miR-206、FAM83A在膀胱尿路上皮癌组织中的表达及临床意义

目的:探讨微小RNA-206（microRNA-206,miR-206）、83序列相似成员A（family with sequence similarity 83 member A,FAM83A）在膀胱尿路上皮癌（bladder urothelial carcinoma,BUC）组织中的表达及临床意义。方法:选取2015年02月至2017年02月在本院肿瘤外科进行手术治疗的86例BUC患者为研究对象,选择患者癌组织及癌旁组织分别作为BUC组和对照组。采用实时荧光定量PCR（qRT-PCR）法检测miR-206、FAM83A mRNA相对表达量;免疫组化法检测癌组织及癌旁组织中FAM83A的表达情况;分析miR-206、FAM83A表达水平与BUC患者临床病理特征的关系;Kaplan-Meier法分析miR-206、FAM83A表达水平与BUC患者3年生存期的关系。结果:BUC组中miR-206表达水平明显低于对照组（P＜0.05）,FAM83A mRNA表达水平明显高于对照组（P＜0.05）。免疫组化结果显示,BUC组中FAM83A阳性率高于对照组（P＜0.001）。BUC组织中miR-206、FAM83A表达与患者肿瘤分期、淋巴结转移、组织学分级、肿瘤直径密切相关（P＜0.05）,而与患者年龄、性别无相关性（P＞0.05）。Kaplan-Meier法分析显示,BUC患者3年累积生存率为52.33%（45/86）。miR-206高表达患者3年累积生存率高于miR-206低表达患者;FAM83A高表达患者3年累积生存率低于FAM83A低表达患者。多因素COX分析显示,miR-206低表达、FAM83A水平偏高是BUC患者不良预后的独立危险因素（HR=2.598、3.342,P＜0.05）。结论:BUC患者癌组织中miR-206低表达、FAM83A高表达,miR-206、FAM83A表达与患者肿瘤分期、淋巴结转移、组织学分级、肿瘤直径及不良预后的发生有关。     

Automated 3-D registration of MR and CT images of the head

This paper discusses the application of voxel similarity measures in the automated registration of clinically acquired MR and CT data of the head. We describe a novel single-start multi-resolution approach to the optimization of these measures, and the issues involved in applying this to data having a range of different fields of view and sampling resolution. We compare four proposed measures of voxel similarity using the same optimization scheme when presented with 10 pairs of images with a range of initial misregistrations. The registration estimates are compared with those provided by manual point-based registration and evaluated by visual inspection to give an assessment of the robustness and accuracy of the different measures. One full-volume CT image set is used to investigate the performance of each measure when used to align truncated images from different regions in the head. The soft tissue correlation and mutual information measures were found to provide the most robust measures of misregistration, providing results comparable to or better than those from manual point-based registration for all but the most truncated image volumes.     

基于加权逼近理想解排序法的儿童患者注射用伏立康唑的药物利用评价

目的：建立基于加权逼近理想解排序法的儿童患者注射用伏立康唑的药物利用评价，促进其临床合理应用。方法：以注射用伏立康唑药品说明书、儿童侵袭性肺部真菌感染诊治专家共识、抗菌药物临床应用指导原则和相关指南为依据，建立基于加权TOPSIS法的儿童患者注射用伏立康唑的药物利用评价标准，依据建立的评价标准回顾性评价我院2019年1月至2022年6月伏立康唑使用情况。结果：208份评价病历加权TOPSIS法评价显示，与最优方案最高接近度为88.92%，最低接近度为35.27%；相对接近度小于60%的有21例（10.10%），相对接近度介于60%~70%的有22例（10.58%），相对接近度介于70%~80%的有148例（71.15%），相对接近度介于80%~90%的有17例（8.17%），没有相对接近度大于90%的病历。结论：基于加权TOPSIS法的儿童患者注射用伏立康唑药物利用评价标准可以用于该药在儿童患者的用药合理性评价，评价结果显示我院注射用伏立康唑临床应用中基本合理，仍存在不合理用药情况，需进一步加强管控。     

Novel compound FLZ alleviates rotenone-induced PD mouse model by suppressing TLR4/MyD88/NF-κB pathway through microbiota–gut–brain axis

Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota–gut–brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ in vivo. The aims of our study were to assess the protective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool. In the current study, chronic oral administration of rotenone was utilized to induce a mouse model to mimic the pathological process of PD. Here we revealed that FLZ treatment alleviated gastrointestinal dysfunctions, motor symptoms, and dopaminergic neuron death in rotenone-challenged mice. 16S rRNA sequencing found that PD-related microbiota alterations induced by rotenone were reversed by FLZ treatment. Remarkably, FLZ administration attenuated intestinal inflammation and gut barrier destruction, which subsequently inhibited systemic inflammation. Eventually, FLZ treatment restored blood–brain barrier structure and suppressed neuroinflammation by inhibiting the activation of astrocytes and microglia in the substantia nigra (SN). Further mechanistic research demonstrated that FLZ treatment suppressed the TLR4/MyD88/NF-κB pathway both in the SN and colon. Collectively, FLZ treatment ameliorates microbiota dysbiosis to protect the PD model via inhibiting TLR4 pathway, which contributes to one of the underlying mechanisms beneath its neuroprotective effects. Our research also supports the importance of microbiota–gut–brain axis in PD pathogenesis, suggesting its potential role as a novel therapeutic target for PD treatment.     

滇重楼地上部分总皂苷HPLC指纹图谱

目的:建立滇重楼地上部分总皂苷高效液相色谱法(HPLC)指纹图谱,为滇重楼地上部分总皂苷的质量控制提供参考。方法:采用Ecosil HPLC C₁₈色谱柱(250 mm×4.6 mm,5μm)进行分离,流动相为乙腈-水溶液,梯度洗脱,流速为1.0 mL·min^-1,检测波长为203 nm,柱温为31℃。建立6批滇重楼地上部分总皂苷HPLC特征图谱,并进行相似度评价;采用硅胶、反向硅胶RP-C₁₈柱色谱等方法对特征图谱中的3个未知共有峰化合物进行分离,应用质谱法(MS)、核磁共振(NMR)等方法进行结构鉴定;参照各对照品的色谱行为及其二极管阵列检测器(DAD)紫外光谱图,对共有峰进行归属和指认。结果:指纹图谱中的3个未知共有峰化合物为偏诺皂苷元-3-O-α-L-吡喃鼠李糖基-(1→4)-[α-L-吡喃鼠李糖基-(1→4)-β-D-吡喃葡萄糖苷(cld01)、偏诺皂苷元-3-O-α-L-吡喃鼠李糖基-(1→4)-β-D-吡喃葡萄糖苷(cld02)、薯蓣皂苷元-3-O-α-L-吡喃鼠李糖基-(1→4)-[α-L-吡喃鼠李糖基-(1→4)-β-D-吡喃葡萄糖苷(cld03)。cld02为首次从该植物中分离得到,cld03为首次从该植物地上部分分离得到;6批样品特征图谱与对照图谱的相似度均大于0.99,共归属指认了7个共有峰。结论:所建立的HPLC指纹图谱方法稳定、可靠、重复性好,可为滇重楼地上部分总皂苷质量控制提供参考。     

基于中智相似积分算法心肌超声造影系统自动定量分析缺血再灌注大鼠存活心肌

目的 观察基于中智相似积分（NSS）算法的心肌超声造影（MCE）分析系统自动定量评估缺血再灌注大鼠存活心肌的准确性。方法 将12只SD大鼠制成心肌缺血再灌注（I/R）模型，随机分为缺血30 min再灌注组（I/R-30组）及缺血45 min再灌注组（I/R-45组），每组6只。分别于术前、阻断即刻、再灌注后7、14及28天行MCE，获取左心室短轴（乳头肌水平）切面图像，采用MCE-NSS系统自动勾勒心内膜及心外膜边界，并将心肌均分为18个节段，获得各心肌节段室壁增厚率（WT）及标化造影剂灌注强度（CI）值。阻断即刻将室壁收缩运动减弱或消失节段（WT<0.3）定义为危险节段；再灌注后危险节段划分为3个区域：WT<0.3且CI<-54 Pix为危险中央区，WT<0.3且CI>-54Pix为危险周边区，WT>0.3且CI>-54Pix为危险恢复区；观察阻断即刻及术后7、14、28天危险中央区、周边区和恢复区面积变化情况。术后28天取大鼠心脏行Masson染色及免疫组织化学检查，计算梗死面积和微血管密度（MVD），分析其与MCE-NSS系统测得梗死面积的相关性。结果 ①危险节段各区域面积变化：术后7、14和28天，2组危险中央区面积百分比变化与阻断即刻变化无明显差异（P均>0.05），而危险周边区面积逐渐减小（P均<0.01），危险恢复区面积逐渐增加（P均<0.01）；I/R-45组危险中央区面积各时间点均大于I/R-30组（P均<0.01），2组危险周边区和危险恢复区面积差异均无统计学意义（P均>0.05）。②与病理结果比较：危险中央区面积与Masson染色测得梗死面积呈正相关（r=0.81，P<0.01），危险周边区CI值与免疫组织化学测得MVD呈正相关（r=0.86，P<0.01）。结论 新型MCE-NSS系统可评估大鼠心肌I/R后左心室局部收缩功能及微循环情况，并能识别存活心肌。     

