超声引导下髂筋膜神经阻滞联合全麻对老年股骨近端骨折患者术后血清疼痛介质PGE2、SP和认知功能及睡眠质量的影响

摘要 目的：观察超声引导下髂筋膜神经阻滞联合全麻对老年股骨近端骨折患者术后血清疼痛介质前列腺素E₂（PGE₂）、P物质（SP）和认知功能及睡眠质量的影响。方法：选取2018年8月~2021年9月期间我院收治的择期行手术治疗的老年股骨近端骨折患者80例,根据随机数字表法分为对照组（40例,常规全麻方案）和观察组（40例,超声引导下髂筋膜神经阻滞联合全麻方案）,对比两组麻醉效果、血流动力学、疼痛情况、认知功能和睡眠质量,观察不同模式麻醉下的安全性。结果：观察组的苏醒及拔管时间均短于对照组,丙泊酚使用量少于对照组（P<0.05）。两组置入喉罩时（T1）~术毕时（T3）心率（HR）先升高后下降,平均动脉压（MAP）先下降后升高（P<0.05）;观察组T1~T3时点HR低于对照组,MAP高于对照组（P<0.05）。两组术后24 h血清PGE₂、SP水平和视觉疼痛模拟量表（VAS）评分均升高,但观察组低于对照组（P<0.05）。两组术后1 d、2 d、3 d 蒙特利尔认知评估量表（MoCA）评分较术前先下降后升高（P<0.05）;观察组术后2 d、3 d MoCA评分高于对照组（P<0.05）。两组术后1 d、2 d、3 d匹兹堡睡眠质量评估量表（PSQI）评分较术前先升高后下降（P<0.05）;观察组术后1 d、2 d、3 d PSQI评分低于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：老年股骨近端骨折患者术中选用超声引导下髂筋膜神经阻滞联合全麻,镇痛效果显著,可稳定机体血流动力学,减少对认知功能和睡眠质量的影响,且安全性良好。     

The db mutation improves memory in younger mice in a model of Alzheimer's disease

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease, while obesity is a major global public health problem associated with the metabolic disorder type 2 diabetes mellitus (T2DM). Chronic obesity and T2DM have been identified as invariant risk factors for dementia and late-onset AD, while their impacts on the occurrence and development of AD remain unclear. As shown in our previous study, the diabetic mutation (db, Lepr^db/db) induces mixed or vascular dementia in mature to middle-aged APP^ΔNL/ΔNL x PS1^P264L/P264L knock-in mice (db/AD). In the present study, the impacts of the db mutation on young AD mice at 10 weeks of age were evaluated. The db mutation not only conferred young AD mice with severe obesity, impaired glucose regulation and activated mammalian target of rapamycin (mTOR) signaling pathway in the mouse cortex, but lead to a surprising improvement in memory. At this young age, mice also had decreased cerebral Aβ content, which we have not observed at older ages. This was unlikely to be related to altered Aβ synthesis, as both β- and γ-secretase were unchanged. The db mutation also reduced the cortical IL-1β mRNA level and IBA1 protein level in young AD mice, with no significant effect on the activation of microglia and astrocytes. We conclude that the db mutation could transitorily improve the memory of young AD mice, a finding that may be partially explained by the relatively improved glucose homeostasis in the brains of db/AD mice compared to their counterpart AD mice, suggesting that glucose regulation could be a strategy for prevention and treatment of neurodegenerative diseases like AD.     

Occlusion of the human serotonin transporter is mediated by serotonin-induced conformational changes in the bundle domain

The human serotonin transporter (hSERT) terminates neurotransmission by removing serotonin (5HT) from the synaptic cleft, an essential process for proper functioning of serotonergic neurons. Structures of the hSERT have revealed its molecular architecture in four conformations, including the outward-open and occluded states, and show the transporter’s engagement with co-transported ions and the binding mode of inhibitors. In this study, we investigated the molecular mechanism by which the hSERT occludes and sequesters the substrate 5HT. This first step of substrate uptake into cells is a structural change consisting of the transition from the outward-open to the occluded state. Inhibitors such as the antidepressants citalopram, fluoxetine, and sertraline inhibit this step of the transport cycle. Using molecular dynamics simulations, we reached a fully occluded state, in which the transporter-bound 5HT becomes fully shielded from both sides of the membrane by two closed hydrophobic gates. Analysis of 5HT-triggered occlusion showed that bound 5HT serves as an essential trigger for transporter occlusion. Moreover, simulations revealed a complex sequence of steps and showed that movements of bundle domain helices are only partially correlated. 5HT-triggered occlusion is initially dominated by movements of transmembrane helix 1b, while in the final step, only transmembrane helix 6a moves and relaxes an intermediate change in its secondary structure.     

How Spike Synchronization Among Olfactory Neurons Can Contribute to Sensory Discrimination

Recent studies in honeybees have demonstrated that, when odor-evoked action potentials in antennal lobe neurons are pharmacologically desynchronized, the bees are impaired in their ability to discriminate chemically similar odor stimuli. Using a reduced computational model of the honeybee antennal lobe, we show how changes in spike-synchronization properties alone, independent of changes in overall spike-discharge rate or differences in activity levels among responsive neurons, can produce changes in associative learning similar to those observed experimentally.     

