Oridonin ameliorates neuropathological changes and behavioural deficits in a mouse model of cerebral amyloidosis

Alzheimer's disease (AD) is the most common form of neurodegeneration and the major cause of dementia. This multifactorial disorder is clinically defined by progressive behavioural and cognitive deficits, and neuropathologically characterized by β‐amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Oridonin, a diterpenoid isolated from Chinese herb Rabdosia rubescens, has multiple biological properties, especially anti‐inflammatory and neuroregulatory activities. Potential therapeutic effects of Oridonin were investigated in an animal model of cerebral amyloidosis for AD, transgenic APP/PS1 mice. Oridonin was suspended in carboxymethylcellulose or loaded with a nanostructured emulsion, and was orally administrated or injected. Before, during and following the experimental treatments, behavioural tests were performed with these transgenic mice and their naive littermates. Following relatively short‐term treatments of 10 days, brain tissue of mice were removed for immunohistochemical assays. The results indicate that both oral treatment and injection of Oridonin significantly attenuated β‐amyloid deposition, plaque‐associated APP expression and microglial activation in brain of transgenic mice. Furthermore, injection of Oridonin‐nanoemulsion ameliorated deficits in nesting, an important affiliative behaviour, and in social interaction. Additional in vitro studies indicated that Oridonin effectively attenuated inflammatory reaction of macrophage and microglial cell lines. Our results suggest that Oridonin might be considered a promising therapeutic option for human AD or other neurodegenerative diseases.     

重度妊娠期肝内胆汁淤积症对母婴结局影响的临床分析

目的：分析重度妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy,ICP）对母婴结局的影响,以提高对ICP的认识与治疗水平。方法：选择ICP产妇58例,根据ICP分度标准分为轻度组（n=26例）和重度组（n=32例）,比较两组产妇的母婴结局。结果：与轻度组相比,重度组产妇剖宫产率、产后出血与平均产后出血量显著升高或增加,阴道分娩率显著降低,组间比较差异均具有统计学意义（P〈0.05）;重度组新生儿早产、胎儿窘迫、羊水污染和新生儿窒息的发生率均显著上升,新生儿平均出生体重显著降低,组间比较差异均具有统计学意义（P〈0.05）。结论：ICP对产妇及新生儿均有不良影响,对ICP严重程度进行划分,有利于临床处理。对于重度ICP产妇,应尽早采取剖宫产分娩的方式终止妊娠。     

Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance

Cerebral ischemia-reperfusion (I-R) is a complex pathological process. Although autophagy can be evoked by ischemia, its involvement in the reperfusion phase after ischemia and its contribution to the fate of neurons remains largely unknown. In the present investigation, we found that autophagy was activated in the reperfusion phase, as revealed in both mice with middle cerebral artery occlusion and oxygen-glucose deprived cortical neurons in culture. Interestingly, in contrast to that in permanent ischemia, inhibition of autophagy (by 3-methyladenine, bafilomycin A₁, Atg7 knockdown or in atg5^?/? MEF cells) in the reperfusion phase reinforced, rather than reduced, the brain and cell injury induced by I-R. Inhibition of autophagy either with 3-methyladenine or Atg7 knockdown enhanced the I-R-induced release of cytochrome c and the downstream activation of apoptosis. Moreover, MitoTracker Red-labeled neuronal mitochondria increasingly overlapped with GFP-LC3-labeled autophagosomes during reperfusion, suggesting the presence of mitophagy. The mitochondrial clearance in I-R was reversed by 3-methyladenine and Atg7 silencing, further suggesting that mitophagy underlies the neuroprotection by autophagy. In support, administration of the mitophagy inhibitor mdivi-1 in the reperfusion phase aggravated the ischemia-induced neuronal injury both in vivo and in vitro. PARK2 translocated to mitochondria during reperfusion and Park2 knockdown aggravated ischemia-induced neuronal cell death. In conclusion, the results indicated that autophagy plays different roles in cerebral ischemia and subsequent reperfusion. The protective role of autophagy during reperfusion may be attributable to mitophagy-related mitochondrial clearance and inhibition of downstream apoptosis. PARK2 may be involved in the mitophagy process.     

晚期早产儿颅内出血的相关因素分析

目的：探讨晚期早产儿颅内出血的相关因素,指导晚期早产儿颅内出血的防治。方法：2011年9月至2012年8月我院收治晚期早产儿253例,其中有210例行头颅MRI检查,以经头颅MRI检查确诊颅内出血30例为ICH组,同时随机抽取同期住院的经头颅MRI证实无颅内出血晚期早产儿60例作为对照组。应用SPSS 17.0进行统计学分析。结果：1.ICH组产前激素应用率显著低于对照组（P〈0.05）。2.ICH组经阴分娩、胎膜早破、代谢性酸中毒发生率显著高于对照组（P〈0.05）。3.Logistic回归分析显示产前激素是颅内出血的保护因素（P〈0.05）,而经阴分娩、胎膜早破（P〈0.01）、代谢性酸中毒（P〈0.05）是颅内出血的危险因素。结论：产前应用激素是晚期早产儿颅内出血的保护因素,经阴分娩、胎膜早破、代谢性酸中毒是晚期早产儿颅内出血高危因素。     

