Association Between Abnormal Fetal Head Growth and Autism Spectrum Disorder

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Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury

Apelin-13 is a novel endogenous ligand for an angiotensin-like orphan G-protein coupled receptor, and it may be neuroprotective against cerebral ischemia injury. However, the precise mechanisms of the effects of apelin-13 remain to be elucidated. To investigate the effects of apelin-13 on apoptosis and autophagy in models of cerebral ischemia/reperfusion injury, a rat model was established by middle cerebral artery occlusion. Apelin-13(50 μg/kg) was injected into the right ventricle as a treatment. In addition, an SH-SY5 Y cell model was established by oxygen-glucose deprivation/reperfusion, with cells first cultured in sugar-free medium with 95% N2 and 5% CO2 for 4 hours and then cultured in a normal environment with sugar-containing medium for 5 hours. This SH-SY5 Y cell model was treated with 10–7 M apelin-13 for 5 hours. Results showed that apelin-13 protected against cerebral ischemia/reperfusion injury. Apelin-13 treatment alleviated neuronal apoptosis by increasing the ratio of Bcl-2/Bax and significantly decreasing cleaved caspase-3 expression. In addition, apelin-13 significantly inhibited excessive autophagy by regulating the expression of LC3 B, p62, and Beclin1. Furthermore, the expression of Bcl-2 and the phosphatidylinositol-3-kinase(PI3 K)/Akt/mammalian target of rapamycin(mTOR) pathway was markedly increased. Both LY294002(20 μM) and rapamycin(500 nM), which are inhibitors of the PI3 K/Akt/mTOR pathway, significantly attenuated the inhibition of autophagy and apoptosis caused by apelin-13. In conclusion, the findings of the present study suggest that Bcl-2 upregulation and mTOR signaling pathway activation lead to the inhibition of apoptosis and excessive autophagy. These effects are involved in apelin-13-induced neuroprotection against cerebral ischemia/reperfusion injury, both in vivo and in vitro. The study was approved by the Animal Ethical and Welfare Committee of Jining Medical University, China(approval No. 2018-JS-001) in February 2018.     

山东省青岛市城阳区糖尿病患者慢性并发症现状调查

目的对山东省青岛市城阳区糖尿病(DM)患者的慢性并发症现状进行横断面调查。方法对2019年3—12月青岛市城阳区参与“三高共管”项目的8个辖区街道的DM患者进行随机抽样调查,按有无慢性并发症将患者分为2组,对患者的人口学资料、人体测量学等指标进行问卷调查,比较2组DM患者的特点,并对DM慢性并发症的影响因素进行Logistic回归分析。结果本研究共随机抽取DM患者26090例进行调查,其中男12560例,女13530例,有慢性并发症者18950例,无慢性并发症者7140例;肥胖、文化程度低、血糖控制欠佳、遵医嘱行为差、合并基础疾病的DM患者更容易出现并发症。亚组分析表明,女性DM患者的心血管疾病、神经病变和眼科疾病的发生率高于男性,差异有统计学意义(P<0.05或P<0.01);糖化血红蛋白(HbA1c)水平越高,DM病程越长,DM患者的慢性并发症发生率均越高,差异有统计学意义(P<0.05或P<0.01)。患者慢性并发症越多,则人均治疗费用越高,年住院次数越多,住院时间越长,差异有统计学意义(P<0.05或P<0.01)。多因素Logistic回归分析显示,性别、年龄、体质量指数(BMI)、DM病程、HbA1c、空腹血糖(FBG)、低密度脂蛋白(LDL)、尿白蛋白肌酐比值(UACR)、24 h尿蛋白定量、文化程度、规律服药程度、规律测量血糖程度均是DM慢性并发症的影响因素(P<0.05或P<0.01)。结论青岛市城阳区DM患者慢性并发症发生率较高,且影响因素较多,尽早明确危险因素有助于防治DM慢性并发症。     

Method to examine how geometry affects the release and retention of alpine touring boot-binding systems

ObjectivesDevelop a method to examine the effects of component geometry and force-deflection on the release process of Tech/Pin alpine touring (AT) ski boots and bindings.Design and methodsFor seven AT boots, we measured the critical geometric dimensions of the metal inserts at the toe region of the boots. Binding geometry (including the pins and rocker arms) and the force-angular deflection curves of typical AT bindings were measured. A kinematic model was derived to predict the contact force between the metal inserts of the AT boots and the pins of the AT bindings, dependent on angular displacement of the binding rocker arms. By combining the kinematic model, the force-angular deflection curves, and moment equilibrium, we determined the force and binding rotation angle needed to release the AT boot in a direction normal to the ski.ResultsThe metal AT boot insert geometry and AT binding pin geometry and dimensions can affect significantly the contact states and kinematics of release. Two load-deflection curves of similar peak loads can result in significantly different maximal forces and angles to release the binding, even when the geometry and dimensions of the binding pins and boot inserts remain unchanged.ConclusionsThe geometry and dimensions of the binding (pins and rocker arm) and the boot inserts define the kinematics of the binding release. The model can be used to test the effects of varying parameters on the release and retention characteristics of Tech/Pin boot-binding systems to optimize the release and retention characteristics.     

