Cell—科学家使用TALENs编辑技术建立Rett综合征猴模型 Abstract Summary 1.Generation of MECP2 Mutant Cynomolgus Monkeys via TALENs 2.Dynamic Changes of Cortical and Sub-cortical Volume Monitored by MRI Scanning 3.The EKG of MECP2 Mutant and WT Monkeys 4.Behavioral Phenotypes of MECP2 Mutant Monkeys 5.Eye-Tracking Patterns in MECP2 Mutants and WT Monkeys
Susac综合征的诊断标准 Susac综合征的诊断标准 欧 洲 S u s a c 协 会（ E u r o p e a n S u s a c C o n s or t iu m，Eu S aC）制定了S u s a c 综 合征 的诊断标准，并于2016 年12月发 表在 Jou r n a l of Neurology，Neursurgery Psychiatry （ JNNP）上。 1 脑 ①症状和临床所见： 新发 认知缺损 和（或） 行为改变 和（或）新发 局灶神经系统症状 和（或） 新发头痛 。 ② 影 像 ： 颅 脑 磁 共 振 成 像（ m a g n e t i c resonance imaging，MRI）典型表现——T2（或FLAIR）加权序列显示 高信号、多灶、圆形小病灶 ，至少一个病灶累及 胼胝体 （雪球状）。 满足1的标准：必须具备至少一个临床所见和典型MRI表现。 2 视网膜 ①不要求临床所见和症状。 ②眼科检查：荧光血管造影显示 视网膜分支动脉闭塞 （branch retinal artery occlusions，BRAOs）或 动脉壁高荧光显影 （arterial wall hyperfluorescence，AWH），或 眼底镜检查或频域光相干断层扫描 （spectral domain optical coherence tomography，SD-OCT）发现 视网膜分支动脉缺血 。 满足2的标准： 荧光血管造影显示BRAOs或（AWH） ，或眼底镜检查或SD-OCT发现 视网膜分支动脉缺血 ，至少具备其中一项。 3 前庭耳蜗 ①症状和临床所见： 新发耳鸣和（或）听力丧失和（或）外周性眩晕。 ②内耳功能检查： 听力丧失 必须被 听力敏度图 证实； 前庭性眩晕必须被特异性诊断方法证实。 满足3的标准，至少具备一个临床所见，听力丧失或前庭性眩晕必须被内耳功能特异性诊断方法证实。 Ⅰ 确诊Susac：满足每一条标准（1；2；3）和亚标准（①；②）。 Ⅱ 很可能Susac：不完全满足3条标准，仅满足1～3条标准中的两条。 Ⅲ 可能Susac（Susac不是最可能的诊断）：具备上述3条中的一些临床表现和（或）特异性临床（paraclinical）表现，但是不能满足Ⅰ或Ⅱ，Susac作为鉴别诊断，但不是最可能的诊断。 说明： 如果为新发头痛并且头痛出现在其他症状前不超过6个月， 这时头痛可以作为脑部受累的症状。 必须为偏头痛或紧张性头痛， 不是三叉自主神经性头痛。 如果病灶符合以下特点， MRI T1可以是唯一的诊断标准： 病灶低密度界限清楚， 灰质受累， Gd强化。 T1软脑膜Gd强化也支持诊断。 脑部临床所见无典型MRI损害或典型MRI损害无脑部临床症状， 作为诊断标准是不充分的。 临床所见和症状并不是必需的条件， 因为BRAO可能处于静息状态。 听力丧失： 主要为感音神经性听觉丧失， 低或中频，以及泛调 （ pantonal） 。 眩晕： 前庭器官变温试验和前庭诱发肌源性反应。 文献出处： Kleffner I， Dörr J， Ringelstein M， et al. Diagnostic criteria for Susac syndrome . J Neurol Neurosurg Psychiatry，2016， 87： 1287-1295. 指南目录 “腰椎间盘突出症的康复治疗”中国专家共识 2017急性深静脉血栓形成诊断和治疗指南 2017年GOLD慢性阻塞性肺疾病定义和诊断的全球策略解读 2017年最新克罗恩病治疗指南 2017年最新溃疡性结肠炎治疗指南 2017 ADA糖尿病视神经病变最新指南推荐 儿童及成人惊厥性癫痫持续状态(CSE)的治疗 中国急/慢性非特异性腰背痛诊疗专家共识 中国帕金森病的诊断标准(2016版) 中国血管性认知障碍诊疗指导规范 2016年中国偏头痛防治指南 阿尔茨海默病诊疗指南 关于肥厚型心肌病诊断和猝死防治建议 心房颤动诊疗指南 2016 ESC 和 AHA/AHA/HFSA慢性心力衰竭新指南解读
2013年Alport综合征和薄基底膜肾病指南推荐 Recommendation 1 The term “Alport syndrome” should be reserved for patients with the characteristic clinical features and a lamellated GBM with an abnormal collagen IV composition, and in whom a COL4A5 mutation (X-linked disease) or two COL4A3 or two COL4A4 mutations in trans (autosomal recessive disease) are identified or expected. The term “thin basement membrane nephropathy” (TBMN) should be reserved for individuals with persistent isolated glomerular hematuria who have a thinned GBM due to a heterozygous COL4A3 or COL4A4 (but not COL4A5) mutation. TBMN should not be used where there is a thinned GBM and the diagnosis is likely to be X-linked Alport syndrome. This distinction is to ensure patients who have X-linked Alport syndrome are not falsely reassured by the usually benign prognosis seen with TBMN. Alport syndrome should not necessarily be diagnosed where there is renal impairment together with a heterozygous COL4A3 or COL4A4 mutation. This is more likely to be due to TBMN , based on its prevalence, together with a coincidental renal disease, such as IgA GN, or to autosomal recessive Alport syndrome, with a second, undetected mutation. In these circumstances, the correct diagnosis may require further discussions among the nephrologist, pathologist, clinical geneticist, ophthalmologist, and audiologist, and interpretation of the relevant test results. Recommendation 2 The diagnosis of Alport syndrome is suspected when an individual has glomerular hematuria or renal failure and a family history of Alport syndrome or renal failure without another obvious cause. These individuals should undergo testing for microalbuminuria/proteinuria, as well as audiometry, an ophthalmologic examination , and, preferably,renal biopsy for GBM ultrastructure,collagen IV composition, and an assessment of damage. The diagnosis of Alport syndrome is highly likely if there are glomerular hematuria and a family history of Alport syndrome with no other cause for the hematuria ; if bilateral high-tone sensorineural hearing loss, lenticonus, or fleck retinopathy is present ; or if the GBM lacks the collagen IV a5 chain. The diagnosis of Alport syndrome is confirmed with the demonstration of a lamellated GBM or a COL4A5 or two COL4A3 or COL4A4 mutations. In individuals in whom the diagnosis is still unclear and genetic testing is not available,it is often useful to examine the child’s mother or an older affected male relative using the same