女，36岁，3年前无诱因出现双手无力，表现为手指屈曲力弱、握拳不紧(图1A、1B)，症状缓慢进展。1年前出现走路姿势异常，腰部前倾。1月前发现双足踇不能上翘，双手肌肉轻度萎缩。家族中无类似患者。查体：颅神经功能正常，转头、耸肩力弱，屈颈2级，伸颈4级。四肢肌张力正常，肌力检查臂外展、伸、屈肘均为5级，伸、屈腕4级，伸指4-级，屈指4-/3级(左/右)，伸、屈髋5级，伸、屈膝5-级，跖屈4级，背伸4-级，踇背伸2级，双手大鱼际肌萎缩(图1C)，双上肢腱反射+，双下肢腱反射++，双侧病理征均为阴性。起蹲正常，无法用足跟行走。内科系统查体未见异常。

Objective:To investigate the clinical characteristics and electron transfer flavoprotein dehydrogenase ( ETFDH) genetic mutations in patients with riboflavin responsive lipid storage myopathy (RR-LSM). Methods:A retrospective analysis was performed. The clinical data and muscular pathology of 26 patients with RR-LSM, admitted to our hospital from January 2009 to June 2021, were collected. Peripheral venous blood DNA was extracted, and the mutations of ETFDH gene were detected and analyzed by whole exome sequencing. Results:These 26 patients had onset of proximal limb myasthenia, 17 patients had difficulty in raising their head, 12 patients had mastication weakness, 6 had dysphagia, 5 had nausea and vomiting, and one was complicated with rhabdomyolysis and one was with reversible splenic lesion syndrome. Muscle biopsy indicated pathological deposition of lipid droplet, which type I fibers were involved mainly; degenerative necrotic muscle fibers were seen in a few cases. ETFDH gene mutations were detected in 26 patients; 23 patients had compound heterozygous mutation, two had single heterozygous mutation and one had homozygous mutation; 25 different mutation sites were found, mainly missense mutations; the C.770A>G frequency was the highest, accounting for 20% alleles (10/50); two novel mutation sites were found: c.1115A>G and c.1781T>C. Conclusion:RR-LSM is mainly characterized by proximal limb muscle weakness and fatigue intolerance, often accompanied by neck extensor and masticatory weakness; c. 770A>G is the hot site of ETFDH genetic mutations in RR-LSM patients.

Objective:To investigate the characteristics of clinical, muscle pathology and gene mutation in patients with nemaline myopathy caused by NEB gene mutation.Methods:The clinical and pathological data of patients with nemaline myopathy caused by NEB gene were collected from Neuromuscular Center of Jiaozuo People′s Hospital from January 1997 to January 2020. The next generation sequencing was preformed to detect NEB gene in all patients, and characteristics of gene mutation were analyzed.Results:Among the 11 patients, there were 8 males and 3 females, and 6 of them came from 2 families. The age of seeing a doctor ranged from 11 to 52 years, the age of onset was from 6 to 23 years, and the course of disease ranged from 5 to 35 years. Neurological examination showed that among the 11 patients, 8 patients had high palatal arch and long face. The muscle tone of both upperlimbs was normal, the tendon reflex was depressed, the proximal muscle strength was grade Ⅲ-Ⅴ, and the distal muscle strength was grade Ⅴ. The muscle tone of both lower extremities was reduced and the tendon reflex was absent. The proximal muscle strength was grade Ⅱ-Ⅳ and the distal muscle strength was grade Ⅲ-Ⅴ. No dysphagia or respiratory muscle involvement was found. Muscle biopsies were performed in 7 of the 11 patients, the pathological changes were muscle fibers of different sizes, circular atrophic muscle fibers and compensatory hypertrophic fibers, and occasionally denatured and necrotic muscle fibers were found. Different degrees of rod aggregation could be seen in all the 7 patients. Electron microscopic examination of 5 patients showed that there was rod aggregation between myofibrils, and most of them were located near the Z band, but no intranuclear rod was found. NEB gene was found in all 11 patients, and a total of 9 different mutation sites were detected, including 8 in exon region and 1 in intron region. Among them, c.21522+3A>G was found in 10 cases, c.1623delT was found in 3 cases and c.17611C>T was found in 3 cases. There was 1 case of c.4417C>T, c.2549delA, c.21065dupA, c.3520G>A, c.20943G>A, c.192G>A respectively.Conclusions:The clinical phenotype of nemaline myopathy caused by NEB gene has great heterogeneity. Muscle pathology shows that rod aggregation is an important basis for the diagnosis of this disease. Mutation c.21522+3A>G in intron is the most common mutation in this group of NEB gene. And the novel mutation sites of NEB gene are respectively c.17611C>T, c.2549delA, c.3520G>A, c.21065dupA, c.20943G>A and c.192G>A.

