骨关节炎的遗传学因素

遗传学因素在骨关节炎发病中的作用越来越受到人们重视。该文综述了骨关节炎的分子遗传学研究进展，特别述及Ⅱ型前胶原基因突变导致骨关节炎发生的目前研究热点。     

COL2A1基因突变所致先天性脊柱骨骺发育不良的产前分子诊断

目的：对COL2A1基因（typeⅡcollagen gene）G504S突变导致的先天性脊柱骨骺发育不良（SEDC）家系的2例中期妊娠患者进行产前分子诊断。方法：分别对患者于19＋3孕周和18＋6孕周进行羊膜囊穿刺术抽取羊水,提取羊水脱落细胞DNA,对COL2A1基因的第23外显子扩增,对其产物测序。同时第1例胎儿从17＋3孕周～27＋3孕周、第2例胎儿从16＋1孕周～19＋1孕周对股骨长度进行B超动态检测。结果：COL2A1的23外显子测序结果显示第1例胎儿带有与母亲同样的COL2A1基因G504S突变。第2例胎儿COL2A1基因无突变。B超的追踪检测显示2例胎儿颅骨双顶径都与孕龄相符。第1例患病胎儿股骨增长随孕龄的增加而逐渐减慢,但孕23周前减慢不十分明显。病例2的胎儿股骨长度与孕龄相符,现继续妊娠观察。于第27＋5孕周对第1例患病胎儿行引产术后,影像学检测显示胎儿脊柱扁平、长骨明显短小,证实胎儿患有SEDC。结论：对于有SEDC风险的胎儿进行基因检测非常重要,可以在B超诊断前了解胎儿基因型并明确诊断。B超对胎儿股骨长度的动态检测有助于SEDC的诊断。     

2型糖尿病分子遗传学研究的现今认识

近年研究表明,遗传因素在2型糖尿病(2-DM)的发生中起重要作用。但2-DM的遗传模式不符合单纯的孟德尔遗传,而是呈复杂性遗传模式,即多个基因变异与环境因素的影响共同决定疾病的易     

甲型血友病分子遗传学检测研究的进展

甲型血友病分子遗传学检测研究的进展张宇舟综述陈竺王鸿利邵慧珍王振义审校自１９８４年Ｇｉｔｓｃｈｉｅｒ等克隆了因子ＶＩＩＩ（ＦＶＩＩＩ）全长ｃＤＮＡ以来，对血友病甲发病机制有了新的认识，对血友病甲基因诊断技术也不断提高。明确血友病甲发病机制和对其家系进...     

儿童多动症分子遗传学研究进展

注意缺陷多动障碍 (ａｔｔｅｎｔｉｏｎｄｅｆｉｃｉｔ/ｈｙ ｐｅｒａｃｔｉｖｉｔｙｄｉｓｏｒｄｅｒ,ＡＤＨＤ)是一种最多见于学龄期儿童的精神障碍 ,主要表现为活动过度、注意缺陷 ,可以伴有学习成绩低下和冲动行为。它在学龄期儿童的患病率约 3 %～6 % ,其中有 2 2 %～ 33 %患者的症状将持续至青少年或成人[1 ] ,给患者及其家庭带来明显的不良影响 ,而且大量前瞻性和回顾性研究显示 :与正常对照相比 ,此类儿童有较高的精神疾病发病率 ,如抑郁障碍、焦虑障碍、品行障碍、酒精和其他物质滥用等。因此 ,该疾病愈来愈引起人们的关注。许多研…     

