冠状动脉磁共振血管成像和CT对可疑冠心病患者心脏事件的预测价值的比较研究

摘要 目的：探讨与比较冠状动脉核磁共振(MR)血管成像和CT对可疑冠心病患者心脏事件的预测价值。方法：2018年4月到2020年10月选择在本院诊治的103例可疑冠心病患者作为研究对象,所有患者都给予冠状动脉MRI血管成像与64层螺旋CT冠状动脉成像检查,记录影像学特征。随访患者的预后并进行预测价值分析。结果：103例可疑冠心病患者随访到2021年4月1日,发生心血管不良终点事件23例(不良事件组),发生率为22.3%。不良事件组的MRI血管成像显示右冠状动脉血管长度与内径都低于非不良事件组(P<0.05)。不良事件组的CT显示斑块率、斑块性质等与非不良事件组对比差异有统计学意义(P<0.05),两组斑块位置对比差异无统计学意义(P>0.05)。多因素Cox回归分析显示斑块性质、斑块率、右冠状动脉血管长度与内径都为导致心血管不良终点事件的重要因素(P<0.05)。结论：冠状动脉MRI血管成像和CT都可有效预测可疑冠心病患者心脏事件发生情况,能满足临床诊断可疑冠心病与预测预后的要求。     

Real‐time functional optical‐resolution photoacoustic microscopy using high‐speed alternating illumination at 532 and 1064 nm

Optical‐resolution photoacoustic microscopy (OR‐PAM), which has been widely used and studied as a noninvasive and in vivo imaging technique, can yield high‐resolution and absorption contrast images. Recently, metallic nanoparticles and dyes, such as gold nanoparticles, methylene blue, and indocyanine green, have been used as contrast agents of OR‐PAM. This study demonstrates real‐time functional OR‐PAM images with high‐speed alternating illumination at 2 wavelengths. To generate 2 wavelengths, second harmonic generation at 532 nm with an LBO crystal and a pump wavelength of 1064 nm is applied at a pulse repetition rate of 300 kHz. For alternating illumination, an electro‐optical modulator is used as an optical switch. Therefore, the A‐line rate for the functional image is 150 kHz, which is half of the laser repetition rate. To enable fast signal processing and real‐time displays, parallel signal processing using a graphics processing unit (GPU) is performed. OR‐PAM images of the distribution of blood vessels and gold nanorods in a BALB/c‐nude mouse's ear can be simultaneously obtained with 500 × 500 pixels and real‐time display at 0.49 fps.      

3.0 T磁共振T2×mapping成像技术定量评估膝关节骨性关节炎的临床价值及与WOMAC评分的相关性分析

摘要 目的：研究3.0 T磁共振T2×mapping成像技术定量评估膝关节骨性关节炎（OA）的临床价值及与西安大略和麦克马斯特大学骨关节炎指数（WOMAC）评分的相关性。方法：将我院于2017年4月～2019年12月期间收治的膝关节OA患者80例纳入研究。根据K-L分级标准将膝关节OA患者分成轻度组（K-L分级为Ⅰ～Ⅱ级）32例,重度组（K-L分级为Ⅲ～Ⅴ级）48例。另取同期于我院进行体检的健康者30例作为对照组。所有受试者均接受3.0 T磁共振T2×mapping扫描,比较各组膝关节不同部位软骨T2值、WOMAC评分以及血清炎症因子水平,以Pearson相关性分析膝关节OA患者膝关节不同部位软骨T2值和WOMAC评分的关系。结果：重度组膝关节不同部位软骨T2值均高于轻度组以及对照组,且轻度组膝关节不同部位软骨T2值均高于对照组（均P＜0.05）。重度组各项WOMAC评分及总分均高于轻度组以及对照组,且轻度组各项WOMAC评分及总分均高于对照组（均P＜0.05）。经Pearson相关性分析发现：膝关节OA患者膝关节不同部位软骨T2值和各项WOMAC评分及总分均呈正相关（均P＜0.05）。重度组血清白介素-1β（IL-1β）、白介素-18（IL-18）、肿瘤坏死因子α（TNF-α）均高于轻度组以及对照组,且轻度组血清IL-1β、IL-18、TNF-α均高于对照组（均P＜0.05）。结论：3.0 T磁共振T2×mapping成像技术定量评估膝关节OA的临床价值较高,且患者膝关节不同部位软骨T2值与WOMAC评分密切相关。     