strategy. Recommendation 3 The mode of inheritance of Alport syndrome is determined most accurately with the demonstration of a pathogenic mutation in the COL4A5 gene or two mutations in either the COL4A3 or COL4A4 gene on different chromosomes. Recommendation 4 The demonstration of a pathogenic COL4A5 variant confirms the diagnosis of Alport syndrome and X-linked inheritance. The mutation’s location and nature help predict the likelihood of early-onset renal failure and extrarenal features. These are sometimes already obvious from the disease manifestations in other affected family members. The mutation itself or a disease-associated haplotype can be used in preimplantation and prenatal diagnosis. Recommendation 5 All affected members of a family with X-linked Alport syndrome, including females, should be identified. Most mothers of affected boys are also affected. At-risk family members should be screened for hematuria on at least 2 occasions and offered other screening tests, but genetic testing is preferred, especially if a mutation has already been identi fi ed in the family (cascade testing). Recommendation 6 Affected individuals should be referred to an interested nephrologist for long term management and offered a consultation with a clinical geneticist to discuss the disease, its inheritance,and the indications for genetic testing of other family members. There should be a non-directive discussion about available reproductive options, including prenatal and preimplantation genetic diagnosis, preferably prior to any pregnancy. Individuals and their families should be advised of their diagnosis, their risk of renal failure, and their children’s likelihood of inheriting the causative mutation and developing renal failure. Affected individuals should be advised of the availability of local, national, and international patient support groups and relevant websites (Table 5). They should also be encouraged to participate in patient registries that will help improve understanding of Alport syndrome and its management. Recommendation 7 Males with X-linked Alport syndrome should be managed lifelong by a nephrologist and have their risk factors for progressive renal failure optimized,including careful management of hypertension, proteinuria, and dyslipidemia . Treatment with ACE inhibitors ,even before the onset of proteinuria,especially in individuals with genetic mutations or a family history consistent with early-onset renal failure,may delay the onset of end-stage disease and improve life expectancy. Affected individuals should avoid ototoxic medication and industrial noise exposure to minimize further hearing loss. Recommendation 8 Males with X-linked Alport syndrome and increased risk of anti-GBM disease post-transplant (early-onset renal failure, extrarenal features) should be monitored closely and undergo prompt allograft biopsy for new-onset glomerular hematuria, proteinuria, or renal impairment. Recommendation 9 Female carriers of X-linked Alport syndrome typically have a good renal outcome, but, on average, 15% develop end-stage renal failure by the age of 60 years. Thus, the carrier state should be viewed as at-risk rather than a benign condition. Clinicians should endeavor to convey this information in a way that encourages regular followup examinations for signs of progression, such as the development of hypertension, proteinuria, or renal impairment, and for hearing loss, without engendering undue anxiety. Some women with hematuria want the diagnosis of Alport syndrome confirmed or excluded prior to making reproductive decisions. This requires genetic testing. Most mothers of an affected boy are carriers and may have clinical manifestations. Clinicians caring for an affected child should explain to the mother the importance of ascertaining her status and refer her to a clinical geneticist for predictive testing if the family’s mutation is known, and to a nephrologist for clinical assessment and management. Assessment includes a renal biopsy if proteinuria or renal impairment is present. Carrier females should be monitored carefully and treated with renin-angiotensin blockade if they develop hypertension, microalbuminuria, or renal impairment. Carrier females should be strongly discouraged from kidney donation because of their own increased risk of renal impairment and hypertension. Predonation kidney biopsy is mandatory to accurately determine the extent of renal damage and further discourage donation if the damage is severe. If a female carrier proceeds