核黄素反应性脂质沉积性肌病20个家系的电子转移黄素蛋白脱氢酶基因存在热点突变

目的 报道20个核黄素反应性脂质沉积性肌病(RR-LSM)患者的电子转移黄素蛋白脱氧酶(ETFDH)基因检查结果.方法 对2003年1月至2010年5月我院神经科收治的24例RRLSM患者(来自20个我国大陆北方地区RR-LSM家系,其中16个家系各有1例患者,其余4个家系各有2例发病者)的临床特点进行分析.对24例患者、11名无症状家系成员以及100名健康人行ETFDH基因检查.结果 24例患者发病年龄为(27.9±9.9)岁,主要症状为四肢无力(21例,87.5%)、咀嚼困难(15例,62.5%)、颈肌无力(14例,58.3%)和肌痛(14例,58.3%)等.18例患者的血代谢筛查均提示脂酰肉碱升高,17例患者中有15例存在戊二酸尿症.我们发现19个家系存在17种ETFDH基因点突变,包括13种错义突变、2种剪切突变和2种无义突变.其中患者的c.998A>G、c.1450T>C、c.1703T>C、c.11717C>T、c.821G>A、c.643G>A、c.25IC>T、c.1763A>T、c.IVS7+2T>C、c.IVS6+1G>A没有出现在100名健康人中.有9个家系存在c.770A>G(P.Y257C)突变;5个家系存在c.1227A>C(P.L409F)突变.结论 诸多ETFDH基因新突变提示国人RR-LSM可能存在特殊的基因突变谱,其中P.Y257C与P.L409F突变可能为我国大陆北方地区的热点突变.

Abstract：

Objective To report the spectrum of electron transfer flavoprotein dehydrogenase (ETFDH)gene mutations in 20 Chinese RR-LsM families.Methods Twenty-four RR-LSM patients in the First Hospital of Peking University from January 2003 to May 2010 were collected and the clinical characteristics were analyzed.These patients came from 20 families in North Mainland China.Sixteen families had 1 patient each.and the other 4 families had 2 patients.ETFDH gene analysis was performed in all patients,11 family members and 100 healthy controls.Results The mean onset age was(27.9±9.9)years.The main symptoms were limb weakness(21,87.5%),dysmasesia(15,62.5%),neck weakness (14,58.3%)and myalgia(14,58.3%).Eighteen patients had high level of acyleamitine.Fifteen of 17patients had glutaric aciduria.Seventeen ETFDH mutations,including 13 missense mutations,2 splice mutations,and 2 nonsense mutations,were identified in 19 families:c.998A>G,c.1450T>C,c.1703T>C,c.1717C>T,c.821G>A,c.643G>A,c.251C>T,c.1763A>T,c.IVS7+2T>C and c.IVS6+1G>A were Hovel mutations which were not found in 100 healthy controls.Nine families had the mutation of c.770A>G(P.Y257C)and 5 families had the mutation of c.1227A>C(P.L409F).Conclusions The numerous novel mutations in ETFDH gene indicate that Chinese RR-LSM might have special mutation pattern.c.770A>G(P.Y257C)and c.1227A>C(p.L409F)may be hot spot mutations in North Mainland China.     

中枢神经系统表面含铁血黄素沉积症1例报道

中枢神经系统表面含铁血黄素沉积症(superficial siderosis of central nervous system)是一种罕见的综合征,表现为进行性小脑性共济失调,感觉神经性耳聋,锥体束征;影像学上的特征性表现是MR上在脑、脊髓表面含铁血黄素信号。我们在临床中遇到1例,报道如下。1资料患者,男,27岁,2005年11月14日入院。入院前4年患者无明显诱因出现右耳高调耳鸣,继而出现双耳听力进行性下降至完全丧失听力,伴张口困难、双下肢屈侧及腰背部肌肉紧缩感,双下肢主动伸直困难,尚能被动伸直,他人搀扶下可行走,当地医院小针刀治疗症状仍逐渐加重,出现腰背部肌肉僵硬,…     

促排卵周期黄素化未破裂卵泡综合征的预测指标初探

目的探讨促排卵周期中黄素化未破裂卵泡综合征（LUFS）的激素预测值。方法选择自然周期有排卵障碍的99例患者使用克罗米芬＋HCG促排,分别在月经周期的第3天（C3）、第10天（C10）、卵泡成熟日（CM）（卵泡直径≥18mm）采静脉血进行性激素六项『黄体生成素（LH）、卵泡刺激素（FSH）、雌二醇（E2）、睾酮（T）、催乳素（PRL）、孕酮（P）I测定,观察患者的排卵结局。结果99例促排患者中正常排卵患者58例（58．6％）,LUFS患者41例（41．4％）。两组患者年龄、不孕年限、体重、身高、BMI进行统计分析,无显著性差异（P〉0．05）。对LUFS的相关因素进行Logistic回归分析,结果显示C3日黄体生成激素（LC3）、C3日孕酮（PC3）、CIO日的促卵泡成熟激素（FC10）与LUFS的发生相关,概率方程为P=e^4.612-0.318LC3-4.074PC3-0.304FC3/（1＋e^4.612-0.318LC3-4.074PC3-0.304FC3）,方程有效性检验X2=14．679,P=0．002。结论月经周期的第3天的LH、P及第10天的FSH能有效预测LUFS的发生。     

