Pharmacological basis for use of madecassoside in gouty arthritis: anti-inflammatory,anti-hyperuricemic,and NLRP3 inhibition

Objectives: Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints, which is associated with the rise of serum urate content. This study aims to investigate the therapeutic effect of Madecassoside on gouty arthritis and hyperuricemia.

Methods: DBA/1 mice were intradermally injected with MSU to stimulate joint inflammation or intraperitoneally injected with MSU to trigger peritonitis. Moreover, ICR mice were exposed to potassium oxonate to stimulate hyperuricemia.

Results: Madecassoside repressed MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation in DBA/1 mice with gouty arthritis. Neutrophil infiltration and IL-1β & IL-6 & MCP-1 secretion was also alleviated in lavage fluids from DBA/1 mice with peritonitis due to Madecassoside treatment. Furthermore, Madecassoside decreased MSU-induced neutrophil cytosolic factor 1, caspase-1 and NLRP3 expression in mice with peritoneal inflammation. In hyperuricemic mice, Madecassoside improved renal dysfunction. Serum uric acid, BUN, and creatinine were down-regulated by Madecassoside.

Conclusion: These findings indicate that Madecassoside has potential to ameliorate inflammation in both acute gouty arthritis model and peritonitis model, probably via regulating IL-1β and NLRP3 expression.

Practical point: Madecassoside also exhibited a urate-lowering effect and a renal protective effect in hyperuricemic mice.     

基于CNN算法的稳态体感诱发电位的特征识别

脑-机接口研究可为瘫痪病人的康复带来一种新的治疗方法。已有研究表明对手指或者正中神经施加一定频率的体感刺激,会引发相同频率且具有空间特异性的稳态体感诱发电位。为优化基于稳态体感诱发电位的脑-机接口的性能,通过快速傅里叶变换寻找12个健康被试的个人左手特定共振频率,采用事件相关谱扰动进行时频分析,检测其稳态体感诱发电位信号。基于共振频率对实验诱发的脑电信号进行1 Hz带通滤波,获得特定频带的数据,采用卷积神经网络(CNN)学习算法对其进行分类,并与采用共空间模式和支持向量机的特征提取及特征分类的方法(CSP+SVM)进行比较。所有被试的结果显示:基于共振频率滤波方法,采用CNN学习算法获得的离线分类准确率均高于85%,并且CNN学习算法的分类准确率显著性优于CSP+SVM的分类准确率(91.8%±5.9% vs 77.4%±8.5%,P<0.05)。因此,在基于稳态体感诱发电位的脑机接口的特征识别中,CNN学习算法相比传统使用的机器学习分类算法(如共空间模式+支持向量机)能够显著提升分类准确率,提高脑机接口的整体性能。     

永磁体磁共振电特性成像方法研究

磁共振电特性成像,是利用磁共振原始数据对被测生物组织的电特性进行重建的一种成像方法。利用有限元仿真软件,建立0.4 T主磁场下的射频线圈模型,测量仿真中射频场的分布情况。通过射频场空载和负载下射频场的均匀性,证明电特性的不同影响射频场的分布。用0.4 T永磁体磁共振设备对仿体和人体头部进行实验,并根据仿真数据和实验数据对电特性进行重建。结果表明,低场磁共振电特性在有无负载下,感兴趣区域的磁通密度均匀性相差将近4倍,磁通密度模值明显增加,这为磁共振电特性低场下发展提供一定的参考。     

Phenotype delineation of ZNF462 related syndrome

Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features.     

Temporal dynamic modulation of acute stress on error processing in healthy males

Error processing is critical for adaptive behaviors. Acute stress has been found to influence error processing. However, the neural dynamic correlates underlying this modulation remain elusive. To address this issue, we recruited 39 healthy male participants, who performed a two‐session task before and after an acute stress test while their behavioral and EEG data were recorded. The participants were randomly exposed to either a stress condition (Maastricht Acute Stress Test) or a control condition. The stress test consisted of several hand immersion tasks (ice‐cold water, 2°C) and mental arithmetic tasks. A color‐word Stroop task was used to investigate the stress effect on error responses. Based on the level of stress‐induced cortisol, the participants in the stress group were further classified as low (N = 13) or high (N = 13) cortisol responders. The results indicated that only in the high cortisol responders, the error‐related negativity (ERN) amplitude was reduced after acute stress. In addition, the ?ERN in the high cortisol responders was significantly smaller than that in the low cortisol responders. These results suggest that acute stress impairs error detection. However, the error positivity amplitudes increased in the stress group compared to the control group, indicating that acute stress leads to greater error assessment. Taken together, these results suggest that acute stress impairs error detection, which is modulated by individuals’ response level following acute stress, and leads to more emotional and/or motivational responses to the error signal once the error is consciously realized.     

