12 例多系统萎缩患者的临床特点和诊断分析

目的:研究12例多系统萎缩(multiple system atrophy MSA)患者的临床特点,分析诊断要点。方法:回顾性分析12例多系统萎缩病例,探讨其临床特点和早期诊断的要点。结果:本组病例均为慢性、隐袭性起病,男性居多,男:女=1.4:1。平均发病年龄49.2岁(35.0岁～72.0岁)。平均病程33个月(6个月～60个月)。MSA-P亚型4例,MSA-C亚型8例,以MSA-C亚型占优势。MSA-P亚型中以行动迟缓为主要首发表现(75%),主要体征分别为肌张力增高(100%)、直立性低血压(75%)、锥体束征(75%);MSA-C亚型以行走不稳为主要首发表现(62.5%),主要体征为共济失调(100%),直立性低血压、小脑性语言、锥体束征(分别为62.5%)。结论:多系统萎缩是一种散发性的神经系统变性疾病,成年起病,临床表现多样。对于早期单纯以帕金森综合征、小脑功能障碍或自主神经功能紊乱为主要症状的患者,特别是无家族史者,要注意甄别有无其他系统受累的症状或体征,同时结合影像学检查、左旋多巴类药物治疗反应性等临床特点,对于早期正确诊断MSA有一定帮助。     

85例多系统萎缩患者预后影响因素的分析

目的:探讨多系统萎缩(multiple system atrophy,MSA)患者预后的影响因素。方法:连续收集2016年1月到2019年1月空军军医大学第一附属医院神经内科住院及门诊收治的85名临床确诊MSA患者的临床资料,每隔6月对患者进行随访记录,直至需辅助行走时间,研究时限3.5年,筛选10个可能影响MSA独立行走的危险因素,应用Cox比例风险回归模型进行单因素及多因素回归分析。结果:85例MSA患者中,很可能MSA38例(44.7%),可能MSA47例(55.3%),以帕金森表现(MSA-P)43例(50.6%),以小脑性共济失调表现(MSA-C)42例(49.4%),男性46例(54.1%),女性39例(45.9%),起病年龄54.7±8.8岁,首发运动症状30例(35.3%),首发非运动症状55例(64.7%)。起病至非运动症状合并运动症状中位时程27.9(11.5, 40.5)月。截至本研究终止,28例(32.9%)患者独立行走,57例(67.1%)患者不能独立行走,起病至辅助行走中位时程36.0(22.5, 54.0)月。Cox比例风险回归模型显示起病年龄大(HR=1.041, 95%CI 1.000-1.083, P=0.049)、HY高分期(HR=2.015,95%CI 1.031-3.938,P=0.040)、起病至非运动症状合并运动症状短时程(HR=0.980,95%CI 0.967-0.993, P=0.003)是MSA患者发展至辅助行走状态的危险因素。结论:起病年龄大、HY高分期、起病至非运动症状合并运动症状短时程是MSA患者辅助行走的不良预后因素。     

多层螺旋计算机断层扫描联合磁共振成像对早期中央型肺癌及术后复发的诊断价值

目的:探讨多层螺旋计算机断层扫描(MSCT)联合磁共振成像(MRI)对早期中央型肺癌及术后复发的诊断价值。方法:选取2015年8月到2017年2月我院收治的早期中央型肺癌患者98例,所有患者均经MSCT和MRI检查。分析并对比单独MSCT的诊断结果及MSCT联合MRI的诊断结果。随访1年,观察并比较疑似复发的患者单独MSCT的诊断结果及MSCT联合MRI的诊断结果,并比较其对复发诊断的灵敏度、特异度。结果:MSCT联合MRI对早期中央型肺癌诊断的准确率、误诊率、漏诊率分别为94.90%、1.02%、4.08%,与单独MSCT诊断的82.65%、9.18%、8.16%比较,MSCT联合MRI诊断的准确率明显升高,误诊率明显降低(P0.05),而两种诊断方法的漏诊率比较差异无统计学意义(P0.05)。随访1年后,98例患者共复查122例次,共有49例复发。MSCT联合MRI诊断早期中央型肺癌患者术后复发的灵敏度、特异度分别为97.96%、93.15%,均高于单独MSCT诊断的83.67%、82.19%(P0.05)。结论:MSCT联合MRI诊断早期中央型肺癌准确率较高,且在诊断术后复发中可提高灵敏度、特异度。     

