CHPF高表达在结直肠癌预后评估中的意义

目的探讨软骨素聚合因子(chondroitin polymerizing factor, CHPF)在结直肠癌预后评估中的意义。方法采用免疫组化SP法检测206例结直肠癌原发灶及癌旁组织中CHPF蛋白的表达,应用Western blot法检测结直肠原发灶癌组织及其癌旁组织中CHPF蛋白的表达。结果 CHPF蛋白在原发灶癌组织(122/206,59.2%)中的表达显著高于癌旁组织;Western blot实验显示在新鲜结直肠癌组织中检测到CHPF蛋白(5/5,100%)。CHPF蛋白高表达与结直肠癌神经或脉管侵犯(P=0.011)、TNM分期(P0.01)、癌结节(P=0.035)明显相关;与患者性别、年龄、肿瘤分化程度和KRAS状态无关(P0.05)。Kaplan-Meier生存分析结果表明,CHPF蛋白高表达与结肠癌患者不良预后显著相关(P0.001)。Cox多因素风险回归模型分析显示,CHPF蛋白可以作为结直肠癌患者不良预后的独立预测因子。结论 CHPF蛋白高表达是结直肠癌患者不良预后的预测因子之一。     

Gab2在结直肠癌组织中的表达及其意义

目的:探讨Gab2在结直肠癌组织中的表达及其意义。方法:应用免疫组化方法检测78例结直肠癌及46例癌旁正常组织中Gab2的表达水平,并结合临床病理学资料进行统计学分析,Western blot方法检测10对结直肠癌组织及相对应的癌旁正常组织中Gab2的表达状况。结果:免疫组化检测结果显示78例结直肠癌组织中Gab2蛋白表达阳性率为53.85%,而癌旁正常组织中Gab2蛋白多不表达或弱表达,两组结果比较差异有显著性(P0.001);Gab2蛋白在结直肠癌中的表达与肿瘤TNM分期及有无淋巴结转移呈正相关(P0.05),与肿瘤大小、分化程度无明显相关性(P0.05);Western blot检测结果显示结直肠癌组织中Gab2蛋白表达显著高于相对应的癌旁正常组织(P0.05)。结论:Gab2在结直肠癌组织中过表达,可能在结直肠癌的发生发展中起重要作用。     

结直肠癌中SPOCD1的表达及相关分子机制

目的 探讨含SPOC结构域蛋白1(SPOC domain-containing protein 1, SPOCD1)在结直肠癌中的表达及相关分子机制。方法 利用TCGA数据库和GEO数据库分析结直肠癌和癌旁正常组织中SPOCD1 mRNA的表达;采用免疫组化和Western blot法检测结直肠癌和癌旁正常组织或细胞系中SPOCD1蛋白表达,并分析其与临床病理特征的关系;应用GEPIA和Prognoscan数据库分析SPOCD1表达与结直肠癌患者预后的关系;基因集富集分析SPOCD1可能参与的通路;采用GEPIA数据库分析基因表达之间的相关性;利用siRNA沉默结直肠癌细胞系HCT116中SPOCD1蛋白表达,Western blot法验证下游基因。结果 TCGA和GEO数据库分析结果显示,SPOCD1 mRNA在结直肠癌组织中的表达显著增加;免疫组化结果显示,SPOCD1蛋白在结直肠癌组织中高表达(67.8%,40/59),显著高于癌旁正常组织(37.3%,22/59)(P<0.001);SPOCD1在结直肠癌细胞系(HCT116和LoVo)中的表达高于正常结直肠细胞系(NCM...     

