Activation of NR1a/NR2B receptors by soluble factors from APP-stimulated monocyte-derived macrophages: implications for the pathogenesis of Alzheimer's disease

Amyloid-beta peptide (Abeta), the major component of amyloid plaques, can activate brain mononuclear phagocytes (MP; macrophages and microglia), leading to their secretion of neurotoxins. Recent studies strongly suggest that MP-mediated neurotoxicity plays an important role in the pathogenesis of Alzheimer's disease (AD). To further explore this notion, human monocyte-derived macrophages (MDM) were stimulated with naturally secreted alpha-processing soluble amyloid precursor protein/p3 (alphaAPPs/p3) or beta-processing APP/Abeta (betaAPPs/Abeta). MDM conditioned media (MCM) was recovered and tested for its ability to activate recombinant N-methyl-d-aspartate (NMDA) receptor subtype NR1a/NR2B expressed in Xenopus oocytes. Pressure ejection of alphaAPPs/p3- and betaAPPs/Abeta-stimulated MCM produced inward currents of 59.5 +/- 8.9 nA (mean +/- S.E.M., n = 31) and 111.1 +/- 21.0 nA (n = 42) in NR1a/NR2B-expressing oocytes, respectively. The MCM-induced currents were concentration dependent and blocked by 50 microM of the NMDA receptor antagonist 2-amino-5-phosphnovalerate, but not by a non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 microM). The alphaAPPs/p3- and betaAPPs/Abeta-stimulated MCM placed in non-injected oocytes failed to generate inward current. These results demonstrate that APPs/Abeta-stimulated MCM directly activate NMDA receptor subtypes relevant in the pathogenesis of AD.     

含银介孔二氧化硅-壳聚糖复合材料的制备与性能研究

目的探讨含银介孔二氧化硅-壳聚糖复合材料(Ag/MSN-Chi)的制备方法及其微观表征、细胞毒性、吸水性能、抗菌性能及止血性能。 方法以正硅酸乙酯为前驱体，十六烷基三甲基溴化铵为致孔剂，采用离子交换法在介孔二氧化硅纳米粒子(MSN)中引入银离子，制备出具有抗菌作用的新型有序的含银介孔二氧化硅纳米粒子(Ag/MSN)材料。再利用烷基化壳聚糖负载Ag/MSN，制备出Ag/MSN-Chi。根据所用材料不同将实验分为实验组和空白对照组，实验组又分为3个亚组：MSN组、Ag/MSN组、Ag/MSN-Chi组，空白组为不加任何材料的阳性对照。计算MSN和Ag/MSN的比表面积、孔容、孔径和Ag/MSN与Ag/MSN-Chi的电荷。并通过吸水实验、体外凝血实验、抗菌实验对MSN、Ag/MSN和Ag/MSN-Chi的细胞毒性、吸水性能、止血性能及抗菌性能进行评价，计算细胞相对存活率、吸水率、凝血酶原时间(PT)、凝血活酶时间(APTT)及抑菌率。取健康成年新西兰大白兔18只，随机分成3组：对照组(采用医用纱布处理)、Ag/MSN组(采用Ag/MSN处理)、Ag/MSN-Chi组(采用Ag/MSN-Chi处理)，每组6只，建立肝创伤出血模型，计算止血时间。数据比较采用方差分析和t检验。 结果MSN的比表面积为(523.8±12.4) m²/g、孔容为(1.2±0.4) m³/g、孔径为(3.5±0.9) nm；Ag/MSN的比表面积为(521.6±11.7) m²/g、孔容为(1.15±0.5) m³/g、孔径为(3.6±0.7) nm，2种材料的比表面积、孔容、孔径比较差异均无统计学意义(t＝0.224、0.135、0.015，P值均大于0.05)。经测量，Ag/MSN的Zeta电位为－19.7 mV，Ag/MSN-Chi的Zeta电位为10.27 mV，表明Ag/MSN表面电荷从负值变为正值。Ag/MSN-Chi组、Ag/MSN组和MSN组与小鼠成肌细胞共培养1、4、7 d的细胞相对存活率比较，差异均无统计学意义(F＝2.61、4.72、3.52, P值均大于0.05)。Ag/MSN组吸水率分别与MSN组和Ag/MSN-Chi组比较，差异均无统计学意义(t＝0.482、1.159，P值均大于0.05)。经检测，Ag/MSN-Chi组、Ag/MSN组、MSN组和空白对照组的PT比较，差异无统计学意义(F＝10.28，P>0.05)；Ag/MSN-Chi组、Ag/MSN组、MSN组和空白对照组APTT分别为(20.9±2.1)、(28.5±3.4)、(31.4±2.6)、(38.7±2.5) s，4组比较差异有统计学意义(F＝8.70，P<0.05)；Ag/MSN-Chi组、Ag/MSN组、MSN组APTT分别与空白对照组比较，差异均有统计学意义(t＝9.443、4.186、3.506，P值均小于0.05)；Ag/MSN-Chi组APTT与Ag/MSN组比较，差异有统计学意义(t＝3.294，P<0.05)。MSN组在培养0.5、2、4、6、24 h 5个时间点抑菌率比较差异无统计学意义(F＝5.437，P>0.05)；培养0.5 h，Ag/MSN组和Ag/MSN-Chi组抑菌率分别为(99.7±5.2)%、(97.1±5.4)%，与培养0.5 h MSN组抑菌率(11.2±5.8)%比较，差异均有统计学意义(t＝19.678、18.775, P值均小于0.05)；培养24 h，Ag/MSN组和Ag/MSN-Chi组抑菌率分别为(73.2±5.1)%和(72.9±6.9)%，与MSN组(11.8±5.7)%比较，差异均有统计学意义(t＝13.904、11.825, P值均小于0.05)。Ag/MSN-Chi组、Ag/MSN组和对照组止血时间分别为(12.3±1.5)、(17.2±3.4)、(28.1±3.8) s，3组比较差异有统计学意义(F＝5.892，P<0.05)；Ag/MSN-Chi组和Ag/MSN组止血时间分别与对照组比较，差异均有统计学意义(t＝9.473、5.236, P值均小于0.05)；且Ag/MSN-Chi组与Ag/MSN组止血时间比较，差异有统计学意义(t＝3.230，P<0.05)。 结论Ag/MSN-Chi在不增加细胞毒性的基础上具有有较好的吸水性能、止血性能及抗菌性能。     

