应力刺激下p38MAPK信号通路在软骨损伤中的作用

软骨组织由软骨细胞、基质和纤维构成,无直接的血液供应、神经支配和淋巴循环。软骨的损伤好发于腰、颈椎、髋、膝、肘、踝等关节部位,可见于多种疾病,如骨性关节炎、风湿性关节炎、末端病等。其中,应力刺激作为一种外界环境刺激,是使软骨发生损伤的主要因素之一。近年研究表明,在力学因素影响下,软骨细胞中重要的信号传导通路p38MAPK信号通路被激活,其激活后通过对细胞核内相关转录因子及激酶的调控,在软骨损伤的病理过程中发挥着重要作用。     

足细胞Notch信号通路研究进展

Notch通路是一条进化高度保守的信号传导通路,它广泛参与各器官的发育过程,在器官形成及其形态发生中起重要作用,并且能调节包括干细胞在内的多种细胞的分化、增殖和凋亡,决定细胞命运。近年来,有关Notch通路在肾脏发育中的作用以及足细胞Notch通路活化致病作用的研究日趋深入,本文就足细胞Notch信号通路的研究进展作一综述。     

Notch信号通路与心脏发育的关系

细胞发育受到自身或外在的、近程或远程的信号调控,其中细胞之间的相互通讯在细胞发育中扮演重要角色[1]。在调控细胞发育的若干信号通路中,Notch是相邻细胞之间互相通讯进而调控细胞发育的典型信号通路,并且越来越多的证据表明Notch信号介导的细胞间通讯在心脏发育过程中起重要作用,Notch信号通路的突变会导致小鼠和人类心脏发育异常。现将Notch信号通路与心脏发育的关系综述如下。     

运动与Keap_1-Nrf_2-ARE抗氧化信号通路研究进展

Keap1-Nrf2-ARE信号通路是机体重要的抗氧化应激调节通路,在清除活性氧,保护机体免受缺氧、炎症、氧化应激等反应带来的细胞损伤中发挥着关键性作用。本文综述Nrf2的分子结构、Nrf2基因多态性与运动能力、运动激活Keap1-Nrf2-ARE信号通路以及影响Keap1-Nrf2-ARE信号通路与运动关系等方面的最新研究进展,以期为运动训练、运动员选材、运动性疲劳的预防及低氧训练等相关领域的研究提供理论参考。     

免疫调节剂与辐射所致免疫损伤对辐射免疫重建的启示

免疫细胞之间、免疫细胞与细胞因子之间构成关系复杂的调节网络,通过正向激活和负向抑制作用维护免疫功能的稳定和平衡。近年来在器官移植领域对免疫抑制研究较为深入,临床上对抗移植排异的免疫抑制剂快速增长,其作用中心是T细胞相关受体和3条信号通路。研究发现电离辐射所致免疫抑制受体高表达与移植免疫抑制存在类似分子机制,解除其免疫抑制对辐射损伤免疫重建的作用值得探索。新的免疫激活剂提出通过TLR受体（Toll-like receptor）对抗辐射损伤发挥免疫促进作用也取得进展,探索新型免疫激活剂以及逆转免疫抑制对放射病免疫重建可以发挥重要作用。     

失重对IGF-I及整合素信号通路影响的研究进展

胰岛素样生长因子-Ⅰ(IGF-Ⅰ)是属于胰岛素家族的一类多肽。整合素是一类普遍存在于细胞表面的跨膜糖蛋白,参与细胞与细胞、细胞与细胞外基质的相互作用。研究证实整合素在IGF-Ⅰ信号通路中具有重要作用。重力影响IGF-Ⅰ信号级联和整合素的表达,但详细机制还不是很清楚。重力与整合素、IGF-Ⅰ关系十分密切。在不同的重力条件下,它们的关系正在成为重点和热门的研究对象。本文就IGF-Ⅰ的信号通路、整合素信号通路以及失重对整合素以及IGF-Ⅰ信号通路的影响进行综述。     

盐霉素在前列腺癌治疗中的进展

前列腺癌是男性泌尿系统常见恶性肿瘤之一,且有年轻化趋势.盐霉素是一种离子载体抗生素,后被发现对乳腺癌细胞有特异性杀伤作用,因此盐霉素成为抗肿瘤的热门药物.现研究发现盐霉素可通过Wnt/β-catenin信号通路、PI3 K/AKT信号通路、mTOR信号通路、内质网应激等方面对前列腺癌有抗肿瘤疗效,这对治疗前列腺癌有着重要意义.本文从盐霉素对前列腺癌抗肿瘤机制角度进行综述.     

