神经丝轻链蛋白与多聚谷氨酰胺病

多聚谷氨酰胺(polyQ)病作为一组遗传性神经退行性疾病,患者在临床前期已出现大脑结构和功能的病理改变。随着检测技术的进步,神经丝轻链蛋白(NfL)作为轴突损伤的敏感标志,已成为神经系统疾病最有前景的生物标志物之一。NfL可作为polyQ病临床前期和临床期神经退行性变的生物标志物,并与疾病的严重程度和病程的进展密切相关,尤其是在疾病分期方面具有较大的潜力。本文对NfL作为polyQ病生物标志物的价值及其潜在的研究方向进行了综述。

关注多聚谷氨酰胺病的修饰基因研究

多聚谷氨酰胺病是一组具有高度临床和遗传异质性的神经退行性疾病,由致病基因外显子中CAG三核苷酸重复发生动态突变引起,表现为神经系统特定区域选择性的神经元死亡。总体而言,CAG重复序列拷贝数可解释多聚谷氨酰胺病发病年龄50%~70%的变异,修饰基因也对其临床异质性有影响。文中回顾了多聚谷氨酰胺病的修饰基因研究历程,简述了主要发现和对研究现状的思考。

异环磷酰胺脑病全身抽搐发作表现1例并文献回顾

目的:整理、分析异环磷酰胺致中枢神经系统毒性的临床特点、危险因素、影像学及电生理特点、治疗及预后,为临床及早发现和治疗异环磷酰胺脑病提供参考。方法:参与1例异环磷酰胺致中枢神经系统毒性患者的治疗过程。该患者行第3疗程异环磷酰胺方案化疗第4天时出现全身抽搐症状,查体示肌张力增高、病理征阳性,经多学科会诊后,考虑该不良反应与异环磷酰胺有关,停用该药并给予支持治疗后24小时内症状好转。结合上述病例,收集异环磷酰胺致中枢神经系统毒性的相关文献,归纳、总结其临床表现、发病机制、危险因素、干预及转归等特征。结论:神经系统毒性为异环磷酰胺的罕见不良反应,多发生在用药后12小时到6天内,可表现为嗜睡、昏迷、全身抽搐发作等多种症状。当患者出现该不良反应时,应及时停药并给予支持治疗,必要时静脉给予亚甲蓝或硫胺素治疗。临床医师应加强对异环磷酰胺神经系统毒性的认识,及时识别相关症状,保证用药安全。

组蛋白去乙酰化酶抑制剂治疗多聚谷氨酰胺病的研究进展

近年研究发现基因转录异常可导致亨廷顿病（Huntington’s disease，HD）等多聚谷氨酰胺（polyglutamine，PolyQ）病中的神经元功能异常。组蛋白去乙酰化酶（histone deaeetylases，HDACs）作为一种转录抑制因子，可与辅阻遏物复合体相互作用导致染色质重塑，最终抑制目的基因的转录。PolyQ蛋白与基因转录调控因子异常的相互作用可能是PolyQ病转录失调的原因之一。作者就PolyQ病转录失调的可能发生机制，尤其是组蛋白乙酰转移酶（histone acetyltransferases，HATs）和HDACs在其中所起的作用，以及组蛋白去乙酰化酶抑制剂（histone deaeetylases inhibitors，HDACIs）的治疗潜能等方面予以综述。

微小RNA与多聚谷氨酰胺病

多聚谷氨酰胺（polyglutamine，PolyQ）病是一类具有明显的临床和遗传异质性的神经系统退行性疾病，尽管拥有致病基因编码区CAG三核苷酸重复动态突变这一共同发病机制，它们的临床表现却各不相同，且缺乏有效的治疗手段。近年来，微小RNA作为一类重要的转录后重要因子在PolyQ病的发病中所扮演的角色及其潜在的治疗价值受到了研究者的关注。

微RNA在多聚谷氨酰胺病中的作用研究进展

多聚谷氨酰胺（polyglutamine,PolyQ）病是一类因致病基因编码区的三核苷酸重复异常扩增而形成PolyQ肽链,最终导致选择性神经元变性乃至死亡的神经退行性疾病,其发病机制仍未完全阐明.微RNA（microRNA,miRNA）作为一种新的非蛋白质的基因表达调控因子,对真核生物的基因表达有非常重要的调控作用.近年来国内外学者日益关注miRNA在神经退行性疾病尤其是Po1yQ病中的功能及其作用机制.就目前miRNA在PolyQ病发病机制中的作用研究进展予以综述.

氟乙酰胺中毒性脑病（附1例病理、毒理报告）

氟乙酰胺中毒性脑病（附１例病理、毒理报告）张昀，陈秋惠，田雪红，许二赫，姚广川，姚建华我科收治１例神经型氟乙酰胺中毒患者，死后经法医解剖、毒理学检验证实，现报告如下。患女，４１岁，小学教师。患者于入院前１８天受惊吓，翌日自觉心难受。３日后突然四肢强直...

