Vascular endothelial growth factor expressing mesenchymal stem cells improves cardiac function in chronic myocardial infarction in pigs

Transplantation of mesenchymal stem cells （MSCs） for myocardial reconstruction has shown promise in both animal models and human phase 1 clinical studies. Vascular endothelial growth factor （VEGF） is a strong therapeutic agent for treating ischaemia by inducing angiogenesis. The feasibility of ex vivo MSCs mediated gene transfer is documented. Matsumoto and colleagues have recently reported genetically engineered MSCs carrying VEGF165 delivery for revascularization in a model of acute myocardial infarction （MI）. The promising data from our laboratory in both angiogenesis and MSCs transplantation in cunicular heart model of acute MI have prompted us to attempt the combined and simultaneous application of the two strategies.     

计算机放射摄影(CR)的前景分析

本文针对我国大中型医院传统X线摄影的现状,结合对DR、PACS的发展分析,全面阐述了运用CR成像技术的潜力和前景.     

MiniQuest网络探究性学习研究

在介绍M iniQuest的基础上,对M iniQuest教学设计中的各个环节进行了分析。并通过一个完整的M iniQuest实例分析,探索了如何利用M iniQuest更好的进行网络研究性学习研究。     

巨噬细胞泡沫化抑制剂的研究进展

胆固醇酯蓄积的巨噬细胞(泡沫细胞)是早期动脉粥样硬化斑块的主要组成和特征。它通过其细胞表面的多种受体无限制地摄取氧化型低密度脂蛋白(ox-LDL)颗粒及其他配体,结果在巨噬细胞内有大量的胆固醇酯和三酰甘油蓄积,使巨噬细胞发展成为泡沫细胞。因此,通过各种途径抑制这种在巨噬细胞的过量脂质蓄积,可以起到预防和治疗动脉粥样硬化的作用。     

Metabolic activation of fluoropyrrolidine dipeptidyl peptidase-IV inhibitors by rat liver microsomes.

The current study evaluated the potential for two dipeptidyl peptidase-IV (DPP-IV) inhibitor analogs (1S)-1-(trans-4-([(4-trifluoromethoxyphenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride and (1S)-1-(trans-4-([(2,4-difluorophenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride (MRL-A and MRL-B), containing a fluoropyrrolidine moiety in the structure, to undergo metabolic activation. The irreversible binding of these tritium-labeled compounds to rat liver microsomal protein was time- and NADPH-dependent and was attenuated by the addition of reduced glutathione (GSH) or N-acetylcysteine (NAC) to the incubation, indicating that chemically reactive intermediates were formed and trapped by these nucleophiles. Mass spectrometric analyses and further trapping experiments with semicarbazide indicated that the fluoropyrrolidine ring had undergone sequential oxidation and defluorination events resulting in the formation of GSH or NAC conjugates of the pyrrolidine moiety. The bioactivation of MRL-A was catalyzed primarily by rat recombinant CYP3A1 and CYP3A2. Pretreatment of rats with prototypic CYP3A1 and 3A2 inducers (pregnenolone-16alpha-carbonitrile and dexamethasone) enhanced the extent of bioactivation which, in turn, led to a higher degree of in vitro irreversible binding to microsomal proteins (5- and 9-fold increase, respectively). Herein, we describe studies that demonstrate that the fluoropyrrolidine ring is prone to metabolic activation and that GSH or NAC can trap the reactive intermediates to form adducts that provide insight into the mechanisms of bioactivation.     

