Neutrophil activation in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis of protein markers in blood and cerebrospinal fluid

Inflammation is involved in the pathophysiology of Alzheimer’s disease (AD), with multiple inflammatory processes implicated in its risk and progression. This review included original peer-reviewed studies measuring the cerebrospinal fluid or peripheral blood concentrations of protein markers specifically related to neutrophil activity in healthy controls (HC) and in patients with AD or mild cognitive impairment (MCI). A total of 35 studies (N_HC = 3095, N_AD = 2596, N_MCI = 1203) were included. Random-effects meta-analyses were used to estimate between-groups standardized mean differences (SMD) and 95 % confidence intervals. In blood, concentrations of myeloperoxidase (MPO; N_AD/N_HC = 271/209, SMD = 0.41 [0.20, 0.62]; I² = 15.7 %) and neutrophil gelatinase associated lipocalin (NGAL; N_AD/N_HC = 273/185, SMD = 0.30 [0.11, 0.49]; I² < 0.005 %) were significantly higher in AD relative to HC. Peripheral blood concentrations of NGAL were also higher in MCI compared to HC (N_MCI/N_HC = 489/145, SMD = 0.39 [0.11, 0.67]; I² = 38.6 %). None of the protein markers exhibited a significant difference between HC, MCI, or AD groups in the cerebrospinal fluid. The evidence suggests that peripheral neutrophil activation, as indicated by blood concentrations of NGAL and MPO, may be a pathological feature of cognitive impairment due to AD, evident at stages of MCI and AD dementia.     

Multinutrient diets improve cerebral perfusion and neuroprotection in a murine model of Alzheimer's disease

Nutritional intervention may retard the development of Alzheimer's disease (AD). In this study we tested the effects of 2 multi-nutrient diets in an AD mouse model (APP_swe/PS1_dE9). One diet contained membrane precursors such as omega-3 fatty acids and uridine monophosphate (DEU), whereas another diet contained cofactors for membrane synthesis as well (Fortasyn); the diets were developed to enhance synaptic membranes synthesis, and contain components that may improve vascular health. We measured cerebral blood flow (CBF) and water diffusivity with ultra-high-field magnetic resonance imaging, as alterations in these parameters correlate with clinical symptoms of the disease. APP_swe/PS1_dE9 mice on control diet showed decreased CBF and changes in brain water diffusion, in accordance with findings of hypoperfusion, axonal disconnection and neuronal loss in patients with AD. Both multinutrient diets were able to increase cortical CBF in APP_swe/PS1_dE9 mice and Fortasyn reduced water diffusivity, particularly in the dentate gyrus and in cortical regions. We suggest that a specific diet intervention has the potential to slow AD progression, by simultaneously improving cerebrovascular health and enhancing neuroprotective mechanisms.     

Neuroimaging in dementia

Over the last few years, advances in neuroimaging have generated biomarkers, which increase diagnostic certainty, provide valuable information about prognosis, and suggest a particular pathology underlying the clinical dementia syndrome. We aim to review the evidence for use of already established imaging modalities, along with selected techniques that have a great potential to guide clinical decisions in the future. We discuss structural, functional and molecular imaging, focusing on the most common dementias: Alzheimer's disease, fronto-temporal dementia, dementia with Lewy bodies and vascular dementia. Finally, we stress the importance of conducting research using representative cohorts and in a naturalistic set up, in order to build a strong evidence base for translating imaging methods for a National Health Service. If we assess a broad range of patients referred to memory clinic with a variety of imaging modalities, we will make a step towards accumulating robust evidence and ultimately closing the gap between the dramatic advances in neurosciences and meaningful clinical applications for the maximum benefit of our patients.     