with donation, she must be aware of the risks of developing renal failure in later life and should use nephroprotective strategies to minimize the effects of hypertension and proteinuria from the time of surgery. Fifteen percent of boys with X-linked Alport syndrome are affected as the result of a spontaneous gene mutation and their mothers are not carriers . These women should have disease excluded by testing for hematuria, and preferably by genetic testing. Recommendation 10 Individuals with autosomal recessive Alport syndrome should be referred to an interested nephrologist for long-term management and offered the opportunity to consult a clinical geneticist to discuss the disease, its inheritance, and the risks for other family members. A nondirective discussion about the reproductive options, including prenatal and preimplantation genetic diagnosis , should take place,preferably prior to any pregnancy. Individuals and their families should be advised of their diagnosis and risk of renal failure and their children’s risk of inheriting one or more of the mutations and developing renal failure. Affected individuals should be advised of the availability of local, national, and international patient support groups and relevant websites. They should also be encouraged to participate in registries to help improve understanding of Alport syndrome and its management. Recommendation 11 Parents, siblings, and offspring of the individual with autosomal recessive Alport syndrome should be tested for hematuria, proteinuria, and renal impairment and preferably undergo cascade testing for the causative mutations. Those with a heterozygous mutation should be managed as for TBMN. Recommendation 12 Individuals with autosomal recessive Alport syndrome should be managed by a nephrologist and have their risk factors for progressive renal failure optimized, including hypertension, proteinuria, and dyslipidemia. Again,treatment with ACE inhibitors, from the time of diagnosis, even before the onset of proteinuria , may delay the onset of renal failure and improve life expectancy. Affected individuals should avoid ototoxic medication and industrial noise exposure to minimize further hearing loss. Recommendation 13 Individuals from families with autosomal recessive Alport syndrome who have only one of the causative mutations (parents, offspring, some siblings) may be renal donors if they have normal BP, proteinuria levels,and renal function; if coincidental renal disease has been excluded by renal biopsy; and if X-linked Alport syndrome has been excluded by genetic testing. Recommendation 14 TBMN is usually suspected clinically where there is persistent glomerular hematuria, normal levels of proteinuria,and normal BP and renal function , without another obvious explanation. There may be a family history of hematuria ,but not of Alport syndrome or renal failure (except in families with autosomal recessive Alport syndrome). Individuals suspected of having TBMN should underg o renal biopsy if they have atypical features (proteinuria in adults 1.0 g/d or renal impairment ), or if X-linked Alport syndrome or a coincidental glomerular or tubulointerstitial abnormality cannot be excluded. Recommendation 15 Genetic testing for COL4A3 and COL4A4 mutations is not usually required for the diagnosis of TBMN. Screening for COL4A5 mutations to exclude X-linked Alport syndrome is often more important. Recommendation 16 Individuals with TBMN should be assessed at presentation for poor prognostic indicators (hypertension, proteinuria, renal impairment). Those with these features should be managed by a nephrologist, and treatment should include an ACE inhibitor to delay the onset of renal failure. Other individuals with TBMN may be reviewed every 1–2 y ears for hypertension, proteinuria, and renal impairment by their primary care provider. Recommendation 17 All individuals with TBMN and their families should be advised of the diagnosis of TBMN, its inherited nature,and their low risk of renal failure. Recommendation 18 Individuals with TBMN may be kidney donors if they have normal BP, proteinuria, and renal function, and if genetic testing and renal biopsy have excluded X-linked Alport syndrome and coincidental renal disease. A renal biopsy is mandatory prior to donation to assess renal damage. If an individual with TBMN proceeds with renal donation, he or she must be aware of the risks and use nephroprotective strategies to minimize the effects of hypertension and proteinuria from the time of surgery.