Approaching MALDI molecular imaging for clinical proteomic research: current state and fields of application

MALDI imaging mass spectrometry (‘MALDI imaging’) is an increasingly recognized technique for biomarker research. After years of method development in the scientific community, the technique is now increasingly applied in clinical research. In this article, we discuss the use of MALDI imaging in clinical proteomics and put it in context with classical proteomics techniques. We also highlight a number of upcoming challenges for personalized medicine, development of targeted therapies and diagnostic molecular pathology where MALDI imaging could help.     

Radiosynthesis and evaluation of a fluorine-18 labeled radioligand targeting vesicular acetylcholine transporter

Vesicular acetylcholine transporter (VAChT) is a reliable biomarker for assessing the loss of cholinergic neurons in the brain that is associated with cognitive impairment of patients. 5-Hydrotetralin compound (±)-5-OH-VAT is potent (K_i?=?4.64?±?0.32?nM) and selective for VAChT (>1800-fold and 398-fold for σ₁ and σ₂ receptor, respectively) with favorable hydrophilicity (LogD?=?1.78), while (?)-5-OH-VAT originally serves as the radiolabeling precursor of (?)-[¹⁸F]VAT, a promising VAChT radiotracer with a logD value of 2.56. To evaluate (?)-5-OH-[¹⁸F]VAT as a radiotracer for VAChT, we performed in vitro binding assay to determine the potency of the minus enantiomer (?)-5-OH-VAT and plus enantiomer (+)-5-OH-VAT, indicating that (?)-5-OH-VAT is a more potent VAChT enantiomer. Radiosynthesis of (?)-5-OH-[¹⁸F]VAT was explored using three strategies. (?)-5-OH-[¹⁸F]VAT was achieved with a good yield (24?±?6%) and high molar activity (～37?GBq/µmol, at the end of synthesis) using a microwave assisted two-step one-pot procedure that started with di-MOM protected nitro-containing precursor (?)-6. MicroPET studies in the brain of nonhuman primate (NHP) suggest that (?)-5-OH-[¹⁸F]VAT readily penetrated the blood brain barrier and specifically accumulated in the VAChT-enriched striatum with improved washout kinetics from striatum compared to [¹⁸F]VAT. Nevertheless, the lower target to non-target ratio may limit its use for in vivo measurement of the VAChT level in the brain.     

Measurement of the viability of arbuscular-mycorrhizal fungi using three different stains; relation to growth and metabolic activities of soybean plants

Histochemical staining of alkaline phosphatase (ALP) and succinate dehydrogenase (SDH) activities in four arbuscular mycorrhizal fungi (Glomus intraradices, G. fasciculatum, G. monosporum and G. mosseae) and their relation to growth and metabolic activities of soybean plants were investigated in a greenhouse experiment. In general, mycorrhizal inoculation significantly increased the growth responses, phosphorus and nitrogen contents, acid and alkaline phosphatases as well as total soluble protein of soybean compared to non-mycorrhizal plants. Stimulation was related to the viability of each mycorrhizal fungus. The localization of succinate dehydrogenase (as a vital stain of metabolically active fungus) and alkaline phosphatase activity (as a potential marker of efficiency of the symbiosis) in the arbuscular mycorrhizal fungi were variable. The activity appeared in young arbuscles and intercellular hyphae, whereas the collapsed arbuscules were inactive. The histochemical staining results demonstrated that the activity of alkaline phosphatase fungi was lower than succinate dehydrogenase. The use of nitroblue tetrazolium chloride as a vital stain for SDH activity showed that all mycorrhizal infection revealed by trypan blue staining was not physiologically active. Thus, the possible utilization of these enzymes to assess the activity of mycorrhizal fungi and its relation with effectively for plant growth and mineral contents is discussed.     

