年龄相关性黄斑变性中医证型与CFH基因Y402H、CFB基因R32Q多态性的相关性研究

目的 探讨补体因子H(CFH)及补体因子B(CFB)基因变异与年龄相关性黄斑变性(AMD)中医证型的相关性.方法 门诊确诊AMD患者125例,按脾虚湿困、痰瘀互结及肝肾亏虚3个证型分成3组.采集患者的外周血,提取DNA,PCR扩增后测序,检测CFH与CBF单核昔酸多态性,分析所得到的基因变异结果与AMD中医证型的相关性...     

补体疗法在年龄相关性黄斑变性所致地图状萎缩中的治疗进展

年龄相关性黄斑变性(age-related macular degeneration, AMD)所致地图状萎缩(geographic atrophy, GA)目前仍缺乏有效的治疗方法。越来越多的证据表明,AMD所致GA的发生和发展与补体级联失调密切相关。作为先天性免疫系统的一部分,补体系统在维持人体内环境稳态中起到了重要作用,补体过度激活将打破这一平衡,促进年龄相关性黄斑变性的进展。基于此,针对补体激活途径的潜在靶点包括C1q、C3、C5、CFB、CFD、CFH、CFI和膜攻击复合物,依据药物形式又可分为生物大分子药物、化学小分子药物及基因治疗药物。目前已有多种治疗AMD所致GA的药物进入临床试验,本文总结了GA的补体疗法的临床试验进展,以评估其安全性和有效性。     

CFH Y402H多态性与新生血管性年龄相关性黄斑变性的相关性

目的探讨补体因子H(CFH) Y402H多态性与新生血管性年龄相关性黄斑变性(AMD)的相关性。方法选取山东大学齐鲁医院眼科新生血管性AMD患者100例及与其年龄匹配的健康人100例作为对照,收集外周血,提取基因组DNA,采用多聚酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术,分析CFH Y402H多态性在两组的分布频率,Y402H多态性表现为CFH基因的外显子9的核苷酸1277碱基T突变为碱基C。采用χ²检验计算CFH多态性与AMD的相关性。结果风险等位基因1277C在两组的频率分别为14.0%和5.0% (χ²=9.42,P<0.05),病例组的突变纯合子显著增加,两组差异有统计学意义（χ²=9.08,P＜0.05)。结论CFH Y402H多态性与新生血管性AMD相关,且表现出明显的人种差异。     

年龄相关性黄斑变性治疗进展

2004年2月25日,中国医学科学研究院眼科研究中心主任赵家良教授发表了题为“年龄相关性黄斑变性的治疗进展”的学术演讲。该病主要是由于视网膜中心凹负责视力和中心视野的“黄斑”出现病理改变而引起。发病率随年龄增加而升高,因此称为“年龄相关性黄斑变性”简称AMD(Age Related Macular Degeneration)。     

评估年龄相关性黄斑变性的临床分级系统

目的:采用简单分级评分法,创建年龄相关性黄斑变性(ARM)的临床病例和病历记录。并评估患者的临床分类和年龄相关性黄斑变性的临床分级(CARM S)系统。受试者:采用CARM S系统评估246例处于不同时期ARM的患者,该患者在第4年纳入本研究,设计:横断面对照研究。方法:CARM S系统依据裂隙灯所见的玻璃疣、视网膜色素上皮、地图状萎缩、视网膜色素上皮脱离和脉络膜新生血管对患者进行分类。采用受试者的眼底照相和临床数据评估CARM S系统的评分值。不同时期的ARM的246例患者的492只眼的临床分级与由读片中心评估的眼底照片分级进行对比,…     

高升糖指数膳食可能增加年龄相关性黄斑变性发病危险

2006年4月出版的《美国临床营养杂志》上（Am J Clin Nutr，2006，83：880—860）发表的一份研究结果显示，早期年龄相关性黄斑变性（AMD）与高升糖指数（GI）膳食有关。AMD是导致美国人群不可逆视力丧失的主要原因之一，在≥40岁人群中的发病率估计为1．47％，患者达175万。发病率随年龄增长而增加，预计未来20年将增加50％。年龄相关性黄斑病变（ARM）是AMD的早期表现形式，其特征为视网膜色素病变。     

补体因子H多态性、补体激活物与罹患老年性黄斑变性的风险

背景:炎症反应是老年性黄斑变性(AM D)发生重要途径的观点已经为越来越多的事实所证明。近期的病例对照研究显示一种补体调控因子:补体因子H(CFH)的基因与AM D发生相关。目的:评估人群中CFH基因与AM D的相关性以及其他因素如吸烟、血清炎性标记以及C反应蛋白(CRP)基因多态性对C     