肝纤维化相关信号通路研究进展

肝纤维化是继发于病毒性肝炎、脂肪肝、酒精肝、自身免疫性疾病等病因后出现的肝组织自身病理性修复,是发展成为肝硬化的必经之路。病理学结果显示肝纤维化的肝脏组织中,细胞外基质（ECM）大量沉积。在正常肝组织内,合成细胞外基质最主要的细胞为肝星状细胞。当肝脏受到损伤时,肝星状细胞可被激活成为肌成纤维细胞,一方面导致细胞外基质大量分泌;另一方面,其降解机制受到影响,导致过量产生的细胞外基质难以降解。最终发展成为肝纤维化。研究表明,多条信号通路共同参与了肝星状细胞的激活。针对与肝纤维化相关的信号通路进行预防,对于阻止肝纤维化的进程,进而防治肝硬化有着至关重要的意义,现就参与肝纤维化的相关通路加以阐述。     

EV71抑制I型干扰素信号通路中ISGF3的核转位

目的探讨肠道病毒71型（enterovirus71,EV71）感染对I型干扰素信号通路中核转位复合物干扰素刺激基因因子3（ISGF3）核转位的影响。方法Western印迹检测VRl432感染VeroE6对干扰素诱导的sTATl和STAT2磷酸化的影响。将pEGFP-C1-STATl重组质粒转染VeroE6细胞,随后进行EV71感染以及IFN-ot2b刺激,将细胞进行亚细胞分离检测ISGF3的核转位情况。结果VRl432以感染复数（MOI）为1感染VeroE6细胞后未影响干扰素刺激的STATl和STAT2的磷酸化;亚细胞分离后Western印迹检测磷酸化的STATl,结果显示VRl432感染后,p-STATl在细胞核内表达水平明显降低,说明Ev71感染抑制了p-STATl的核转位。结论EV71感染抑制I型干扰素信号通路中ISGF3（STATl／STAT2／IRF9）的核转位,从而影响干扰素效应途径中抗病毒蛋白的表达。     

Calculation of signal intensities in hybrid sequences for fast NMR imaging

A number of techniques that recently have been used for fast NMR-imaging are based on a hybrid sequence of echo planar imaging (EPI) and FLASH imaging: after each NMR excitation several k-space lines are measured. The complete k-space is covered by performance of several excitations. It has been observed that there is usually an optimal hybrid sequence that maximizes the signal-to-noise ratio. In this work, a method is presented that allows a determination of the optimal sequence as a function of the relaxation times T₁ and T₂^*.     

Paradoxical signal pattern of mediastinal cysts on T2-weighted MR imaging: phantom and clinical study

Purpose

To evaluate the intracystic MRI (magnetic resonance imaging) signal intensity of mediastinal cystic masses on T2-weighted images.

Materials and methods

A phantom study was performed to evaluate the signal intensity of a mediastinal cystic mass phantom (rubber balloon containing water) adjacent to a cardiac phantom pulsing at the rate of 60/min. T2-weighted images (sequence, fast spin echo [FSE] and single shot fast spin echo [SSFSE]) were acquired for the mediastinal cystic mass phantom. Further, a clinical study was performed in 33 patients (16 men, 17 women; age range, 19-85 years; mean, 65years) with thymic cysts or pericardial cysts. In all patients, T2-weighted images (FSE and SSFSE) were acquired. The signal intensity of cystic lesion was evaluated and was compared with that of muscle. A region of interest (ROI) was positioned on the standard MR console, and signal intensity of the cystic mass (cSI), that of the muscle (mSI), and the rate of absolute value of cSI–mSI to standard deviation (SD) of background noise (|cSI–mSI|/SD = CNR [contrast-to-noise ratio]) were measured.