FRET-based genetically encoded sensors allow high-resolution live cell imaging of Ca²⁺ dynamics

Temporally and spatially defined calcium signatures are integral parts of numerous signalling pathways. Monitoring calcium dynamics with high spatial and temporal resolution is therefore critically important to understand how this ubiquitous second messenger can control diverse cellular responses. Yellow cameleons (YCs) are fluorescence resonance energy transfer (FRET)-based genetically encoded Ca(2+) -sensors that provide a powerful tool to monitor the spatio-temporal dynamics of Ca(2+) fluxes. Here we present an advanced set of vectors and transgenic lines for live cell Ca(2+) imaging in plants. Transgene silencing mediated by the cauliflower mosaic virus (CaMV) 35S promoter has severely limited the application of nanosensors for ions and metabolites and we have thus used the UBQ10 promoter from Arabidopsis and show here that this results in constitutive and stable expression of YCs in transgenic plants. To improve the spatial resolution, our vector repertoire includes versions of YCs that can be targeted to defined locations. Using this toolkit, we identified temporally distinct responses to external ATP at the plasma membrane, in the cytosol and in the nucleus of neighbouring root cells. Moreover analysis of Ca(2+) dynamics in Lotus japonicus revealed distinct Nod factor induced Ca(2+) spiking patterns in the nucleus and the cytosol. Consequently, the constructs and transgenic lines introduced here enable a detailed analysis of Ca(2+) dynamics in different cellular compartments and in different plant species and will foster novel approaches to decipher the temporal and spatial characteristics of calcium signatures.     

Synthesis of [¹¹C]PBR06 and [¹⁸F]PBR06 as agents for positron emission tomographic (PET) imaging of the translocator protein (TSPO)

The translocator protein 18 kDa (TSPO) is an attractive target for molecular imaging of neuroinflammation and tumor progression. [¹⁸F]PBR06, a fluorine-18 labeled form of PBR06, is a promising PET TSPO radioligand originally developed at NIMH. [¹¹C]PBR06, a carbon-11 labeled form of PBR06, was designed and synthesized for the first time. The standard PBR06 was synthesized from 2,5-dimethoxybenzaldehyde in three steps with 71% overall chemical yield. The radiolabeling precursor desmethyl-PBR06 was synthesized from 2-hydroxy-5-methoxybenzaldehyde in five steps with 12% overall chemical yield. The target tracer [¹¹C]PBR06 was prepared by O-[¹¹C]methylation of desmethyl-PBR06 with [¹¹C]CH₃OTf in CH₃CN at 80 °C under basic condition and isolated by HPLC combined with SPE purification with 40–60% decay corrected radiochemical yield and 222–740 GBq/μmol specific activity at EOB. On the similar grounds, [¹⁸F]PBR06 was also designed and synthesized. The previously described Br-PBR06 precursor was synthesized from 2,5-dimethoxybenzaldehyde in two steps with 78% overall chemical yield. A new radiolabeling precursor tosyloxy-PBR06, previously undescribed tosylate congener of PBR06, was designed and synthesized from ethyl 2-hydroxyacetate, 4-methylbenzene-1-sulfonyl chloride, and N-(2,5-dimethoxybenzyl)-2-phenoxyaniline in four steps with 50% overall chemical yield. [¹⁸F]PBR06 was prepared by the nucleophilic substitution of either new tosyloxy-PBR06 precursor or known Br-PBR06 precursor in DMSO at 140 °C with K[¹⁸F]F/Kryptofix 2.2.2 for 15 min and HPLC combined with SPE purification in 20–60% decay corrected radiochemical yield, >99% radiochemical purity, 87–95% chemical purity, and 37–222 GBq/μmol specific activity at EOB. Radiosynthesis of [¹⁸F]PBR06 using new tosylated precursor gave similar radiochemical purity, and higher specific activity, radiochemical yield and chemical purity in comparison with radiosynthesis using bromine precursor.     