基于影像组学分类器术前预测直肠非黏液性腺癌淋巴结转移

目的：探讨影像组学方法在术前预测直肠非黏液性腺癌淋巴结转移中的价值。方法：回顾性分析91例手术病理切片证实为直肠非黏液性腺癌患者的影像学资料,其中61例为训练样本,30例为验证样本。基于全瘤体积,从每个原发病灶术前高分辨T2加权成像(T2-weighted imaging,T2WI)图像中提取影像组学特征1 301个。基于训练样本,利用最小绝对收缩和选择算子(the least absolute shrinkage and selection operator,LASSO)逻辑回归方法筛选关键特征并构建影像组学分类器。采用受试者工作特征(receiver operating characteristic,ROC)曲线评价影像组学分类器的辨别效能,并将其与形态学标准进行比较。在验证样本中验证影像组学分类器的价值。结果：由5个影像组学特征构建的分类器与淋巴结转移状态有关(P<0.001)。在训练样本和验证样本中,影像组学分类器诊断淋巴结转移的曲线下面积分别为0.874(95% CI：0.787~0.960)和0.878(95% CI：0.727~1.000),形态学标准诊断淋巴结转移的曲线下面积分别为0.619(95% CI：0.487~0.752)和0.556(95% CI：0.355~0.756)。无论是训练样本还是验证样本,影像组学分类器的诊断效能均高于形态学标准(均P<0.05)。结论：影像组学分类器可术前个体化预测直肠非黏液性腺癌淋巴结转移,而且其诊断效能高于形态学标准。     

脊髓型颈椎病患者三维有限元模型的构建与生物力学分析

目的：构建颈部三维有限元模型(finite element model,FEM),初步分析脊髓型颈椎病(cervical spondylotic myelopathy,CSM)患者与对照者颈部生物力学的差异,为CSM发病机制的研究提供生物力学依据。方法：以1名CSM患者作为力学模拟实验对象进行三维CT扫描,并构建颈部三维FEM依照患者的年龄、性别、身高、体重等参数选取本团队已有的健康颈部三维FEM作为对照,比较患者和对照者在颈椎正常受力情况下椎体、椎间盘、韧带及脊髓的应力差异,以及后仰伸运动后最大应力的差异。结果：成功构建CSM患者及对照者FEM模型,并进行力学分析,CSM患者颈椎椎体受力差异C5~C6节段最明显,对照者和患者的最大应力部位均在椎体前缘,CSM患者椎体前缘的最大应力小于对照者;CSM患者椎间盘应力分布不均匀,最大应力部位集中在椎间盘底部后缘的两侧;CSM患者各韧带的应力分布不均匀,其中后纵韧带应力最大。CSM患者颈椎在后仰伸运动时范围受限。结论：CSM患者相对于对照者可能存在颈部椎体、椎间盘及韧带受力平衡的改变和颈椎运动范围的受限,这可能与CSM力学发病机制相关。     

肝细胞癌NF κ-B表达与CT表现的相关性

目的 探讨核因子（NF κ-B）在肝细胞癌组织中的表达与CT影像特点间的关系。方法 收集华西医院有完整临床资料和全肝CT扫描图像并经手术完整切除的肝癌组织标本患者80例,采用免疫组织化学方法染色定量分析癌组织中NF κ-B表达情况和在不同的临床参数中表达的差异;再分别以肿瘤坏死、血供、瘤体直径和瘤周子灶的有无分四组,探讨NF κ-B表达量在不同CT影像特征中有无差异。结果 CT检测80例患者中肝癌细胞核内NF κ-B表达阳性有74例（92.5%）。肝细胞癌NF κ-B表达与临床参数,包括性别、肝炎病史无相关性,瘤体大小与NF κ-B表达无统计学差异。CT检测肿瘤血供、坏死及瘤周子灶的有无与NF κB表达相关（P＜0.05）,富血供肝细胞癌NF κ-B表达较乏血供者明显增高,而瘤体有坏死者较未发生坏死者低,瘤周出现子灶的病例NF κ-B表达也增高,且差异有统计学意义（P＜0.05）。结论 肝癌血供、坏死及瘤周子灶CT影像特点与NF κ-B水平密切相关。瘤体血供丰富、瘤内无坏死、瘤周伴有子灶的肝癌组织NF κ-B表达水平明显增高,NF κ-B表达水平量可能与肿瘤的生物学特性,疾病的转归和预后相关,CT检测可为肝癌的治疗及预防评估提供重要依据。     

Prediction of Hidden Blood Loss During Posterior Spinal Surgery

Objective Identification of the risk factors for extraordinary hidden blood loss (HBL) could clarify the underlying causes and provide more appropriate management. This study aims to identify the predictors of HBL in spinal surgery.     