CT灌注、MR灌注和DWI成像综合应用在肝脏疾病的诊断价值

目的:探讨CT、MR几种功能成像(包括CT灌注、MR灌注和DWI成像)综合应用在肝脏疾病的诊断价值。方法:37例常规CT和/或MR诊断信心不足的患者,补充进行了DWI成像、CT和MR灌注成像以辅助诊断。其中,18例为肝癌术后或TACE、RFA、PEI等方法治疗后,对肝脏复发或原病灶治疗后活性情况的判断;7例为对肝内多发病灶的检出及诊断;4例肝脓肿;肝腺瘤3例,FNH5例。结果:37例患者在结合了功能成像后做出的综合影像诊断,较单纯常规CT和/或MR扫描,诊断准确率和病灶检出率均有提高。7例肝癌术后患者,常规平扫及增强扫描对术区是否有有活性的肿瘤残存还是局部复发诊断困难,DWI成像诊断为术后的炎性增生或肝脏局限性灌注异常。后患者经随访3-6个月,一般状况和生化指标无明显异常,且影像表现基本无变化。11例原发性肝癌TACE、RFA、PEI等方法治疗后的患者,CT和/或MR常规平扫及增强扫描可疑病灶仍有部分活性区但不能确定,加扫了DWI成像,其中的7例进行了MR灌注成像,6例进行了CT灌注成像。经ADC值以及灌注值的评估,病灶坏死区和残留活性区的区分更加明确。7例肝内多发病灶的患者,DWI图像较MR常规扫描检出病灶数目多且病灶显示更为清晰;4例肝脓肿、3例肝腺瘤,5例FNH患者常规CT/MR表现不典型,未能明确良恶性诊断,经DWI和灌注扫描均获明确定性,3例肝脓肿经超声导引下肝穿刺证实,2例肝腺瘤和3例FNH经受术证实,其余病例经临床及影像随访证实。结论:功能成像作为常规扫描的有益补充,其诊断价值不容忽视,可以提高病灶检出率和诊断准确率。     

MRI多序列扫描在肝细胞癌诊断和微血管侵犯评估中的应用价值

摘要 目的：探讨磁共振（MRI）多序列扫描在肝细胞癌（HCC）诊断和微血管侵犯（MVI）评估中的应用价值。方法：回顾性选取2019年10月-2022年10月在本院收治的疑似100例HCC患者临床资料,均已完善MRI多序列扫描检查和病理检查,以病理检查为金标准,利用Kappa检验分析MRI多序列扫描在肝细胞癌诊断和微血管侵犯评估与病理检查的一致性。结果：100例患者经病理检测,有51例患者确诊为HCC（51.00%）,有49例患者为良性肝脏病变（49.00%）。51例HCC中存在MVI 17例（33.33%）。与病理结果比较,T2WI序列诊断HCC的敏感度为82.35%,特异度为79.59%,Kappa值为0.620,诊断MVI的敏感度为64.71%,特异度为85.29%,Kappa值为0.507;T1WI序列诊断HCC的敏感度为76.47%,特异度为81.63%,Kappa值为0.580,诊断MVI的敏感度为58.82%,特异度为88.24%,Kappa值为0.492;LAVA序列诊断HCC的敏感度为84.31%,特异度为83.67%,Kappa值为0.580,诊断MVI的敏感度为64.71%,特异度为91.18%,Kappa值为0.585;MRI多序列联合诊断HCC的敏感度为96.08%,特异度为79.59%,Kappa值为0.759,诊断MVI的敏感度为94.12%,特异度为82.35%,Kappa值为0.712。MRI多序列联合诊断HCC和MVI的敏感度均高于单独序列（P<0.05）。MVI阳性者肿瘤边缘形态不光滑型、有瘤周强化占比高于MVI阴性者（P<0.05）。结论：MRI多序列成像可有助于临床HCC诊断及MVI评估,具有较好的应用价值;肿瘤边缘形态不光滑、瘤周强化在预测HCC MVI方面有意义。     

