Improved prediction of brain age using multimodal neuroimaging data

Brain age prediction based on imaging data and machine learning (ML) methods has great potential to provide insights into the development of cognition and mental disorders. Though different ML models have been proposed, a systematic comparison of ML models in combination with imaging features derived from different modalities is still needed. In this study, we evaluate the prediction performance of 36 combinations of imaging features and ML models including deep learning. We utilize single and multimodal brain imaging data including MRI, DTI, and rs‐fMRI from a large data set with 839 subjects. Our study is a follow‐up to the initial work (Liang et al., 2019. Human Brain Mapping) to investigate different analytic strategies to combine data from MRI, DTI, and rs‐fMRI with the goal to improve brain age prediction accuracy. Additionally, the traditional approach to predicting the brain age gap has been shown to have a systematic bias. The potential nonlinear relationship between the brain age gap and chronological age has not been thoroughly tested. Here we propose a new method to correct the systematic bias of brain age gap by taking gender, chronological age, and their interactions into consideration. As the true brain age is unknown and may deviate from chronological age, we further examine whether various levels of behavioral performance across subjects predict their brain age estimated from neuroimaging data. This is an important step to quantify the practical implication of brain age prediction. Our findings are helpful to advance the practice of optimizing different analytic methodologies in brain age prediction.     

Altered resting‐state functional connectivity and effective connectivity of the habenula in irritable bowel syndrome: A cross‐sectional and machine learning study

Irritable bowel syndrome (IBS) is a disorder involving dysfunctional brain–gut interactions characterized by chronic recurrent abdominal pain, altered bowel habits, and negative emotion. Previous studies have linked the habenula to the pathophysiology of negative emotion and pain. However, no studies to date have investigated habenular function in IBS patients. In this study, we investigated the resting‐state functional connectivity (rsFC) and effective connectivity of the habenula in 34 subjects with IBS and 34 healthy controls and assessed the feasibility of differentiating IBS patients from healthy controls using a machine learning method. Our results showed significantly enhanced rsFC of the habenula‐left dorsolateral prefrontal cortex (dlPFC) and habenula‐periaqueductal grey (PAG, dorsomedial part), as well as decreased rsFC of the habenula‐right thalamus (dorsolateral part), in the IBS patients compared with the healthy controls. Habenula‐thalamus rsFC was positively correlated with pain intensity (r = .467, p = .005). Dynamic causal modeling (DCM) revealed significantly decreased effective connectivity from the right habenula to the right thalamus in the IBS patients compared to the healthy controls that was negatively correlated with disease duration (r = ?.407, p = .017). In addition, IBS was classified with an accuracy of 71.5% based on the rsFC of the habenula‐dlPFC, habenula‐thalamus, and habenula‐PAG in a support vector machine (SVM), which was further validated in an independent cohort of subjects (N = 44, accuracy = 65.2%, p = .026). Taken together, these findings establish altered habenular rsFC and effective connectivity in IBS, which extends our mechanistic understanding of the habenula's role in IBS.     

益母草制剂的开发与应用

益母草制剂在临床中应用广泛,主要用于多种妇产科疾病的治疗,且效果显著。其中,益母草注射剂、益母草颗粒、益母草片是临床上最常见的益母草剂型,其有效性和安全性在长期的临床实践中得到认可。本论文结合项目组对益母草制剂的二次开发研究思路,对上述具有代表性的益母草制剂的制剂工艺、质量控制和临床应用进行介绍,以期为益母草制剂的现代研究和临床安全应用提供一定的参考。     

耳穴埋豆治疗胸腔镜手术后疼痛临床观察

目的观察耳穴埋豆治疗胸腔镜术后疼痛的临床效果。方法选取80例胸腔镜术后患者随机分为2组,每组40人。对照组患者术后采用WHO推荐的三阶梯镇痛疗法,给予对症治疗。观察组患者在进行三阶梯镇痛治疗的基础上加用耳穴埋豆止痛。记录2组患者6 h,12 h,24 h,36 h静息时、咳嗽时VAS评分。结果手术后患者6 h,12 h,24 h,36 h静息时、咳嗽时VAS评分结果有统计学差异。结论耳穴埋豆能减轻胸腔镜术后患者的疼痛。     

SU11274抑制人子宫内膜癌细胞增殖的分子机制

目的:探索HGF/c-met传导通路抑制剂SU11274抑制子宫内膜癌细胞增殖的分子机制。方法:使用不同浓度SU11274（0.5 μmol/L、1.0 μmol/L、1.5 μmol/L）作用ishikawa 和HEC-1B 两种细胞株1小时后，加入40 ng/ml的HGF，继续培养48小时，然后使用RT-PCR检测c-met、Survivin、XIAP水平以及Western blot检测细胞中Survivin、XIAP蛋白表达水平。结果:ishikawa细胞c-met低表达，而HEC-1B细胞c-met明显高表达，HEC-1B细胞中c-met mRNA表达量为ishikawa中的2.5倍。SU11274可以使HEC-1B、ishikawa细胞的Survivin、XIAP蛋白表达下调，呈现剂量依赖性，并且在HEC-1B细胞中，该下调作用明显强于ishikawa细胞（P<0.05）。结论:SU11274可以通过下调HGF/c-met传导通路中Survivin、XIAP的表达来抑制人子宫内膜癌细胞增殖。     

