VDBP基因多态性及血清维生素D水平与多囊卵巢综合征代谢紊乱的相关性

目的 旨在讨论维生素D结合蛋白（VDBP）基因多态性（SNPs）及血清维生素D(VitD)水平与多囊卵巢综合征（PCOS）代谢紊乱的关系。方法 从2019年1月1日至2022年12月31日在陕西省西安市共招募644例PCOS女性作为研究对象，另外纳入同地区年龄和种族相匹配的450例排卵周期正常的育龄期女性作为对照。确定VDBP基因多态性的基因型分布频率，并研究这些遗传变异与PCOS、代谢综合征（MetS）易感性以及血清25(OH)D3水平之间的关联。结果 PCOS组血清25(OH)D3水平普遍低于对照组（P<0.001）。根据AACE临床实践指南，89例（13.82%）PCOS患者存在VitD缺乏，95例（14.75%）PCOS患者VitD不足。在PCOS组中，有98例（15.22%）患有MetS。与非MetS亚组相比，MetS亚组PCOS患者血清25(OH)D3水平更低（P=0.006），调整混杂因素后，VitD缺乏仍是PCOS患者MetS易感性的独立风险因素（OR=1.913;95%CI:1.109～3.300,P=0.020）。PCOS组和对照组所有4个SNPs均服从Har...     

维生素D水平与2型糖尿病合并抑郁症相关性研究

目的 测定2型糖尿病合并抑郁症患者血清25-羟维生素D3水平,探讨维生素D缺乏与2型糖尿病合并抑郁症的关系。方法 选择2015年9月~2017年3月于我院住院的2型糖尿病患者84例,根据HAMD评分将患者分为T2DM组44例和T2DMD组40例。收集两组患者临床资料,检测FBG、HbA1c、TC、TG、LDL-C、HDL-C、血清25-羟维生素D3水平,进行Pearson相关分析和Logistic回归分析,并比较两组患者血清25-羟维生素D3缺乏患病率。结果 两组患者年龄、BMI、TC、TG比较,差异无统计学意义（P＞0.05）;T2DMD组FBG、HbA1c、LDL-C均高于T2DM组,且糖尿病病程长于T2DM组,差异具有统计学意义（P＜0.05）。T2DM组血清25-羟维生素D3平均水平为（20.94±1.68）ng/ml,高于T2DMD组的（16.44±2.05）ng/ml,差异具有统计学意义（P＜0.05）。T2DMD组血清25-羟维生素D3缺乏患病率为95.00%,高于T2DM组的31.82%,差异具有统计学意义（P＜0.05）。Pearson相关分析显示,血清25-羟维生素D3水平与FBG、HbA1c、LDL-C、病程均呈负相关（P＜0.05）,与HDL-C呈正相关（P＜0.05）,与BMI、TC及TG均无相关性（P＞0.05）。多元Logistic回归分析显示,血清25-羟维生素D3水平、FBG、HbA1c及病程是2型糖尿病合并抑郁症的独立危险因素（P＜0.05）。结论 2型糖尿病合并抑郁症患者维生素D缺乏更加普遍,维生素D缺乏可能参与2型糖尿病合并抑郁症的发病过程。     

维生素B_(12)对抑郁症的辅助治疗

目的观察抑郁症患者血清维生素B12水平,探讨抗抑郁剂合并维生素B12治疗维生素B12缺乏抑郁症的疗效及安全性。方法对400名抑郁症患者进行血清维生素B12浓度测查,将筛查出的维生素B12缺乏的抑郁症患者70例,随机分为两组,各35例。对照组根据病情口服西酞普兰20~40 mg/次,每日1次,治疗8周;研究组根据病情口服西酞普兰20~40 mg/次,每日1次,同时合并使用维生素B12,治疗8周。研究组及对照组治疗前后1,2,4,8周末分别进行汉密尔顿抑郁量表(HAMD)评定;治疗后1,2,4,8周末分别评定副反应量表(TESS);治疗前及治疗后4,8周末分别查血清维生素B12浓度。结果抑郁症患者血清维生素B12平均水平(359.7±183.2)pg/ml,维生素B12缺乏发生率为19.5%,研究组与对照组第1周末汉密尔顿抑郁量表评分差异无显著性(P0.05),治疗第2,4、8周末有显著性差异(P0.01),研究组有效率为94.3%,对照组为74.3%,两组差异有显著性(P0.01),血清维生素B12浓度治疗后4,8周末有显著性差异(P0.01),且研究组汉密尔顿抑郁量表评分与血清维生素B12浓度负相关。两组不良反应均较轻微,TESS评分比较差异无显著性(P0.05)。结论抑郁症患者血清维生素B12平均水平较正常明显降低,维生素B12缺乏发生率高,维生素B12辅助抗抑郁剂治疗可明显提高疗效,且不增加不良反应。     