BS69 在结直肠癌组织中的表达以及病理相关性研究

目的:探讨BS69在结直肠癌组织及细胞系中蛋白和mRNA的表达水平,分析BS69与患者病理特征的相关性。方法:选择2016年8月至2017年10月间手术切除的60例结直肠癌组织和25例癌旁正常组织,采用免疫组化和RTq PCR法检测组织中BS69蛋白和mRNA的表达情况。采用蛋白印迹(Western blot)法检测BS69在三种结直肠癌细胞系和正常结直肠上皮细胞中的蛋白表达。结果:BS69免疫组化染色主要定位于细胞核,少量位于细胞浆。其在结直肠癌和正常结直肠组织中的阳性率分别为65%和87%,差异具有统计学意义(P0. 05); BS69在结直肠癌组织中的表达水平与Dukes分期、肿瘤组织分级、淋巴结转移及远处转移有相关性(P0. 05); Western blot检测BS69在3种结直肠癌细胞系与正常结直肠上皮细胞中蛋白表达,各细胞系中结果有明显差异;结直肠癌组织中BS69 mRNA的表达明显低于正常组织,差异有统计学意义(P0. 05)。结论:BS69是重要的转录抑制因子,可能参与了结直肠癌的发生、发展过程,有望成为特异性较高的肿瘤标志物。     

结直肠腺癌中TKT的表达及临床意义

目的探讨结直肠腺癌中转酮醇酶(transketolase, TKT)的表达及与临床病理特征的关系。方法通过Oncomine和GEO数据库分析TKT基因在结直肠腺癌和癌旁组织中的表达。收集配对结直肠腺癌及癌旁正常肠黏膜组织,分别采用qRT-PCR、Western blot法检测TKT mRNA和蛋白表达,运用免疫组化法检测TKT蛋白表达,并分析其与临床病理特征的相关性。结果 qRT-PCR结果显示:与癌旁组织相比,27例结直肠腺癌组织中TKT mRNA表达显著升高(P<0.001);Western blot结果显示:8例结直肠腺癌组织中TKT蛋白表达高于癌旁组织,在常见结直肠癌细胞株中TKT蛋白表达高于FHC细胞株;两种检测与数据库样本分析一致。免疫组化检测结果显示:92例结直肠腺癌组织中TKT高表达率显著高于癌旁组织(P<0.001),TKT高表达与肿瘤直径(P=0.003)、脉管侵犯(P=0.021)、淋巴结转移(P=0.005)及T分期(P=0.007)相关。结论 TKT在结直肠腺癌中呈高表达,与肿瘤侵袭转移临床病理特征密切相关,其可能参与结直肠腺癌的发生、发展,TKT有望成为结直肠癌预后标志物或潜在的治疗靶点。     

TIMP-3基因甲基化与结直肠癌临床病理的关系

目的：探讨TIMP-3基因甲基化与结直肠癌临床病理指标和转移复发的关系。 方法： 采用巢式甲基化特异性PCR技术（nMSP法）检测100例结直肠癌组织和100例癌旁非癌组织TIMP-3基因甲基化；采用RT-PCR检测100例结直肠癌组织和100例癌旁非癌组织TIMP-3 mRNA的表达。 结果： 肿瘤组织TIMP-3 mRNA的表达阳性率为64%，肿瘤组织TIMP-3 mRNA的表达率明显低于癌旁非癌组织（P＜0.01）；TIMP-3 mRNA的表达率无淋巴结转移组（34/42）高于淋巴结转移组（30/58）（P＜0.01），甲基化阳性率Duke’s C+D期伴淋巴结转移组明显高于Duke’s A+B期不伴淋巴结转移组（P＜0.05）。结肠近端、分化程度差的结直肠癌组织甲基化阳性率明显高于远端直肠和分化程度高者（P＜0.05）。 结论： TIMP-3基因甲基化容易发生在结肠近端、Duke’s C、D期、伴淋巴结转移、细胞分化差和浸润型结直肠癌患者。     

