Crim1KST264/KST264 mice display a disruption of the Crim1 gene resulting in perinatal lethality with defects in multiple organ systems.

Crim1 is a transmembrane protein, containing six vWF-C type cysteine-rich repeats, that tethers growth factors to the cell surface. A mouse line, KST264, generated in a LacZ insertion mutagenesis gene-trap screen, was examined to elucidate Crim1 function in development. We showed that Crim1(KST264/KST264) mice were not null for Crim1 due to the production of a shortened protein isoform. These mice are likely to represent an effective hypomorph or a dominant-negative for Crim1. Transgene expression recapitulated known Crim1 expression in lens, brain, and limb, but also revealed expression in the smooth muscle cells of the developing heart and renal vasculature, developing cartilage, mature ovary and detrusor of the bladder. Transgene expression was also observed in glomerular epithelial cells, podocytes, mesangial cells, and urothelium in the kidney. Crim1(KST264/KST264) mice displayed perinatal lethality, syndactyly, eye, and kidney abnormalities. The severe and complex phenotype observed in Crim1(KST264/KST264) mice highlights the importance of Crim1 in numerous aspects of organogenesis.     

Reduced dynamic functional connectivity between salience and executive brain networks in insomnia disorder

Research into insomnia disorder has pointed to large‐scale brain network dysfunctions. Dynamic functional connectivity is instrumental to cognitive functions but has not been investigated in insomnia disorder. This study assessed between‐network functional connectivity strength and variability in patients with insomnia disorder as compared with matched controls without sleep complaints. Twelve‐minute resting‐state functional magnetic resonance images and T1‐weighed images were acquired in 65 people diagnosed with insomnia disorder (21–69 years, 48 female) and 65 matched controls without sleep complaints (22–70 years, 42 female). Pairwise correlations between the activity time series of 14 resting‐state networks and temporal variability of the correlations were compared between cases and controls. After false discovery rate correction for multiple comparisons, people with insomnia disorder and controls did not differ significantly in terms of mean between‐network functional connectivity strength; people with insomnia disorder did, however, show less functional connectivity variability between the anterior salience network and the left executive‐control network. The finding suggests less flexible interactions between the networks during the resting state in people with insomnia disorder.     

MRI征象鉴别IDH-1突变型与野生型较低级别胶质瘤

目的:对比分析较低级别胶质瘤WHO Ⅱ～Ⅲ级异柠檬酸脱氢酶-1（IDH-1）突变型与野生型MRI征象。方法:回顾性分析手术及病理证实的69例较低级别胶质瘤患者的临床、MRI征象及分子病理资料,所有病例均行T1WI、T2WI、FLAIR及T1WI增强序列扫描。对肿瘤的发病性别、年龄、位置、病变数目、肿瘤直径、囊变坏死、肿瘤边界、出血、瘤周水肿、是否跨越中线、强化程度等征象及指标进行统计学分析。结果:较低级别胶质瘤IDH-1突变型与野生型在肿瘤位置方面差异具有统计学意义（P<0.05）,IDH-1突变型比野生型更好发于额叶;IDH-1突变型强化程度为轻度强化、中度强化、重度强化分别占比83%、14%、3%,野生型分别占比41%、44%、15%,差异具有统计学意义（P<0.05）;IDH-1突变型坏死最大径大于野生型,差异具有统计学意义（P<0.05）。两组间患者发病年龄及性别、病变个数、肿瘤边界、是否跨越中线、有无出血、水肿最大径、囊变最大径、坏死最大径等差异无统计学意义（P>0.05）。结论:较低级别胶质瘤的位置、强化程度、坏死最大直径对于术前评估IDH-1的突变状态具有重要价值。     

SGK1抑制剂EMD638683对膀胱出口梗阻小鼠肾组织细胞焦亡的作用及机制研究

目的:确定小鼠膀胱出口梗阻(bladder outlet obstruction,BOO)模型引起下尿路梗阻介导的肾脏炎性损伤;研究血清和糖皮质激素调节激酶1(serum and glucocorticoid-regulated kinase 1, SGK1)抑制剂EMD638683抗梗阻性肾病炎症的作用机制,探讨SGK1与NLRP3-caspase-1-IL-1β/细胞焦亡(pyroptosis)通路诱导细胞损伤的关系。方法:构建小鼠BOO模型,HE染色观察肾组织病理变化及炎症细胞浸润,PAS染色观察肾脏的组织病变,Masson染色法检测肾小管的胶原沉积,免疫组化法和Western blot法检测NLRP3、caspase-1、F4/80、gasdermin D-N末端片段(GSDMD-N)、IL-1β和SGK1的表达。醛固酮(aldosterone, ALD)处理小鼠肾小管上皮细胞(mouse renal tubular epithelial cells, mRTECs),EMD638683进行干预,Western blot法检测NLRP3、caspase-1、IL-1β、SGK1...     