多囊卵巢综合征患者25-(OH)VD、AMH水平表达及AMH和其Ⅱ型受体基因多态性分析

目的了解深圳地区多囊卵巢综合征(PCOS)患者血清中25-羟基维生素D[25-(OH)VD]、抗苗勒管激素(AMH)水平及AMH和其Ⅱ型受体(AMHR II)基因多态性,并探讨其与PCOS发病之间的相关性。方法选取2019年1月至2020年7月在深圳市龙华区人民医院及各社康服务中心妇产科就诊并确诊为PCOS患者107例为PCOS组,并选择同期来医院检查的健康育龄妇女95例为对照组,分别检测血清中25-(OH)VD和AMH水平,同时采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法对AMH G/T和AMHR II A/T基因多态性进行检测,并对检测结果进行统计分析。结果 PCOS组患者血清中25-(OH)VD水平为32.97±6.41nmol/L,明显低于对照组的63.84±12.60nmol/L,而AMH水平为17.68±6.84ng/ml,明显高于对照组的5.28±1.97ng/ml,差异有统计学意义(P0.05);PCOS组患者AMH G/T基因TT基因型和T等位基因检出率分别为39.26%和52.80%,明显高于对照组的28.42%和42.73%,差异均有统计学意义(P0.05);PCOS组患者AMHRⅡA/T基因TT基因型及T等位基因检出率分别为22.43%和38.32%,明显高于对照组的11.58%和26.32%,差异有统计学意义(P0.05);携带AMH基因TT基因型的PCOS患者血清中AMH水平为21.85±7.63ng/ml,明显高于AT基因型的14.96±5.42ng/ml,且AT基因型明显高于AA基因型的9.25±2.78ng/ml,而TT基因型的25-(OH)VD低于AT基因型,且AT基因型低于TT基因型,不同基因型PCOS患者血清中AMH、25-(OH)VD水平之间差异均有统计学意义(P0.05);PCOS患者25-(OH)VD水平明显降低,而AMH水平明显升高,经Spearman相关性分析,结果显示两者呈负相关(r=-0.6275,P0.05)。结论深圳地区PCOS患者血清中25-(OH)VD水平明显降低,而AMH水平明显升高,且两者呈负相关。同时PCOS患者AMH G/T基因TT基因型和AMHRⅡA/T基因TT基因型检出率明显升高,可能是该地区PCOS发病的遗传易感基因。     

血清25羟维生素D及维生素D结合蛋白水平与慢性荨麻疹相关性研究

目的 检测慢性荨麻疹(CU)患者外周血中25(OH)D及维生素D结合蛋白(VDBP)水平并探讨其临床意义.方法 ELISA方法检测30例CU患者和30例对照组血清中25(OH)D和VDBP水平,并分析两组间的差异及25 (OH)D和VDBP水平的相关性.结果 血清25(OH)D水平在CU组中显著低于对照组,差异有统计学意义(P＜0.001).对照组和CU组血清VDBP水平无明显差异(P＞0.05).CU组中25(OH)D缺乏/不足的比例显著高于对照组(P＜0.05).结论 CU患者外周血中25(OH)D水平显著下降,VDBP水平未见明显变化.25(OH)D水平与疾病严重程度及病程无显著相关性.维生素D及VDBP与CU的关系仍需大样本研究.     

维生素B〈sub〉12〈/sub〉对抑郁症的辅助治疗

目的观察抑郁症患者血清维生素B12水平,探讨抗抑郁剂合并维生素B12治疗维生素B12缺乏抑郁症的疗效及安全性。方法对400名抑郁症患者进行血清维生素B12浓度测查,将筛查出的维生素B12缺乏的抑郁症患者70例,随机分为两组,各35例。对照组根据病情口服西酞普兰20～40 mg/次,每日1次,治疗8周;研究组根据病情口服西酞普兰20～40 mg/次,每日1次,同时合并使用维生素B12,治疗8周。研究组及对照组治疗前后1,2,4,8周末分别进行汉密尔顿抑郁量表（HAMD）评定;治疗后1,2,4,8周末分别评定副反应量表（TESS）;治疗前及治疗后4,8周末分别查血清维生素B12浓度。结果抑郁症患者血清维生素B12平均水平（359.7±183.2）pg/ml,维生素B12缺乏发生率为19.5%,研究组与对照组第1周末汉密尔顿抑郁量表评分差异无显著性（P＞0.05）,治疗第2,4、8周末有显著性差异（P〈0.01）,研究组有效率为94.3%,对照组为74.3%,两组差异有显著性（P〈0.01）,血清维生素B12浓度治疗后4,8周末有显著性差异（P〈0.01）,且研究组汉密尔顿抑郁量表评分与血清维生素B12浓度负相关。两组不良反应均较轻微,TESS评分比较差异无显著性（P＞0.05）。结论抑郁症患者血清维生素B12平均水平较正常明显降低,维生素B12缺乏发生率高,维生素B12辅助抗抑郁剂治疗可明显提高疗效,且不增加不良反应。     