Multidimensional representation of odors in the human olfactory cortex

What is known as an odor object is an integrated representation constructed from physical features, and perceptual attributes mainly mediated by the olfactory and trigeminal systems. The aim of the present study was to comprehend how this multidimensional representation is organized, by deciphering how similarities in the physical, olfactory and trigeminal perceptual spaces of odors are represented in the human brain. To achieve this aim, we combined psychophysics, functional MRI and multivariate representational similarity analysis. Participants were asked to smell odors diffused by an fMRI‐compatible olfactometer and to rate each smell along olfactory dimensions (pleasantness, intensity, familiarity and edibility) and trigeminal dimensions (irritation, coolness, warmth and pain). An event‐related design was implemented, presenting different odorants. Results revealed that (i) pairwise odorant similarities in anterior piriform cortex (PC) activity correlated with pairwise odorant similarities in chemical properties (P < 0.005), (ii) similarities in posterior PC activity correlated with similarities in olfactory perceptual properties (P <0.01), and (iii) similarities in amygdala activity correlated with similarities in trigeminal perceptual properties (P < 0.01). These findings provide new evidence that extraction of physical, olfactory and trigeminal features is based on specific fine processing of similarities between odorous stimuli in a distributed manner in the olfactory system. Hum Brain Mapp 37:2161–2172, 2016. © 2016 Wiley Periodicals, Inc.     

色谱指纹图谱相似度方法的研究进展

色谱指纹图谱相似度是中药质量控制的重要方法之一,研究中药色谱指纹图谱的相似度计算方法对于中药质量控制很有意义。作者介绍了数量相似度、相似性相似度和差异性相似度3类相似度方法的研究现状,分析了3类相似度方法各自的特点与局限,对相似度方法的改进进行了总结,并对相似度方法存在的问题、改进趋势与应用作出了展望。     

Drug–drug interaction through molecular structure similarity analysis

Background

Drug–drug interactions (DDIs) are responsible for many serious adverse events; their detection is crucial for patient safety but is very challenging. Currently, the US Food and Drug Administration and pharmaceutical companies are showing great interest in the development of improved tools for identifying DDIs.

Methods

We present a new methodology applicable on a large scale that identifies novel DDIs based on molecular structural similarity to drugs involved in established DDIs. The underlying assumption is that if drug A and drug B interact to produce a specific biological effect, then drugs similar to drug A (or drug B) are likely to interact with drug B (or drug A) to produce the same effect. DrugBank was used as a resource for collecting 9454 established DDIs. The structural similarity of all pairs of drugs in DrugBank was computed to identify DDI candidates.

Results

The methodology was evaluated using as a gold standard the interactions retrieved from the initial DrugBank database. Results demonstrated an overall sensitivity of 0.68, specificity of 0.96, and precision of 0.26. Additionally, the methodology was also evaluated in an independent test using the Micromedex/Drugdex database.

Conclusion

The proposed methodology is simple, efficient, allows the investigation of large numbers of drugs, and helps highlight the etiology of DDI. A database of 58 403 predicted DDIs with structural evidence is provided as an open resource for investigators seeking to analyze DDIs.     

叶下珠种质资源遗传多样性的ISSR分析

目的 对分布于我国30个居群的叶下珠进行遗传多样性分析。方法 采用ISSR分子标记技术,研究来自我国重庆、陕西、河南、云南、广西、广东、浙江、贵州、福建、海南省区共30个叶下珠居群的遗传多样性。结果 从60个ISSR引物中筛选出24个用于扩增,共扩增得到264条条带,其中共有条带19条,多样性条带245条,多态位点百分率（PPB）为92.80%,遗传相似性系数（GS）值在0.579 5～0.916 7,多态性较高。UPGMA聚类结果显示我国叶下珠居群大致可以分为3支,即内陆分支、沿海分支及位于云南省区的过渡分支;个别居群呈现明显的居群特异性。结论 叶下珠种质资源遗传多样性较高。