How structural and functional MRI can inform dual-site tACS parameters: A case study in a clinical population and its pragmatic implications

BackgroundAbnormalities in frontoparietal network (FPN) were observed in many neuropsychiatric diseases including substance use disorders. A growing number of studies are using dual-site-tACS with frontoparietal synchronization to engage this network. However, a computational pathway to inform and optimize parameter space for frontoparietal synchronization is still lacking. In this case study, in a group of participants with methamphetamine use disorders, we proposed a computational pathway to extract optimal electrode montage while accounting for stimulation intensity using structural and functional MRI.MethodsSixty methamphetamine users completed an fMRI drug cue-reactivity task. Four main steps were taken to define electrode montage and adjust stimulation intensity using 4x1 high-definition (HD) electrodes for a dual-site-tACS; (1) Frontal seed was defined based on the maximum electric fields (EF) predicted by simulation of HD montage over DLPFC (F3/F4 in EEG 10–10), (2) frontal seed-to-whole brain context-dependent correlation was calculated to determine connected regions to frontal seeds, (3) center of connected cluster in parietal cortex was selected as a location for placing the second set of HD electrodes to shape the informed montage, (4) individualized head models were used to determine optimal stimulation intensity considering underlying brain structure. The informed montage was compared to montages with large electrodes and classic frontoparietal HD montages (F3-P3/F4-P4) in terms of tACS-induced EF and ROI-to-ROI task-based/resting-state connectivity.ResultsCompared to the large electrodes, HD frontoparietal montages allow for a finer control of the spatial peak fields in the main nodes of the FPN at the cost of lower maximum EF (large-pad/HD: max EF[V/m] = 0.37/0.11, number of cortical sub-regions that EF exceeds 50% of the max = 77/13). For defining stimulation targets based on EF patterns, using group-level head models compared to a single standard head model results in comparable but significantly different seed locations (6.43 mm Euclidean distance between the locations of the frontal maximum EF in standard-space). As expected, significant task-based/resting-state connections were only found between frontal-parietal locations in the informed montage. Cue-induced craving score was correlated with frontoparietal connectivity only in the informed montage (r = ?0.24). Stimulation intensity in the informed montage, and not in the classic HD montage, needs 40% reduction in the parietal site to reduce the disparity in EF between stimulation sites.ConclusionThis study provides some empirical insights to montage and dose selection in dual-site-tACS using individual brain structures and functions and proposes a computational pathway to use head models and functional MRI to define (1) optimum electrode montage for targeting FPN in a context of interest (drug-cue-reactivity) and (2) proper transcranial stimulation intensity.     

小分子抗血管生成药物在非小细胞肺癌中的研究进展

肺癌是世界上发病率最高的癌症之一，且尚无二线进展后的标准治疗方案，而肿瘤血管生成目前已被确定为恶性肿瘤的重要治疗靶点，小分子多靶点血管激酶抑制剂可通过抑制血管生成相关信号通路，抑制肿瘤血管的生成。目前已开展多项小分子抗血管生成药物治疗非小细胞肺癌的临床试验，且已有部分血管内皮生长因子受体酪氨酸激酶抑制剂（vascular endothelial growth factor receptor-tyrosine kinase inhibitors, VEGFR-TKIs）获批治疗晚期非小细胞肺癌，本文基于国内外多项小分子抗血管生成药物治疗非小细胞肺癌的发展现状，归纳了多个VEGFR-TKIs及成纤维细胞生长因子受体（fibroblast growth factor receptor, FGFR）-TKI单药或联合[包括分别与化疗、表皮生长因子受体（epidermal growth factor receptor, EGFR）-TKIs、免疫治疗、放疗等联合）]治疗非小细胞肺癌的疗效与安全性研究，同时探讨了VEGFR-TKIs可能存在的耐药机制及疗效预测指标等，并对未来抗血管治疗非小细胞肺癌的发展趋势以及存在的潜在问题进行展望，同时为肺癌后续的精准治疗及个体化治疗提供新的思路。     

人乳头瘤病毒感染超微结构观察

本文对5例典型尖锐湿疣标本及10例可疑人乳头瘤病毒感染标本进行透射电子显微镜观察。结果典型尖锐湿疣标本中仅1例于细胞核内见到人乳头瘤病毒,排列规则呈结晶状。其余14例标本的细胞内均见不同程度的由病毒感染所引起的非特异性病理变化。本文对人孔头瘤病毒及受感染细胞的超微结构进行了初步探讨。     

