Constitutive deficiency in DNA mismatch repair: is it time for Lynch III?

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome types I and II, and the related subtypes Turcot and Muir-Torre syndrome, have all been associated with inheritance of germ line mutations in the DNA mismatch repair (MMR) genes. Fifty individuals have recently been identified with an early onset of a different spectrum of cancers associated with inheritance of two MMR mutations--resulting either in a constitutive loss of MMR function, or greatly impaired MMR function. In contrast to Lynch I and II individuals, individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein, present with hematological and brain malignancies in the first decade of life. Biallelic mutations with compromised but residual protein function present with a broader spectrum of cancers (brain, hematological or gastrointestinal) in the second to fourth decades of life. We propose that inheritance of two MMR mutations in an individual and the unique tumor spectrum that occurs with an early onset should be defined separately from Lynch syndrome I and II, or the subtypes Turcot and Muir-Torre. We suggest Lynch III as an appropriate name for identifying individuals with constitutively compromised MMR associated with biallelic mutations.     

常染色体隐性遗传性皮肤松弛症的相关基因研究进展

常染色体隐性遗传性皮肤松弛症是遗传性皮肤松弛症的常见类型,其发病机制尚未完全明确,但其可能的致病基因功能及其下游信号通路逐渐成为当前的研究热点。对与皮肤松弛症相关的基因及相应的信号通路的深入研究不仅为明确其发病机制奠基了良好的基础,同时,也为指导优生优育咨询指明了方向。本文主要综述近年来与常染色体隐性遗传性皮肤松弛症发病相关的基因及其信号通路的最新研究进展。     

基于数据挖掘技术探讨郭勇教授治疗肝癌的用药规律

[目的] 探讨郭勇教授治疗肝癌的处方用药规律,传承名中医治疗肝癌的指导思想并推广应用。[方法] 收集郭师治疗肝癌的处方,基于信息管理系统软件建立数据库,统计药物使用频次,并对药物的药性、药味、归经等进行描述性分析。[结果] 药性频率最高的是寒(34.46%),其次是温(29.94%)、平(27.12%),累计频率达91.52%;药味频率最高的是甘(37.09%),其次是苦(23.64%)、辛(17.45%),累计频率达78.18%;药物归经频率最高的是肝(19.61%)、其次是脾(15.50%)、肺(15.25%)、胃(14.29%),累计频率达64.65%。采用关联法则、复杂网络分析、聚类分析等数据挖掘方法,确定处方中各种药物的使用频次和药物之间的关联规则,前6位中药依次为:白芍、郁金、预知子、猫爪草、猫人参、太子参。从核心处方总结出,郭师治疗肝癌多用猫人参、猫爪草、郁金、预知子、白芍等药物。[结论] 郭师治疗肝癌,重视辨病与辨证相结合,应用灵活,配伍严谨。数据挖掘应用对于挖掘名老中医临床经验具有重要的价值。     

基于数据挖掘的中医药治疗血栓闭塞性脉管炎的用药规律研究

目的:基于中医传承辅助平台挖掘中国知网数据库(CNKI)中以中医药治疗血栓闭塞性脉管炎的组方用药规律,为中医药治疗血栓闭塞性脉管炎提供临床参考。方法:检索CNKI 数据库中近30 年有关中医药治疗血栓闭塞性脉管炎的文献,筛选出符合条件的治疗血栓闭塞性脉管炎的中药方剂,利用中医传承辅助平台(V2.5)集成的数据分析方法,挖掘中医药治疗血栓闭塞性脉管炎的用药规律。结果:共筛选出410 篇文献,符合条件处方600 首,涉及233 味中药。处方中药物出现频次≥ 60 的药物得到33 个,演化得到核心组合28 个,新处方14 个;药物主归肝、心、脾经,性味分别以温、寒、平和苦、辛、甘为主。结论:治疗血栓闭塞性脉管炎的药物立足于“血瘀”病机,以活血化瘀为主要治则,辅以清热、补虚、温通、息风止痉、止痛、托毒生肌、燥湿、通络等药物,在临床应用中灵活辨证施治。     

基于中医传承辅助平台探讨张伦忠治疗中老年郁证经验及组方用药规律

目的基于中医传承辅助平台,分析和总结张伦忠教授治疗中老年郁证的组方规律和用药经验。方法收集张伦忠教授治疗中老年郁证的门诊首诊处方122首,运用中医传承辅助平台软件,分析其组方规律和用药经验。结果122首处方中得出12个核心组合和6个新处方。结论张伦忠教授治疗中老年郁证善于从阴阳角度辨焦虑与抑郁,重视肝、脾、肾三脏,治以疏肝解郁、顾护中焦、补肾填精,多以桑麻地黄汤为基础方临证加减,采用复方治疗,标本兼治。     

The genetic control of host responses to Dipetalonema viteae (Filarioidea) infections in mice

