大黄虫庶虫丸抑制乙型肝炎后肝纤维化的临床研究

目的探讨破血逐瘀经典方剂“大黄虫庶虫丸”对乙型肝炎后肝纤维化的治疗作用。方法将乙型慢性肝炎患者92例,随机分为两组,治疗组与对照组,治疗组使用大黄虫庶虫丸,对照组使用甘利欣治疗,疗程均为6个月,分别检测两组治疗前后透明质酸(HA)、血清Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)、层粘蛋白(LN)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、白蛋白与球蛋白比(A/G),并进行对比观察。结果经过治疗后,两组血清LN、Ⅳ型胶原、ALT、AST均显著下降(P<0.01),但治疗组LN、Ⅳ型胶原水平下降较之对照组更明显(P<0.05),而对于ALT、AST,两组治疗后无差异;另经治疗后,治疗组血清HA、PCⅢ水平下降(P<0.01),A/G水平升高(P<0.01),而对照组的血清HA、PCⅢ、A/G水平无明显变化(P>0.05)。结论大黄虫庶虫丸对乙型肝炎后肝纤维化有一定的治疗作用。     

大黄蟅虫超微粉剂对大鼠肾间质纤维化的影响

目的比较大黄蟅虫传统丸剂与超微粉剂对肾间质纤维化大鼠模型的药效作用。方法实验动物分为假手术组、模型组、传统丸剂组（0．54g／kg／d）、超微粉剂组（0．27g／kg／d）4组。采用单侧输尿管结扎的方法复制大鼠肾间质纤维化模型,用大黄蟅虫传统丸剂与超微粉剂进行干预,观察不同剂型对肾间质纤维化大鼠肾功能指标、血清纤维化指标、病理组织变化的影响。结果与假手术组相比,模型组血清肌酐（Cr）、尿素氮（Urea）、透明质酸（HA）、层黏蛋白（LN）、Ⅳ型胶原（IV—C）、Ⅲ型前胶原（PCⅢ）显著升高（P〈0．01）,肾间质纤维化明显。与模型组相比,大黄蟅虫传统丸剂组与超微粉剂组血清Cr、Urea、HA、LN、PCⅢ、Ⅳ—C降低（P〈0．01）,肾小管损害和肾间质纤维化程度减轻。与传统丸剂组相比,超微粉剂组血清Cr、Urea较低（P〈0．05）,其余指标差异无统计学意义。结论大黄蟅虫传统丸剂与超微粉剂对实验性肾间质纤维化都有较好的防治作用,能降低肾间质纤维化程度。改善肾功能;在改善肾功能方面,超微粉剂型优于传统丸剂型。复方“大黄蟅虫”药材超微粉碎后减少药量的同时有助于提高药效,有利于剂型现代化。     

Graves'病患者肝纤维化指标测定的意义

目的：探讨Graves’Disease（GD）与肝纤维化指标的关系及其可能的机理。方法：用放射免疫分析（RIA）检测GD患者治疗前40例，治疗后35例和30例健康成人的血清Ⅳ型胶原（Ⅳ—C）、Ⅲ型前胶原（PCⅢ）、透明质酸（HA）、层粘连蛋白（LN）的含量。结果：GD患者血清中Ⅳ—C、PCⅢ含量比正常对照组显著性升高（P〈0.01），治疗后甲状腺激素水平下降，Ⅳ—C、PCⅢ含量也随之下降（与治疗前比较P〈0．01），HA、LN在以上各组中无显著性差异（P〉0．05）。结论：GD患者甲状腺激素水平升高时，Ⅳ-C、PCⅢ含量也增高，在判断肝纤维化时应注意有无合并GD。     

