心源性脑卒中患者血栓弹力图检测与抗凝因子蛋白S、蛋白C的相关性研究

目的:探讨心源性脑卒中(CES)患者血栓弹力图检测与抗凝因子蛋白S、蛋白C的相关性。方法:选取2018年9月~2020年6月入院治疗的CES患者86例纳入CES组,同时选取同期健康体检者40例纳入健康组。检测两组TEG及抗凝因子蛋白S、蛋白C水平,对不同神经功能损伤严重程度及不同预后患者上述参数进行比较,分析TEG与蛋白S、蛋白C的相关性。结果:与健康组相比,CES组R值、K值、蛋白S、蛋白C水平明显降低,α值、MA值明显增高(P<0.05);随着病情严重程度升高,患者R值、K值、蛋白S、蛋白C水平明显降低,α值、MA值明显升高(P<0.05)。预后良好组R值、K值、蛋白S、蛋白C水平明显高于预后不良组,α值、MA值明显低于预后不良组(P<0.05);CES患者蛋白S及蛋白C水平与R值、K值呈正相关,与MA值呈负相关(P<0.05)。结论:CES患者TEG部分参数与抗凝因子蛋白S、蛋白C存在相关性,临床可以两种指标相互补充,增强患者凝血功能功能监测效果。     

慢性高原病脑部多体素1H-MRS研究

目的利用多体素氢质子磁共振波谱成像(hydrogen proton magnetic resonance spectroscopy,¹H-MRS)探讨慢性高原病(chronic mountain sickness,CMS)长期缺氧状态下脑部代谢物的特点,并比较各代谢物与血液指标之间的相关性。材料与方法前瞻性纳入青海大学附属医院经临床确诊为CMS的17例男性患者作为实验组,年龄(53.29±9.03)岁,居住海拔(3989.12±937.45)m,血红蛋白(hemoglobin,HGB)(224.35±11.81)g/mL,并招募与实验组年龄及居住海拔相匹配的18名健康男性志愿者作为对照组,年龄(48.61±8.76)岁,居住海拔(3674.94±634.27)m,HGB(156.67±9.46)g/mL。采用Siemens Prisma 3.0 T MR扫描仪20通道头颅线圈对所有受试者行常规头颅MRI及多体素;H-MRS检查,通过Syngo.via后处理软件获得;H-MRS图,ROI选取双侧额叶及海马区,并获得相应脑区N-乙酰天门冬氨酸/肌酸(NAA/Cr)、胆碱/肌酸CHo/Cr、乙酰天门冬氨酸/胆碱(NAA/CHo)、乳酸/肌酸(Lac/Cr)的比值。结合独立样本t检验及非参数曼-惠特尼U检验以比较两组间代谢物相对浓度差异,然后将CMS组双侧额叶及海马区各代谢物比值与血液生化指标作相关性分析。结果(1)两组受试者年龄、长期居住海拔差异均无统计学意义(P>0.05),而与对照组相比,CMS组HGB、红细胞计数(red blood cell count,RBC)、血细胞比容(hematocrit,HCT)增高,血小板(blood platelet,简称PLT)减低,差异均有统计学意义(P<0.01);(2)与对照组相比,CMS组双侧额叶及海马区NAA/Cr及NAA/CHo均减低(P<0.05),Lac/Cr增高(P<0.05),差异均具有统计学意义;(3)与对照组相比,CMS组双侧额叶及双侧海马区CHo/Cr均增高(P>0.05),差异无统计学意义;(4)CMS组右侧额叶及左侧海马CHo/Cr与RBC明显正相关,左侧额叶CHo/Cr与HCT低度正相关,右侧额叶及左侧海马Lac/Cr与HCT低度正相关。结论CMS长期缺氧状态下脑组织局部代谢物改变,神经元受损,无氧代谢增加,且这些代谢物的改变与血液指标呈一定的相关性,可为临床后续进一步预防或干预CMS患者脑损害提供影像学证据及监测指标。     

Magnetic resonance elastography with guided pressure waves

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.     

C反应蛋白和白蛋白比值预测单发小肝癌患者微血管侵犯的价值研究

背景 既往对肝癌微血管侵犯病理诊断的重要性重视不够，目前国内外缺乏对微血管侵犯统一的病理诊断标准，也未将微血管侵犯列为病理常规诊断指标。C反应蛋白/白蛋白比值（CAR）作为新型系统性炎性因子，与肝癌的增殖、侵袭转移等恶性生物学行为密切相关。 目的 探讨CAR预测单发小肝癌患者微血管侵犯的价值。 方法 选择2017年6月至2021年6月在新疆医科大学第一附属医院行肝切除术的单个、肿瘤直径≤5 cm的术后病理检查证实为肝癌的患者346例为研究对象。收集患者一般资料，并计算CAR。绘制CAR预测单发小肝癌患者微血管侵犯的受试者工作特征（ROC）曲线，并计算CAR的最佳诊断截点，根据CAR最佳诊断截点将患者进行分组，采用1∶1最近邻居倾向性评分匹配（PSM）法将Logistic模型估计的倾向性评分相近患者进行配对，得到两组间各临床特征比较均衡性较高的样本。比较匹配后两组患者微血管侵犯率，采用Logistic回归分析评估匹配前、后CAR对单发小肝癌患者微血管侵犯的预测价值。 结果 346例患者中微血管侵犯阳性131例（37.9%），微血管侵犯阴性215例（62.1%）。ROC曲线分析结果显示，CAR预测单发小肝癌患者微血管侵犯的灵敏度为82.9%，特异度为76.4%，ROC曲线下面积为0.787〔95%CI（0.697，0.877）〕，最佳诊断截点为0.03。根据CAR最佳诊断截点，将患者分为CAR<0.03组（A组，n=145）和CAR≥0.03组（B组，n=201）。采用1∶1最近邻居PSM法，共92对匹配成功，匹配后两组临床资料均衡。匹配后，B组患者微血管侵犯发生率〔43.5%（40/92）〕高于A组〔13.0%（12/92）〕（χ2=6.314，P=0.013）。采用3种Logistic回归分析结果显示，匹配前、后CAR均为单发小肝癌患者微血管侵犯的独立影响因素（P<0.05）。 结论 CAR作为新型系统性炎症指标，可用于预测单发小肝癌微血管侵犯，当CAR≥0.03时提示单发小肝癌微血管侵犯发生率较高。     