Age-related increase of superoxide generation in the brains of mammals and birds

Oxidative stress, an imbalance between endogenous levels of oxygen radicals and antioxidative defense, increases with aging. However, it is not clear which of these two factors is the more critical. To clarify the production of oxygen radicals increases with age, we examined oxygen radical-dependent chemiluminescent signals in ex vivo brain slices using a novel photonic imaging method. The chemiluminescent intensity was significantly decreased by the membrane permeable superoxide dismutase (SOD)/catalase mimic, but not by Cu,Zn-SOD. Inhibitors for complex I, III, and IV of the mitochondrial electron transport chain transiently enhanced the chemiluminescent signal. The superoxide-dependent chemiluminescent intensity in senescence accelerated mouse (SAM) brain tissues increases with age. Moreover, the slope of the age-dependent increase was steeper in SAMP10, a strain characterized by a short lifespan and atrophy in the frontal cerebral cortex, than the senescence-resistant strain SAMR1, which has a longer lifespan. An increase in chemiluminescence with age was also observed in C57/BL6 mice, Wistar rats, and pigeons, although levels of chemiluminescence were lower in the pigeons than murines. The rate of age-related increases of superoxide-dependent chemiluminescence was inversely related to the maximum lifespan of the animals. The activity of superoxide dismutase was unchanged during the aging process in the brain. This suggested that superoxide production itself may increase with age. We speculated that reactive oxygen may be a signal to determine the aging process.     

Cd2+、Cu2+胁迫对黑藻(Hydrilla verticillata)的生长及光合荧光特性的影响

以黑藻(Hydrilla verticillata)为供试材料,采用Cd2+和Cu2+等两种重金属分别在5个浓度梯度水平下的河砂水培方法,研究Cd2+或Cu2+不同浓度胁迫对黑藻株高、生物量、成活率和叶绿素含量的影响,以及对黑藻叶片最小荧光(Fo)、最大荧光(Fm),PSⅡ最大量子产率(QYmax,)、稳态下的PSⅡ反应中心关闭程度(1-Qp_Lss)、稳态下的非光化学淬灭(NPQ_Lss)等光合荧光参数及其荧光成像的影响,探讨各个参数分别随镉、铜浓度递增的变化规律。研究结果表明,Cd2+胁迫下黑藻的株高显著下降,说明Cd2+可能对黑藻叶片的维管束结构产生伤害作用;Cd2+和Cu2+胁迫对黑藻鲜重均无显著影响,说明与水生植物自由水含量存在一定关系;Cd2+和Cu2+胁迫均使黑藻干重显著下降,其中Cu2+胁迫对黑藻干重的影响更显著,说明Cu2+胁迫对黑藻累积生物量的影响远大于Cd2+;Cd2+和Cu2+胁迫下叶绿素各值均呈下降趋势,而Cu2+胁迫对叶绿素的影响更大,说明Cu2+对黑藻叶绿体的毒害比Cd2+更大。随着Cd2+或Cu2+胁迫浓度梯度的增加,黑藻的叶绿素荧光参数(Fo、Fm、QYmax)呈显著下降趋势,(1-Qp_Lss)呈上升趋势,而NPQ_Lss先上升后下降。黑藻在不同重金属胁迫下的生理指标、荧光参数及成像特征等方面所表现出的变化差异性,反映出同等浓度下黑藻受重金属胁迫的影响程度为:Cd2+胁迫Cu2+胁迫;黑藻可以在Cu2+浓度低于1 mg/L的环境下具有正常的光合活性,可推测将黑藻用于低浓度Cu污染水域的修复;在Cu2+浓度达3 mg/L以上环境下黑藻即无法长时间生存,可推测黑藻可以作为Cd污染水环境的指示种。