Predicting intellectual outcome among children treated with 35-40 Gy craniospinal irradiation for medulloblastoma

Fifty children diagnosed with medulloblastoma completed 188 psychological evaluations using the Wechsler Intelligence Scales for Children (D. Wechsler, 1974, 1991) over a 7-year study period following 35-40 Gy postoperative craniospinal irradiation. Random coefficient models were used to predict the trend in the children's intellectual performance as a function of time since diagnosis, with both patient and treatment variables as parameters of this function. A quadratic model demonstrated a delay prior to decline in performance for older patients, whereas the younger patients showed an immediate loss of performance with a plateau at approximately 6 years postdiagnosis. A steeper decline was found for those with higher baseline performance. Clinicians may use the proposed predictive model to identify those patients who are at risk of significant intellectual decline.     

pH Sensitivity of non-synaptic field bursts in the dentate gyrus

Under conditions of low [Ca(2+)](o) and high [K(+)](o), the rat dentate granule cell layer in vitro develops recurrent spontaneous prolonged field bursts that resemble an in vivo phenomenon called maximal dentate activation. To understand how pH changes in vivo might affect this phenomenon, the slices were exposed to different extracellular pH environments in vitro. The field bursts were highly sensitive to extracellular pH over the range 7.0-7.6 and were suppressed at low pH and enhanced at high pH. Granule cell resting membrane potential, action potentials, and postsynaptic potentials were not significantly altered by pH changes within the range that suppressed the bursts. The pH sensitivity of the bursts was not altered by pharmacologic blockade of N-methyl-D-aspartate (NMDA), non-NMDA, and GABA(A) receptors at concentrations of these agents sufficient to eliminate both spontaneous and evoked synaptic potentials. Gap junction patency is known to be sensitive to pH, and agents that block gap junctions, including octanol, oleamide, and carbenoxolone, blocked the prolonged field bursts in a manner similar to low pH. Perfusion with gap junction blockers or acidic pH suppressed field bursts but did not block spontaneous firing of single and multiple units, including burst firing. These data suggest that the pH sensitivity of seizures and epileptiform phenomena in vivo may be mediated in large part through mechanisms other than suppression of NMDA-mediated or other excitatory synaptic transmission. Alterations in electrotonic coupling via gap junctions, affecting field synchronization, may be one such process.     

抗轮状病毒卵黄免疫球蛋白的蛋白酶水解及被动免…

用婴幼儿轮状病毒抗原免疫产卵母鸡，制备出抗婴幼儿轮状病毒鸡卵黄免疫球蛋白（抗－ＨＲＶＩｇＹ）同时研究抗－ＨＲＶＩｇＹ的抗人类胃酸屏障能力，抗消化道蛋白酶的酶解以及临床使用的安全性和效果，研究结果表明：抗－ＨＲＶＩｇＹ具有一定的抗胃酸屏障能力和抗消化道蛋白酶酶解作用，抗－ＨＲＶＩｇＹ安全无毒，对婴幼儿轮状病毒感染具有被动免疫保护作用。     