Individual and joint effects of borderline ankle-brachial index and high plasma total homocysteine on all-cause death in hypertensive adults

BACKGROUNDThe cardiovascular hazards of total homocysteine (tHcy) are long known. In addition, despite the acknowledgment on the importance of low ankle-brachial index (ABI) (< 0.9), borderline ABI (0.91-0.99) was once commonly overlooked. This study aims to explore the independent and joint effect of tHcy level and borderline ABI on all-cause death in hypertensive population.METHODSThis study included 10,538 participants from China H-type Hypertension Registry Study. ABI was described into two groups: normal ABI (1.00-1.40) and borderline ABI. tHcy level was also divided into two groups: < 15.02 and ≥ 15.02 μmo/L. Four groups were analyzed, using COX proportional hazard regression model, separately and pairwise to observe the independent and joint effect on all-cause death.RESULTSA total of 126 (1.2%) deaths were observed in the 1.7 years follow-up time. Borderline ABI has a higher predicted risk of death than normal ABI (HR = 1.87, 95%CI: 1.17-3.00) after adjusting for potential covariates. Compare with tHcy level < 15.02 μmo/L (low tHcy), those with tHcy ≥ 15.02 μmo/L (high tHcy) had higher risk to event outcome (HR = 1.99, 95% CI: 1.30-3.05). According to the cumulative hazard curve, group with borderline ABI and high tHcy level has significantly higher altitude and larger increasing rate over follow-up period compare to other groups. Among those with borderline ABI, participants with high tHcy had higher death risk than those with low tHcy, nevertheless, no significant different between borderline and normal ABI among those with low tHcy levels.CONCLUSIONSBorderline ABI and tHcy level both have independent predictive value on all-cause death. The combined group of borderline ABI and high tHcy has highest risk factor of outcomes, which suggested the mutual additive value of borderline ABI and tHcy. More attention should be given to the importance of borderline ABI in hypertensive population, especially with elevated tHcy level.

Homocysteine (Hcy) is a sulfur-containing, non-proteinogenic amino acid synthesized through the transmethylation of amino acid methionine from one-carbon metabolism. Elevated plasma total homocysteine (tHcy) level is associated with endothelial dysfunction, increased blood coagulation, and metabolic disturbance, promoting cardiovascular diseases, stroke, and coronary artery disease.^[1,2] Notably, patients with high Hcy levels and concomitant hypertension were suggested to be at particularly higher risk.^[3] Moreover, increasing studies have explored a positive association between advanced Hcy level with all-cause mortality. According to a recent dose-response meta-analysis, for each 5-μmol/L increment of tHcy levels, the risk for all-cause mortality increased by 33.6%.^[4]The ankle-brachial index (ABI) is an effective, well-established measure that is commonly used in the diagnosis of peripheral artery disease (PAD),^[5] meanwhile was well studied as an important indicator of atherosclerosis and CVD events.^[6] Although ankle-brachial index (ABI) ≤ 0.90 has been recognized as the threshold value for abnormal/low ABI, which was proven to increase the risk of all-cause mortality,^[7] a study from the American Heart Association has suggested ABI between 0.91 and 1.00 should be considered as “borderline area” in terms of cardiovascular risks,^[8] considering of prior probability and sensitivity of ABI calculation. Emerging studies have aimed to explore the predictive value of borderline ABI,^[9-11] however, controversy remains because of limited and inconsistent data. The current study aimed to explore the individual and joint effect of borderline ABI and tHcy on all-cause mortality among hypertensive adults. Although ABI level ≤ 0.90 has been and is going to remain significant in clinical practice, we believe broader concern should be placed on borderline ABI, especially for its value in risk differentiation and identification. To the best of our knowledge, there are no similar previous studies.