年龄相关性黄斑变性的治疗进展

年龄相关性黄斑变性(Age-related macular degeneration,AMD)又称老年性黄斑变性,是发达国家视功能障碍和失明的主要原因,在发展中国家发病率有明显上升趋势。近年来,随着我国人民生活水平的提高,人口日益老龄化,该病发病率增加,成为眼科防盲研究的重要课题之一。目前相关学者对AMD治疗研究也取得了相当大的进展。本文就AMD治疗方法及其进展做一综述。     

老年性黄斑变性的14年发病率、病程进展及视力改变:哥本哈根市眼病研究

目的:描述老年性黄斑变性(ARM)损害的14年发病率和相关的视力下降。设计:基于人群的队列研究。受试者:1986年到1988年间参加这项研究的946例哥本哈根市居民(60～80岁)。在研究过程中死亡的参与者被排除,有359例(占生存者的97.3%)在2000年到2002年间进行了复查。方法:受试者接受全面的眼科检查。老年性黄斑变性病变的诊断应用改良的W is-consin老年性黄斑变性评分系统对眼底照相的颜色进行评分来确定。主要观察指标:不同玻璃膜疣类型和大小的发生率、色素异常、单纯地图样萎缩、渗出性ARM、视力障碍及失明。结果:早期和晚期ARM的14年发病…     

治疗年龄相关性黄斑变性的中药研究概况

近年来年龄相关性黄斑变性的中医药研究取得了可喜的进展,但在发病机理、辩证分型等方面仍有必要做进一步研究,本文对近年来中医对年龄相关性黄斑变性的病因病机、辨证论治及中药药效机理的实验研究进行汇总分析,以期望对该疾病机制的研究和临床治疗提供帮助。     

Genetic variants in three genes and smoking show strong associations with susceptibility to exudative age-related macular degeneration in a Chinese population

Background The present study was undertaken to replicate the associations of representative polymorphisms in three genes （complement factor H （CFH）, complement factor B （BF） and HtrA serine peptidase 1 （HTRA1）） with exudative age-related macular degeneration （AMD） in a Han Chinese population, and to test if the modifiable environmental factors affect AMD susceptibility associated with different type of genotype in these genes. Methods An age, gender and ethnicity matched case-control study was conducted to genotype the representative single neucleotide polymorphisms （SNPs） loci including rs1061170 and rs1410996 in CFH, rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP and direct resequencing. The demographic characteristics and behavioral risk factors were also recorded. Allelic and genotypic associations for individual SNP and joint associations with two loci were performed. The gene-gene and gene-environment interactions were analyzed using multivariate non-conditional Logistic regression analysis. Results The C risk allele frequencies for CFH Y402H （rs1061170） in cases and controls were 12.5% and 5.4% respectively, which were much lower than those in Caucasians （P 〈0.001）. Compared with TT homozygous genotype, the CT heterozygous genotype was positively associated with AMD with odds ratio （OR） of 3.23 （1.36-5.07）. However, the population attributable risk （PAR） of C allele was only 3.3% （1.4%-4.3%）. rs1410996 was also associated with AMD independent of Y402H. The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.57 （1.21-5.45） and 4.76 （2.15-10.55） respectively, with correspondent PARs of 28.3% （2.0%-40.5%） and 38.2% （21.8%-45.4%）. rs11200636 in HTRA1 was another susceptible locus for AMD and the risk homozygotes were significantly susceptible for exudutive AMD （OR=3.98, 1.88-8.43） with PAR of 38.9% （24.3%-45.8%）     

ARMS与NGS对比检测NSCLC患者标本EGFR、KRAS、BRAF、EML4-ALK融合等基因探索

目的 探讨突变扩增阻滞系统(ARMS)法和下一代测序(NGS)法检测非小细胞肺癌(NSCLC)患者标本多驱动基因改变上的差异,指导临床个体化治疗.方法 51例NSCLC患者标本首先采用ARMS法,对所有样本进行表皮生长因子受体(EGFR)、鼠类肉瘤病毒癌基因(KRAS)、鼠类肉瘤滤过性毒菌致癌基因同源体B1 (BRAF)、棘皮动物微管相关类蛋白4-间变性淋巴瘤激酶(EML4-ALK)等基因检测,随后采用NGS对上述标本进行高通量检测对比,收集临床资料,定期随访.结果 51例NSCLC样本应用ARMS法与NGS检测EGFR、KRAS、EML4-ALK突变阳性率(48.9％vs53.3％、11.1％ vs 8.9％、13.7％ vs 5.9％)差异无统计学意义.两种方法检测出的EGFR-19del突变组比EGFR-L858R突变组靶向治疗生存期较长,差异有统计学意义(P=0.0L0),但两组在性别、年龄、靶向治疗阶段等方面差异无统计学意义.NGS法检测出EGFR-19del、L858R突变患者肿瘤特有基因平均数量分别为7.1、4.6个,EGFR-L858R多为抑癌基因突变(91％).2例EGFR/KRAS双突变患者较EG-FR单突变患者预后差.结论 ARMS法和NGS均适用于NSCLC患者突变驱动基因检测.对于DNA点突变检测,NGS不仅显示ARMS检测的遗漏,还显示突变丰度、伴随突变及非常规突变等,对ARMS检测有补充作用.EGFR-19del患者靶向治疗生存期比EGFR-L858R突变患者长,EGFR-L858R主要为抑癌基因突变.EGFR合并KRAS双突变患者预后较差,但仍需进一步研究证实.     