血友病分子遗传学研究进展

近年来,借助分子生物学和分子遗传学技术,有关血友病的基础研究取得了较大进展。本文拟简要阐述血友病的发病机理,基因治疗及携带者检测和产前诊断等方面的研究进展。     

膝骨关节炎的非手术治疗

膝骨关节炎是一种常见、缓慢发展的关节疾病。从国内现有资料看，非手术疗法中，迄今为止还缺乏一种特效、能够治愈膝关节骨关节炎的治疗方法。     

一例成骨不全Ⅱ型高危胎儿的产前基因诊断

目的对广东一疑似致死性侏儒症或成骨不全Ⅱ型的高危胎儿实施产前基因诊断,以阐明胎儿骨发育异常的真实病因,及时预防患胎出生。方法对经超声检查初诊为致死性侏儒症或成骨不全、已孕25周的高危胎儿,在抽取脐血制备DNA模板后,采用PCR-DNA直接测序法,分别对胎儿的FGFR3基因和COL1A1基因进行突变检测,然后对所发现的突变进行分析和鉴定。结果 FGFR3基因未发现病理性突变,而COL1A1基因发现一典型的杂合错义突变(c.3065G>T,p.G1022V),经查HGMD数据库证实为成骨不全Ⅱ型的致病性突变。结论 (1)此高危胎儿为成骨不全Ⅱ型患胎,应及时终止妊娠(胎儿已经引产,经复查证实与产前基因诊断结果完全一致)。(2)在超声初诊基础上,采用产前基因诊断可快速、有效对高危胎儿做出确诊,为出生缺陷的预防提供技术保障。     

髓母细胞瘤的分子遗传学研究

髓母细胞瘤是儿童最常见的脑肿瘤.占中枢神经系统肿瘤的10%～20%.在过去的几年中,人们对该肿瘤进行了大量的研究工作并且发现了一些常见的分子遗传学改变,包括17p、8p、6q、10q、11、16号染色体的丢失和17q、7q、14q的获得以及某些与患者预后相关的基因,如c-myc、erbB-2等.随着人们对髓母细胞瘤相关基因功能的不断探索,该肿瘤的发病机制将会更加明确.其临床治疗也会得到进一步的改善.本文对髓母细胞瘤近年来分子遗传学研究结果和不同亚型髓母细胞瘤的遗传学特点及与该亚型肿瘤患者预后的关系作一介绍.     

Charcot-Marie-Tooth病1X型的临床与分子遗传学研究进展

在Charcot-Marie-Tooth病(CMT)中,1X型发病率居于第2位,它由GJB1基因突变致Connexin32蛋白结构或功能异常,引起细胞间通道缺陷导致发病.文章综述了CMT1X的典型临床特征和分子遗传学进展,总结了CMT发病机制的研究.     

Genetic biomarkers for migraine

Biomarkers are physical signs or laboratory measurements that occur in association with a pathological process and have putative diagnostic and/or prognostic utility. In migraine, clinical, radiological, and biochemical biomarkers might be helpful to improve diagnosis, get insight in pathophysiology, and facilitate treatment choices. Genetic biomarkers are defined as genetic variations (mutations or polymorphisms) that can predict disease susceptibility, disease outcome, or treatment response. As yet, only a few genetic biomarkers for migraine are available. Mutations in 3 different genes responsible for familial hemiplegic migraine, a monogenetic subtype of migraine with aura, and the MTHFR C677T polymorphism in common forms of migraine are clear examples. Many positive findings from linkage studies and association studies in common forms of migraine have not been replicated, and are therefore of less clinical use. In this review, we will discuss genetic biomarkers in migraine.     

Three novel polymorphic sequence variants in the type I collagen gene COL1A1, the main disease locus for Osteogenesis Imperfecta

Three novel polymorphic variants were found within COL1A1 genomic sequence (accession number AF017178) while screening several patients in the search of OI causal mutations. The three polymorphisms, located in intron 12, exon 26, and intron 29, respectively, can be detected by PCR amplification and digestion with appropriate restriction enzymes (Mbo II, Bst NI, Pvu II, respectively). Allelic frequencies within the Italian population were calculated.     

Risk factors for incident osteoarthritis of the hip and knee

This article reviews the published risk factors associated with incident osteoarthritis of the lower extremity weight-bearing joints. Systemic risk factors include factors such as age, ethnicity, gender and genetic variables. Local risk factors are variables such as obesity, previous knee injury and occupational activities. Challenges in the study of incident osteoarthritis, and promising potential future study directions are also reviewed.     

康复膏对退行性关节炎疗效的实验研究

目的研究康复膏对退行性关节炎的治疗作用和机制。方法制作兔膝关节退行性变模型。用康复膏治疗观察疗效2周,并用免疫组织化学技术对滑膜细胞和膝关节软组织血管内皮细胞的凋亡相关基因表达进行了观察研究。结果康复膏对退行性变有明显的疗效。仅治疗3d开始出现效果,治疗2周症状基本消失。与对照组相比,用康复膏治疗后存活基因(Bcl-2)的表达明显增加,且阳性细胞率高于凋亡基因(Bax)(P<0.01)。结论康复膏对骨退行性变有明显的疗效,并对关节血管内皮细胞增殖和调节微循环有重要作用。     

