超声造影联合微血管成像技术与钆塞酸二钠增强MRI评价原发性肝癌TACE术后复发的诊断效能对照分析

摘要 目的：探讨超声造影（CEUS）联合微血管成像（SMI）技术与钆塞酸二钠磁共振增强（Gd-EOB-DTPA MR增强）扫描对于原发性肝癌（HCC）经导管肝动脉化疗栓塞（TACE）术后复发的诊断效能。方法：收集2014年1月-2019年6月间我院HCC-TACE术后定期随访期间复发且存在完整CEUS、SMI、Gd-EOB-DTPA MR增强、DSA检查影像资料的患者74例,以最终DSA检查为金标准,分别比较CEUS联合SMI、Gd-EOB-DTPA MR增强及CEUS联合SMI+Gd-EOB-DTPA MR增强对于术后复发诊断的准确度、特异度、敏感度、阳性预测值、阴性预测值、约登指数,应用Kappa检验几种检查方式与DSA检查结果的一致性,并对不同诊断方式的诊断效力行组间两两比较。结果：74例HCC-TACE术后DSA证实复发者病灶共99个,CEUS+SMI+Gd-EOB-DTPG MR增强联合检查方法具有最高的诊断价值,其准确度、敏感度、特异度、阳性预测值、阴性预测值、约登指数及Kappa值分别为94.66%,95.96%,90.63%,96.94%,87.88%,0.87,0.90。组间比较CEUS联合SMI与Gd-EOB-DTPA MR增强诊断HCC-TACE术后复发具有统计学差异（P＜0.05）,但Gd-EOB-DTPA MR增强对于≤2 cm的病灶诊断率明显高于CEUS联合SMI（P＜0.05）,CEUS联合SMI+Gd-EOB-DTPA MR增强较CEUS联合SMI或Gd-EOB-DTPA MR增强诊断率比较均具有统计学差异（P＜0.05）。结论：CEUS联合SMI、Gd-EOB-DTPA MR增强检查均能发现HCC-TACE术后复发病灶,其中Gd-EOB-DTPA MR增强对于≤2 cm病灶诊断效果佳,但CEUS联合SMI+Gd-EOB-DTPA MR增强更有助于HCC-TACE术后复发的早期诊断,可进一步指导临床治疗。     

NBI及AFE在喉癌早期诊断中的应用

研究表明,喉癌的早期诊断、及时治疗不仅可以提高治愈率,而且也减少了患者的手术创伤和经济负担。积极开展喉癌的早期诊断研究具有重要的临床和社会意义。发现早期喉癌常规方法主要有电子喉镜、纤维喉镜、颈部CT及MRI检查,但并不能明显有效提高早期诊断率。而窄带成像(narrow band imaging,NBI)及自体荧光内镜(autofluorescence endoscopy AFE)是近几年用于喉癌早期诊断的两种新颖的内镜技术。NBI是一种通过变窄光波的波长,使粘膜上皮内乳头样毛细血管袢及粘膜下静脉的结构形成鲜明的对比,从而提高组织表面细微结构的对比度,便于发现病灶。而AFE技术是一种利用自发荧光聚集于病变组织的某个区域产生的差异强度,来区别正常组织与肿瘤性病变,从而用于肿瘤的早期诊断及识别癌前病变。因此,对NBI及AFE的进一步研究及认识对喉癌早期诊断提供非常重要的临床应用价值。     

Imaging the Brain Marijuana Receptor: Development of a Radioligand that Binds to Cannabinoid CB1 Receptors In Vivo

