宫颈细胞学与阴道镜活检组织学诊断一致性分析北大核心CSCD

目的探讨宫颈疾病患者细胞学检查为阳性而组织学未发现阳性病灶的现况及原因。方法以低级别鳞状上皮内病变及以上为细胞学阳性标准,收集2008至2016年复旦大学附属妇产科医院病理科细胞学诊断阳性的病例12097例,首次活检阴性3107例,其中675例复核活检,细胞学与组织学活检诊断的一致性采用Kappa值表示。结果首次活检的总阳性率为74．3％（8990／12097）,首次活检阴性经复核活检证实确有病变287例（42．5％,287／675）,患者的年龄明显大于首次活检阳性的患者,且再次送检标本类型较初次送检切取范围更广,包括更多比例的阴道壁活检、锥切活检和全子宫切除标本。复核原细胞学结果,最终阳性组织学诊断与初始细胞学诊断具有一定的相关性,Kappa值为0．505（P〈0．01）。结论合格的宫颈细胞学诊断是活检组织学的有益补充且一致性较好,在活检阴性时不能忽略初始细胞学阳性结果。在细胞学与活检组织学结果不符的病例中,重复阴道镜活检以及适当扩大活检范围有助于发现隐匿的宫颈病变。     

液基细胞学联合DNA定量细胞学在筛查宫颈病变中的应用价值

目的探讨宫颈液基细胞学和DNA定量细胞学在宫颈癌前病变及宫颈癌诊断中的应用价值。方法对2156例患者进行宫颈液基细胞学和DNA定量细胞学检查,对其中221例液基细胞学和（或）DNA定量分析阳性者行宫颈活检,以活检结果为金标准,比较两种方法的检测结果及DNA定量细胞学对ASCUS患者的分流作用。结果1．液基细胞学以≥ASCUS,DNA定量细胞学以可见DNA倍体异常细胞作为活检标准及联合两种方法检测,活检结果以CINI及以上病理改变作为阳性结果,其敏感度、特异度、阳性预测值、阴性预测值分别为69．77％、77．52％和89．15％,38．04％、48．91％和84．09％,61．22％、63．69％和86．47％,47．30％、60．81％和84．09％。2．TCT与DNA定量细胞学检测方法灵敏度及特异度对比,均无统计学意义（P〉0．05）;TCT联合应用DNA定量细胞学与单独应用TCT检测方法灵敏度及特异度对比,均有统计学意义（P〈0．01）;TCT联合应用DNA定量细胞学与单独应用DNA定量细胞学检测方法灵敏度对比,无统计学意义（P〉0．05）,特异度对比,有统计学意义（P〈0．01）。3．ASCUS患者宫颈病变的检出率为56．25％。ASCUS患者以DNA定量细胞学作为分流方法：阳性组检出率为74．00％,阴性组检出率为26．67％,两组检出率对比,有高度统计学差异（P〈0．01）;DNA定量细胞学阳性组与ASCUS患者未分流前检出率对比,有统计学意义（P〈0．05）。结论DNA定量分析方法与液基薄层细胞学联合筛查,可提高宫颈癌前病变及宫颈癌筛查的敏感度和特异度,对于细胞学检测为ASCUS的人群有分流作用。     

罕见乳腺病变的细胞学特点

细针吸取细胞活检是良性及恶性乳腺病变手术前的主要检查方法。相对于带芯针穿组织活检 ,细针吸取细胞活检具更快速、更经济、痛楚少和基本无合并症的优点。但在另一方面 ,由于直接细胞涂片和离心细胞涂片在保持组织结构方面逊于组织活检 ,要减少假阳性和假阴性 ,诊断者的经验就成为准确诊断的关键。细胞学诊断低分化的乳腺导管癌 ,一般不难。但要正确诊断良恶交界或是罕见的乳腺病变 ,就要在熟悉常见病变细胞学特点的基础上 ,留意罕见病变独特的、有时可能是非常细微的变化。这些罕见病变都有各自的细胞学特征。认识这些细微又独特的细胞学…     

