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。     

Uncommon causes of nerve compression in the distal forearm

IntroductionNerve compression by anomalous masses located at the wrist and distal forearm is an infrequent condition. They may compress underlying structures in the carpal tunnel region, causing pain and paresthesias, which leads to the wrong diagnosis of carpal tunnel syndrome.Clinical casesWe present three cases of patients with symptomatology and clinical tests compatible with compression of the median nerve in the carpal tunnel but whose physical examination showed a soft mass in the distal region of the forearm which was compressing the median nerve, as demonstrated by ultrasound evaluation.DiscussionThe reported cases of accessory muscles or lipomas described in the literature as causes of median nerve compression clinic are mainly described only after the surgical decompression of the carpal tunnel, due to the maintenance of residual symptoms.ConclusionCareful examination with an ultrasound evaluation prior to surgery may help to identify these cases and help planning surgical treatment.     

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.     

基于CT图像的评分模型预测食管鳞癌喉返神经旁淋巴结转移风险

目的:基于原发肿瘤及淋巴结CT特征建立评分模型预测食管鳞癌患者喉返神经旁淋巴结(RLN-LN)转移风险。方法:回顾性收集2014年1月至2019年12月于北京大学肿瘤医院行食管癌根治术并清扫RLN-LN的92例食管鳞癌患者。根据术后淋巴结病理结果分为RLN-LN转移组(n=37)和非转移组(n=55)。评估术前CT图像,记录食管癌患者年龄、性别、分化程度、肿瘤位置、肿瘤大小(肿瘤长度、肿瘤厚度、厚度/长度)、RLN-LN大小(淋巴结短径、长径、短径/多平面重建(MPR)最长径]。采用多元logistic回归筛选独立预测因子并建立评分模型,采用ROC曲线评估评分模型及独立预测因子诊断RLN-LN转移的效能,采用Z检验比较曲线下面积(AUC)的差异。应用Hosmer-Lemeshow检验和校准曲线评估模型拟合度。结果:肿瘤位置、肿瘤长度、RLN-LN短径、短径/MPR最长径是RLN-LN转移的独立预测因子,其诊断RLN-LN转移的AUC分别为0.586、0.705、0.831、0.777。基于以上4个CT特征建立评分模型,评分模型诊断RLN-LN转移的AUC为0.903(95%CI 0.846~0.959),优于各单一CT特征(Z=5.812,P<0.001;Z=2.161,P=0.030;Z=2.929,P=0.003;Z=4.052,P<0.001)。拟合优度Hosmer-Lemeshow检验结果显示P=0.555,校准曲线提示评分模型预测RLN-LN转移风险与实际转移风险之间具有良好的一致性。结论:基于CT图像的评分模型有助于食管鳞癌RLN-LN转移状态危险分层。     

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.     

CGF联合根尖刮治术及单一根尖刮治术治疗慢性窦道型根尖周炎的比较

目的探讨血小板浓缩生长因子(CGF)联合根尖刮治术及单一根尖刮治术治疗慢性窦道型根尖周炎的临床疗效。方法选择80例慢性窦道型根尖周炎患者为研究对象,分成CGF组和对照组。对照组采取根尖刮治术治疗,CGF组在对照组基础上给予CGF覆盖根尖区创面治疗。结果 CGF组治疗后总有效率95.00%显著高于对照组77.50%。CGF组治疗后PD、BOP和PLI显著低于治疗前及对照组治疗后。CGF组治疗后EGF、VEGF和IGF显著高于治疗前及对照组治疗后。CGF组颜色匹配、边缘着色和表面光滑度评分显著低于对照组。两组并发症总发生率对比无显著差异。结论 CGF联合根尖刮治术治疗慢性窦道型根尖周炎患者,可提高治疗效果,安全性较高。     

香萱益神方对血管性痴呆模型大鼠神经元凋亡机制研究

目的:探讨香萱益神方治疗血管性痴呆(VD)模型大鼠认知功能作用及其对神经元凋亡机制的研究。方法:两血管阻断法建立VD大鼠模型,给予中药方香萱益神方灌胃治疗6周,分别于造模后、中药喂养6周后进行Morris水迷宫行为学检测,测试大鼠认知行为能力改变,行为学测试结束后,检测VD模型大鼠海马中海马组织脑源性神经营养因子(BDNF)表达水平的变化。结果:香萱益神方治疗6周后,血管性痴呆大鼠模型学习记忆能力得到改善,上调脑内海马组织神经营养因子水平,海马神经元凋亡率下降。结论:香萱益神方是治疗血管性痴呆的有效方剂,可以有效改善VD大鼠模型认知行为功能的障碍情况,起到减少海马神经元细胞凋亡,诱导海马神经元细胞修复的作用。香萱益神方可能是通过激活BDNF相关通路,起到保护海马神经元的作用。