瞬时受体电位通道蛋白在多功能性系统萎缩中的调控作用

多系统萎缩(multiple system atrophy,MSA)是一类神经系统退行性疾病,其病理特征是胶质细胞中出现含有不溶性α突触核蛋白(α-synuclein)的胞质包涵体.研究显示,α-synuclein在多系统萎缩的发病机制中有重要作用,但其毒性的分子机制目前还不清楚.本文在前期研究氧化应激条件下α-synuclein引起细胞内钙稳态失衡,提出了以氧化应激为连接的多系统萎缩中,胶质细胞死亡的新假说的基础上,深入分析了α-synuclein过表达导致U251细胞变性死亡的分子机制.首先证明过表达α-synuclein的U251细胞出现生长速度减慢、氧化应激水平增加和钙离子瞬时受体电位通道蛋白(transient receptor potential channel-1,TRPC1)表达量升高,而且细胞存活率的变化可通过下调TRPC1的表达得以恢复,说明TRPC1在α-synuclein过表达细胞死亡中发挥了重要作用;其次,研究发现α-synuclein稳转U251细胞中出现了明显的自噬水平增加和细胞凋亡的特征,表明α-synuclein通过作用于内质网钙泵以及细胞膜上的瞬时受体电位钙通道TRPC1,破坏了细胞内的钙稳态,进而影响自噬和凋亡,增加了U251细胞对于过氧化氢的敏感性,这可能是导致多系统萎缩病人脑内胶质细胞死亡的原因.     

积分系统参与MDS诊断的可行性研究

目的:骨髓增生异常综合征(MDS)是一种起源于造血干细胞,以高风险向急性髓系白血病转化为特点的难治性血细胞质、量异常的异质性疾病。对不明原因血细胞减少或者有巨幼红细胞血症的老年人,如果得不到明确的诊断就不会获得有效的治疗。探讨对伴有不明原因血细胞减少或大红细胞血症患者采用一种积分系统来预测诊断为骨髓增生异常综合征(MDS)的可行性。方法:应用四个因子即年龄≥65,红细胞平均体积(MCV),红细胞分布宽度(RDW),和乳酸脱氢酶(LDH)的一个积分系统来计算诊断MDS的概率。结果:调查了303个病人,他们都因为不明原因的血细胞减少或者大红细胞血症在过去三年(2010~2012)进行了骨髓检查,最终三分之二患者被诊断为MDS,9%为疑似MDS,采用积分系统前后的MDS诊断率分别为12%和48%。结论:此四个因子的积分系统可以用于指导MDS患者的诊断。提高MDS的诊断率,减少不必要的骨髓穿刺,减轻病人的疼痛和医疗费用。     