泰山医学院氢气临床研究论文2013.pdf 代谢综合征可以说是经济发展到一定高度后社会必然出现的流行病。肥胖、 Ⅱ 型糖尿病、糖耐量异常、高血压、高甘油三脂血症等临床疾病的聚集并非偶然。 1988 年美国著名内分泌专家 Reaven 发现胰岛素抵抗，并胰岛素抵抗、高胰岛素血症、糖耐量异常、高甘油三脂血症和高血压统称称为 “X 综合征 ” 。现在医学界一般说的代谢综合征，就是指 Reaven 综合征，就是代谢综合症。这是脑血管、心血管、肝脏、肾脏等多种疾病的最普遍诱因。因此针对代谢综合征治疗开展研究可以说具有重要意义。但是由于这一疾病或状态本身似乎并不是严重的疾病状态，给治疗这类疾病也带来困惑，因此医生对这些患者的最常见方式是吓唬加改善生活方式。 日本学者曾经报道过使用氢水治疗代谢综合征，也有学者曾经有关于脑干梗死、血液透析、红斑狼疮、类风湿关节炎、巴金森病、运动后疲劳、化疗副作用等临床研究的报道。中国学者目前在国际上发表的研究论文在国际上超过 1/3 ，但遗憾地是过去没有一篇临床研究论文。今天这一局面被山东泰山医学院动脉粥样硬化研究所的一篇关于氢水治疗代谢综合征的研究论文打破。而且在研究深度上，远远超过国外同类研究，不仅证明氢气水对代谢综合征具有治疗效果，而且从多种角度分析了这种治疗效果的分子机制。泰山医学院动脉粥样硬化研究所秦树存研究团队长期致力于动脉硬化脂蛋白相关分子的研究，最近几年在氢气和动脉硬化和脂蛋白相关基础研究中领先于国际，现在中国第一篇临床研究报道的发表将再次确立该团队在氢气生物学效应研究中的领先地位。 论文摘要：该团队过去发现氢气有利于高脂饮食喂养叙利亚金黄地鼠。本研究的目的是证明氢水（ 0.9-1.0 升 / 天）对人类代谢综合征患者是否有效。研究对象为 20 个潜在的代谢综合征患者，通过观察氢气水对患者血清脂蛋白和生物活性物质的影响。结果发现，连续饮氢水 10 周后，血清总胆固醇（ TC ）和低密度脂蛋白胆固醇（ LDL-C ）发生降低。 Western blot 分析显示载脂蛋白 B100 （载脂蛋白 B100 ）和 apoE 血清中显着减少。此外还发现，氢气水可显着提高高密度脂蛋白（ HDL ）功能，他们对这种影响进行了四个方面的深入分析，即（ i ）防止低密度脂蛋白氧化损伤；（ ii ）抑制 TNF- α诱导的单核细胞黏附内皮细胞；（ iii ）促进泡沫细胞释放胆固醇；（ⅳ）保护 TNF- α诱导的血管内皮细胞凋亡。此外发现氢气水可增加抗氧化酶活性如超氧化物歧化酶增加，使硫代巴比妥酸反应物质和全血清低密度脂蛋白减少。总之，补充富氢气水可降低血清 LDL-C 和 apoB 水平，改善血脂异常受伤 HDL 功能，减少氧化应激，会产生许多有益作用，是代谢综合征潜在理想的预防手段。 该论文目前在线发表在 J LipidRes 。论文题目为 Hydrogen-rich water decreases serum low-density lipoprotein cholesterollevels and improves high-density lipoprotein function in patients withpotential metabolic syndrome. J Lipid Res. 2013 Apr 22. Hydrogen-richwater decreases serum low-density lipoprotein cholesterol levels and improveshigh-density lipoprotein function in patients with potential metabolicsyndrome. Song G , Li M , Sang H , Zhang L , Li X , Yao S , Yu Y , Zong C , Xue Y , Qin S . Source TaiShanMedical University, China; Abstract Wehave found hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects inhigh-fat diet-fed Syrian golden hamsters. The objective of this study was tocharacterize the effects of H2-rich water (0.9-1.0 L/day) on the content,composition, and biological activities of serum lipoproteins on 20 patients withpotential metabolic syndrome. Serum analysis showed that consumption of H2-richwater for 10 weeks resulted in decreased serum total-cholesterol (TC) andlow-density lipoprotein-cholesterol (LDL-C) levels. Western blot analysisrevealed a marked decrease of apolipoprotein B100 (apoB100) and apoE in serum.Besides, we found H2 significantly improved high-density lipoprotein (HDL)functionality assessed in four independent ways, namely (i) protection againstLDL oxidation, (ii) inhibition of TNF-α induced monocyte adhension toendothelial cells, (iii) stimulation of cholesterol efflux from macrophage foamcells, (iv) protection of endothelial cells from TNF-α induced apoptosis.Further, we found consumption of H2-rich water resulted in an increase inantioxidant enzyme superoxide dismutase and a decrease in thiobarbituricacid-reactive substances in whole serum and LDL. In conclusion, supplementationwith H2-rich water appear to decrease serum LDL-C and apoB levels, improvedyslipidemia injured HDL functions, and reduce the oxidative stress and mayhave a beneficial role in prevention of potential metabolic syndrome. PMID: 23610159