超声内镜引导下细针穿刺传统涂片细胞学、液基细胞学及组织学结果对比及不一致原因分析

目的探讨超声内镜引导下细针穿刺(endoscopic ultrasound guided fine needle aspiration, EUS-FNA)传统涂片细胞学和液基细胞学的诊断价值,并分析与穿刺组织学结果不一致的原因。方法收集2016年1月～2018年9月武汉大学人民医院存档的193例EUS-FNA标本的传统涂片细胞学、液基细胞学及组织学结果。以组织学结果作为对照标准,分别对传统涂片细胞学与液基细胞学结果进行统计分析,并计算两种细胞学方法的准确性、特异性、敏感性、阳性预测值、阴性预测值、假阳性率及假阴性率。对细胞学与组织学不一致的病例重新阅片,并追踪临床随访情况,分析不一致原因。结果 193例EUS-FNA标本中,97例胰腺实性占位病灶穿刺、43例纵隔病灶及纵隔淋巴结穿刺、36例消化道管壁占位病灶穿刺、17例腹腔病灶及腹腔淋巴结穿刺。传统涂片细胞学与液基细胞学两种细胞学方法的准确性、特异性、敏感性、阳性预测值、阴性预测值、假阳性率及假阴性率差异均无显著性(分别为92.23%vs 88.60%,96.97%vs 96.21%,81.97%vs 72.13%,92.59%vs 89.80%,92.09%vs 88.19%,3.03%vs 3.79%,18.03%vs 27.87%;P均0.05)。传统涂片细胞学/液基细胞学结果与组织学结果不一致的病例共24例。分析不一致原因包括细胞学制片方式及诊断的局限性、穿刺取材所致组织学标本不满意或穿刺部位不准确、细胞病理医师判读有误。结论 EUS-FNA的传统涂片细胞学与液基细胞学两种评估方法的准确性、敏感性、特异性、阳性预测值、阴性预测值、假阳性率及假阴性率差异无显著性,但两种方法互为补充。联合使用EUS-FNA的细胞学和组织学评估,能提高诊断价值。     

传统宫颈细胞学检查与薄层细胞学检测的分析比较与评价

目的探讨宫颈液基细胞学检测系统用于宫颈癌防癌涂片的筛查与传统宫颈涂片检查相比的优越性。方法回顾性分析了1051例TCT普查人群及同时期1050例CS普查人群的宫颈涂片结果。对两种方法的标本满意率及宫颈病变的阳性检出率进行了比较，并对两种方法与组织学的符合率进行了比较。结果TCT组标本满意率明显高于CS组（P〈0．01）；对非典型鳞状上皮细胞及其以上病变的检出率TCT组亦明显高于CS组（P〈0．05）。以阴道镜下组织学活检结果为标准，TCT组与CS组对LSLL及HSIL的诊断符合率分别为86．44％，88．88％及66．7％，83．33％。结论与CS相比，TCT技术明显提高了标本满意率及宫颈病变的阳性检出率，TCT技术是宫颈病变筛查的有效手段。     

57例骨肿瘤的穿刺细胞学诊断分析

目的 评价CT引导下穿刺活检涂片细胞学对骨肿瘤诊断的意义和价值。方法 57例临床疑为骨肿瘤患者采取穿刺活检送病理检查的同时，做细胞涂片，分别进行组织学和细胞学观察。结果 细胞学检查总准确性80．7％，敏感性和特异性分别为80．0％和100％，无假阳性。结论 骨穿刺细胞涂片方法快速．经济实用，安全可靠和准确性高。     

ThinPrep液基细胞学在宫颈病变上的临床应用

目的 评价ThinPrep液基细胞学在筛查宫颈病变的临床应用价值。方法 ThinPrep液基细胞学检测了1036例妇科病例,同时做宫颈巴氏涂片检测。细胞学诊断采用TBS分级系统,阳性诊断包括意义不明的非典型鳞状上皮细胞(atypicalsquamous cells of undetermined significance,ASCUS)以上的病变,诊断结果与阴道镜下多点组织活检病理结果相对照。结果 Thi-nPrep液基细胞学检出100％(4/4)的鳞状细胞癌(SCC);96.97％(32/33)的鳞状上皮内高度病变(HSIL)及89.71％(61/68)的低度鳞状上皮内病变(LSIL)。ThinPrep液基细胞学的敏感性与阳性预测值分别为97.32％、83.89％,且显著降低了标本的不满意率。结论 ThinPrep液基细胞学检查敏感性高,标本质量高,利于宫颈病变的早期诊断。     