抗苗勒管激素水平在不同卵巢储备功能的女性之间的差异研究

目的检测抗苗勒管激素(AMH)在卵巢早衰(POF)、多囊卵巢综合征(PCOS)患者以及正常健康女性血清中的变化水平并探讨其在产前筛查方面的临床意义与价值。方法选取本院POF患者(POF组)39例,PCOS患者(PCOS组)42例,并选取同期接受健康体检且月经周期正常的女性45例作为对照组。测定上述3组女性血清中AMH、卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)及睾酮(T)的水平。结果 PCOS组AMH、E2和T水平高于POF组和对照组,而对照组AMH和E2水平高于POF组,差异有统计学意义(P0.05);POF组FSH、LH高于PCOS组和对照组,而PCOS组LH高于对照组,差异有统计学意义(P0.05),PCOS组与对照组FSH相比无统计学差异(P0.05)。结论 AMH在不同卵巢储备功能的PCOS、POF患者以及正常健康女性中表达水平不同,因而联合检测血清中AMH与性激素水平在诊断PCOS和POF以及产前筛查方面具有一定的临床应用价值。     

多囊卵巢综合征与抗苗勒氏管激素的相关分析

目的探讨抗苗勒氏管激素（AMH）与多囊卵巢综合征（PCOS）的发生、发展的关系；方法测定56例PCOS患者血清AMH、性激素并与30例正常妇女进行对照；结果PCOS组血清AMH明显高于对照组，PCOS组中高睾酮组AMH明显高于非高睾酮组，差异有极显著性；PCOS组中血清AMH水平与睾酮水平呈显著相关（r=0．713，P=0．001）；结论AMH可能参与PCOS卵泡发育异常的发生、发展并与性激素合成失调有关，测定血清AMH水平为诊断和研究PCOS提供了一个重要的突破点。     

血清25(OH)D3、超敏C反应蛋白水平与老年2型糖尿病合并骨质疏松的相关性分析

目的分析血清25-羟维生素D3[25(OH) D3]、超敏C反应蛋白(hs-CRP)水平与老年2型糖尿病(T2DM)合并骨质疏松的相关性。方法将218例T2DM患者中存在骨质疏松者纳入观察组(n=80),骨量减少者纳入对照组A(n=50),无骨质疏松和骨量减少者纳入对照组B(n=88),另选择同期体检的健康老年人群62例作为健康组,比较各组血清25(OH)D3、hs-CRP水平及骨代谢指标[骨钙素(BGP)、总1型前胶原氨基端延长肽(T-P1NP)、Ⅰ型胶原羧基端肽β特殊序列(β-CTX)],根据血清25(OH)D3水平将观察组受试者分为25(OH)D3严重缺乏组、缺乏组、不足组,对比三组的血清hs-CRP及骨代谢指标,分析血清25 (OH) D3、hs-CRP、骨代谢指标的相关性。结果观察组血清25 (OH) D3、BGP、T-P1NP水平低于对照组A、对照组B、健康组,观察组血清hs-CRP、β-CTX水平高于其他各组(P <0.05);25(OH) D3水平严重缺乏组血清hs-CRP、β-CTX高于25(OH)D3缺乏组、不足组,而血清BGP、T-P1NP水平低于25(OH) D3缺乏组、不足组(P <0.05),25(OH) D3缺乏组、不足组上述指标比较差异也有统计学意义(P <0.05);老年T2DM合并骨质疏松患者血清25(OH)D3与其BGP、T-P1NP呈正相关,而与hs-CRP、β-CTX呈负相关,hs-CRP与BGP、T-P1NP呈负相关,与β-CTX呈正相关(P <0.05)。结论血清25 (OH) D3、hs-CRP参与T2DM发生与发展,能敏感地反映早期骨代谢情况,预测骨质疏松的发生风险。     

HBeAg阴性慢性乙型肝炎患者血清25-羟基维生素D3的检测及临床意义

目的 探究HBeAg阴性慢性乙型肝炎患者血清25-羟基维生素D3的水平变化及临床意义。方法 选取2015年3月~2018年5月81例HBeAg阴性且非肝硬化的慢性乙型肝炎患者作为观察组,依据血清谷丙转氨酶（ALT）水平分为观察组A 41例（ALT处于正常水平且HBV DNA水平＜2000 IU/ml,持续时间高于6个月）和观察组B 40例（ALT处于升高水平且HBV DNA水平≥2000 IU/ml,持续时间高于6个月）。同时选取同期健康体检人群40例作为对照组。分别检测三组血清25-羟基维生素D3的浓度。结果 观察组血清25-羟基维生素D3低于健康人群,统计学意义显著（P＜0.001）,三组间比较,统计学意义显著（P＜0.001）。观察组患者血清25-羟基维生素D3与年龄、BMI、ALT、AST、Hb、WBC、PLT及AFP均无明显相关性（P＞0.05）。而与HBV DNA含量间存在显著负相关（r=-3.981,P＜0.05）。结论 HBeAg阴性慢性乙型肝炎患者血清25-羟基维生素D3存在异常,并与乙肝病毒复制相关,可能参与机体和乙肝病毒的免疫反应过程。     

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.