3.0T磁共振多序列成像对鉴别胰头癌与胰头肿块型慢性胰腺炎的应用价值

目的：探讨磁共振多序列成像对鉴别胰头癌与胰头肿块型慢性胰腺炎的临床价值及意义。方法：对已确诊的16例胰头癌患者和5例胰头肿块型慢性胰腺炎患者的磁共振多序列成像MR进行回顾性分析。主要征象包括：①肿块信号及形态学特点;②胰管及胆管扩张情况;③动态增强的特征;④胰周及大血管受累情况;⑤邻近器官受累与淋巴结肿大情况。检查方法包括：平扫T1WI＋FST2WI＋FS,MRCP,3D—VIBE动态增强扫描。结果：1）肿块形态信号异常：胰头癌与胰头肿块型胰头慢性胰腺炎的信号有较多重叠,在TlwI上均表现为相对低信号,T2WI表现为不均匀稍高、相等或低信号。2）胰管与胆管的异常：胰头癌表现为胰管扩张至肿块处突然截断12例,胆总管突然截断10例,“双管征”10例。胰头肿块型慢性胰腺炎胰管扩张3例,2例为串珠样扩张,扩张的胰管可贯通病灶区,胆总管5例均扩张,远端呈短锥形狭窄3例,鼠尾样狭窄2例。3）3D—VIBE强化特征分析结果：随着时间的延长胰头癌强化程度和强化百分率较胰头肿块型慢性胰腺炎明显减低。4）胰周大血管受累情况：胰头癌肿块与血管分界不清者8例,部分包绕血管6例完全包绕血管6例;胰头肿块型慢性胰腺炎1例与血管分界不清,1例部分被包绕。5）邻近器官受累与淋巴结肿大情况：胰头癌有7例淋巴结肿大主要分布在胰周及腹主动脉旁,胰头肿块型慢性胰腺炎,未见明显肿大淋巴结,有四例肾周筋膜增厚,两例肾前筋膜增厚。结论：磁共振多序列成像的联合使用及征象分析,有助于鉴别胰头癌与胰头肿块型慢性胰腺炎。     

红壤旱地多熟种植系统的综合效益评价

采用加权灰色关联聚类分析的方法,按生态效益、经济效益和社会效益的各项指标,对1984～2004年在江西农业大学农学试验站红壤旱地上进行的多元多熟种植系统定位对比试验中筛选出的23种多熟种植系统的综合效益进行了定量分析和聚类评价。结果表明：“白菜／马铃薯／玉米-芝麻”关联度值最大,灰色聚类为优;生态、经济、社会效益最高,明显优于其他种植系统。适合于大面积推广,是红壤旱地增产、增收、增效和维持农业可持续发展的优化模式;“油菜｜｜紫云英／玉米／玉米｜｜绿豆”次之。适合在劳动力相对充足的城郊红壤旱作区推广,以上两种种植模式对今后红壤旱作区种植业结构布局的调整和种植模式的优化具有积极意义。     

对早期多器官功能障碍综合征合并急性肾损伤患者行高容量血液滤过的疗效

目的:探讨合并有急性肾损伤(AKI)的多器官功能障碍综合征(MODS)患者早期行高容量血液滤过(HVHF)治疗后对器官保护作用.方法:选择重症监护室于2008年6-2012年1月收治的MODS合并AKI并接受HVHF治疗的患者86例作为研究对象.根据RIFLE分级分为Risk组10例,Injury组17例,Failure组59例.记录患者HVHF治疗前后血肌酐(SCr)、氧合指数(PaO2/FiO2)、血管外肺水指数(EVLWI)、动脉血乳酸(Lac)、凝血酶原时间(PT)、天冬氨酸转氨酶(AST)、急性生理学与慢性健康状况评分系统Ⅱ (APACHE Ⅱ)评分以及28天存活率.结果:HVHF治疗后,Failure组SCr、EVLWI、Lac、PT、AST、APACHEⅡ评分均显著高于Risk组和Injury组,PaO2/FiO2显著低于Risk组和Injury组,差异有统计学意义(P＜0.05).Risk组和Injury组在HVHF治疗后各指标差异均无统计学意义(P＞0.05).Risk组28天存活率为60.0％,Injury组64.71％,Failure组存活率为66.10％,3组间差异均无统计学意义(P＞0.05).结论:早期HVHF治疗对MODS合并AKI患者的器官具有保护作用,值得临床进一步研究.     