Survey of attitudes of mental health professionals in Singapore towards at-risk mental states

INTRODUCTION: Schizophrenia is a severe, chronic mental illness with a worldwide prevalence of about one percent. It is possible to define at-risk mental states (ARMS) that predict conversion to schizophrenia in up to 40 percent of help-seeking individuals within a year of screening. Treatment of ARMS is controversial due to difficulties with diagnosis and uncertainties of treatment effectiveness. There is currently no consensus among psychiatrists in Singapore or internationally, regarding the diagnosis of ARMS, or its treatment. This survey was conducted to assess current attitudes of Singaporean psychiatrists towards ARMS. METHODS: An anonymous survey containing a clinical vignette and questions related to the diagnosis and management of ARMS was sent out to all registered psychiatrists and psychiatric trainees in Singapore. RESULTS: There was a response rate of 62.1 percent (87/140). 60.9 percent of respondents were fully-trained psychiatrists. 44.8 percent versus 43.7 percent of respondents diagnosed ARMS versus psychosis, respectively. 74.4 percent (29/39) of respondents who diagnosed ARMS would treat the patient with active management rather than watchful waiting. 64.4 percent felt that there was no consensus regarding the management of ARMS. There was no significant relationship between responses and age, gender, training or place of practice. CONCLUSION: There is currently clinical equipoise with regard to both diagnosis and management of ARMS in Singapore. Most psychiatrists would manage ARMS actively rather than with watchful waiting.     

血浆超敏C反应蛋白和补体因子H浓度与冠心病的关系研究

目的:研究血浆超敏C反应蛋白(hsCRP)和补体因子H(CFH)浓度与冠心病(CAD)的关系。方法:采用Judkins法进行冠状动脉造影。应用酶联免疫法测定血浆hsCRP和CFH浓度。冠状动脉病变分为1、2和3支病变,采用病例对照的方法进行研究。结果:hsCRP对CAD易感性预测的ROC曲线下面积为0.607(95%CI为0.540~0.675,P=0.002),敏感性72%,特异性59%。CFH对CAD易感性预测的ROC曲线下面积为0.483(95%CI为0.414~0.552,P=0.624),敏感性52%,特异性48.7%。2支病变组hsCRP水平较对照组差别有统计学意义(P<0.05)。血浆CFH浓度在不同血管病变支数组间无统计学差异(P>0.05)。校正性别、糖尿病、高脂血症等参数后,吸烟和高血压仍然是CAD的独立危险因子,hsCRP与CAD无关。结论:hsCRP和CFH与CAD之间无相关性,hsCRP与冠状动脉病变程度弱相关。     

肺腺癌表皮生长因子受体基因突变与组织病理学的相关性研究

目的研究肺腺癌（LAC）表皮生长因子受体（EGFR）基因突变与组织病理学的相关性。方法选取179例行LAC根治手术病人的癌组织石蜡标本,采用扩增阻滞突变系统检测LAC组织中EGFR基因突变及突变丰度情况,分析EGFR基因突变及突变丰度与临床病理特征的相关性。结果179例LAC病人中,EGFR基因突变者共108例（60.34%）,其中以19号外显子和21号外显子突变为主。不同年龄、淋巴结转移情况、胸膜浸润程度的LAC病人癌组织中EGFR基因突变差异无统计学意义（P>0.05）,不同性别、吸烟情况、肿瘤直径、临床分期、组织学亚型的LAC病人癌组织中EGFR基因突变和突变丰度差异均有统计学意义（P < 0.05~P < 0.01）。结论LAC病人EGFR基因突变与性别、吸烟情况、肿瘤直径、临床分期、组织学亚型相关,女性、肿瘤直径较小、不吸烟者、临床分期较早、腺泡状肺腺癌有较高的EGFR基因突变率。     