The endogenous inflammatory reflex inhibits the inflammatory response to different immune challenges in mice

The splanchnic anti-inflammatory pathway, the efferent arm of the endogenous inflammatory reflex, has been shown to suppress the acute inflammatory response of rats to systemic lipopolysaccharide (LPS). Here we show for the first time that this applies also to mice, and that the reflex may be engaged by a range of inflammatory stimuli. Experiments were performed on mice under deep anaesthesia. Half the animals were subjected to bilateral section of the splanchnic sympathetic nerves, to disconnect the splanchnic anti-inflammatory pathway, while the remainder underwent a sham operation. Mice were then challenged intravenously with one of three inflammatory stimuli: the toll-like receptor (TLR)-4 agonist, LPS (60 µg/kg), the TLR-3 agonist Polyinosinic:polycytidylic acid (Poly I:C, 1 mg/kg) or the TLR-2 and -6 agonist dipalmitoyl-S-glyceryl cysteine (Pam2cys, 34 µg/kg). Ninety minutes later, blood was sampled by cardiac puncture for serum cytokine analysis. The splanchnic anti-inflammatory reflex action was assessed by comparing cytokine levels between animals with cut versus those with intact splanchnic nerves. A consistent pattern emerged: Tumor necrosis factor (TNF) levels in response to all three challenges were raised by prior splanchnic nerve section, while levels of the anti-inflammatory cytokine interleukin 10 (IL-10) were reduced. The raised TNF:IL-10 ratio after splanchnic nerve section indicates an enhanced inflammatory state when the reflex is disabled. These findings show for the first time that the inflammatory reflex drives a coordinated anti-inflammatory action also in mice, and demonstrate that its anti-inflammatory action is engaged, in similar fashion, by inflammatory stimuli mimicking a range of bacterial and viral infections.     

双侧延髓内侧梗死临床分析

目的分析并探究双侧延髓内侧梗死(BMMI)的血管病因、临床表现、MRI特征和预后,以期提高BMMI的早期诊断率.方法对青岛大学附属烟台毓璜顶医院诊治的14例BMMI患者临床资料进行分析.结果BMMI血管病因以动脉粥样硬化为主;临床症状表现为四肢瘫痪、舌瘫、感觉异常、头晕、构音障碍、饮水呛咳等,危重时出现呼吸衰竭.头颅DWI示双侧延髓内侧可呈特征性"心型"、"Y"字型、"V"字型或倒"八"字型高信号影.出院NIHSS评分、卒中进展(尤其呼吸衰竭)为BMMI的预后不良因素.结论BMMI临床少见,临床表现多样,预后较差;头颅MRI为其主要的影像学检查,有助于早期诊断.     

弥漫型大B细胞淋巴瘤EZH2、XIAP和Survivin蛋白表达水平及意义

目的探讨弥漫型大B细胞淋巴瘤Zeste同源物增强子2(EZH2)、X连锁凋亡抑制蛋白(XIAP)和生存素(Survivin)蛋白表达水平及意义。方法选取弥漫型大B细胞淋巴瘤组织92例作为观察组,同时选取反应性增生淋巴结组织50例作为对照组,采用免疫组化染色法检测EZH2、XIAP和Survivin蛋白表达。结果观察组EZH2、XIAP和Survivin蛋白阳性表达率分别为77.17%、55.43%和60.87%,明显高于对照组(P<0.05)。观察组临床分期Ⅲ~Ⅳ期EZH2、XIAP和Survivin蛋白表达阳性率分别为90.70%、86.05%和81.40%,明显高于临床分期Ⅰ~Ⅱ期(P<0.05);EZH2与XIAP、Survivin蛋白表达呈正相关(γ=0.547、0.360,P均<0.05),XIAP与Survivin蛋白表达呈正相关(γ=0.581,P<0.05)。结论弥漫型大B细胞淋巴瘤EZH2、XIAP和Survivin蛋白表达水平上调,与临床分期有一定关系,三者间存在相关关系。