孤独症谱系障碍社会脑神经网络基础及其研究进展

孤独症谱系障碍(ASD)的核心诊断特征是社会交流障碍以及受限和重复的行为和兴趣,症状常在生命的最初几年出现。过去的二十年内,神经成像揭示了许多“社会性”大脑的非典型活动和异常连通性的发现,包括梭状回对面部和凝视的分析、杏仁核的情绪处理、默认模式网络的心智化以及镜像神经元相关区域对他人行为的模仿和理解,但对于社交功能缺陷潜在的神经生理机制还未达成一致。除了方法学上的挑战以及聚焦于单个大脑网络的连通性研究以外,更深层次的问题是ASD的极强异质性。这种不一致的发现,可能是由于诊断标准的变化以及学龄前期的ASD患儿存在非典型的神经发育轨迹,因此,有必要进行孤独症亚型的队列研究和大样本的纵向队列研究。     

凉血通瘀方干预高血压大鼠急性脑出血模型对脑组织中差异miRNA表达的影响＊

目的 研究凉血通瘀方对高血压大鼠急性脑出血模型脑组织miRNA表达的影响，对差异表达的miRNA靶基因进行分析，探索凉血通瘀方可能的药效机制。方法 将自发性高血压大鼠随机分成对照组（B）和实验组（C）。适应性饲养一周后，C组灌胃凉血通瘀方，B组灌胃等体积生理盐水，连续5天，每天1次。构建脑出血模型后收集脑组织，借助全转录组测序技术获得miRNA表达量，与miRBase数据库比对获取已知miRNA，使用miRDeep2预测新miRNA。差异分析软件为DESeq2，筛选阈值为|log₂FC| ≥1 并且P <0.05。对显著差异表达的miRNA进行靶基因预测，对靶基因进行GO功能、KEGG通路富集和PPI网络分析。结果 实验组和对照组对比，共发现21个显著差异表达的miRNA，上调有9个，下调有12个，共预测得到1243个有统计学意义的靶基因。GO富集分析发现，生物过程中突触囊泡分泌的调节、神经递质分泌的调节和神经递质运输的调节占前三位，神经元投射终点、全膜、质膜区域和细胞投射则是主要的细胞成分。分子功能分别为小GTPase绑定、底物特异性跨膜转运蛋白活性和离子跨膜转运体活性。通路分析结果显示，靶基因在癌证通路、pI3K-Akt信号通路、人类乳头瘤病毒感染、神经活性配体-受体相互作用和MAPK通路等分布广泛。采用STRING网站和Cytoscape软件，根据MCC算法筛选出ADRA2C、CASR、CCL28、CCR1、DRD2、GNAT3、GRM2、DYNC1LI1、GABBR1、GNAI1等核心靶基因。结论 凉血通瘀方对脑出血急性期鼠脑组织内miRNA的表达有重要影响；显著差异表达miRNAs可能通过靶向核心基因调控凉血通瘀方干预急性脑出血的病理过程及预后。     

Selecting patients for early interdisciplinary rehabilitation during neurointensive care after moderate to severe traumatic brain injury

Background

Early interdisciplinary rehabilitation (EIR) in neurointensive care is a limited resource reserved for patients with moderate to severe traumatic brain injury (TBI) believed to profit from treatment. We evaluated how key parameters related to injury severity and patient characteristics were predictive of receiving EIR, and whether these parameters changed over time.

Methods

Among 1003 adult patients with moderate to severe TBI admitted over 72 h to neurointensive care unit during four time periods between 2005 and 2020, EIR was given to 578 and standard care to 425 patients. Ten selection criteria thought to best represent injury severity and patient benefit were evaluated (Glasgow Coma Scale, Head Abbreviated Injury Scale, New-Injury-Severity-Scale, intracranial pressure monitoring, neurosurgery, age, employment, Charlson Comorbidity Index, severe psychiatric disease, and chronic substance abuse).

Results

In multivariate regression analysis, patients who were employed (adjOR 1.99 [95% CI 1.41, 2.80]), had no/mild comorbidity (adjOR 3.15 [95% CI 1.72, 5.79]), needed neurosurgery, had increasing injury severity and were admitted by increasing time period were more likely to receive EIR, whereas receiving EIR was less likely with increasing age (adjOR 0.97 [95% CI 0.96, 0.98]) and chronic substance abuse. Overall predictive ability of the model was 71%. Median age and comorbidity increased while employment decreased from 2005 to 2020, indicating patient selection became less restrictive with time.

Conclusion

Injury severity and need for neurosurgery remain important predictors for receiving EIR, but the importance of age, employment, and comorbidity have changed over time. Moderate prediction accuracy using current clinical criteria suggest unrecognized factors are important for patient selection.     

A guide to oral vaccination: Highlighting electrospraying as a promising manufacturing technique toward a successful oral vaccine development

Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development.