染料木素和大豆黄素对海马神经细胞H19-7增殖和神经营养因子表达的影响

Objective To determine the effects of genistein and daidzein on the proliferation and survival of the hippocampal neural cells and underlying mechanism. Methods H19-7/IGF-IR neural cell line was cultured in phenol red free DMEM absented of serum for 72h. Genistein, daidzein or 17β-estradiol was added to the culture at various concentrations. Their proliferation and protective effects on the neuronal cells were determined by BrdU and MTT assay respectively. The effect of phytoestrogens on cell cycle regulation was determined using flow cytometry. The effects of the soy isoflavones on brain-derived neurotrophic factor (BDNF) expression were determined by ELISA and RT-PCR respectively. Results It was observed that, with 72h of treatment, 20nM and 200 nM 17B-estradiol significantly promoted the neuronal cell proliferation at 33% and 36% ;20nM and 200nM genistein significantly promoted the neuronal cell proliferation at 15% and 13% ; 200nM daidzein significantly promoted the neuronal cell proliferation at 11% compared to the control (P＜0.05). Genistein and daidzein induced an significantly increase in the S phase arrest at (17.64 ± 0.43) % and (19.48 ± 1.01) % compared to the control (P ＜ 0. 05). Moreover, genistein and daidzein significantly increased the expression of mature BDNF and BDNF mRNA level (P＜0.05). The effect of genistein and daidzein on hippocampal neuronal cell proliferation was blocked by K252a, selective inhibitor of tyrosine kinase receptors. Conclusion Genistein and daidzein improved hippocampal neuronal cell proliferation and viability in vitro. The effects might be mediated by increasing in BDNF expression.     

金雀异黄素抑制缺氧人视网膜色素上皮细胞VEGF表达机制的初步研究

目的:进一步明确金雀异黄素(Gen)抑制缺氧人视网膜色素上皮细胞(RPE)血管内皮生长因子(VEGF)表达的机制。方法:以体外正常情况为对照,建立人RPE缺氧模型并经不同浓度Gen干预后,通过RT-PCR检测VEGF及其转录调节因子c-fos、c-jun、缺氧诱导因子(HIF)-1α、HIF-2α、HIF-3αmRNA的表达水平,了解Gen是否通过对VEGF的转录因子活性调节而影响VEGF的表达。结果:缺氧能使人RPE细胞的VEGF、c-fos、c-jun及HIF-2α、HIF-3αmRNA水平增高,对HIF-1α无影响;Gen能抑制缺氧诱导的VEGF表达;在所检测的VEGF转录因子中,Gen只对HIF-2α的转录有抑制作用。结论:Gen抑制VEGF表达的作用部分是通过抑制其转录调节因子HIF-2α转录实现的。     

多囊卵巢综合征患者促排卵中发生卵泡未破裂黄素化综合征临床分析

目的探讨多囊卵巢综合征(PCOS)促排卵治疗中出现的卵泡未破裂黄素化综合征(LUFS)的原因和治疗措施。方法对计划生育科就诊的PCOS不孕患者经口服避孕药治疗3周期后给予促排卵治疗,对发生LUFS的51例患者分别给予卵泡穿刺(29例)和针灸(22例)治疗,比较治疗后的妊娠率。结果29例穿刺组患者10例妊娠,妊娠率34.48%。22例针灸患者2例妊娠,妊娠率9.09%。经χ2检验P<0.05,两组治疗效果比较差异有统计学意义。结论PCOS患者促排卵治疗中发生LUFS给予卵泡穿刺术治疗效果肯定,是一种有效的治疗方法。     

儿童特发性肺含铁血黄素沉着症误诊分析

特发性肺含铁血黄素沉着症(id iopathic pulmonaryhemosiderosis,IPH)是一种肺泡毛细血管出血性疾病,以大量含铁血黄素积累于肺内为特征。主要在小儿时期发病,常反复发作,临床误诊率高达57%~100%[1~3]。我院20余年来收治12例IPH,其中10例误诊,误诊率83·3%。现对其诊断、治疗和     

加味五子衍宗丸基于视黄素X受体表达防治ApoE-/-小鼠骨质疏松的作用机制研究

目的：探讨加味五子衍宗丸防治载脂蛋白E敲除(ApoE^-/-)小鼠骨质疏松的相关作用机制。方法：8周龄ApoE^-/-小鼠随机分为阴性对照组、模型组、治疗组和阳性对照组,每组6只。阴性对照组和模型组小鼠给予常规饲料;治疗组和阳性对照组小鼠给予高脂饲料,同时分别灌胃给予加味五子衍宗丸和阿仑膦酸钠悬液。各组小鼠连续干预24周后,取股骨做微型电子计算机断层扫描(Micro CT)、HE染色、Trap染色及免疫组化染色,观察各组小鼠骨质疏松情况、破骨细胞数量及视黄素X受体(RXR)的表达情况。结果：(1)与阴性对照组比较,模型组小鼠股骨Micro CT检测指标骨密度(BMD)、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)和骨小梁数量(Tb.N)均显著下降(P<0.05);与模型组相比,治疗组的BMD、BV/TV、Tb.Th、Tb.N均显著增加(P<0.05)。(2)与阴性对照组比较,模型组骨质疏松面积显著增加(P<0.01);与模型组比较,治疗组及阳性对照组骨质疏松面积显著减少(P<0.01)。(3)模型组破骨细胞数量显著高...     

磁敏感加权成像技术对中枢神经系统表面含铁血黄素沉积症的诊断价值

目的 探讨中枢神经系统表面含铁血黄素沉积症(SSCNS)应用磁敏感加权成像技术诊断的价值.方法 选择新乡医学院第二附属医院2019年1月至2019年12月收治的82例中枢神经系统表面含铁血黄素沉积症患者进行研究,纳入对象有完整资料,自愿配合研究,均接受核磁共振成像及磁敏感加权成像技术诊断,总结并分析磁共振成像与磁敏感加...