姜黄素保护关节软骨抑制骨关节炎的作用和机制

背景：研究证实姜黄素具有抗炎抗氧化抗凋亡作用。目的：综合阐述姜黄素保护关节软骨及抑制骨关节炎等方面的机制和作用。方法：作者检索1973至2014年 PubMed、Embase、Elseveir数据库文献。检索词为“Osteoarthritis, curcumin,chondrocyte,articular cartilage”,按照事先制定的标准逐一评价纳入研究的文献,提取有效资料进行综合分析。结果与结论：姜黄素可通过抑制氧化作用酶,清除自由基,完成抗氧化作用,从而防止骨关节炎的发生和进展。姜黄素抑制基质金属蛋白酶的对软骨基质的消耗,增加Ⅱ型胶原的产生。姜黄素通过抑制胞浆型磷脂酶A2,环氧化酶2,脂氧合酶5,从而完成抗炎反应。姜黄素抑制白细胞介素1β导致的线粒体肿胀和凋亡,完成抗凋亡作用。临床研究提示,姜黄素或者其衍生物骨关节炎患者膝关节功能、关节疼痛等均有改善。高浓度姜黄素对体外培养的细胞和组织有毒性作用。     

Genetic and environmental factors in the aetiology of simple goiter

The aetiology of simple goitre, affecting up to 5% of a population in iodine-sufficient areas and over 10% in endemic areas, is incompletely understood. It is generally believed that the development of simple goitre, whether endemic or sporadic, depends on complex interactions between genetic, environmental and endogenous factors. The importance of genetic factors is evident from the clustering of simple goitre within families and from a higher concordance rate for goitre in monozygotic than in dizygotic twins. Recently, studies assessing the role of specific candidate genes or genetic markers in the aetiology of simple goitre have given conflicting data in various families. However, there may well be single genes playing a major role within certain families, eg the thyroglobulin (Tg) gene, the thyroid-stimulating hormone receptor (TSHR) gene, the Na⁺/I^- symporter (NIS) gene, and the multinodular goitre marker 1 (MNG1) on chromosome 14, but the genes will vary from family to family. In addition, family and twin studies also indicate a modest to major role for environmental factors in the aetiology of simple goitre. Clearly, iodine deficiency and cigarette smoking are the most important environmental risk factors associated with the genesis of simple goitre. Other suggested risk factors include naturally occurring goitrogens, emotional stress and certain drugs and infections. Ongoing studies focus on whole-genome screening in multiplex families as well as on large population-based case-control studies. However, the possibility that simple goitre is a heterogeneous disease without a single well-defined genotype and phenotype should be left open.     

The effect of intraarticular serum rich in growth factors (SRGF) on knee osteoarthritis in the rat model

Osteoarthritis (OA) is a degenerative joint disease with high incidence in world. Various treatments have been used for decreasing pain and improving physical function without clearly beneficial evidences. Nowadays, platelet-rich therapy is used as a novel approach in field of regenerative medicine. The present study evaluated the effect of intraarticular serum rich in growth factors (SRGF) on the monosodium iodoacetate induced-osteoarthritis in rat model. SRGF was injected 3 times weekly. Femorotibial joints were examined 2 weeks after last injection. Histopathologic results showed remarkable articular regeneration in the SRGF treated rats. Our findings were less surface irregularities and articular clefts, proliferation of chondrocytes and increasing synthesis of matrix proteoglycan with toluidine blue staining. Destroyed articular cartilage was repaired by fibro-hyaline cartilage in contrast to the OA rats that filled with fibrovascular tissues. The microscopic score had decreased in the treatment group. We concluded that SRGF, as a source of growth factors, have chondroinductive capacity with regard to enhancement of cartilage regeneration.     

Management of osteoarthritis

PURPOSE: To review the classification, epidemiology, pathophysiology, differential diagnosis, and medical management of osteoarthritis. DATA SOURCES: Selected studies, review articles, rheumatology primers, and clinical practice guidelines. CONCLUSIONS: Osteoarthritis is the most common form of arthritis and the second most common cause of long-term disability among adults in the United States. It is a heterogeneous condition causing pathogenic changes that are presumably irreversible; it should not be considered part of "normal aging." IMPLICATIONS FOR PRACTICE: Medical management of OA includes various treatment modalities and should be based on the distribution and severity of joint involvement, as well as the presence of comorbid conditions. Treatment goals include decreasing stress on involved joints, limiting physical disability, maintaining or improving function, reducing pain, and avoiding drug toxicity.