干细胞转录因子OCT4在结直肠癌组织中的表达及其意义

目的探讨干细胞转录因子OCT4在结直肠癌组织中的表达及临床意义。方法应用免疫组化EnVision两步法及Western blot法检测60例结直肠癌手术切除组织及癌旁正常组织中OCT4的表达,分析其与结直肠癌临床病理特征的关系,运用Kaplan-Meier法分析OCT4表达与结直肠癌患者总生存率的关系。结果结直肠癌组织中OCT4的阳性率为80.00%,高于癌旁正常组织(16.67%),差异有统计学意义(P0.05),OCT4阳性与结直肠癌的淋巴结转移及Dukes分期有关(P0.05),与其他临床病理特征尚无相关性(P0.05)。Western blot实验显示:结直肠癌组织中OCT4蛋白的相对表达量为7.70±0.07,高于癌旁正常组织(0.70±0.07),差异有统计学意义(P0.05);OCT4阳性与结直肠癌的淋巴结转移及Dukes分期有关(P0.05),与其他临床病理特征无相关性(P0.05)。生存分析显示:OCT4阳性患者的总生存期低于阴性患者。结论 OCT4在结直肠癌中过表达,可作为预测结直肠癌患者预后的潜在分子标志物。     

叉头框M1在结直肠癌中的表达及临床意义

目的探讨叉头框M1(FOXM1)在结直肠癌中的表达及与临床病理特征、预后的关系。方法采用免疫组化SP法检测297例结直肠癌组织和80例对应癌旁正常组织中FOXM1的表达;Western blot法检测20例新鲜结直肠癌组织及对应癌旁组织中FOXM1的表达。结果 FOXM1在结直肠癌组织中的阳性率(70.97%)显著高于癌旁组织(17.50%,P0.01);FOXM1表达与结直肠癌浸润深度、淋巴结转移、脉管内癌栓转移、远处转移和TNM分期有关(P0.05);与患者年龄、性别、肿瘤部位、大小、分化程度、CEA、CA199等无关(P0.05)。结直肠癌组织中FOXM1蛋白相对表达量(0.855±0.063)明显高于相应癌旁组织(0.150±0.041,P0.01)。FOXM1阳性患者的3年生存率明显低于阴性患者(P0.01),且FOXM1为结直肠癌预后的独立性危险因素。结论 FOXM1蛋白在结直肠癌组织中过表达,且与患者临床病理特征、预后等因素有关,可能在结直肠癌的发生、转移等过程中起重要作用,有望成为结直肠癌新的肿瘤标志物和潜在的治疗靶点。     

丙酮酸羧化酶在胃腺癌中的表达及临床意义

目的 检测丙酮酸羧化酶(PC)在胃腺癌组织中的表达并分析其临床意义.方法 应用免疫组织化学方法及Western blot法检测PC蛋白在胃腺癌及其对应癌旁组织的表达情况,分析其在肿瘤中表达水平与患者年龄、性别、TNM分期及病理分级等临床病理资料之间的关系,并用Western blot法检测PC蛋白在不同分化胃癌细胞系及永生化胃黏膜上皮细胞系的表达情况.结果 免疫组化及Western blot法均显示PC在胃腺癌组织表达水平显著高于其对应癌旁组织(P＜0.01).PC高表达与患者TNM分期及病理分级显著相关(P＜0.05),而与患者性别、年龄无明显相关性(P＞0.05).Western blot法显示PC在不同分化胃癌细胞系表达水平显著高于永生化胃黏膜上皮细胞(P＜0.01).结论 PC高表达与肿瘤的恶性进展密切相关,提示PC有可能作为胃癌生物治疗的潜在靶点.     

SDF-1/CXCR4及VEGF在结直肠腺癌中的表达及其意义

目的:研究VEGF、SDF-1及CXCR4在结直肠腺癌中的表达及其与临床病理学参数之间的相关性;探讨SDF-1/CXCR4轴与VEGF在结直肠腺癌发生发展浸润转移中的作用。方法:利用实时荧光定量PCR(RT-q PCR)法及免疫组织化学SP法检测80例结直肠腺癌及其对应癌旁组织中SDF-1、CXCR4和VEGF mRNA及蛋白的表达。结果:在mRNA水平上,结直肠癌组中SDF-1、CXCR4、VEGF的表达显著高于对应的癌旁组织。免疫组化结果显示,肿瘤中c蛋白表达阳性率分别为78.7%、60%和66.3%高于对应癌旁组织的37.5%、42.5%和28.8%,差异显著(P0.05);结直肠癌中SDF-1表达水平与肿瘤细胞淋巴结转移、远处转移及TNM分期密切相关(P0.05),与患者的年龄、性别、肿瘤的大小、浸润深度等无关;CXCR4的表达与患者的淋巴结转移及TNM分期密切相关;SDF-1的表达与CXCR4及VEGF的表达成显著正相关。结论:SDF-1/CXCR4及VEGF在结直肠癌组织中高表达,并且与肿瘤生物学行为密切相关,提示其在肿瘤的发生发展浸润转移过程中发挥重要作用。     

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.     