病毒性肝炎患者血清中肝纤维化标志物的检测及分析

目的探讨病毒性肝炎患者血清中肝纤维化标志物的水平及意义。方法酶标法检测基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶抑制剂-1（TIMP-1）和转化因子-β1（TGF-β1），放免法检测转化因子α（TGF-α）、透明质酸（HA）、Ⅲ型前胶原（PCⅢ）、Ⅳ型胶原（C-Ⅳ）和层粘蛋白（LN）。结果病毒性肝炎患者血清中TIMP-1、HA、PCⅢ、C-Ⅳ和LN水平与对照组比较明显升高（P〈0.01）；MMP-1、TGF-β1，水平与对照组比较差异无统计学意义（P〉0.05）。结论病毒性肝炎患者血清中肝纤维化标志物中TIMP-1、HA、PCⅢ、C-Ⅳ和LN具有较好的临床价值，MMP-1、TGF-β1价值欠佳。     

α-干扰素和苦参素可以减轻慢性乙型肝炎患者血清肝纤维化的程度

目的了解α-干扰素(IFN-α)、苦参素对慢性乙型肝炎患者血清肝纤维化指标的影响。方法84例患者随机分为干扰素、苦参素和联合治疗组,采用放射免疫法测定治疗前后血清透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(Ⅳ-C)的变化。结果3组患者治疗后血清HA、LN、PCⅢ、Ⅳ-C水平较治疗前显著降低(P<0.05),联合治疗组降低幅度较干扰素组及苦参素组大(P<0.05)。治疗结束后血清乙型肝炎病毒E抗原(HBeAg)及乙型肝炎病毒DNA转阴情况3组间无明显差异。抗病毒治疗有效组与无效组治疗前血清HA、LN、PCⅢ、Ⅳ-C水平无显著差异,治疗后均明显降低(P<0.05),但有效组较无效组降低更加明显(P<0.01)。结论IFN-α与苦参素联合应用抗病毒效果与单一用药效果无差别,但有助于减轻慢性乙型肝炎纤维化程度,提高抗纤维化的效果。     

脂联素与非酒精性脂肪肝肝纤维化及胰岛素抵抗的关系

目的：研究脂联素水平与非酒精性脂肪肝（NAFLD）患者肝纤维化指标及胰岛素抵抗指数（IRI）的关系。方法：采用ELISA法检测NAFLD患者和正常对照组的脂联素水平及Ⅲ型前胶原（PCⅢ）、透明质酸（HA）、Ⅳ型胶原（CⅣ）、层黏蛋白（LN）水平,采用稳态模式胰岛素抵抗指数（HOMA IRI）评估胰岛素抵抗。结果：NAFLD组脂联素水平显著低于对照组,胰岛素抵抗指数与肝纤维化指标显著高于对照组（P〈0.05）,IRI与PCⅢ、PCⅣ、HA和LN呈显著正相关（P〈0.05）,脂联素水平与WHR、BMI、FBG、Tg、FINS、HOMA-IRI、PCⅢ、PCⅣ、HA和LN呈显著负相关（P〈0.01或〈0.05）。结论：NAFLD患者血清脂联素水平降低,脂联素的表达在NAFLD患者肝纤维化与胰岛素抵抗进程中可能起重要作用。     

蓝莓对大鼠肝纤维化模型中转录因子KLF11表达的影响

目的:观察蓝莓对肝纤维化模型中抗纤维化转录因子Krüppel样因子11(KLF11)的影响,探讨其可能的机制。方法:40只健康同周龄SD大鼠被随机分为正常对照组、蓝莓对照组、模型组和蓝莓预防组,每组10只,使用四氯化碳制作肝纤维化模型。测定各组大鼠血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、Ⅳ型胶原、Ⅲ型前胶原(PCⅢ)、透明质酸(HA)和层粘连蛋白水平;Masson和HE染色对肝组织进行病理学检查;Western blot和免疫组织化学染色检测肝组织中KLF11的蛋白表达,Western blot检测肝组织中α-平滑肌肌动蛋白(α-SMA)的蛋白表达;real-time PCR检测肝组织中KLF11和Ⅰ型胶原(ColⅠ)的mRNA表达情况。结果:与正常对照组比较,模型组KLF11蛋白表达显著降低(P<0.01),而α-SMA蛋白表达显著升高(P<0.01);与模型组比较,蓝莓预防组KLF11的mRNA表达显著升高(P<0.01)而ColⅠ的mRNA表达显著降低(P<0.01);与模型组比较,其它各组大鼠血清ALT、AST、HA和PCⅢ水平均显著降低(P<0.01),蓝莓预防组大鼠肝纤维化分级显著降低(P<0.01)。结论:蓝莓对四氯化碳所致大鼠肝纤维化有一定的预防作用,其机制可能与其影响KLF11表达有关。     