15 393例宫颈液基细胞学与组织病理学的对照分析

目的探讨宫颈液基细胞学诊断与组织病理学诊断的符合情况。方法对15393例做SurePath宫颈液基细胞学检查,结果异常者依次做Hybrid Capture-Ⅱ肿瘤相关人乳头状瘤病毒（HPV）-DNA检测、5％醋酸宫颈染色肉眼观察并拍照、阴道镜检查及宫颈多点活检行组织病理学检查。细胞学诊断采用TBS（2001）分级报告系统,阳性诊断包括意义不明的不典型鳞状细胞（ASC-US）以上病变;本组细胞学阳性病例有组织病理诊断结果,并对两者进行了对照分析。结果15393例宫颈细胞学检查与组织病理学对照结果显示：7例鳞状细胞癌（SCC）均符合,高级别鳞状上皮内病变（HSIL）为93．6％（103／110）、低级别鳞状上皮内病变（LSIL）为82．0％（443／540）。HPV—DAN阳性检出率与细胞学TBS分级及组织病理学分级正相关。结论应用液基细胞学制片方法、准确掌握TBS的诊断标准可确保宫颈细胞学检查的准确性。     

液基薄层细胞学检测及TBS分类在宫颈病变诊断中的应用

目的探讨液基薄层细胞学（TCT）检测在宫颈病变诊断中的价值。方法对648例宫颈异常的患者进行液基薄层细胞学检测，将诊断意义不明的不典型细胞（ASCUS）以上病变者行阴道镜下活检，将细胞学检测结果与活检结果作对比分析。结果648例TCT检测的患者中，宫颈病变发生率达81．9％，其中良性病变348例，占53．7％，宫颈上皮内病变183例，占28．2％，对183例异常者进行阴道镜下活检与组织病理学诊断比较，符合率为83．6％。宫颈上皮内病变高发年龄为30～40岁，占37．8％。结论TCT技术在宫颈病变的诊断中，具有简便、实用，准确率高的特点，配合阴道镜检查能及时发现宫颈早期病变，是防止宫颈癌的关键。     

5615例宫颈液基细胞检测结果的分析

目的探讨液基薄层细胞技术(LCT)在宫颈病变筛查中的应用。方法对5615例门诊受检者的宫颈细胞采用LCT技术检测和TBS分类诊断,将诊断意义不明的不典型鳞状细胞(ASCUS)以上病变均列为细胞阳性病例,进行阴道镜下多点取材活检,以病理学结果为金标准,传统宫颈刮片巴氏染色结果作对照分析。结果LCT法阳性病例总检出率9.68%,阳性率和准确率显著优于传统巴氏涂片,阳性病例与病理检查结果相符。结论LCT技术比传统的巴氏染色法更能准确、全面地反映宫颈癌和癌前病变,提高了各种宫颈阴道细胞学疾病的检出率及准确性。     

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.     

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.     

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.     

'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.     

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.     

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.     

The case for allele‐specific recognition by the TCR

There is a sharp difference in how one views TCR structure–function–behaviour dependent on whether its recognition of major histocompatibility complex‐encoded restriction elements (R) is germline selected or somatically generated. The generally accepted or Standard model is built on the assumption that recognition of R is by the V regions of the αβ TCR, which is not driven by allele specificity, whereas the competing model posits that recognition of R is allele‐specific. The establishing of allele‐specific recognition of R by the TCR would rule out the Standard model and clear the road to a consideration of a competing construct, the Tritope model. Here, the case for allele‐specific recognition (germline selected) is detailed making it obvious that the Standard model is untenable.