干细胞的基础研究及其临床应用前景

干细胞是一类较为原始的细胞群体,具有极强的更新复制和增殖分化能力,主要分为两大类,包括胚胎干细胞和成体干细胞。近年来,随着科研人员对细胞研究的深入,造血干细胞、间充质干细胞、神经干细胞逐渐成为生物医学领域中极有价值的研究热点。随着干细胞分离、提取、纯化技术的不断发展,且因其特有的生物特性,干细胞在组织修复和再生医学上的应用获得突破性进展,并在临床治疗中发挥重要作用。除此之外,干细胞在药物研发、分子影像示踪以及3D支架等技术中也充当重要角色。针对干细胞在基础科学研究以及临床治疗的作用进行综述,为进一步深入干细胞疗法和提升干细胞研究技术提供参考。     

血液相关指标与系统性红斑狼疮活动性分析

目的探讨白细胞(white blood cell,WBC)、红细胞(red blood cell,RBC)、血小板(platelet,PLT)、血红蛋白(hemoglobin,HB)、淋巴细胞绝对值(absolute lymphocyte value,Lym#)、平均血小板体积(mean platelet volume,MPV)与系统性红斑狼疮(systemic lupus erythematosus,SLE)病情活动性关系。方法随机收集2017年12月至2018年11月我院风湿免疫科SLE病人样本37例,根据SLE活动指数(systemic lupus erythematosus disease activity index,SLEDAI)分为活动组与非活动组,同时收集同期健康体检者22例作为对照组,检测样本的血常规相关指标Lym#、MPV、WBC、RBC、HB、PLT及血清补体3(serum complement 3,C3),红细胞沉降率(erythrocyte sedimentation rate,ESR),比较各指标之间的相关性。结果 SLE活动组与对照组比较,Lym#、C3、MPV、PLT、RBC、HB均小于对照组,差异具有统计学意义(P<0.05),两组间WBC无差异(P>0.05)。SLE非活动组与对照组间比较,Lym#、RBC、HB差异有统计学意义(P<0.05),二组间WBC、PLT、C3、MPV无差异(P>0.05)。SLE活动组与非活动组比较,活动组MPV、Lym#、C3、WBC、PLT、HB均低于非活动组,差异有统计学意义(P<0.05),ESR高于非活动组(P<0.05),两组间RBC无统计学差异(P>0.05)。WBC、RBC、HB、PLT、Lym#、MPV与SLE活动性指标SLEDAI、ESR呈负相关,与C3呈正相关。结论 WBC、RBC、HB、 PLT、Lym#、MPV可作为系统性红斑狼疮活动性的观察指标。     

胰岛素联合唑来膦酸治疗糖尿病骨质疏松症对患者血清指标的影响

目的 分析胰岛素联合唑来膦酸治疗对糖尿病骨质疏松（DOP）患者血糖血脂以及骨代谢指标的影响。方法 选择2016年12月~2019年4月于我院诊治的DOP患者共136例进行研究,采用随机数字表法分为对照组和实验组,每组68例,对照组采用二甲双胍联合唑来膦酸治疗,实验组采用胰岛素联合唑来膦酸治疗,比较两组干预后血脂水平（TG、TC、LCL-C、HDL-C）、血糖指标（空腹、餐后2h、糖化血红蛋白）以及骨代谢相关指标（BAP、TRAP-5b、BGP以及s-CTX）。结果 治疗后实验组空腹、餐后2h血糖及HbA1c均低于对照组（P＜0.05）;实验组治疗后TG、TC、LCL-C、HDL-C水平均低于对照组（P＜0.05）;实验组BAP、BGP水平均高于对照组（P＜0.05）;实验组TRAP-5b水平均低于对照组（P＜0.05）;两组s-CTX指标比较,差异无统计学意义（P＞0.05）。结论 对DOP患者使用胰岛素与唑来膦酸联合治疗方案,有助于改善患者的血脂以及血糖水平,同时利于患者骨骼骨质的沉积,值得临床应用。     

The cellular mechanism of thalamic ponto-geniculo-occipital waves

The cellular mechanisms underlying the genesis of thalamic ponto-geniculo-occipital waves were studied in reserpinized cats under urethane anaesthesia. Simultaneous field potential and intracellular recordings were performed in the lateral geniculate nucleus after acute lesions of retinal and visual cortical inputs. In most relay cells, reserpine-induced ponto-geniculo-occipital waves were associated with a transient depolarization that was often interrupted by a unitary inhibitory postsynaptic potential. The depolarization grew in size with membrane hyperpolarization and was accompanied by an increase in membrane conductance. The inhibitory postsynaptic potential is likely to have resulted from the activation of intrageniculate interneurons since perigeniculate cells were always inhibited during the occurrence of ponto-geniculo-occipital waves. Under reserpine, thalamic ponto-geniculo-occipital waves could also be triggered by peribrachial or auditory stimulation. These evoked ponto-geniculo-occipital waves were associated with intracellular events identical to those occurring spontaneously after reserpine administration. In addition, thalamic spindle oscillations were readily blocked by the occurrence of spontaneous or evoked ponto-geniculo-occipital waves. On the basis of the present results and those already published in the literature, the conclusion is reached that lateral geniculate ponto-geniculo-occipital waves result from a nicotinic activation of relay cells and from a parallel muscarinic inhibition of perigeniculate cells by peribrachial afferents. The functional significance of the ponto-geniculo-occipital activity is discussed on the basis of the antagonistic action of these signals on thalamic oscillations. It is proposed that these signals are the central correlates of orienting reactions elicited by sensory stimuli during waking (the so-called eye movement potentials) and by internally generated drives during paradoxical sleep.     

应激致血压升高大鼠压力反射敏感性的频谱分析方法测定

通过心率变异性和高血压变异性的频谱分析，计算机血压为输入 ，心搏间隔为输出的传递函数，以传递函数的模量作为压发作敏性的指标。