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.     

What will studies of Fulani individuals naturally exposed to malaria teach us about protective immunity to malaria?

There are an estimated over 200 million yearly cases of malaria worldwide. Despite concerted international effort to combat the disease, it still causes approximately half a million deaths every year, the majority of which are young children with Plasmodium falciparum infection in sub-Saharan Africa. Successes are largely attributed to malaria prevention strategies, such as insecticide-treated mosquito nets and indoor spraying, as well as improved access to existing treatments. One important hurdle to new approaches for the treatment and prevention of malaria is our limited understanding of the biology of Plasmodium infection and its complex interaction with the immune system of its human host. Therefore, the elimination of malaria in Africa not only relies on existing tools to reduce malaria burden, but also requires fundamental research to develop innovative approaches. Here, we summarize our discoveries from investigations of ethnic groups of West Africa who have different susceptibility to malaria.     

The universal muscular chain reaction,muscle spasm,Torsions, ruptures and extravasations. Chameleons of pathology and some manifestations of simple muscular disorders

Most bodily functions require the coordinated actions of complementary and supplementary paired muscle groups. Where this essential muscular cooperation is lacking, hollow organs may burst and others become literally screwed up, giving rise to many similar spastic diseases such as Torticollis, Twisted ovarian cyst, Torsion of the Testis, Volvulus of the intestines, Varicose Veins, Megacolon, Aortamegaly, Scoliosis, Erb's Palsy, Peyronie's Disease, Main-en-Griffe, Undescended Foot (Pes Cavus), Talipes, Strabismus. Spasm is “panenepidemic” and unclassified examples of Torsion Dystonia and Dyskinesia really are as common as debt and taxes.     

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.     

Hypo- und Hypermagnesämie aus kardiologischer Sicht

Zusammenfassung Eine Reihe pathologischer Zustände bedingen Magnesiummangel. Zustände mit Hypermagnesämie sind ebenfalls bekannt, doch wesentlich seltener. Für den Kardiologen beachtenswert ist, daß unter Therapie mit bestimmten Diuretica bei Herzinsuffizienz, bei Herzinfarkt, Kardiomyopathie, Digitalisintoxikation und bestimmten Herzrhythmusstörungen Hypomagnesämie beobachtet wurde. Leider kann in der klinischen Routine nur ein extracelluläres Magnesiumdefizit durch Serumbestimmungen gemessen werden; über Magnesiummangel einzelner Organe kann nichts ausgesagt werden. Hinweise für Magnesiummangel geben aber neben der Messung des Serumspiegels Anamnese, klinischer Befund, bestimmte EKG-Veränderungen wie auch evtl. Hypokalämie, ein Zustand, bei dem sich oft — besonders bei Aldosteronismus — parallele Veränderungen zeigten.Tierexperimente deuten darauf hin, daß infarktähnliche Läsionen unter Magnesiummangel entstehen, doch ob Herzinfarkt beim Menschen durch Magnesiummangel ausgelöst werden kann, ist noch ungeklärt. In Leichenherzen zeigte sich im Infarktgebiet neben Calciumakkumulation signifikanter Magnesiumverlust, wobei unklar blieb, ob sich Ursache oder Folge des Infarktes widerspiegelten. Falls ein ursächlicher Zusammenhang besteht, ist er im Myokardstoffwechsel selbst zu suchen, wie bei der Alkoholkardiomyopathie, wo myokardialer Magnesiummangel zumindest als pathogenetischer Teilfaktor anerkannt wird. Andererseits versucht man aber auch Beziehungen zwischen Atherosklerose, Blutgerinnung und Hypomagnesämie herzustellen, in der Meinung, daß Magnesiummangel auch über den coronaren Pathomechanismus des Herzinfarktes wirken könnte. Sicher scheint, daß gewisse EKG-Veränderungen und Herzrhythmusstörungen durch einen irritierten Magnesiumhaushalt bedingt sein können, da sie bei Gabe bzw. Entzug von Magnesium verschwinden. Daß Magnesiummangel die Glykosidtoleranz verringert, wird tierexperimentell bestätigt. Unter Hypomagnesämie bewirkt Acetylstrophanthidin eher und länger Rhythmusstörungen als ohne, außerdem lassen diese sich durch Magnesiumgaben eliminieren. Da in gewissen Fällen spontane und digitalisinduzierte Herzrythmusstörungen durch Magnesiuminjektionen beseitigt wurden, scheint Magnesium als Therapeuticum angebracht. Einsatz verschiedener Magnesiumsalze bei Angina pectoris, degenerativen Herzerkrankungen und Herzinsuffizienz ohne geprüften und offensichtlich gestörten Magnesiumhaushalt ist fragwürdig, weil keine eindeutigen klinischen Erfolgsbeweise vorliegen. Immerhin mag es aber larvierte, durch Serumbestimmungen nicht erfaßbare Mangelzustände geben. Allgemein erscheint es aus kardiologischer Sicht ratsam, den Magnesiumhaushalt zu überwachen und in entsprechenden Fällen auszugleichen, um möglichen Myokardläsionen oder fatalen Herzrhythmusstörungen entgegenzuwirken.     