强迫症患者脑岛功能连接异常磁共振成像研究

目的:探讨静息态下强迫症患者脑岛的功能连接特点。方法:纳入符合DSM-IV强迫症诊断标准的患者32例及性别、年龄、教育年限相匹配的正常对照37例,采用Y-BOCS量表评定强迫思维、强迫行为严重程度,应用3.0T磁共振成像系统进行静息态数据扫描。以双侧脑岛为感兴趣区(ROI)进行全脑功能连接(FC)分析,比较强迫症组与正常对照组之间的功能连接差异,并分析差异脑区功能连接强度与临床症状之间的关系。结果:与正常对照组相比,强迫症患者组的左侧脑岛与右侧缘上回、右侧顶下回、右侧顶上回的功能连接增强(FDR校正,P<0.01);右侧脑岛与右侧岛盖部额下回、左侧缘上回、右侧缘上回、右侧中央后回的功能连接增强(FDR校正,P<0.05);进一步分析发现,右侧脑岛与右侧中央后回的功能连接强度与强迫行为得分呈负相关(r=-0.35,P<0.05)。结论:强迫症患者脑岛的功能连接网络模式可能存在异常。     

正常脑老化中静息态功能磁共振成像功能连接的研究进展

【摘要】静息态功能磁共振成像（fMRI）作为一种不需要任务刺激就能呈现功能脑影像的技术手段,在临床上被广泛应 用。基于静息态fMRI的静息态功能连接（RSFC）,作为一种重要的计算机辅助分析法,能够度量不同脑区的脑功能连接 强度,对脑老化相关的神经科学领域的研究具有重要意义。本文介绍了功能连接的基本概念,总结了近年来脑老化相关 的人脑功能连接的研究成果,最后提出了该研究领域存在的问题及未来的研究方向。     

厌食儿童和正常儿童食物刺激下丘脑功能区fMRI的研究

为了研究小儿厌食症患者和正常儿童在食物刺激时下丘脑食欲中枢的兴奋情况,本论文搜集了10名厌食儿童、10名正常儿童在口服葡萄糖后下丘脑的功能性核磁共振(functional magnetic resonance imaging,fMRI)共35min的信号数据,并比较两组间功能区信号强度的差异。结果显示:所有受试者的下丘脑室旁核(PVN)、腹内侧核(VMH)及外侧区(LHA)在口服葡萄糖刺激后均出现了fMRI信号的激活,在厌食儿童下丘脑PVN及LHA此激活信号强度低于正常儿童,而VMH则高于正常儿童。本实验结果提示,下丘脑PVN、VMH及LHA功能的异常可能与小儿厌食症的发病密切相关。     

Altered cortical and subcortical local coherence in obstructive sleep apnea: a functional magnetic resonance imaging study

Obstructive sleep apnea (OSA) syndrome is the most common sleep‐related breathing disorder, characterized by excessive snoring and repetitive apneas and arousals, which leads to fragmented sleep and, most importantly, to intermittent nocturnal hypoxaemia during apneas. Considering previous studies about morphovolumetric alterations in sleep apnea, in this study we aimed to investigate for the first time the functional connectivity profile of OSA patients and age–gender–matched healthy controls, using resting‐state functional magnetic resonance imaging (fMRI). Twenty severe OSA patients (mean age 43.2 ± 8 years; mean apnea–hypopnea index, 36.3 h^?1) and 20 non‐apneic age–gender–body mass index (BMI)‐matched controls underwent fMRI and polysomnographic (PSG) registration, as well as mood and sleepiness evaluation. Cerebro‐cerebellar regional homogeneity (ReHo) values were calculated from fMRI acquisition, in order to identify pathology‐related alterations in the local coherence of low‐frequency signal (<0.1 Hz). Multivariate pattern classification was also performed using ReHo values as features. We found a significant pattern of cortical and subcortical abnormal local connectivity in OSA patients, suggesting an overall rearrangement of hemispheric connectivity balance, with a decrease of local coherence observed in right temporal, parietal and frontal lobe regions. Moreover, an increase in bilateral thalamic and somatosensory/motor cortices coherence have been found, a finding due possibly to an aberrant adaptation to incomplete sleep–wake transitions during nocturnal apneic episodes, induced by repetitive choke sensation and physical efforts attempting to restore breathing. Different hemispheric roles into sleep processes and a possible thalamus key role in OSA neurophysiopathology are intriguing issues that future studies should attempt to clarify.     