肝纤维化标志物在慢性肝病中的临床意义

为探讨肝纤维化标志物Ⅲ型前胶原(PCⅢ)、透明质酸(HA)、Ⅳ型胶原(C-Ⅳ)和层粘连蛋白(LN)在慢性肝病肝纤维化的诊断和疗效观察中的临床意义, 采用RIA对52例慢性肝病患者, 42名健康对照者, 38例慢性肝病患者经保肝抗纤维化治疗后血清中的PCⅢ、HA、C-Ⅳ和LN进行检测, 同时与对照组和治疗后进行对比分析.慢性肝病患者血清PCⅢ、HA、C-Ⅳ和LN有不同程度升高, 与对照组比较差异显著(P＜0.05),38例慢性肝病治疗后血清PCⅢ、HA、C-Ⅳ和LN都有不同程度的下降, 与治疗前比较差异显著(P＜0.05).血清PCⅢ、HA、C-Ⅳ和LN的测定对慢性肝病肝纤维化的诊断及疗效观察具有重要的临床意义.     

免疫性食蟹猴肝纤维化模型的实验研究

目的：在食蟹猴上,通过皮下注射异种血清的方法建立免疫性肝纤维化模型,阐明该模型的特点。方法：选择雄性食蟹猴12例,随机分为模型组和对照组。模型组皮下注射小牛血清,剂量为0.4 ml/kg;对照组注射相同剂量的生理盐水。每周均注射两次。结果：造模第8周开始,模型组血清HA、PCⅢ、ⅣC、TGF-β1和α-SMA均较造模前显著升高（P<0.05,P<0.01）,模型组HA和PCⅢ比对照组显著升高（P<0.05）。造模第12周后,模型组血清ⅣC、TGF-β1和α-SMA均比对照组显著升高（P<0.05）,模型组血清LN和TCH水平较造模前显著升高（P<0.05）;模型组血清AST和ALT水平比对照组以及造模前均显著升高（P<0.05）,模型组ALB比造模前显著下降（P<0.05）。造模16周,模型组血清LN、TCH和TG水平比对照组显著升高（P<0.05）;模型组ALB水平明显低于对照组（P<0.05）;B超显示模型组肝脏光点较对照组粗糙,显示强光回声团;HE染色下显示,模型组肝细胞坏死和单核细胞浸润;Van-Gieson胶原染色下显示,模型组肝脏汇管区胶原纤维增生。结论：给予皮下注射小牛血清16周,成功建立食蟹猴肝纤维化模型。     

血清肝纤维化指标在各型肝病诊断中的应用

探讨联合检测层粘连蛋白（LN）、IV型胶原（C IV）、血清透明质酸（HA）和Ⅲ型前胶原（PCⅢ）在肝纤维化诊断中的应用价值。采用放射免疫分析法检测143例肝病患者的LN、C IV、HA、PCⅢ,同时与41名健康体检者进行比较。结果显示：各组肝病患者血清肝纤维化指标均高于正常对照组（P〈0.01）,且与慢性肝炎病情严重程度密切相关,在慢性肝炎重度组和肝硬化组中表达最高,以HA、PCⅢ升高最为显著。结论：血清LN、C IV、HA、PCⅢ联合检测可明显提高肝纤维化诊断的准确性和可靠性,对诊断肝纤维化有较高的临床价值,但不能用于慢性肝炎重度和肝硬化的鉴别诊断。     

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.     

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.