端粒酶及nm23的表达与胃腺癌预后的关系探讨

目的 :探讨端粒酶和nm2 3癌基因蛋白表达与胃癌根治术后复发及预后的关系。方法 :采用端粒酶原位分子杂交技术及免疫组化S P法分别对 4 5例原发性胃腺癌组织中端粒酶的活性及nm2 3进行检测 ,并结合内镜及随访资料进行分析。结果 :胃腺癌端粒酶阳性表达率及nm2 3低表达率在有淋巴结转移组显著高于无淋巴结转移组 ;在术后 5年内复发者中显著高于无复发者。虽然随着胃腺癌分化程度的降低及浸润深度的增加 ,端粒酶活性及nm2 3低表达呈增强趋势 ,但其差异无统计学意义。结论 :胃腺癌组织中端粒酶的活性表达及nm2 3的低表达与淋巴结转移及术后复发显著相关 ,两者的表达变化对判断胃癌术后复发及预后判断有重要临床意义     

Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson’s disease: a systematic review

Neurosurgical Review - Magnetic resonance imaging-guided focused ultrasound (MRgFUS) neurosurgery is a new option for medication-resistant Parkinson’s disease (PD), but its safety and...     

Minority Race and Ethnicity is Associated With Higher Complication Rates After Revision Surgery for Failed Total Hip and Knee Joint Arthroplasty

BackgroundRacial and ethnic disparities in access to hip and knee total joint arthroplasty (TJA) and postoperative outcomes have wide-reaching implications for patients and the health care system. The aim of this study is to evaluate the effect of ethnicity on clinical outcomes and complications following revision hip and knee TJA.MethodsA single-institution, retrospective analysis of a consecutive series of 4424 revision hip and knee TJA patients was evaluated. Student’s t-test and chi-squared analysis were used to identify significant differences in patient demographics and clinical outcomes between Caucasians and various ethnic minorities, including African Americans, Hispanics, and Asians.ResultsWhen compared with white patients, African American patients demonstrated a significantly higher BMI (P = .04), ASA score (P = .04), length of hospital stay (P = .06), and postoperative infection rates (P = .04). Hispanics demonstrated a significantly higher BMI (P = .04), when compared with white patients, alongside a significantly higher risk for postoperative infection (P < .01). African American demonstrated a significantly higher ASA score (P = .02; P = .03), when compared with Hispanics and Asians, alongside a significantly increased length of stay (P = .01) and higher risk for postoperative infection (P = .02).ConclusionThe study findings demonstrate an underutilization of revision TJA by ethnic minority groups, suggesting that disparities in access to orthopedic surgery increase from primary to revision surgery despite higher failure rates of minority ethnic groups reported after primary TJA surgery. In addition, inferior postoperative outcomes were associated with African Americans and Hispanics, when compared to white patients, with African Americans demonstrating the highest risk of postoperative complications.     

动态增强磁共振成像在评估女性乳房乳头乳晕血供的应用

目的探究动态增强磁共振成像(DCE-MRI)用于评估女性乳房乳头乳晕血供特点的可行性,为乳房整形手术提供乳头乳晕的血供参考。方法从2012年3月至2019年10月华中科技大学同济医学院附属同济医院影像数据库中收集女性乳腺DCE-MRI图像资料,选择未发现肿物的正常乳房的DCE-MRI图像进行研究。在西门子工作站将患者乳腺DCE-MRI图像通过图像减影获取乳房血管图像,分别对轴位、冠状位和矢状位的最大密度投影(MIP)图像进行评估,结合三维MIP图像识别所有供应乳头乳晕的血管。乳头乳晕的血供被划分为内上、内侧、内下、外上、外侧、外下、中央、上方和下方9个象限,对各个象限血管进行统计和分析,并测量血管至乳房皮肤表面投影的最大距离。采用SPSS 19.0软件进行统计分析,通过卡方检验分别比较左侧与右侧乳房的乳头乳晕复合体(NAC)血供象限分布构成比。计算血管到皮肤距离的平均值、标准差及95%置信区间,通过方差分析比较各象限血管至皮肤距离的差异。P<0.05为差异具有统计学意义。结果共收集到245例患者490只女性乳房DCE-MRI图像,其中97例患者97只乳房发现有乳腺肿物,其余393只为正常乳房(97例单侧乳房、148例双侧乳房),将其作为研究对象。患者年龄23~72岁,平均43.7岁。393只乳房(左侧200只、右侧193只)共发现有637条(左侧311条、右侧326条)乳头乳晕供应血管。在637条血管中,内上象限269条(42.2%),外上180条 (28.3%),内侧57条(8.9%),下方37条(5.8%),中央30条(4.7%),内下25条(3.9%),外下25条(3.9%),上方11条(1.7%),外侧3条(0.5%)。卡方检验表明左侧乳房和右侧乳房在NAC血供象限分布构成比差异无统计学意义(χ2 =6.4,P=0.602)。除中央象限血管以外,所有血管到皮肤表面投影最大距离的平均值为0.91 cm, 95%置信区间为0.86~0.96 cm。方差分析表明各象限供血血管到皮肤投影的最大距离,差异有统计学意义(F=11.4,P<0.001)。结论 DCE-MRI可以清晰地显示乳头乳晕的血供来源。乳头乳晕血供主要来源于内上象限和外上象限的血管,血管在皮下约1 cm深度走行。