The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo

Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.     

“六气为一气”及其文化内涵

从文理、医理以及文化内涵多角度剖析《灵枢·决气》所载"六气为一气"的思想内涵。精、气、津、液、血、脉"六气"为人体之基础,然同源于"一气",其功能体现了阴阳互根互用。"六气为一气"观的文化内涵包括三个方面:一是在中国古代地理、社会、政治、哲学文化大环境下,其思维方式以"尚同""求一"为根本;二是万物为"一气"的哲学思维,即"气一元论";三是"气一元论"的延伸即"整体思维",正是中国古代文化"同源"思想的体现。     

Dietary fish oil,and to a lesser extent the fat-1 transgene,increases astrocyte activation in response to intracerebroventricular amyloid-β 1–40 in mice

Objectives: Increases in astrocytes and one of their markers, glial fibrillary acidic protein (GFAP) have been reported in the brains of patients with Alzheimer’s disease (AD). N-3 polyunsaturated fatty acids (PUFA) modulate neuroinflammation in animal models; however, their effect on astrocytes is unclear.

Methods: Fat-1 mice and their wildtype littermates were fed either a fish oil diet or a safflower oil diet deprived of n-3 PUFA. At 12 weeks, mice underwent intracerebroventricular infusion of amyloid-β 1-40. Astrocyte phenotype in the hippocampus was assessed at baseline and 10 days post-surgery using immunohistochemistry with various microscopy and image analysis techniques.

Results: GFAP increased in all groups in response to amyloid-β, with a greater increase in fish oil-fed mice than either fat-1 or wildtype safflower oil-fed mice. Astrocytes in this group were also more hypertrophic, suggesting increased activation. Both fat-1- and fish oil-fed mice had greater increases in branch number and length in response to amyloid-β infusion than wildtype safflower animals.

Conclusion: Fish oil feeding, and to a lesser extent the fat-1 transgene, enhances the astrocyte activation phenotype in response to amyloid-β 1-40. Astrocytes in mice fed fish oil were more activated in response to amyloid-β than in fat-1 mice despite similar levels of hippocampal n-3 PUFA, which suggests that other fatty acids or dietary factors contribute to this effect.     

五味子醇甲对APP/PS1小鼠学习记忆和NF-κB p65的影响

目的研究五味子醇甲(SCH)对APP/PS1双转基因痴呆小鼠行为学和NF-κB p65的影响。方法将35只APP/PS1双转基因痴呆小鼠随机分为模型(APP/PS1)组、五味子醇甲(SCH+APP/PS1)组;另以同背景同月龄的C 57 BL/6 J阴性小鼠为空白(WT)组。SCH+APP/PS1组给予SCH悬浊液灌胃(2.6 mg·kg^-1·d^-1),模型组和空白组给予等量蒸馏水灌胃。各组灌胃30 d进行Mirror水迷宫空间探索试验后取材。HE染色法观察皮层及海马CA1区神经细胞的形态结构。运用DCFH-DA法检测脑组织活性氧(ROS)含量。Western印迹检测法检验磷酸化核转录因子(NF-κB p65,pp65)的表达。结果与APP/PS 1组相比,APP/PS 1+SCH组有效区停留距离及时间明显延长,差异有统计学意义(P<0.05,P<0.01);APP/PS 1+SCH组穿越有效区次数和平台区停留距离增加,均差异有统计学意义(P<0.01)。APP/PS 1+SCH组HE染色观察皮层有部分神经细胞萎缩、减少,较APP/PS1组明显好转,海马细胞排列整齐度尚可、较均匀。与APP/PS1组相比,APP/PS1+SCH组能降低ROS含量,差异有统计学意义(P<0.05)。APP/PS 1+SCH组皮层及海马pp65蛋白相对表达量下调(P<0.05,P<0.01)。结论SCH可能通过降低ROS含量和抑制pp65保护脑组织形态结构和提高APP/PS1鼠空间探索记忆能力。     

The Impact of Frailty and Comorbidity on Institutionalization and Mortality in Persons With Dementia: A Prospective Cohort Study

Objectives

The predictive value of frailty and comorbidity, in addition to more readily available information, is not widely studied. We determined the incremental predictive value of frailty and comorbidity for mortality and institutionalization across both short and long prediction periods in persons with dementia.