AVPR2 基因变异致先天性肾性尿崩症2 例报告并文献复习

目的探讨先天性肾性尿崩症的临床特点、基因诊断及治疗。方法回顾分析2例先天性肾性尿崩症患儿的临床资料。结果 2例男性患儿分别为5岁和3岁2个月,均以多饮多尿、生长迟缓为主要表现。经禁水-加压素试验证实为持续低比重尿。尿崩症相关基因检测发现,例1患儿精氨酸加压素受体2(AVPR2)基因外显子2杂合错义突变c.650CT(p.P217L),且为新发变异。例2患儿AVPR2基因外显子1及外显子2缺失,亦为新发变异,其母亲为携带者,父亲AVPR2基因未见异常变异。对新发的变异位点通过Mutation-taster及Polyphen2软件预测为致病性变异。2例患儿口服氢氯噻嗪联合吲哚美辛治疗1年,尿量及夜尿减少,无电解质紊乱及肾功能受损等。结论 AVPR2基因为先天性肾性尿崩症的主要致病基因,发现2种国内外未见报道的新变异位点。     

六西格玛在肿瘤标志物质量目标选择上的应用

目的应用6σ理论对肿瘤标志物项目的分析性能进行评价，并初步确定各项目的质量目标。 方法收集本实验室2018年1至12月室内质控数据和国家卫生健康委临床检验中心室间质量评价结果，以生物学变异导出的质量规范和国家室间质量评价标准作为允许总误差(TEa)计算6项肿瘤标志物的σ水平，并依据质量目标选择流程图和肿瘤标志物分析性能验证图评价肿瘤标志物的分析性能，进而为肿瘤标志物选择合适的质量目标。 结果应用不同层级的生物学变异导出的质量规范和国家室间质量评价标准，肿瘤标志物项目的σ水平存在显著差异；依据质量目标选择流程图：选择生物学变异导出的"适当的"质量规范作为CA125项目的质量目标，选择生物学变异导出的"最低的"质量规范作为t-PSA、CEA、AFP、CA199和CA153项目的质量目标。 结论6σ能够客观评价肿瘤标志物的分析性能，并为实验室质量目标的选择提供重要的参考价值。     

枸杞多糖对大鼠角膜缘干细胞体外增殖的影响研究

目的通过体外分离和培养大鼠角膜缘干细胞(Limbal Stem Cells, LSCs)，观察枸杞多糖(Lyciumbarbarum Polysaccharide, LBP)对LSCs体外增殖的影响，为中药体外培养LSCs的研究提供实验资料。 方法体外分离和培养LSCs，显微镜观察LSCs的细胞形态特征，通过免疫荧光检测转录因子p63初步鉴定大鼠LSCs；分对照组和枸杞多糖处理组，每组20例，免疫印迹检测增殖细胞核抗原(Proliferating Cell Nuclear Antigen, PCNA)，初步探讨枸杞多糖对LSCs的增殖影响。 结果镜下观察LSCs体积小，呈多边形或椭圆形，胞核较大，核质比例大，免疫荧光结果显示体外分离的LSCs可表达p63(阳性率为76.41±1.66%)；枸杞多糖处理后LSCs的PCNA蛋白的表达水平高于对照组，并且随着枸杞多糖浓度的增加，PCNA蛋白的表达升高(P<0.05)。 结论枸杞多糖对LSCs的增殖和生长具有促进和维持的作用。     

基于血清代谢组学技术考察通阳化浊方与四妙勇安汤治疗冠心病模型家兔的作用机制＊

目的 通过血清代谢组学技术，考察通阳化浊方与四妙勇安汤在治疗冠心病家兔中的作用机制。方法 40只雄性白兔，随机分为空白组、模型组、通阳化浊方组与四妙勇安汤组4组，每组10只。空白组正常饮食，模型组给予高脂饲料喂养至第8周，于第4周结束后，用球囊法手术损伤实验兔的右侧颈总动脉；在模型组基础上，两个实验组分别在术后，灌胃给予通阳化浊方和四妙勇安汤，连续4周，每日1次。给药结束后，模型组与实验组每组抽取3只家兔，采集全血后，用LC-MS技术进行血清代谢组学检测，运用PCA与OPLS-DA分析法来寻找差异性表达的代谢物和代谢途径。结果 相较于模型组，通阳化浊方与四妙勇安汤组分别存在45和27个差异化合物，通阳化浊方组涉及18条代谢通路，根据Impact值 > 0.05筛选出5条主要代谢通路，包括精氨酸和脯氨酸代谢、组氨酸代谢、牛磺酸和牛磺酸代谢、精氨酸生物合成和α-亚麻酸代谢；四妙勇安汤组涉及11条代谢通路，筛选出2条主要代谢通路分别为牛磺酸和牛磺酸代谢、组氨酸代谢。结论 通阳化浊方与四妙勇安汤在治疗冠心病模型家兔的过程中存在差异性代谢产物，干预相应的代谢通路可能会对药物在模型中的作用产生影响。