Results

The phantom study demonstrated that the rate phantom-ROI/saline-ROI was higher in SSFSE (0.36) than in FSE (0.19). In clinical cases, the degree of the signal intensity was higher in SSFSE than in FSE. The CNR was significantly higher in SSFSE (mean ± standard deviation, 111.0 ± 47.6) than in FSE (72.8 ± 36.6) (p < 0.001, Wilcoxon signed-rank test).

Conclusions

Anterior mediastinal cysts often show lower signal intensity than the original signal intensity of water on T2-weighted images. SSFSE sequence reduces this paradoxical signal pattern on T2-weighted images, which may otherwise cause misinterpretation when assessing cystic lesions.     

Robust,unbiased general linear model estimation of phMRI signal amplitude in the presence of variation in the temporal response profile

Purpose:

To determine a simple yet robust method to generate parsimonious design matrices that accurately estimate the “pharmacological MRI” (phMRI) response amplitude in the presence of both confounding signals and variability in temporal profile. Variability in the temporal response profile of phMRI time series data is often observed. If not properly accounted for, this variation can result in inaccurate and unevenly biased signal amplitude estimates when modeled within a general linear model (GLM) framework.

Materials and Methods:

The approach uses a low‐rank singular value decomposition (SVD) approximation to a set of vectors capturing anticipated variations of no interest around the signal model to generate additional regressors for the design matrix. The method is demonstrated for both plateau and bolus type phMRI response profiles in the presence of variation in signal onset and/or shape, and applied to an in vivo blood oxygenation level‐dependent (BOLD) phMRI study of buprenorphine in healthy human subjects.

Results:

In general, 2–3 additional regressors, capturing >75% of the anticipated variance, resulted in robust and unbiased signal amplitude estimates in the presence of substantial variability.

Conclusion:

This method provides a simple and flexible means to provide robust phMRI amplitude estimates within a GLM framework. J. Magn. Reson. Imaging 2010;31:1445–1457. © 2010 Wiley‐Liss, Inc.     

Comparison of a digital and an analog signal processing system for neutron inelastic gamma-ray spectrometry

We compared the value of using a digital signal processing unit for gamma-ray spectroscopy with that of an analog one for in situ measurements of gamma-rays generated by inelastic neutron scattering reactions with soil elements. A large cylindrical NaI(Tl) scintillation detector, 15.24 cm high by 15.24 cm diameter was used to measure carbon (C) and oxygen (O). The performance of the systems was assessed as a function of input count rate (ICR) by monitoring the peak areas of the C, 4.43 MeV, and O, 6.13 MeV, gamma-rays. In separate experiments, the digital and the analog systems were also compared using an intense 10.3 mCi ¹³⁷Cs source to vary the ICR, and the 1.17 MeV peak area of ⁶⁰Co was used as the reference.     

Kinetic assessment of breast tumors using high spatial resolution signal enhancement ratio (SER) imaging.

The goal of this study was to investigate the relationship between an empirical contrast kinetic parameter, the signal enhancement ratio (SER), for three-timepoint, high spatial resolution contrast-enhanced (CE) MRI, and a commonly analyzed pharmacokinetic parameter, kep, using dynamic high temporal resolution CE-MRI. Computer simulation was performed to investigate: 1) the relationship between the SER and the contrast agent concentration ratio (CACR) of two postcontrast timepoints (tp1 and tp2); 2) the relationship between the CACR and the redistribution rate constant (kep) based on a two-compartment pharmacokinetic model; and 3) the sensitivity of the relationship between the SER and kep to native tissue T1 relaxation time, T10, and to errors in an assumed vascular input function. The relationship between SER and kep was verified experimentally using a mouse model of breast cancer. The results showed that a monotonic mathematical relationship between SER and kep could be established if the acquisition parameters and the two postinjection timepoints of SER, tp1, tp2, were appropriately chosen. The in vivo study demonstrated a close correlation between SER and kep on a pixel-by-pixel basis (Spearman rank correlation coefficient=0.87+/-0.03). The SER is easy to calculate and may have a unique role in breast tissue characterization.     