2D1H-MRS与PWI技术相结合在评价胶质瘤中的应用

目的探讨胶质瘤内含胆碱化合物(Cho),肌酸(Cr)、脂质(Lip)、乳酸(Lac)含量与肿瘤相对性脑血流容积(rCBV)间的相关性,间接评价胶质瘤细胞增殖、缺氧与坏死及血管生成情况。方法采用二维质子磁共振波谱分析技术(2D ~1H-MRS)与灌注成像技术(PWI),分别定量测量40例胶质瘤代谢物(Cho/Cr、Lac、Lip)与rCBV,并采用统计学分析探讨不同级别胶质瘤代谢物含量变化及代谢物含量与rCBV的相关性。结果经MRI影像诊断的40例胶质瘤术后病理证实为星形细胞瘤20例,间变性星形细胞瘤12例,胶质母细胞瘤8例。t检验表明,rCBV、Cho/Cr、Lip-Lac在低级别组(星形细胞瘤20例)和高级别组(包括间变性星形细胞瘤12例和胶质母细胞瘤8例)间均有非常显著的差异(t=3.29,p<0.01;t=6.73,p<0.01;t=28.9,p<0.01)。相关性分析表明,rCBV与Cho/Cr具有非常显著的正相关(r=0.635,p<0.01),rCBV与Lip-Lac具有显著正相关(r=0.554,p<0.05)。结论2D ~1H-MRS与PWI技术相结合可用于胶质瘤恶性度分级,对胶质瘤临床诊断和治疗方案选择具有一定的指导作用。     

Genetic and diagnostic considerations in three families with abnormalities of facial expression and congenital urinary obstruction: “The Ochoa syndrome”

Seven patients (4 females, and 3 males) born in unrelated families, one of them consanguineous (first cousins), were affected by peculiar facies and gestures while smiling and crying, and by hydronephrosis, hydroureter and intravesical stenosis of the ureter, abnormal caliber of the urether in the prostatic and membranous portions, urethral valves, abnormal bladder with trabeculation, and diverticula associated with severe hypertrophy of the mucosa with sclerotic changes. The genetic analysis of these families indicates that the condition is probably autosomal dominant, with variable expressivity and incomplete penetrance. The syndrome represents alteration of facial and urinary developmental fields. The peculiar facies allows early recognition of the condition, and this can be helpful for early assessment and treatment, leading perhaps to a better prognosis.     

Somatotopical relationships between cortical activity and reflex areas in reflexology: A functional magnetic resonance imaging study

We examined the somatotopical relationship between cortical activity and sensory stimulation of reflex areas in reflexology using functional magnetic resonance imaging. Three reflex areas on the left foot, relating to the eye, shoulder, and small intestine were stimulated during the experiment. A statistical analysis showed that reflexological stimulation of the foot reflex areas corresponding to the eye, shoulder, and small intestine activated not only the somatosensory areas corresponding to the foot, but also the somatosensory areas corresponding to the eye, shoulder, and small intestine or neighboring body parts. Thus, the findings showed that reflexological stimulation induced a somatosensory process corresponding to the stimulated reflex area and that a neuroimaging approach can be used to examine the basis of reflexology effects.     

Morphometric and functional connectivity changes in the brain of patients with obstructive sleep apnea: A meta‐analysis

Existing evidence for brain morphometric changes and functional connectivity alterations in patients with obstructive sleep apnea is mixed. The current study aimed to meta‐analyse the neuroimaging data, and thus synthesize a brain map showing locations with morphometric and functional connectivity differences between patients with obstructive sleep apnea and controls. Published studies to 2018 were retrieved and included into the analysis if they reported such between‐group differences using voxel‐based morphometry or resting‐state functional magnetic resonance imaging, and reported the results in the form of brain coordinates based on whole‐brain analysis. Twelve voxel‐based morphometry and seven resting‐state functional magnetic resonance imaging studies that comprised a total of 1,113 participants fulfilled the inclusion criteria. Compared with healthy controls, patients with obstructive sleep apnea had reduced resting‐state connectivity in the right anterior cingulate and larger grey matter volume in the right insula. Patients with obstructive sleep apnea do have morphometric and resting‐state connectivity alterations in the brain. These neural correlates may help explain the effects of obstructive sleep apnea on the emotion, cognition and quality of life of patients, and may be used in future for evaluating its treatment outcome.     