Dipetalonema viteae (Filarioidea) infections were established in inbred strains of mice by the s.c. implantation of adult female worms and the resulting microfilaraemia and adult worm survival monitored. BALB/c mice were the most susceptible strain examined, showing a high level microfilaraemia of approximately 6 month's duration. C57Bl/10, CBA/Ca and C3H/He mice were all equally resistant to infection, showing a low level of microfilaraemia of approximately 1 month's duration. The response of NIH mice was intermediate. Relatively little strain difference was seen in adult worm survival although worms lived slightly longer in C57Bl/10 mice than in BALB/c mice. The adult females became depleted of microfilariae over a period of approximately 1 month before becoming encapsulated in host tissue. Challenge infections given to mice previously implanted with worms resulted in lower level, shorter lasting microfilaraemias than those seen in the initial primary infections. All strains showed immunity when challenged. High responsiveness (resistance) was inherited as a dominant trait in F1 hybrids produced by crossing high and low responder strains. Genes linked with the major histocompatibility complex (H-2) were found to have no effect on the response phenotype as demonstrated by the similar responses of H-2 congenic mice on the BALB/c or C57bl/10 backgrounds. The response phenotype of radiation chimaeras was determined by the phenotype of the donor from which bone marrow (BM) cells were taken for reconstitution. Susceptible BALB/c mice reconstituted with resistant B10D2/n BM behaved identically to the donor strain, indicating that the genetic variation which exists between mouse strains in their responses to D. viteae is expressed through a population of BM derived cells and is not simply a consequence of host structure or physiology.     

Synergistic effects of the apolipoprotein E epsilon3/epsilon2/epsilon4, the cholesteryl ester transfer protein TaqIB, and the apolipoprotein C3 -482 C>T polymorphisms on their association with coronary artery disease

The single nucleotide polymorphisms (SNPs) apolipoprotein E (APOE) 3/2/4, cholesteryl ester transfer protein (CETP) TaqIB, and apolipoprotein C3 (APOC3) −482 C > T have been associated with an atherogenic lipid profile and, in some studies, with increased cardiovascular risk. However, no data exist on their combined impact on atherosclerotic disease. We therefore aimed at investigating the combined impact of these SNPs on the presence of angiographically determined coronary artery disease (CAD). Genotyping was performed in 557 consecutive Caucasian patients undergoing coronary angiography for the evaluation of CAD.From the individual SNPs, only the APOE 34/44 genotype was significantly associated with an increased risk of significant coronary stenoses with lumen narrowing ≥50% (odds ratio (OR) = 1.77 [1.16–2.71]; p = 0.008). However, the risk of CAD strongly increased when more than one of the analysed genetic variants was present: ORs were 2.74 [1.29–5.83]; p = 0.009 for patients with both the APOE 34/44 and the CETP B1B1 genotype, 1.97 [1.06–3.66]; p = 0.031 for patients with both the APOE 34/44 genotype and the APOC3 −482T allele, 2.12 [1.31–3.44]; p = 0.002 for patients with both the CETP B1B1 genotype and the APOC3 −482T allele, and 3.99 [1.57–13.79]; p = 0.029 for patients with all three variants. Multivariate analyses confirmed these results.We conclude that there are strong synergistic effects of the APOE 3/2/4, the CETP TaqIB, and the APOC3 −482 C > T polymorphisms on their association with CAD.     

What community-level strategies are needed to secure women's property rights in Western Kenya? Laying the groundwork for a future structural HIV prevention intervention

Despite the recognized need for structural-level HIV prevention interventions that focus on economic empowerment to reduce women's HIV risks, few science-based programs have focused on securing women's land ownership as a primary or secondary HIV risk reduction strategy. The current study focused on a community-led land and property rights model that was implemented in two rural areas of western Kenya where HIV prevalence was high (24–30%) and property rights violations were common. The program was designed to reduce women's HIV risk at the community level by protecting and enhancing women's access to and ownership of land. Through in-depth interviews with 50 program leaders and implementers of this program we sought to identify the strategies that were used to prevent, mediate, and resolve property rights violations. Results included four strategies: (1) rights-based education of both women and men individually and at the community level, (2) funeral committees that intervene to prevent property grabbing and disinheritance, (3) paralegal training of traditional leaders and community members and local adjudication of cases of property rights violations, and (4) referring property rights violations to the formal justice system when these are not resolved at the community level. Study participants underscored that local mediation of cases resulted in a higher success rate than women experienced in the formal court system, underscoring the importance of community-level solutions to property rights violations. The current study assists researchers in understanding the steps needed to prevent and resolve women's property rights violations so as to bolster the literature on potential structural HIV prevention interventions. Future research should rigorously test property rights programs as a structural HIV prevention intervention.     

一例OCRL基因外显子重复变异所致的眼脑肾综合征患儿的临床及遗传学分析

目的探讨1例表现为先天性白内障、脑发育迟缓、蛋白尿的男性患儿的遗传学病因。方法收集患儿的临床资料,采集患儿及其正常表型的亲代的外周血样,提取基因组DNA,应用高通量测序法筛查OCRL基因的变异,并用定量PCR法进行验证。通过变异序列分析和PubMed检索,预测候选变异的致病性。结果患儿曾接受先天性白内障手术,脑发育迟缓,脑部成像显示脑沟裂增宽、双侧额颞部蛛网膜下腔增宽、脑室后角旁白质髓鞘化不良等,此外有蛋白尿及双肾弥漫性回声。患儿X染色体OCRL基因第5~16外显子存在重复变异。患儿母亲为该变异的携带者,父亲未携带。结论OCRL基因第5~16外显子重复变异是该患儿的发病原因。由OCRL基因外显子重复所致的眼脑肾综合征尚无文献报道。鉴于眼脑肾综合征临床表现的异质性,基因检测对于该病的确诊具有重要的意义。