氟乙酰胺中毒性脑病327例临床分析

目的：总结氟乙酰胺中毒性脑病的救治体会。方法：对３２７例口服氟乙酸胺中毒性脑病的临床资料进行回顾性分析。结果及结论：３２７例口服中毒均以意识障碍、癫痫样发作及精神异常为主要临床表现；９６．９％的患者脑电图异常，提示大脑皮层广泛受累；救治主要应用解氟灵；本组３０７例治愈，２０例死亡。本病的预后与接触毒物的剂量、时间长短以及治疗是否及时有关。

急性氟乙酰胺中毒性脑病1报道

氟乙酰胺是一种致痉挛性鼠药，人体误服后会出现严重的中毒症状，其中中枢神经系统的中毒症状极为突出，在病史询问不详细的情况下，容易误诊和漏诊．甚至出现危及生命的严重后果。在20世纪末及21世纪初，该药中毒病人急诊科非常常见，中毒病例临床上报道很多，对此病治疗也已明确，

急性氟乙酰胺中毒性脑病53例临床分析

对53例急性氟乙酰胺中毒性脑病的临床表现、实验室检查和急救对策进行临床分析。患者多以意识障碍、癫痫样发作及精神异常为主要临床表现,94.3%的患者脑电图异常,提示大脑皮层广泛受累。救治以特效解毒剂乙酰胺为主,配合抗癫痫及精神药物,同时予以综合性对症支持疗法。

HLA单倍体与全相合异基因造血干细胞移植治疗恶性血液病

背景:异基因造血干细胞移植是治疗恶性血液病的一种非常有效的方法。单倍体相合的造血干细胞移植扩大了移植的应用范围,是无HLA相合供者患者的一种重要选择。目的:比较HLA单倍体相合与全相合异基因造血干细胞移植治疗恶性血液病的临床疗效。方法:回顾性分析接受异基因造血干细胞移植79例恶性血液病患者的临床资料,其中HLA单倍体相合组26例、全相合组53例,对比两组受者移植物抗宿主病的发生率、复发率、2年生存率等。结果与结论:78例受者获得完全、持久供者干细胞植入;1例受者在移植后28 d尚未植入,后因感染死亡。两组慢性移植物抗宿主病发生率、复发率和2年无病生存率差异无显著性意义(P>0.05)。单倍体相合组急性移植物抗宿主病发生率高于全相合组(P<0.05);2年总生存率低于全相合组(P<0.05)。提示血缘HLA单倍体相合移植治疗恶性血液病的安全性及疗效接近于全相合移植,在缺乏HLA相合供者的情况下,行HLA单倍体相合造血干细胞移植治疗恶性血液病是切实可行的选择。

脊髓小脑共济失调的分子遗传学研究进展

脊髓小脑共济失调（SCAs）是一组具有多变的小脑、脊髓小脑束和脑干神经元变性的异质性神经病．按照目前的分子分类法，SCAs包括SCA1～SCA27等亚型．SCAs同样具有遗传异质性，加上各亚型的临床症状有较多的重叠，使得临床亚型的确诊较为复杂．SCA1、SCA2、SCA3、SCA6、SCA7、SCA17和DRPLA由三核苷酸重复（CAG）n引起，SCA8和SCA10则分别由（CTG）n和（AT—TCT）n重复造成，而易感基因的点突变可能是SCA14和SCA27的分子病因．由于核苷酸重复的不稳定性，SCAs的一个主要特点是存在遗传早现．SCAs患者包含多聚谷氨酰胺的神经元核内及细胞质包涵体的作用不详，但其细胞内的蛋白质聚集现象可能是SCAs不同于其他异质性疾病的常见病理过程．

Baseline Sensitivity of Botrytis cinerea from Liaoning Province to Boscalid

[Objective] This study aimed to avoid and delay the generation of resis- tance in Botrytis cinerea to boscalid. [Method] The sensitivity of Botrytis cinerea to boscalid was tested by the mycelial growth rate method. The distribution of sensitivity variation of B. cinerea to boscalid in different regions was cleared, and the sen- sitivity baseline of B. cinerea from Liaoning Province to boscalid was established. [Result] The ECso values of B. cinerea strains from Liaoning Province ranged from 0.080 0 to 7.787 2μg/ml, and the highest ECho value was 97.34 times higher than the minimum. The average EC50 value （1.973μg/ml） of the 158 strains was treated as the baseline sensitivity of B. cinerea from Liaoning Province to boscalid. [Conclu- sion] It is essential to conduct a risk assessment of drug resistance in B. cinerea to boscalid.

