基于动脉系统旋动流原理的一种血管内支架旋流导引装置的优化

血管内支架是目前治疗心血管疾病的主要方法之一。但是支架植入后的血管再狭窄问题至今未获完全解决。研究表明,支架植入后导致的局部血流紊乱和流场异常是造成再狭窄的主要原因之一。基于动脉系统的旋动流原理,设计了一种能够引导血流产生旋动的血管内支架旋流导引装置,并用计算流体力学的方法,对其进行了优化设计。流场数值研究表明,优化设计得到的旋流导引装置可产生足够强度的旋动流。我们相信,该装置产生的旋动流可有效抑制支架结构对血流的扰动,从而达到减缓血管再狭窄的目的。     

An event-related potential study on cross-modal conversion of Chinese characters

In the current study, we explored the effects of ERPs (event-related potentials), related to the cross-modal transfer from visual input to phonological retrieval. Using Chinese single-character words, participants were asked to make orthographic (intra-modal) and phonological (cross-modal) responses to visually presented words. By comparing the cross-modal and intra-modal tasks, we found that both tasks evoke similar activity in the early stage of lexical processing, showing the same pattern of N2 effect (a negative component peaking around 220 ms) and P2 effect (a positive component peaking around 270 ms). However, the effect of the task was significant in the 300-700 ms time window, consisting of a frontal-based N400 effect and a parietal based late positive component (LPC) effect. These findings suggest that the frontal-based N400 is associated with orthography-to-phonology mapping in Chinese, and the LPC reflects greater requirement of maintaining retrieved information in working memory for the cross-modal processing.     

Chromosomal copy number alterations are associated with tumor response to chemoradiation in locally advanced rectal cancer

Rectal cancer response to chemoradiation (CRT) varies from no response to a pathologic complete response (pCR). Identifying predictive biomarkers of response would therefore be useful. We assessed whether chromosomal copy number alterations (CNAs) can assist in predicting pCR. Pretreatment tumor biopsies and paired normal surgical tissues from the proximal resection margin were collected from 95 rectal cancer patients treated with preoperative CRT and total mesorectal excision in a prospective Phase II study. Tumor and control DNA were extracted, and oligonucleotide array-based comparative genomic hybridization (aCGH) was used to identify CNAs, which were correlated with pCR. Ingenuity pathway analysis (IPA) was then used to identify functionally relevant genes in aberrant regions. Finally, a predictive model for pCR was built using support vector machine (SVM), and leave-one-out cross validation assessed the accuracy of aCGH. Chromosomal regions most commonly affected by gains were 20q11.21-q13.33, 13q11.32-23, 7p22.3-p22.2, and 8q23.3-q24.3, and losses were present at 18q11.32-q23, 17p13.3-q11.1, 10q23.1, and 4q32.1-q32.3. The 25 (26%) patients who achieved a pCR had significantly fewer high copy gains overall than non-pCR patients (P = 0.01). Loss of chromosomal region 15q11.1-q26.3 was significantly associated with non-pCR (P < 0.00002; Q-bound < 0.0391), while loss of 12p13.31 was significantly associated with pCR (P < 0.0003; Q-bound < 0.097). IPA identified eight genes in the imbalanced chromosomal regions that associated with tumor response. SVM identified 58 probes that predict pCR with 76% sensitivity, 97% specificity, and positive and negative predictive values of 91% and 92%. Our data indicate that chromosomal CNAs can help identify rectal cancer patients more likely to develop a pCR to CRT.     

Inhibition of hepatitis B virus gene expression by small interfering RNAs targeting cccDNA and X antigen

To test the possible inhibition of hepatitis B virus (HBV) replication and expression by small interfering RNAs (siRNAs) targeting simultaneously covalenthy closed circular DNA (dnacccDNA) and X antigen, corresponding recombinant plasmids were transfected into HepG2.2.15 cells and the levels of cccDNA, HBXAg, HBcAg, and HBeAg were assayed at various times post transfection. As expected, the single siRNAs showed marked inhibitory effects but their combination was even more efficient. These results provide a new insight into the development of a potential anti-HBV strategy of enhancing the efficacy of individual antivirals and overcoming the high mutation rate of HBV.     