丙泊酚-舒芬太尼TCI全凭静脉麻醉用于非停跳冠脉搭桥手术的可行性和剂量探讨

靶控输注(TCI)已是一种较为成熟的全凭静脉麻醉(TIVA)技术,但针对冠脉搭桥手术(CABG)这一特殊群体的实际应用方面的观察研究尚不多。效应室靶浓度(Ce)的TCI调控更为快速有效,但血浆药物浓度有短时间的超高,对循环的稳定可能不利。目前用吸盘固定局部心肌行非停跳冠脉搭桥手术的     

α7神经型尼古丁受体激动剂PNU282987对APP/PS1小鼠海马组织中DYN-Ⅰ蛋白表达的影响

目的研究特异性激动APP/PS1转基因小鼠脑组织中α7神经型尼古丁受体(α7 nAChR)水平后对海马组织DYN-Ⅰ蛋白的影响;探讨α7 nAChR在阿尔茨海默病(Alzheimer disease,AD)发病机制中的神经保护作用机制。方法实验动物分为对照组(Control)、野生加PNU282987组(WP)、APP/PS1转基因组(APP/PS1)和APP/PS1加PNU282987组(AP)各8只,WP和AP组给予α7 nAChRs特异性激动剂PNU-282987,另两组给予生理盐水,给药方式为小鼠24 w龄时1 mg/kg腹腔注射PNU-282987,连续5 d。采用Real-time PCR法和蛋白免疫印迹(Western Blot)法分别测定小鼠海马组织中发动蛋白Ⅰ(DYN-Ⅰ)mRNA和蛋白表达水平的变化。结果与control组相比,APP/PS1组海马组织中发动蛋白Ⅰ(DYN-Ⅰ)mRNA和蛋白水平下降(P0.05,P0.01);而特异性激动α7 nAChR水平后,与对照组相比WP组中发动蛋白Ⅰ(DYN-Ⅰ)mRNA和蛋白水平升高(P0.05,P0.01);与APP/PS1组相比AP组小鼠大脑海马组织中发动蛋白Ⅰ(DYN-Ⅰ)mRNA和蛋白水平明显升高(P0.01,P0.01)。结论特异性激动APP/PS1转基因小鼠海马组织中α7 nAChR水平能够使网格蛋白内吞调节蛋白DYN-Ⅰ表达升高。这可能提示了α7 nAChR对突触有一定的保护作用,进一步说明α7 nAChR在阿尔茨海默病的发病中起着重要作用。     

过氧化氢溶液局部应用联合强力霉素治疗宫颈支原体感染的疗效

[目的]观察过氧化氢溶液联合强力霉素治疗宫颈支原体感染的疗效。[方法]将78例宫颈支原体感染患者随机分为治疗组和对照组。治疗组用过氧化氢溶液联合强力霉素治疗,对照组用强力霉素治疗。两组均以14 d为1疗程。观察临床疗效并检测支原体阴转率。[结果]两组临床总有效率、支原体阴转率分别为91.67%、81.25%和70%、60%。治疗组明显高于对照组（均P〈0.05）。[结论]过氧化氢溶液联合强力霉素用药治疗宫颈支原体感染疗效好,毒副反应少。     

希罗达联合奥沙利铂治疗老年转移性结直肠癌

[目的]观察希罗达联合奥沙利铂治疗老年(≥70岁)转移性结直肠癌患者的疗效及不良反应.[方法]采用XELOX方案治疗23例老年转移性结直肠癌,d1予奥沙利铂130 mg/m2,d1～14希罗达1 000 mg/(m2·d)口服,2次/天,3周1个周期,至少2个周期.[结果]23例患者中,完全缓解1例(4%),部分缓解9例(39%),稳定8例(35%),肿瘤进展5例(22%).总有效率为43%(10/23),中位肿瘤进展时间8.1(6.7～11.1)个月,中位总生存期13.9(10.9～17.2)个月.最常见的不良反应为消化道反应、骨髓抑制、神经感觉障碍及手足综合征,多为Ⅰ～Ⅱ度.[结论]XELOX是治疗老年转移性结直肠癌安全有效的化疗方案.     

Serum IL-21 levels are elevated in atopic dermatitis patients with acute skin lesions

Background

Interleukin (IL)-21 is a member of the type I cytokine family and plays a role in the pathogenesis of T helper type 2 allergic diseases. It has been reported that IL-21 expression is upregulated in acute skin lesions in atopic dermatitis (AD) patients; however, little is known about the serum IL-21 levels of AD patients. The aim of this study was to quantify the serum IL-21 levels of AD patients and to evaluate the relationships between the serum IL-21 level and disease severity, laboratory markers, and eruption type in AD patients.