Reduction of Noradrenaline in Cerebellum of Patients with Olivopontocerebellar Atrophy

Noradrenaline (NA) was measured in postmortem cerebellar cortex of 15 patients with dominantly inherited olivopontocerebellar atrophy (OPCA). The mean cerebellar cortical NA level was significantly reduced (by 40%) in OPCA as compared with control values. The NA deficit most likely reflects a degeneration of the locus caeruleus noradrenergic system that is known to occur in some patients with OPCA. The relationship between the altered cerebellar NA levels and the clinical symptomatology of OPCA remains to be determined.     

Elevated Stimulatory and Reduced Inhibitory G Protein α Subunits in Cerebellar Cortex of Patients with Dominantly Inherited Olivopontocerebellar Atrophy

Abstract: Although guanine nucleotide binding proteins (G proteins) are one of the critical components of signal transduction units for various membrane receptor-mediated responses, little information is available regarding their status in brain of patients with neurodegenerative illnesses. We measured the immunoreactivity of G protein subunits (G_sα, G_iα, G_oα, G_q/11α, and Gβ) in autopsied cerebellar and cerebral cortices of 10 end-stage patients with dominantly inherited olivopontocerebellar atrophy (OPCA) who all had severe loss of Purkinje cell neurons and climbing fiber afferents in cerebellar cortex. Compared with the controls, the long-form G_sα (52-kDa species) immunoreactivity was significantly elevated by 52% (p < 0.01) in the cerebellar cortex of the OPCA patients, whereas the G_i1α concentration was reduced by 35% (p < 0.02). No statistically significant differences were observed for G_oα, G_i2α, G_β1, G_β2, or G_q/11α in cerebellar cortex or for any G protein subunit in the two examined cerebral cortical subdivisions (frontal and occipital). The cerebellar G_sα elevation could represent a compensatory response (e.g., sprouting, reactive synaptogenesis) by the remaining cerebellar neurons (granule cells?) to neuronal damage but also might contribute to the degenerative process, as suggested by the ability of G_sα, in some experimental preparations, to promote calcium flux. Further studies will be required to determine the actual functional consequences of the G protein changes in OPCA and whether the elevated G_sα is specific to OPCA cerebellum, because of its unique cellular pattern of morphological damage, or is found in brain of patients with other progressive neurodegenerative disorders.     

Benzodiazepine Receptor Binding in Cerebellar Cortex: Observations in Olivopontocerebellar Atrophy

Benzodiazepine receptor binding was measured in cerebellar cortex of 15 patients with dominantly inherited olivopontocerebellar atrophy (OPCA). The majority of these patients had a moderate to marked Purkinje cell loss, as judged by the lowered levels of dentate nucleus gamma-aminobutyric acid (GABA), a marker of Purkinje cells. Despite the reduction in Purkinje cell number cerebellar cortical benzodiazepine receptor density was either normal or slightly elevated in the OPCA patients. These results are in contrast to the findings in a mutant strain of mice deficient in Purkinje cells in which the concentration of benzodiazepine receptors in cerebellum is greatly reduced. Our data indicate that in the human, cerebellar cortical benzodiazepine receptors are either not significantly associated with Purkinje cells or that in OPCA Purkinje cell loss triggers a de novo synthesis of extra benzodiazepine binding sites. It is concluded that, in contrast with the rodent, in the human benzodiazepine receptor binding may not serve as a marker for cerebellar Purkinje cells.     

Crystal Structure of a Bioactive Pactamycin Analog Bound to the 30S Ribosomal Subunit

Biosynthetically and chemically derived analogs of the antibiotic pactamycin and de-6-methylsalicylyl (MSA)-pactamycin have attracted recent interest as potential antiprotozoal and antitumor drugs. Here, we report a 3.1-Å crystal structure of de-6-MSA-pactamycin bound to its target site on the Thermus thermophilus 30S ribosomal subunit. Although de-6-MSA-pactamycin lacks the MSA moiety, it shares the same binding site as pactamycin and induces a displacement of nucleic acid template bound at the E-site of the 30S. The structure highlights unique interactions between this pactamycin analog and the ribosome, which paves the way for therapeutic development of related compounds.     