目的 分析急性前循环缺血性脑卒中(AIS)合并糖尿病患者血糖漂移与其美国国立卫生研究院卒中量表(NIHSS)评分的关联性.方法 选取2018年3月至2021年2月我院63例前循环AIS合并糖尿病患者(观察组),并选取同期糖尿病患者57例(对照1组)、健康体检者71名(对照2组),使用动态血糖监测系统监测其血糖波动水平[空腹血糖(FBG)、平均血糖、空腹胰岛素(Fins)、血糖波动频数、最大血糖波动幅度(LAGE)、平均血糖波动幅度(MAGE)],并比较降糖治疗前及治疗1个月后观察组患者NIHSS评分,同时了解血糖漂移与NIHSS评分的关联性.结果 3组间血糖波动频数对比,差异无统计学意义(P>0.05),而3组间FBG、平均血糖、Fins、LAGE、MAGE对比,差异具有统计学意义,同时,观察组FBG、平均血糖、LAGE、MAGE>对照1组>对照2组(P<0.05);观察组患者治疗前、治疗1个月后NIHSS评分对比,差异具有统计学意义(P<0.05);且相关性分析发现,观察组患者血糖漂移与治疗前、治疗1个月后NIHSS评分具有相关性(P<0.05),其中,MAGE、LAGE均与治疗前、治疗1个月后NIHSS评分呈正相关(P<0.05).结论 前循环AIS合并糖尿病患者血糖漂移与NIHSS评分紧密相关,因此,临床在治疗过程中不仅要关注血糖控制情况,还应重视控制血糖波动幅度.

目的 探讨伴骨骼肌损害的嗜酸性肌筋膜炎的临床特点及病理改变.方法 对5例伴骨骼肌损害的嗜酸性肌筋膜炎的临床特征及组织病理学进行回顾性分析,采用免疫组化EnVision法检测淋巴细胞CD4、CD8、CD20和CD68的表达,并复习相关文献.结果 5例患者临床主要表现为不同程度的肢体肿胀,肌肉疼痛无力,均以肢体远端为主.其中4例患者局部皮肤有色素沉着和橘皮样改变,3例出现双手握拳困难,呈"空心拳"征.肌电图检查肌源性损害4例,血清肌酸激酶升高3例.5例患者骨骼肌和筋膜组织病理活检:均可见不同程度的肌筋膜增厚和小血管增多,并伴有炎性细胞浸润.在与深筋膜相邻的骨骼肌组织中可见部分肌纤维变性坏死,伴炎性细胞浸润.免疫组化提示炎性细胞主要为CD8+和CD68+淋巴细胞浸润.结论 嗜酸性肌筋膜炎可累及相邻的骨骼肌组织引起肢体远端无力,肌肉和筋膜组织活检是确诊的重要手段.

目的 探讨杆状体肌病的临床特点、肌肉MRI改变和基因突变.方法 回顾性分析1例NEB基因新复合杂合突变致儿童型杆状体肌病患者的临床资料.结果 本例患者为男性,6岁发病,以双下肢远端无力起病,逐渐向近端发展,14岁行肌肉活检在肌纤维内发现大量杆状体而被确诊,29岁复诊时做基因检测明确为NEB基因突变.双下肢肌肉MRI提示双侧股外侧肌、股中间肌、大收肌萎缩并脂肪变性.双侧比目鱼肌脂肪变性并萎缩,腓肠肌内侧头和胫前肌水肿.与文献报道不同的是本例患者双下肢远端无力明显重于近端,且发病23年仍未累及颈肌和上肢肌肉.基因检测发现NEB基因有两处杂合突变,c.2549delA发生移码变异,c.21522+3A>G发生点突变,家系验证结果显示这两处杂合突变分别来自其父亲和母亲.目前文献报道NEB基因已发现有312种突变,本例发生在第27号外显子上的c.2549delA突变,在人类基因数据库和HGMDpro数据库中亦均未见有报道,为新发现的突变位点.结论 杆状体肌病临床表型异质性较大,肌肉病理和基因检测是诊断的重要依据,c.2549delA为NEB基因新发的突变位点.