RRx-001 ameliorates inflammatory diseases by acting as a potent covalent NLRP3 inhibitor

The NLRP3 inflammasome plays a crucial role in innate immune-mediated inflammation and contributes to the pathogenesis of multiple autoinflammatory, metabolic and neurodegenerative diseases, but medications targeting the NLRP3 inflammasome are not available for clinical use. RRx-001 is a well-tolerated anticancer agent currently being investigated in phase III clinical trials, but its effects on inflammatory diseases are not known. Here, we show that RRx-001 is a highly selective and potent NLRP3 inhibitor that has strong beneficial effects on NLRP3-driven inflammatory diseases. RRx-001 inhibits the activation of the canonical, noncanonical, and alternative NLRP3 inflammasomes but not the AIM2, NLRC4 or Pyrin inflammasomes. Mechanistically, RRx-001 covalently binds to cysteine 409 of NLRP3 via its bromoacetyl group and therefore blocks the NLRP3-NEK7 interaction, which is critical for the assembly and activation of the NLRP3 inflammasome. More importantly, RRx-001 treatment attenuates the symptoms of lipopolysaccharide (LPS)-induced systemic inflammation, dextran sulfate sodium (DSS)-induced colitis and experimental autoimmune encephalomyelitis (EAE) in mice. Thus, our study identifies RRx-001 as a new potential therapeutic agent for NLRP3-driven diseases.     

遗传病二代测序临床检测全流程规范化共识探讨(2)——样品采集处理及检测

二代测序技术(next generation sequencing,NGS)具有极高的检测通量,相对低的检测成本,高度的准确性(accuracy)和精准性(precision),是遗传病临床检测的有力工具之一。NGS实验室的检测流程是否规范,将直接影响NGS数据的稳定性、可靠性和有效性,将决定其是否能被用于遗传病的临床辅助诊断或筛查。因此.作为遗传病基因检测的重要环节之一,NGS实验室中流程的规范化与标准化非常重要。2019年5月,在第二届基因检测联盟会议上,针对如何规范NGS检测流程,从事遗传病临床诊治、实验室检测以及第三方基因检测机构的专家进行了全面充分的讨论,旨在规范基于NGS的基因检测流程,对检测流程中的前、中、后三个阶段(包括样本采集/接收/保存、NGS建库、上机测序及数据质控)的操作与实施提出了专业性的指导意见,以规范NGS技术在遗传病基因检测领域中的应用。本文根据此次研讨会上各行业专家的讨论,总结并发布NGS实验室检测流程的规范共识,以促进NGS实验室流程的规范化和标准化,推进我国NGS实验室在遗传病基因检测领域的快速和专业化发展。     

单侧双通道内镜下经椎间孔腰椎椎间融合术的研究进展

单侧双通道内镜下腰椎椎间融合术是采用双通道在持续冲洗及内镜直视下行腰椎椎体间减压及融合的手术,具有手术器械简单、操作灵活性强、创伤小、学习曲线相对平缓等优势,常应用于腰椎间盘突出、椎管狭窄及腰椎滑脱等腰椎退行性疾病。随着该术式在脊柱疾病中的广泛应用,一些潜在的优势及不足也逐渐被发现。单侧双通道内镜下腰椎椎间融合术的手术入路有两种：后路腰椎椎体间融合术（PLIF）和经椎间孔腰椎椎体间融合术（TLIF）。目前研究较多的是TLIF,本文就单侧双通道内镜下经椎间孔腰椎椎间融合手术在腰椎退行性疾病中的临床疗效进行阐述。     

急性脑梗死患者血浆NPY、CGRP及血清IGF-Ⅰ水平测定

目的:探讨脑梗死患者血浆NPY、CGRP及血清IGF-Ⅰ水平的变化及其临床意义.方法:随机选择了32例脑梗死患者,采用放射免疫分析分别测定了患者治疗前后的血浆NPY、CGRP及血清IGF-Ⅰ水平,并将组间的差异进行了统计学处理及分析.结果:32例脑梗死患者治疗前NPY水平较对照组升高极显著(P＜0.01),CGRP及IGF-Ⅰ水平则较对照组下降均非常显著(P均＜0.01);经治疗患者血浆NPY水平较治疗前已显著降低(P＜0.05),血浆CGRp及血清IGF-Ⅰ水平较治疗前则均明显上升(P均＜0.05).结论:脑梗死患者血浆NPY、CGRP及血清IGF-Ⅰ水平的变化与其发病关系密切,其测定对于了解患者的病情程度及制订治疗方案有重要临床价值.     

上消化道出血患者检测血清前白蛋白的临床意义

目的:探讨血清前白蛋白在上消化道出血中的意义。方法:对32例肝硬化并发上消化道出血患者及30例胃十二指肠疾病并发上消化道出血患者进行血清前白蛋白(PA)测定,并与34例正常对照相比较。结果:肝硬化并发上消化道出血患者血清PA低于胃十二指肠疾病并发上消化道出血者及正常对照组,且肝硬化组PA分布与后两者无重迭;Child分级间PA有显著差异。结论:上消化道出血患者检测血清PA有助于肝硬化并发出血的诊断,并可帮助判断病情及估计预后。