健康人大脑和小脑空间记忆认知功能的fMRI研究

本研究应用功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,检测了健康人大脑和小脑参与空间记忆的认知过程。通过对10名右利手健康志愿者进行一项短时空间记忆任务作业的同时进行脑功能磁共振扫描,实验采用组块设计,任务与对照任务交替进行,数据采用SPM99软件进行数据分析和脑功能区定位。结果显示:当统计阈值设定为P<0.0001时,大脑皮层和右侧小脑一起被显著激活;大脑皮层所激活的脑区有双侧顶叶的楔前叶、顶上小叶、缘上回(BA7/40,BA:Brodma-nn Area),双侧前额上、中、下回(BA6/9/47),双侧枕叶和枕颞交界处(BA18/19/37),右侧海马回;左侧中脑黑质及被盖部也被激活。上述结果提示:小脑和大脑皮层一起参与了空间记忆的认知过程。     

Combined diffusion weighting and CSF suppression in functional MRI

In this study, EPI pulse sequences with diffusion weighting for reduction of contributions from large vessels and inversion pulses in order to minimize the effects of CSF pulsations and CSF partial volume effects were developed for BOLD contrast investigations in functional MR imaging. One inversion recovery echo-planar imaging (IR-EPI) pulse sequence and one IR-EPI with additional diffusion weighting (DW-IR-EPI) were developed and compared to a standard gradient-echo EPI sequence in a cortical stimulation experiment in nine healthy volunteers. Stimulation of motor cortex was performed using a semi-complex finger-tapping paradigm in seven periods of alternating rest and stimulation. Comparison between the three pulse sequences was made by measuring the activated volume in each subject, as well as by calculating the relative signal increase during stimulation. Due to different baseline signal-to-noise levels in the images generated by the three pulse sequences, artificial noise was added so that the comparative investigation could be performed independently of the noise level. The activated volume was 128 +/- 73 pixels (mean +/- SD) using the standard EPI pulse sequence, 31 +/- 12 pixels using IR-EPI and 15 +/- 13 pixels when DW-IR-EPI was employed. The relative signal increase was 5.7 +/- 1.1% using standard EPI, 11.5 +/- 3.1% using IR-EPI and 9.9 +/- 2.4% using DW-IR-EPI. The activated volume obtained with the addition of extra noise, i.e. at equal S/N, was 70 +/- 50 pixels using the standard EPI, and when using IR-EPI, the activated volume was 28 +/- 13 pixels. At equal S/N, the signal increase was 7.3 +/- 1.4% using standard EPI and 12.0 +/- 3.6% using IR-EPI. In BOLD contrast imaging, a combination of diffusion weighting and inversion recovery appeared to reduce false activation caused by CSF pulsation and blood flow in large vessels.     

膝关节内侧半月板突出与后根部损伤相关性的MRI分析

背景：半月板根部损伤是半月板突出的重要原因。近年来,国外有许多关于半月板根部损伤和半月板突出关系的研究报道,而国内暂无相关的报道。 目的：探讨膝关节内侧半月板突出与内侧半月板后根部损伤的相关性。 方法：回顾性分析84例具有膝关节内侧半月板突出征象患者的MRI及关节镜表现,将半月板突出长度≥ 3 mm或半月板突出长度/半月板最大径≥10%定义为严重突出,采用卡方检验分析两种测量方法下的内侧半月板突出与后根部损伤之间的相关性。 结果与结论：MRI显示内侧半月板严重突出(半月板突出长度≥3 mm或半月板突出长度/半月板最大径≥10%)与关节镜检查显示半月板后根部损伤具有显著相关性(P < 0.05),比值比及95%可信区间分别为25.04 (3.07-204.44),6.96(1.38-35.19)。结果可见膝关节内侧半月板严重突出与内侧半月板后根部损伤密切相关,是半月板根部损伤的重要特征。     

Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21

A yeast artificial chromosome (YAC) transgenic murine model of partial trisomy 21 overexpressing five human genes—including DYRK1A, which encodes a serine threonine kinase involved in cell cycle control—has been shown to present an increase in brain weight. We analyzed this new phenotype by measuring total and regional brain volumes at different ages, using a 7 Tesla magnetic resonance imaging volumetric approach. Volumetric measurements showed a total volume increase of 13.6% in adult mice. Changes in brain morphogenesis were already visible at a very early postnatal stage (postnatal days 2–7). Region‐specific changes were characterized from postnatal day 15 to 5 months. These results, made it possible to define region‐specific effects of DYRK1A overexpression, with the strongest increase seen in the thalamus–hypothalamus area (24%). Anat Rec, 291:254–262, 2008. © 2008 Wiley‐Liss, Inc.     

Active site mutant dimethylarginine dimethylaminohydrolase 1 expression confers an intermediate tumour phenotype in C6 gliomas

Dimethylarginine dimethylaminohydrolase (DDAH) metabolizes the endogenous inhibitor of nitric oxide synthesis, asymmetric dimethylarginine (ADMA). Constitutive over-expression of DDAH1, the isoform primarily associated with neuronal nitric oxide synthase (nNOS) results in increased tumour growth and vascularization, and elevated VEGF secretion. To address whether DDAH1-mediated tumour growth is reliant upon the enzymatic activity of DDAH1, cell lines expressing an active site mutant of DDAH1 incapable of metabolizing ADMA were created. Xenografts derived from these cell lines grew significantly faster than those derived from control cells, yet not as fast as those over-expressing wild-type DDAH1. VEGF expression in DDAH1 mutant-expressing tumours did not differ from control tumours but was significantly lower than that of wild-type DDAH1-over-expressing tumours. Fluorescence microscopy for CD31 and pimonidazole adduct formation demonstrated that DDAH1 mutant-expressing tumours had a lower endothelial content and demonstrated less hypoxia, respectively, than wild-type DDAH1-expressing tumours. However, there was no difference in uptake of the perfusion marker Hoechst 33342. Non-invasive multiparametric quantitative MRI, including the measurement of native T(1) and T(2) relaxation times and apparent water diffusion coefficient, was indicative of higher cellularity in DDAH1-expressing xenografts, which was confirmed by histological quantification of necrosis. C6 xenografts expressing active site mutant DDAH1 displayed an intermediate phenotype between tumours over-expressing wild-type DDAH1 and control tumours. These data suggest that enhanced VEGF expression downstream of DDAH1 was dependent upon ADMA metabolism, but that the DDAH1-mediated increase in tumour growth was only partially dependent upon its enzymatic activity, and therefore must involve an as-yet unidentified mechanism. DDAH1 is an important mediator of tumour progression, but appears to have addition roles independent of its metabolism of ADMA, which need to be considered in therapeutic strategies targeted against the NO/DDAH pathway in cancer.     

Association between cervical lordotic curvature and cervical muscle cross‐sectional area in patients with loss of cervical lordosis

Disruption of the cervical lordotic curve can cause undesirable symptoms such as neck pain, and cord compression. The purpose of this study was to investigate the biomechanics of loss of cervical lordosis by measuring the cross‐sectional area (CSA) of the cervical muscles using magnetic resonance imaging (MRI), and to determine the relationship between cervical lordosis angle and cervical muscle status. The cervical lordosis angle was measured on standing lateral plain radiography using the posterior tangent technique in patients who complained of neck pain. The CSAs of the cervical flexor muscles including the longus cervicis and longus capitis, the cervical extensor muscles including the splenius capitis and semispinalis capitis, and the sternocleidomastoid muscle, were measured at the maximum levels by axial T1‐weighted MRI. We compared neck muscle CSAs between the two groups, the correlation with cervical lordosis angle, and muscle status including CSA and imbalance. The CSA of the semispinalis capitis was significantly lower in the loss of cervical lordosis group, and the ratio of cervical flexor to extensor was significantly different between the two groups (P < 0.05). Partial correlation analysis revealed that the cervical lordotic angle was significantly positively correlated with the ratio of flexor to extensor muscle CSAs (P < 0.05). There is a significant relationship between cervical muscle imbalance, including extensor muscle weakness, and loss of cervical lordosis. An exercise program focusing on cervical extensor muscle strengthening and restoring the balance of flexor and extensor muscles is recommended for patients with loss of cervical lordosis. Clin. Anat. 31:710–715, 2018. © 2018 Wiley Periodicals, Inc.