线粒体神经胃肠型脑肌病(mitochondrial neurogastroint-estinal encephalomyopathy,MNGIE)是一种罕见的常染色体隐性遗传的多系统疾病,由于核基因TYMP突变导致胸苷磷酸化酶(thymidine phosphorylase,TP)缺陷所致[1].TP的活性降低或缺失,可导致脱氧胸苷和脱氧尿嘧啶核苷在组织中的蓄积,引起线粒体功能的异常,从而导致患者出现多系统受累的临床症状.MNGIE典型的临床症状包括严重的胃肠动力障碍、脑白质病变、眼外肌麻痹、周围神经病变和肌肉萎缩[2].自2012年许二赫等首次在国内报道了该病以来[3],目前国内约有13例MNGIE的相关报道[4-8].本文报告1例经肌肉病理与基因检测共同确诊的MNGIE患者,与以往文献报道不同的是本例患者的脑影像不仅有脑白质病变,而且有双侧基底节区和小脑齿状核病变.基因检测发现TYMP基因在7号和10号外显子区域分别有c.914T＞C和c.1319T＞C两处新发的错义突变,扩展了TYMP基因的变异谱系.

目的:研究神经导向因子Slit2及其受体Robo1在大鼠脑梗死模型和尤瑞克林干预后的缺血脑组织中的表达变化.方法:54只雄性SD大鼠随机分为假手术组、模型组和尤瑞克林组,再随机分为梗死后缺血1 d、3 d、7 d三个亚组,每组各6只.采用线栓法制备大鼠永久性大脑中动脉缺血(permanent middle cerebral artery occlusion,pMCAO)模型.尤瑞克林组给予尤瑞克林尾静脉注射,模型组给予等体积生理盐水.应用Western-blot方法检测不同时间点Slit2蛋白和内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOS)在缺血脑组织中的表达情况;RT-PCR方法检测不同时间点Robo1 mRNA的表达情况.结果:与假手术组相比,模型组和尤瑞克林组Slit2蛋白和eNOS蛋白的表达在各时间点均明显增高;尤瑞克林组与模型组相比,两蛋白在各时间点均呈现高表达,差异有统计学意义(P<0.05).且Slit2蛋白和eNOS蛋白的表达变化呈显著正相关(P<0.01).Robo1在模型组和尤瑞克林组中表达较假手术组早期明显降低,在3 d开始上升,呈升高趋势,7 d仍未达到假手术组大鼠的表达水平(P<0.05).结论:局灶性脑梗死后大鼠Slit2蛋白表达升高,且Slit2可能参与大鼠脑梗死后血管新生过程,尤瑞克林可能通过升高Slit2/Robo1促进大鼠脑梗死后的血管新生过程.

目的 探讨伴有肌纤维坏死的脂质沉积性肌病患者的骨骼肌病理改变及其临床特点.方法 回顾性分析8例伴有肌纤维坏死的脂质沉积性肌病患者的肌肉组织病理改变和临床特点.结果 8例患者中上肢近端肌力3级以下者4例(其中2例伴呼吸肌受累),下肢近端肌力3级以下者6例;8例均伴有颈伸肌无力;8例患者除肌纤维内大量脂质沉积外,均伴有不同程度肌纤维变性坏死,其中5例偶见变性坏死肌纤维,坏死肌纤维比率0.1％～0.9％,病程较长且年龄偏大,有反复出现肌无力的病史;3例可见较多变性坏死纤维,坏死肌纤维比率＞1.0％,病程较短、进展迅速且较年轻,其中2例免疫组织化学结果显示CD4(一)、CD8(一)、CD20(--)、CD68(+);3例基因检测显示ETFDH基因突变.结论 部分脂质沉积性肌病患者的肌肉病理中可见变性坏死肌纤维,伴有明显肌纤维坏死者临床症状较重,病情进展较快.

目的:探究阿尔茨海默病患者海马代谢的磁共振波谱的分布规律以及特点,为临床诊断提供重要的参考依据.方法:采用对比实验方法,以20例阿尔茨海默病患者作为实验组患者,选取同期年龄性别等基本相似的20例健康人作为对照组,对两组研究对象的智力状况、认知能力等进行简单的评定,同时采用核磁共振波普成像检查技术和方法对两组研究对象的核磁波谱分布状况和规律进行对比和分析.结果:两组智力状况、认知能力、海马区核磁共振谱的各项指标存在显著差异(P<0.05).结论:阿尔茨海默病患者海马区的图谱明显与健康研究对象有明显的差别,这临床诊断提供了有效的证据,具有重要的价值和意义.