《黄帝内经》水模型化推理研究

模型化推理是指以模型特别是思维模型为中介或工具,由一个或几个前提推出结论的思维方法。《黄帝内经》由于其历史条件的限定,较多地采用了天然实物模型进行推理,而水与人类生活密切相关,自然也就成了人类认识事物乃至人体生命活动的最为普遍的天然模型。通过阐述水模型与《黄帝内经》血脉气血循环、经脉气血运行、十二经脉体系建构、六淫病因认识、气血津液病机以及相关临床诊治思维的关系,分析指出《黄帝内经》天然模型化推理具有直观性、经验性、功能性、非结构性、整体全息性、时序性等特征。     

大补元煎通过上调BDNF/TrkB/CREB信号通路改善APP/PS1双转基因痴呆小鼠海马突触可塑性

目的:观察大补元煎对APP/PS1痴呆小鼠海马突触可塑性及脑源性神经营养因子(BDNF)/酪氨酸蛋白激酶受体B(TrkB)/环磷酸腺苷反应元件结合蛋白(CREB)信号通路的作用,并探讨其改善突触可塑性的可能机制。方法:将APP/PS1小鼠36只分为模型组、多奈哌齐组(6.5×10~(-4)g·kg~(-1)·d~(-1))和大补元煎组(13.2 g·kg~(-1)·d~(-1)),野生鼠12只设为正常组,正常组和模型组给予等体积生理盐水,各组连续灌胃30 d。应用Morris水迷宫检测各组小鼠的学习记忆能力,应用尼氏染色和高尔基染色观察海马区神经元和突触的病理形态变化,应用免疫荧光(IF)观察海马突触后致密蛋白95(PSD95)及突触素(SYN)的蛋白表达水平,采用蛋白免疫印迹法(Western blot)检测海马中BDNF,TrkB,CREB及磷酸化CREB(p-CREB)的蛋白表达水平。结果:与空白组比较,模型组小鼠平台潜伏期和游泳总路程增加(P0.01),穿越平台次数和目标象限停留时间减少(P0.01),小鼠海马CA3区神经元胞内尼氏体减少或消失,小鼠海马CA3区神经元及树突分支数量、树突棘密度减少(P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平减少(P0.01)。与模型组比较,多奈哌齐组和大补元煎组小鼠平台潜伏期和游泳总路程减少(P0.05,P0.01),穿越平台次数和目标象限停留时间增加(P0.05,P0.01),小鼠海马CA3区神经元胞内尼氏体数量增多,小鼠海马CA3区神经元及树突分支数量,树突棘密度增加(P0.05,P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平增加(P0.05,P0.01)。结论:大补元煎改善APP/PS1双转基因小鼠突触可塑性的机制可能与其上调小鼠海马中BDNF/TrkB/CREB信号通路有关。     

杜元灏教授针刺治疗失眠经验

失眠是由各种原因导致的入睡困难和(或)睡眠维持困难的睡眠障碍,主要特征是睡眠感不满意,属于中医学"不得眠""不寐"范畴。传统多从心、肝、胆、脾、胃、肾论治该病,杜元灏教授认为脏腑机能失调,气血不和,阳不能入阴,阴不能涵阳,神不守舍而致失眠。重视"脑为元神之腑"的理论,且因督脉入络脑,夹脊穴为五脏六腑之气转输、流注之处,杜教授多强调从脑、督脉以及夹脊穴论治失眠,为针刺治疗失眠提供新思路。     

王友仁呼吸按动法治疗寒邪客胃型胃脘痛经验

目的:探讨王友仁主任医师推拿手法治疗寒邪客胃型胃脘痛的临床经验。方法:从病因病机和治则治法方面论述王老以"呼吸按动法"为主治疗寒邪客胃型胃脘痛的学术观点和临床经验,对其基本手法及配伍予以总结。结果:王老以"呼吸按动法"为主,配合温中散寒的手法治疗寒邪客胃型胃脘痛,临床疗效佳。结论:王老认为胃脘痛多因胃腑外感寒邪或脾胃阳虚所致,呼吸按动法疗效显著。