der Einfluß von Nahrungsmitteln und Rauchen auf die klinisch-chemische Diagnostik von Phäochromozytom,Neuroblastom und Karzinoid-Syndrom

Zusammenfassung Der Einfluß von verschiedenen Nahrungsmitteln auf Methoden zur Bestimmung von Adrenalin (AD), Noradrenalin (NA), Vanillinmandelsäure (VMS), Metanephrinen (MN), Homovanillinsäure (HVS) und 5-Hydroxyindolessigsäure (5-HIE) im 24 h-Harn zur Diagnose des Phäochromozytoms bzw. Karzinoid-Syndroms wurde untersucht. Die in die Untersuchung einbezogenen Nahrungsmittel waren: Tee, Kaffee, Mandeln, Ananas, Käse, Walnüsse, Vanillepudding, Bananen, Tomaten und Milchschokolade. Außerdem wurde der Einfluß des Zigarettenrauchens auf die Bestimmung von AD, NA, VMS und MN untersucht.Walnüsse führten zu einer starken Erhöhung der 5-HIE-Ausscheidung. Bananen erhöhten die Ausscheidung von AD, NA, VMS, MN und 5-HIE. Kaffee und Ananas bewirkten eine geringe Zunahme der MN-Werte. Rauchen von 20–30 Zigaretten/Tag beeinflußte keine der vier Variablen.Wenn die beschriebenen Methoden benutzt werden, sollte lediglich auf den Verzehr von Bananen und Walnüssen vor und während der Harnsammelperioden verzichtet werden, da die oberen Normgrenzen im Harn überschritten werden könnten. Ein Verzicht auf Kaffee und Ananas in normalen Mengen ist nicht erforderlich. Es besteht kein Anlaß, weiterhin die bisherigen umfangreichen Restriktionen der übrigen Nahrungsmittel beizubehalten.