Class II HLA in Georgia Caucasus Tbilisi Georgians and their Mediterranean ancestry: The Usko Mediterranean languages

Georgia (or Sakartvelo in its own language) is a South Caucasus Mts. country with its easternmost part is enigmatically named Iberia, like the Iberian Peninsula, which may refer to rivers “Kura” and “Ebro” or their valleys respectively. Most of their inhabitants speak Georgian which is included within Dene-Caucasian group and Usko-Mediterranean subgroup of languages. The latter includes Basque, Berber, ancient Iberian-Tartessian, Etruscan, Hittite, Minoan Lineal A and others. In the present paper, HLA class II -DRB1 and -DQB1 alleles has been studied and extended haplotypes calculated. Most frequent haplotypes are also of Mediterranean origin (i. e.: (A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*51)-DRB1*13:01-DQB1*06:03, or (A*24-B*35)-DRB1*01:01-DQB1*05:01) and DA genetic distances show that closest world populations to Georgians are Mediterraneans. Georgians also show common extended haplotypes ((A*02-B*51)-DRB1*11:01-DQB1*03:01, (A*02-B*13)-DRB1*07:01-DQB1*02:01 and (A*03-B*35)-DRB1*11:01-DQB1*03:01) with Svan people, a secluded population in North Georgia mountains. We can conclude that Georgians belong to a very old Mediterranean substratum according to both linguistics (Usko Mediterranean languages) and HLA genetics.     

Environmental risk factors and their role in the management of atopic dermatitis

Introduction: The etiology of atopic dermatitis (AD) is multifactorial with interaction between genetics, immune and environmental factors.

Areas covered: We review the role of prenatal exposures, irritants and pruritogens, pathogens, climate factors, including temperature, humidity, ultraviolet radiation, outdoor and indoor air pollutants, tobacco smoke exposure, water hardness, urban vs. rural living, diet, breastfeeding, probiotics and prebiotics on AD.

Expert commentary: The increased global prevalence of AD cannot be attributed to genetics alone, suggesting that evolving environmental exposures may trigger and/or flare disease in predisposed individuals. There is a complex interplay between different environmental factors, including individual use of personal care products and exposure to climate, pollution, food and other exogenous factors. Understanding these complex risk factors is crucial to developing targeted interventions to prevent the disease in millions. Moreover, patients require counseling on optimal regimens for minimization of exposure to irritants and pruritogens and other harmful exposures.     

'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.