重症肺炎影响极低出生体重儿血小板及凝血功能的研究

目的:通过观察我院收治的极低出生体重新生儿肺炎的临床治疗,研究重症肺炎对该类疾病患儿的血小板及凝血功能的影响,探讨其临床研究价值.方法:将47例一般肺炎的极低出生体重新生儿设为对照组,45例重症肺炎的极低出生体重新生儿设为实验组,对比分析两组患儿的血小板参数的检测指标并行患儿凝血功能检查.结果:在血小板参数方面,实验组在MPV和PDW的数据较对照组高,而在PLT明显较低;在凝血功能方面,实验组在PT、APTT和TT等方面的数据较对照组高,而在FIB方面明显较低.结论:临床上对动态监测重症肺炎患儿血小板的变化情况,对判断该疾病患儿的预后具有积极的参考与预警意义,而对重症肺炎患儿出现凝血系统功能紊乱及时把握具体发病机制,对症进行凝血功能恢复治疗,值得临床进一步研究与探讨.     

Identification of a novel mutation in ZAP70 and prenatal diagnosis in a Turkish family with severe combined immunodeficiency disorder

Protein tyrosine kinases (PTKs) play an important role in T cell development and activation. In vitro and in vivo defects, resulting in variable deficiencies in thymic development and in T cell antigen receptor (TCR) signal transduction, in PTKs have been shown. ZAP70, one of those PTKs, is a 70-kDa tyrosine phosphoprotein and associates with the ζ chain and undergoes tyrosine phosphorylation following TCR stimulation. It is expressed in T and natural killer (NK) cells. Several mutations were shown to lead to an autosomal recessive form of severe combined immunodeficiency disease (SCID).     

Multifaceted applications of nanomaterials in cell engineering and therapy

Nanomaterials with superior physiochemical properties have been rapidly developed and integrated in every aspect of cell engineering and therapy for translating their great promise to clinical success. Here we demonstrate the multifaceted roles played by innovatively-designed nanomaterials in addressing key challenges in cell engineering and therapy such as cell isolation from heterogeneous cell population, cell instruction in vitro to enable desired functionalities, and targeted cell delivery to therapeutic sites for prompting tissue repair. The emerging trends in this interdisciplinary and dynamic field are also highlighted, where the nanomaterial-engineered cells constitute the basis for establishing in vitro disease model; and nanomaterial-based in situ cell engineering are accomplished directly within the native tissue in vivo. We will witness the increasing importance of nanomaterials in revolutionizing the concept and toolset of cell engineering and therapy which will enrich our scientific understanding of diseases and ultimately fulfill the therapeutic demand in clinical medicine.     

Relations between Stimulus Force,Skin Displacement,and Discharge Characteristics of Slowly Adapting Type I Cutaneous Mechanoreceptors in Glabrous Skin of Squirrel Monkey Hand

(1) The contributions of viscoelastic properties of squirrel monkey glabrous skin to slowly adapting Type I (SAI) mechanore-ceptive afferent fiber discharge were examined in the present study. Individual fibers of the median and ulnar nerves were isolated by microdissection in six monkeys anesthetized with pentobarbital sodium. Utilizing mechanical stimulation and data analysis techniques identical to those of a previous study of raccoon glabrous skin and its mechanoreceptors (Pubols, 1982a; Pubols and Maliniak, 1984), we studied and compared responses to punctate mechanical stimuli controlled with respect to force or displacement. (2) Squirrel monkey glabrous skin was found to be more compliant than raccoon glabrous skin, in that a given force applied to either a digital or a palmar skin pad produced a greater displacement of squirrel monkey skin. Skin displacement increased approximately linearly with increasing forces at the beginning of static stimulation, but over time (at least up to 20 sec), the relationship became negatively accelerated. (3) Absolute-force thresholds of individual SAI units were significantly lower in squirrel monkey (mean = 122 mg, range = 48-340 mg) than in raccoon (mean =484 mg, range = 70-1,290 mg). However, absolute-displacement thresholds were insignificantly lower (squirrel monkey: mean = 17.24 μm, range = 5-30μ raccoon: mean = 30 μm, range = 5-185 μm). (4) Application of suprathreshold forces (range = 1-20 g) and displacements (range = 500-1,000 μm) revealed greater interunit variability in response to maintained stimulation than previously found in raccoon. In 8 out of 15 fibers, the rate of adaptation was significantly greater during constant-displacement than during constant-force stimulation; in 4 cases there was no significant difference; and in 3 cases the rate of adaptation was significantly greater during constant-force stimulation. (5) Potential sources of interunit variability include surface topography of the hand, properties of cutaneous and subcutaneous tissues in the vicinity of the receptor, and experimental variables such as stimulus amplitude and rate of stimulus onset. (6) It is suggested that both regional and species differences in functional properties of cutaneous mechanore-ceptors are more likely attributable to differences in mechanical properties of skin and subjacent tissues than to any inherent differences in receptor properties.