23例少年型黄斑营养不良及黄色斑点状眼底病变的眼底荧光血管造影观察

本文报告23例(46眼)Stargardt病及黄色斑点状眼底病变的眼底荧光血管造影所见。单纯黄斑变性16例,中心凹周围有斑点的黄斑变性5例,黄斑变性伴后极部弥散性黄色斑点1例。无黄斑变性的后极部弥散性黄色斑点1例,黄斑变性区表现为密集点状透见荧光,夹杂点状遮蔽荧光。大多数斑点呈透见荧光,少数呈遮蔽荧光.4例显示脉络膜湮没征象。所有病例均未见荧光素渗漏。本病具有典型的荧光征象,眼底荧光血管造影检查对于早期诊断具有十分重要的意义。     

CFH基因rs1061170多态性与重庆汉族人群冠心病的关系研究

目的 探讨CFH基因rs1061170单核苷酸多态性与冠心病的相关性.方法 筛选2008年10月到2009年6月在我院心内科就诊的重庆汉族地区人群中243例,其中冠心病组175例和对照组68例,用荧光定量PCR分析法检测2组CFH基因rs1061170多态位点基因型,分析CFH基因的频率分布及比较不同基因型各亚组间临...     

HTRA1-related autosomal dominant cerebral small vessel disease

BackgroundHomozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1 (HTRA1) gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL). Recently, increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease (CSVD) with an autosomal dominant pattern of inheritance. This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.MethodsWe presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1, 2020. CARASIL probands with genetic diagnosis reported to date were also reviewed. The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.ResultsForty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included. Compared with typical CARASIL, HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors (P < 0.001), a later onset age (P < 0.001), and a relatively slower clinical progression. Alopecia and spondylosis can be observed, but less than those in the typical CARASIL. Thirty-five heterozygous mutations in HTRA1 were reported, most of which were missense mutations. Amino acids located close to amino acids 250–300 were most frequently affected, followed by these located near 150∼200. While amino acids 250∼300 were also the most frequently affected region in CARASIL patients, fewer mutations precede the 200th amino acids were detected, especially in the Kazal-type serine protease domain.ConclusionsHTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL. The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.     

Incidence of associated congenital anomalies in anorectal malformations

The study was undertaken to review the incidence and types of associated congenital urogenital anomalies in patients with anorectal malformations (ARM) and compare the results with previously published world literature. Retrospective review was done of 220 cases of ARM, treated during May 2002 to April 2003. All patients routinely underwent ultrasound study of the KUB region and pelvis and lumbosacral radiography. Voiding cystourethrography, nuclear renography and other investigations like buccal smear and karyotyping were done in selected cases only. Genital anomalies were found in 30 cases (13.63%) and urologic anomalies in 25 cases (11.36%), a direct correlation being found between the level of ARM and the incidence of urogenital anomalies. The high incidence of associated anomalies (24.54%) makes careful clinical examination and evaluation of the urinary tract during the neonatal or early infantile period mandatory in all cases of ARM, particularly to avoid deterioration of renal function in future.     

ARMS在老年2型糖尿病患者中用药依从性的应用评价

目的 评估续配和服药依从性量表（Adherence to Refills and Medications Scale,ARMS）在中国老年2型糖尿病住院患者中的应用,并构建以用药依从性评价预测老年2型糖尿病患者合理用药效能的诊断模型。方法 对2018年7月-2019年1月于复旦大学附属华东医院内分泌病房住院的老年2型糖尿病患者进行访视,在患者入院24 h内进行8项Morisky用药依从性量表（MMAS-8）、ARMS量表以及合理用药效能量表（SEAMS）评估,并进行统计分析。结果 研究共纳入505名患者,其中合理用药效能充足组161人（31.9%）、效能不足组344人（68.1%）;两组患者在性别、病程、MMAS-8评分和ARMS评分上均有显著性差异（P<0.05）,Spearman相关性检验表明患者用药依从性与合理用药效能呈显著相关（MMAS-8显著正相关;ARMS显著负相关）;二元Logistic回归影响因素结果显示患者的用药依从性与合理用药效能显著相关（ARMS：r=0.249,OR=1.282;MMAS-8：r=-1.417,OR=0.242）;受试者工作特征曲线（ROC曲线）检验结果显示,与MMAS-8相比（AUC=0.155,P<0.001,95% CI：0.121~0.189）,ARMS评分具有较高的特异性和敏感性（AUC=0.851,P<0.001,95% CI：0.818~0.885）,其约登指数值为16,理论敏感度80.5%、特异性77.6%;该风险预测模型在验证人群中的灵敏度为96.3%、特异性为73.9%、准确率为86.0%,Kappa一致性检验结果显示该风险预测模型与实际情况存在较高一致性。结论 相比MMAS-8量表,ARMS量表不仅更适合老年糖尿病患者用药依从性的评估,还可以准确预判患者是否存在合理用药效能不足的情况,可应用于中国老年2型糖尿病患者用药依从性及合理用药管理能力的评估。