Consensus Protein Design without Phylogenetic Bias

Consensus design is an appealing strategy for the stabilization of proteins. It exploits amino acid conservation in sets of homologous proteins to identify likely beneficial mutations. Nevertheless, its success depends on the phylogenetic diversity of the sequence set available. Here, we show that randomization of a single protein represents a reliable alternative source of sequence diversity that is essentially free of phylogenetic bias. A small number of functional protein sequences selected from binary-patterned libraries suffice as input for the consensus design of active enzymes that are easier to produce and substantially more stable than individual members of the starting data set. Although catalytic activity correlates less consistently with sequence conservation in these extensively randomized proteins, less extreme mutagenesis strategies might be adopted in practice to augment stability while maintaining function.     

Computational and Experimental Evidence for the Evolution of a (βα)8-Barrel Protein from an Ancestral Quarter-Barrel Stabilised by Disulfide Bonds

The evolution of the prototypical (βα)₈-barrel protein imidazole glycerol phosphate synthase (HisF) was studied by complementary computational and experimental approaches. The 4-fold symmetry of HisF suggested that its constituting (βα)₂ quarter-barrels have a common evolutionary origin. This conclusion was supported by the computational reconstruction of the HisF sequence of the last common ancestor, which showed that its quarter-barrels were more similar to each other than are those of extant HisF proteins. A comprehensive sequence analysis identified HisF-N1 [corresponding to (βα)_1-2] as the slowest evolving quarter-barrel. This finding indicated that it is the closest relative of the common (βα)₂ predecessor, which must have been a stable and presumably tetrameric protein. In accordance with this prediction, a recombinantly produced HisF-N1 protein was properly folded and formed a tetramer being stabilised by disulfide bonds. The introduction of a disulfide bond in HisF-C1 [corresponding to (βα)_5-6] also resulted in the formation of a stable tetramer. The fusion of two identical HisF-N1 quarter-barrels yielded the stable dimeric half-barrel HisF-N1N1. Our findings suggest a two-step evolutionary pathway in which a HisF-N1-like predecessor was duplicated and fused twice to yield HisF. Most likely, the (βα)₂ quarter-barrel and (βα)₄ half-barrel intermediates on this pathway were stabilised by disulfide bonds that became dispensable upon consolidation of the (βα)₈-barrel.     

Structural brain imaging in frontotemporal dementia

Frontotemporal dementia (FTD) is the second commonest young-onset neurodegenerative dementia. The canonical clinical syndromes are a behavioural variant (bvFTD) and two language variants (progressive nonfluent aphasia, PNFA, and semantic dementia, SD) although there is overlap with motor neurone disease and the atypical parkinsonian disorders corticobasal syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). Characteristic patterns of atrophy or hypometabolism are described in each of the variants but in reality imaging studies are rather heterogeneous. This review attempts to address four key questions in the neuroimaging of FTD: 1) what are the early imaging features of the different FTD syndromes (and how do these change as the disease progresses); 2) what do studies of presymptomatic genetic cases of FTD tell us about the very early stages of the disease; 3) can neuroimaging help to differentiate the different FTD syndromes; and 4) can neuroimaging help to differentiate FTD from other neurodegenerative diseases? This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Brain Atrophy in a Murine Model of Chronic Fatigue Syndrome and Beneficial Effect of Hochu-ekki-to (TJ-41)

Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of chronic fatigue sydrome (CFS) and neuron apoptosis. Nevertheless, no study has been performed directly to explore the relationship between CFS, BDNF and neuron apoptosis. We induced a CFS model by six injections of killed Brucella abortus antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running activity, body weight (BW), ratio of cerebral weight to BW (CW/BW) and expression levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily activity and CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA expression levels in the hippocampus were suppressed in the CFS model and TJ-41 treated mice, while no significant difference was found between them. We improved a murine model to investigate the relationship between CFS and brain dysfunction. In this model, reduced daily activity might have been associated with decreased hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41 increased the daily running activity of the model, which was independent of brain recovery.