Abstract: The major active ingredient of marijuana, (−)-Δ⁹-tetrahydrocannabinol, exerts its psychoactive effects via binding to cannabinoid CB1 receptors, which are widely distributed in the brain. Radionuclide imaging of CB1 receptors in living human subjects would help explore the presently unknown physiological roles of this receptor system, as well as the neurochemical consequences of marijuana dependence. Currently available cannabinoid receptor radioligands are exceedingly lipophilic and unsuitable for in vivo use. We report the development of a novel radioligand, [¹²³I]AM281{ N -(morpholin-4-yl)-5-(4-[¹²³I]iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H -pyrazole-3-carboxamide}, that is structurally related to the CB1-selective antagonist SR141716A [ N -(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H -pyrazole-3-carboxamide]. Baboon single photon emission computed tomography studies, mouse brain dissection studies, and ex vivo autoradiography in rat brain demonstrated rapid passage of [¹²³I]AM281 into the brain after intravenous injection, appropriate regional brain specificity of binding, and reduction of binding after treatment with SR141716A. AM281 has an affinity in the low nanomolar range for cerebellar binding sites labeled with [³H]SR141716A in vitro, and binding of [¹²³I]AM281 is inhibited by several structurally distinct cannabinoid receptor ligands. We conclude that [¹²³I]AM281 has appropriate properties for in vivo studies of cannabinoid CB1 receptors and is suitable for imaging these receptors in the living human brain.     

Protein kinase C phosphorylation of PLCβ1 regulates its cellular localization

Activation of phospholipase Cβ (PLCβ) by G proteins leads to a chain of events that result in an increase in intracellular calcium and activation of protein kinase C (PKC). It has been found that PKC phosphorylates PLCβ1 on S887 in vitro without affecting its enzymatic activity or its ability to be activated by Gα(q) proteins. To understand whether S887 phosphorylation affects the enzyme’s activity in cells, we constructed two mutants that mimic the wild type and PKC-phosphorylated enzymes (S887A and S887D). We find that these constructs bind similarly to Gα(q) in vitro. When expressed in HEK293 cells, both mutants associate identically to Gα(q) in both the basal and stimulated states. Both mutants diffuse with similar rates and also interact identically with another known binding partner, translin-associated factor X (TRAX), which associates with PLCβ1 in the cytosol and nucleus. However, the two mutants localize differently in the cell. We find that S887A has a much higher nuclear localization than its S887D counterpart both in HEK293 cells and PC12 cells. Our studies suggest that PKC phosphorylation regulates the level of PLCβ1 cytosolic and nuclear activity by regulating its cellular compartmentalization.     

Multi‐modal acousto‐optic/ultrasound imaging of ex vivo liver tumors at 790 nm using a Sn2P2S6 wavefront adaptive holographic setup

Biological tissues are very strong light‐scattering media. As a consequence, current medical imaging devices do not allow deep optical imaging unless invasive techniques are used. Acousto‐optic imaging is a light‐ultrasound coupling technique that takes advantage of the ballistic propagation of ultrasound in biological tissues to access optical contrast with a millimeter resolution. We have developed a photorefractive‐crystal‐based system that performs self‐adaptive wavefront holography and works within the optical therapeutic window. As it works at an appropriate wavelength range for biological tissues imaging, it was tested on ex vivo liver samples containing tumors as a pre‐clinical study. Optical contrast was obtained even if acoustical one was not significant.

Ultrasound image (left) and acousto‐optic image (right) of a liver biopsy with tumors. Acousto‐optic imaging exhibits tumors that are not detected through ultrasound.     

Molecular imaging of proteolytic activity in cancer

The early detection of both primary tumors and metastatic disease continue to be significant challenges in the diagnosis and staging of cancer. The growing recognition of the role of proteinases and proteolytic cascades in both the growth and metastasis of tumors has led to the development not only of therapeutic strategies using proteinase inhibitors, but also of methods to detect and image tumors in vivo via tumor-associated proteolytic activities. These imaging strategies derive from the enhanced sensitivity afforded by amplification that can be obtained by enzymatic processing to increase the efficacy of imaging "contrast agents" coupled with the inherent substrate specificity and selectivity of proteinases. This review describes key proteinases important in cancer progression, the strategies that have been devised to detect and image proteolytic activity in vivo, and the potential for this kind of functional imaging to serve as a marker for targeted therapy. The intent is to draw attention to the developing methods of molecular imaging to facilitate not only cancer diagnosis, but also for devising strategies for individualized targeted therapy and non-invasive monitoring of therapeutic efficacy.     