美国加州大学洛杉矶分校研究人员日前公布的研究报告称，在睡眠呼吸暂停综合征患者中，女性脑部所受损伤大于男性。 在这项研究中，研究人员对比了10名新确诊患有阻塞性睡眠呼吸暂停综合征且未接受治疗的女性、20名存在同样情况的男性及50名健康男女的大脑状况。他们发现，女性患者的大脑白质受损更多，其受影响的部位主要是大脑前部的扣带束和前扣带皮层。这些大脑区域主要负责作决定和情绪调控，这些女性患者也因此更容易出现高血压和焦虑症状。 相关研究报告已发表在美国《睡眠》杂志12月刊上。研究人员表示，他们目前还不能确定睡眠呼吸暂停综合征与大脑损伤之间是否存在因果关系，其下一步计划是揭示睡眠呼吸暂停综合征患者大脑发生变化的时间点。 阻塞性睡眠呼吸暂停综合征是一种常见的睡眠障碍，患者睡眠过程中气道反复阻塞导致不断出现呼吸暂停，最典型的症状就是打鼾。症状发作时，患者血液中的氧分下降，最终导致体内细胞受损，如不接受治疗，最终可能导致高血压、中风、心脏病、糖尿病等严重健康问题。（来源：新华社 任海军） Sex Differences in White Matter Alterations Accompanying Obstructive Sleep Apnea renchunxiao 添加于 2013-2-19 15:40:27 28次阅读 | 0次推荐 | 0个评论 Study Objectives: Females with obstructive sleep apnea (OSA) show different psychological and physiological symptoms from males, which may be associated with sex-related variations in neural injury occurring with the disorder. To determine whether male- or female-specific brain injury is present in OSA, we assessed influences of sex on white matter changes in the condition. Design: Two-group factorial. Setting: University medical center. Patients or Participants: 80 subjects total, with newly diagnosed, untreated OSA groups of 10 female (age mean ± SE: 52.6 ± 2.4 years, AHI 22.5 ± 4.1 events/h) and 20 male (age 48.9 ± 1.7, AHI 25.5 ± 2.9) patients, and 20 female (age 50.3 ± 1.7) and 30 male (age 49.2 ± 1.4) healthy control subjects. Interventions: None. Measurements and Results: Brain fiber integrity was assessed with fractional anisotropy (FA), a diffusion tensor imaging-derived measure. Sleep quality, daytime sleepiness, depression, and anxiety were assessed with questionnaires. We identified regions of differing injury in male versus female OSA patients by assessing brain regions with significant interaction effects of OSA and sex on FA. Areas of sex-specific, OSA-related FA reductions appeared in females relative to males, including in the bilateral cingulum bundle adjacent to the mid hippocampus, right stria terminalis near the amygdala, prefrontal and posterior-parietal white matter, corpus callosum, and left superior cerebellar peduncle. Females with OSA showed higher daytime sleepiness, anxiety and depression levels, and reduced sleep quality. Conclusions: Sex differences in white matter structural integrity appeared in OSA patients, with females more affected than males. These female-specific structural changes may contribute to or derive from neuropsychological and physiological symptom differences between sexes. Macey PM; Kumar R; Yan-Go FL; Woo MA; Harper RM. Sex differences in white matter alterations accompanying obstructive sleep apnea. SLEEP 2012;35(12):1603-1613.
标签: 综合征