Nicotinamide overload may play a role in the development of type 2 diabetes

AIM： To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS： Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N^1-methylnicotinamide on glucose metabolism, plasma HzO2 levels and tissue nicotinamide adenine dinucleotide （NAD） contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS： Diabetic subjects had significantly higher plasma N^1-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects （0.89 ± 0.13 μmol/L vs 0.6 ± 0.13 μmol/L, P 〈 0.001）. Cumulative doses of nicotinamide （2 g/kg） significantly increased rat plasma Nl-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by Nl-methy-Inicotinamide. Moreover, cumulative exposure to N^1- methylnicotinamide （2 g/kg） markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/ NADH ratio, and increased plasma H2O2 levels. Decrease in NAD/NADH ratio and increase in H2O2 generation were also observed in human erythrocytes after exposure to N^1-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide （5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load）. Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N^1- methylnicotinamide clearance. CONCLUSION： These findings suggest that nicotinamide overload, which induced an increase in plasma N^1- methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

A Brazilian experience of the self transglutaminase-based test for celiac disease case finding and diet monitoring

AIM： To evaluate the effectiveness of a rapid and easy fingertip whole blood point-of-care test for celiac disease （CD） case finding and diet monitoring. METHODS： Three hundred individuals, 206 females （68.7%） and 94 males （31.3%）, were submitted to a rapid and easy immunoglobulin-A-dass fingertip whole blood point-of-care test in the doctor＇s office in order to make immediate clinical decisions： 13 healthy controls, 6 with CD suspicion, 46 treated celiacs, 84 relatives of the celiac patients, 69 patients with dyspepsia, 64 with irritable bowel syndrome （IBS）, 8 with Crohn＇s disease and 9 with other causes of diarrhea. RESULTS： Upper gastrointestinal endoscopy with duodenal biopsies was performed in patients with CD suspicion and in individuals with positive test outcome： in 83.3% （5/6） of the patients with CD suspicion, in 100% of the patients that admitted gluten-free diet transgressions （6/6）, in 3.8% of first-degree relatives （3/79） and in 2.9% of patients with dyspepsia （2/69）. In all these individuals duodenal biopsies confirmed CD （Marsh＇s histological classification）. The studied test showed good correlation with serologic antibodies, endoscopic and histological findings.CONCLUSION： The point-of-care test was as reliable as conventional serological tests in detecting CD cases and in CD diet monitoring.

Pulse cyclophosphamide therapy for inflammatory bowel disease

AIM:To assess the efficacy of intravenous cyclophos-phamide pulse therapy for refractory inflammatory boweldisease(IBD).METHODS:We included in our cohort eight patientswith(moderate/severe)steroid refractory IBD(4 withulcerative colitis and 4 with Crohn's disease).They allreceived 6 cycles of intravenous cyclophosphamide(800mg)per month.RESULTS:Patients entered into remission after the sec-ond/third cyclophosphamide pulse.Disease activity de-creased.There were no side effects and toxicity.All thepatients went into long lasting remission.All Crohn's diseasepatients and 3 of 4 ulcerative colitis patients achievedcomplete remission.One patient with ulcerative colitisshowed an impressive clinical response but did not enterinto remission.For the maintenance,patients with Crohn'sdisease were treated with methotrexate(15 mg/wk)andpatients with ulcerative colitis were treated with azathio-prine(2.5 mg/kg body weight/d).CONCLUSION:Remission was maintained in all pa-tients for 6 mo on the average.The drug was well toler-ated.These findings suggest that aggressive immuno-suppressive therapy may be useful in some refractorypatients and further controlled study should be consid-ered in order to fully evaluate this type of treatment as apotential therapy for IBD.

Celiac disease

Celiac disease （CD） is a common autoimmune disorder, induced by the intake of gluten proteins present in wheat, barley and rye. Contrary to common belief, this disorder is a protean systemic disease, rather than merely a pure digestive alteration. CD is closely associated with genes that code HLA-Ⅱ antigens, mainly of DQ2 and DQ8 classes. Previously, it was considered to be a rare childhood disorder, but is actually considered a frequent condition, present at any age, which may have multiple complications. Tissue transglutaminase-2 （tTG）, appears to be an important component of this disease, both, in its pathogenesis and diagnosis. Active CD is characterized by intestinal and/or extra-intestinal symptoms, villous atrophy and crypt hyperplasia, and strongly positive tTG auto-antibodies. The duodenal biopsy is considered to be the ＂gold standard＂ for diagnosis, but its practice has significant limitations in its interpretation, especially in adults. Occasionally, it results in a false-negative because of patchy mucosal changes and the presence of mucosal villous atrophy is often more severe in the proximal jejunum, usually not reached by endoscopic biopsies. CD is associated with increased rates of several diseases, such as iron deficiency anemia, osteoporosis, dermatitis herpetiformis, several neurologic and endocrine diseases, persistent chronic hypertransami-nasemia of unknown origin, various types of cancer and other autoimmune disorders. Treatment of CD dictates a strict, life-long gluten-free diet, which results in remission for most individuals, although its effect on some associated extraintestinal manifestations remains to be established.

Breast Fibromatosis after Hydrophilic Polyacrylamide Gel Injection for Breast Augmentation: a Case Report and Review of the Literature

BREAST fibromatosis is a rare kind of lesion. The average incidence is about 2-4 per million every year} So far there have been about 100 cases reported altogether.2 In this report, we describe a case of breast fibromatosis developed after hydrophilic polyacrylamide gel （HPG） injection for breast augmentation. By reviewing the literature, the possible pathogenesis of this case and the proper treatment strategy are investigated.