急性胰腺炎患者的CT、MRI影像学表现及其诊断价值对比研究

摘要 目的：比较急性胰腺炎患者的电子计算机断层扫描（CT）、磁共振成像（MRI）影像学表现及其诊断价值。方法：选择2018年1月-2019年12月我院收治并初步诊断为急性胰腺炎的患者124例，所有患者均同时行CT和MRI检查，并比较两种检查方式诊断急性胰腺炎的影像学表现，以临床最终诊断结果作为参考，比较两种检查方式诊断急性胰腺炎的价值。结果：124例患者，经临床最终诊断为急性胰腺炎96例，28例为非急性胰腺炎，以临床最终诊断结果为"金标准"，CT诊断急性胰腺炎的灵敏度、特异度、阳性预测值、阴性预测值和准确度分别为84.38%、75.00%、92.05%、58.33%、82.26%，MRI诊断急性胰腺炎的灵敏度、特异度、阳性预测值、阴性预测值和准确度分别为95.83%、78.57%、93.88%、84.62%、91.94%，MRI诊断急性胰腺炎的灵敏度、阴性预测值和准确度显著高于CT（P<0.05），两种检查方式诊断急性胰腺炎的特异度、阳性预测值比较无统计学差异（P>0.05）。结论：CT和MRI影像学表现有利于急性胰腺炎的诊断，两者对急性胰腺炎诊断均具有较高的灵敏度、特异度和准确度， 但MRI诊断急性胰腺炎的灵敏度、准确度优于CT。     

Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome‐c release

Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome‐c (cyt‐c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt‐c release in these events. In accordance with single‐cell experiments, our model showed that loss of cyt‐c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨ_m from ?142 to ?88 mV, with active caspase‐3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨ_m. However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt‐c after release and (ii) the cell's glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation.     

扩散加权成像在宫颈癌诊断中的应用及与病理相关性分析

目的:分析宫颈癌扩散加权成像特征及与病理相关性。方法:选取100例宫颈癌患者为观察组,100例健康志愿者为对照组,均接受磁共振检查。观察组患者均行病理学检查,并测定微血管密度。观察宫颈癌磁共振特征,并分析其与病理相关性。结果:1.磁共振共确诊宫颈癌97例,诊断符合率为97.0%。与病理分期比较,磁共振分期正确84例,正确率为84%。2.观察组宫颈癌病变区ADC值平均为(0.893±0.098)s/mm2,显著低于对照组的(1.623±0.132)s/mm2,差异具有统计学意义(P0.05)。病理分期Ⅲ、Ⅳ其病变ADC值及MVD值显著低于Ⅰ、Ⅱ期病变,差异具有统计学意义(P0.05)。经pearson相关分析,宫颈癌ADC值与MVD值间呈显著负相关(r=-0.502,P=0.011)。结论:在宫颈癌的诊断中,磁共振具有很高应用价值。宫颈癌病变于扩散加权成像呈高信号,其ADC值显著低于正常宫颈组织,且与MVD呈显著负相关。     

A transitional extracellular matrix instructs cell behavior during muscle regeneration

Urodele amphibians regenerate appendages through the recruitment of progenitor cells into a blastema that rebuilds the lost tissue. Blastemal formation is accompanied by extensive remodeling of the extracellular matrix. Although this remodeling process is important for appendage regeneration, it is not known whether the remodeled matrix directly influences the generation and behavior of blastemal progenitor cells. By integrating in vivo 3-dimensional spatiotemporal matrix maps with in vitro functional time-lapse imaging, we show that key components of this dynamic matrix, hyaluronic acid, tenascin-C and fibronectin, differentially direct cellular behaviors including DNA synthesis, migration, myotube fragmentation and myoblast fusion. These data indicate that both satellite cells and fragmenting myofibers contribute to the regeneration blastema and that the local extracellular environment provides instructive cues for the regenerative process. The fact that amphibian and mammalian myoblasts exhibit similar responses to various matrices suggests that the ability to sense and respond to regenerative signals is evolutionarily conserved.