重组跨膜型人CD55分子在小鼠NIH3T3细胞上的表达及其补体溶破保护功能的研究

目的 :在小鼠NIH3T3细胞转染表达人天然GPI锚固型CD5 5和重组跨膜型CD5 5 TM分子 ,观察比较它们对人补体溶破异源细胞的抑制功能。方法 :将带有CD5 5cDNA、CD5 5 TMcDNA的重组逆病毒表达质粒CD5 5 pLXSN、CD5 5TM pLXSN经脂质体法转染PA317细胞 ,用病毒上清感染小鼠成纤维母细胞NIH3T3。经G418加压筛选 ,利用FACS检测获得表达CD5 5和CD5 5 TM分子的阳性细胞克隆 ,通过MTT比色法比较两种分子对人血清补体溶破细胞的抑制功能有无差别。结果 :细胞转染筛选获得多个表达跨膜型人CD5 5分子的NIH3T3细胞克隆 ,补体杀伤试验证实其具有抑制人补体溶破的功能 ,且两种分子的补体抑制功能无明显差异。结论 :成功地建立了稳定表达天然CD5 5、跨膜型CD5 5分子的小鼠NIH3T3细胞 ,证实其表达的GPI型CD5 5分子和CD5 5TM分子均具有抑制人补体溶破细胞的功能 ,为进一步探讨应用跨膜型的CD5 5分子对PNH进行基因治疗奠定了基础。     

强直性肌营养不良毛细血管的超微结构变化

５例强直性肌营养不良患者的腓肠肌活检标本超微结构研究结果发现，除肌纤维变性、萎缩和结缔组织增生外，毛细血管病变特别突出。血管壁严重增厚，基板呈多层性改变，周细胞增生。有些复层的毛细血管基板多达９层。内皮细胞外可有多层周细胞半包绕血管，有些周细胞又发出分支沿管壁延伸。周细胞一般位于内皮细胞下第一层基板之外，也可位于复层基板之中，周细胞与周细胞之间有多层基板。内皮细胞和周细胞内富含吞饮小泡。血管病变程度与肌纤维变性程度呈平行关系。     

流行性出血热患者骨髓细胞超微结构的研究

8例流行性出血热患者骨髓细胞的超微结构研究结果发现骨髓细胞出现变性、空泡、粗面内质网及高尔基体扩张。并在胞浆中发现颗粒-丝状病毒包涵体及直径为100nm的病毒颗粒。同时胶体金免疫电镜发现骨髓细胞EHF抗原阳性,说明骨髓细胞是其繁殖、复制的场所。     

家犬实验性附睾淤积症及其超声波治疗对附睾起始部超微结构的影响

实验性附睾淤积症引起家犬附睾起始部主细胞超微结构异常改变,但较附睾体部所见为轻;经超声波处理后(功率0.75W/cm~2,每日一次,每次8min,连续7日)则见其明显改变、或完全恢复,且未造成附睾起始部主细胞新的损伤。本实验结果在与附睾体部主细胞相应变化进行比较后,发现由于附睾淤积症对附睾管不同部位的影响是不同的,因而这种形态和功能均已不同程度改变了的附睾不同部位的主细胞对超声波作用的反应也各不相同,这除因主细胞功能状态不同外,尚与超声波声场的不均匀有关,提示探寻超声波治疗最适宜的量不仅必要,而且是有可能找到的。     

焦痂提取液中丙二醛含量对线粒体呼吸及内膜能化作用的影响

大鼠背部20％光辐射Ⅲ度烧伤7天后的焦痂提取液及1:4、1:8稀释液能对正常大鼠肝线粒体呼吸产生明显的抑制作用,相同方法制成的正常皮提取液只呈轻度抑制,1:4稀释液已无抑制作用,两者丙二醛含量相差悬殊,丙二醛含量与抑制率呈相关,但进一步分析表明这种相关为共存现象,丙二醛含量增高不是呼吸率下降的直接原因。丙二醛增高与膜脂双层的破坏有关,内膜能化作用实验表明,当膜脂受到一定程度破坏时,能化作用受到抑制。然而在能化作用未表现异常时,呼吸率已呈一定程度抑制,故呼吸率抑制还受到提取液其他组分的影响。