Near-infrared fluorescence imaging and histology confirm anomalous edematous signal distribution detected in the rat lung by MRI after allergen challenge

PURPOSE: To address the issue concerning the predominant location, on the left anatomic side, of edematous signals detected by magnetic resonance imaging (MRI) in the lungs of actively sensitized rats following intratracheal (IT) allergen challenge. MATERIALS AND METHODS: Near-infrared fluorescence (NIRF) imaging was used to detect the lobular distribution in the lungs of normal rats of an IT instilled fluorescent dye, Cy5.5. Actively sensitized Brown Norway rats were examined by MRI 24 hours after IT administration of ovalbumin. The perivascular edema was quantified by histology in the different lobes of lungs removed from the same animals immediately after the MRI acquisitions. RESULTS: An uneven distribution of Cy5.5 was found, predominantly on the left lobe, paralleling the localized development of allergic pulmonary inflammation in the left lobe detected as edematous signal by MRI and confirmed by histology. The patterns of the distributions of the dye between and within the lobes were very similar to those of perivascular edema assessed histologically. CONCLUSION: The data indicate a relationship between the molecular deposition of the dye detected by NIRF in the lungs and the distribution of allergen eliciting the development of pulmonary inflammation in actively rats. The combination of MRI with NIRF imaging may provide important information in preclinical pharmacologic research in the area of airway diseases. While MRI is able to address the effects of compounds on the inflammatory response in models of airways diseases, NIRF imaging may provide important insights on drug distribution and interaction in the lung, being thus suited for molecular imaging studies.     

Lipid signal extraction by SLIM: application to 1H MR spectroscopic imaging of human calf muscles.

The measurement of intramyocellular lipid (IMCL) using in vivo (1)H MRS is important for better understanding muscle physiology. However, the accurate measurement of IMCL in muscle adjacent to subcutaneous fat (SF) and bone marrow (BM) is often hampered by contaminations from the fat. In this article a new postacquisition processing method is proposed that selectively removes unwanted lipid signals based on the spectral localization by imaging (SLIM) technique, which can localize spectra from arbitrarily shaped regions. The effectiveness of this lipid extraction method is demonstrated by both computer simulation and in vivo experiments in the human calf. The advantage of this method is that unwanted lipid signal, such as SF signal, can be selectively and completely removed. After the contaminating fat signals are removed, the quality of muscle spectra adjacent to SF improves such that it becomes comparable to that in uncontaminated muscle regions in (1)H MRSI of the calf.     

Gm typing by enzyme-linked immunosorbent assay (ELISA)

Summary A solid-phase ELISA for Gm typing is described. A mixture of anti-Gm serum (or monoclonal anti-Gm antibody) and test serum was incubated in microtiter wells coated with IgG or its fragments of appropriate Gm type. After washing of the wells, the bound antibody was detected with peroxidase-labeled second antibody. The Glm(3), G3m(16), and G3m(21) antigens could be identified by this technique. Since some of the human anti-Gm sera and anti-Rh₀ sera required for the conventional hemagglutination-inhibition method are hard to obtain, the ELISA system using anti-Gm antibodies and no anti-Rh₀ sera may serve as an alternative to the conventional method.Supported in part by grants-in-aid for Scientific Research, nos. 58480206 and 59570267, from the Ministry of Education, Science and Culture     

高原地区进展期胃癌患者红细胞免疫功能和T淋巴细胞亚群的研究

目的：研究高原地区进展期胃癌（AGC）患者的红细胞免疫功能和淋巴细胞免疫功能;方法：对我科住院手术治疗的32例进展期胃癌患者作了红细胞C3b受体花环（RBC－C3bRR)、红细胞免疫复合物花环（RBC－ICR）及淋巴细胞亚群CD3、CD4、CD8、CD4／CD8的检测,并与20例正常人结果进行比较;结果：高原地区进展期胃癌患者RBC－C3bRR,CD3,CD4,CD8、CD4／CD8比值均低于正常人（P＜0．01）,RBCICR高于正常人（P＜0．01）;结论：高原地区进展期胃癌患者红细胞免疫系统与淋巴细胞免疫系统均处于抑制状态,2个免疫系统的改变有着密切的关系,对高原地区进展期癌患者应给予免疫支持。