Learning and memory in disease vectors

All animals can learn to some extent and it should not be surprising to discover that important vectors can also be influenced by experience. The potential effect of memory on vector behaviour, particularly vectorial capacity, has barely been investigated. Yet, how a population of blood-feeding insects distributes between available resources has important epidemiological consequences. Several recent studies have shown that behaviour during oviposition site-selection, host location and even host choice can be influenced by the environment or by experience after eclosion. The significance of these studies and their consequences for epidemiology and control are considered here.     

Proteomic changes in the brain of the western painted turtle (Chrysemys picta bellii) during exposure to anoxia

During anoxia, overall protein synthesis is almost undetectable in the brain of the western painted turtle. The aim of this investigation was to address the question of whether there are alterations to specific proteins by comparing the normoxic and anoxic brain proteomes. Reductions in creatine kinase, hexokinase, glyceraldehyde‐3‐phosphate dehydrogenase, and pyruvate kinase reflected the reduced production of adenosine triphosphate (ATP) during anoxia while the reduction in transitional endoplasmic reticulum ATPase reflected the conservation of ATP or possibly a decrease in intracellular Ca²⁺. In terms of neural protection programed cell death 6 interacting protein (PDCD6IP; a protein associated with apoptosis), dihydropyrimidinase‐like protein, t‐complex protein, and guanine nucleotide protein G_(o) subunit alpha (G_o alpha; proteins associated with neural degradation and impaired cognitive function) also declined. A decline in actin, gelsolin, and PDCD6IP, together with an increase in tubulin, also provided evidence for the induction of a neurological repair response. Although these proteomic alterations show some similarities with the crucian carp (another anoxia‐tolerant species), there are species‐specific responses, which supports the theory of no single strategy for anoxia tolerance. These findings also suggest the anoxic turtle brain could be an etiological model for investigating mammalian hypoxic damage and clinical neurological disorders.     

氯胺酮麻醉的MECT对难治性抑郁症患者认知功能的影响

目的:探讨氯胺酮麻醉下的MECT治疗难治性抑郁症的安全性和治疗前后的认知功能变化。方法:入组60例需要MECT治疗的难治性抑郁症患者,随机分为氯胺酮组(30例)使用氯胺酮诱导麻醉的MECT治疗;异丙酚组(30例)使用异丙酚诱导麻醉的MECT治疗。入组患者在基线期及MECT治疗8次后完成汉密尔顿抑郁量表(HAMD)评定及连线测验AB、威斯康星卡片分类测验、汉诺塔测试,出组时评定副反应量表。结果:两组患者治疗结束后认知功能均较治疗前明显降低,异丙酚组较氯胺酮组降低更明显。结论:氯胺酮MECT治疗难治性抑郁症安全有效,对患者的认知功能损害较异丙酚组轻,未出现严重副作用。     

Maintaining polarization in polarimetric multiphoton microscopy

Polarimetric measurements in multiphoton microscopy can reveal information about the local molecular order of a sample. However, the presence of a dichroic through which the excitation beam propagates will generally scramble its polarization. We propose a simple scheme whereby a second properly‐oriented compensation dichroic is used to negate any alteration regardless of the wavelength and the initial polarization. We demonstrate how this robust and rapid approach simplifies polarimetric measurements in second‐harmonic generation, two‐photon excited fluorescence and coherent anti‐Stokes Raman scattering.

Illustration of the polarization maintaining strategy with the compensating dichroic oriented such that its s‐ and p‐axes are interchanged with these of the primary dichroic.     

Operant Procedures for Assessing Behavioral Flexibility in Rats

Executive functions consist of multiple high-level cognitive processes that drive rule generation and behavioral selection. An emergent property of these processes is the ability to adjust behavior in response to changes in one’s environment (i.e., behavioral flexibility). These processes are essential to normal human behavior, and may be disrupted in diverse neuropsychiatric conditions, including schizophrenia, alcoholism, depression, stroke, and Alzheimer’s disease. Understanding of the neurobiology of executive functions has been greatly advanced by the availability of animal tasks for assessing discrete components of behavioral flexibility, particularly strategy shifting and reversal learning. While several types of tasks have been developed, most are non-automated, labor intensive, and allow testing of only one animal at a time. The recent development of automated, operant-based tasks for assessing behavioral flexibility streamlines testing, standardizes stimulus presentation and data recording, and dramatically improves throughput. Here, we describe automated strategy shifting and reversal tasks, using operant chambers controlled by custom written software programs. Using these tasks, we have shown that the medial prefrontal cortex governs strategy shifting but not reversal learning in the rat, similar to the dissociation observed in humans. Moreover, animals with a neonatal hippocampal lesion, a neurodevelopmental model of schizophrenia, are selectively impaired on the strategy shifting task but not the reversal task. The strategy shifting task also allows the identification of separate types of performance errors, each of which is attributable to distinct neural substrates. The availability of these automated tasks, and the evidence supporting the dissociable contributions of separate prefrontal areas, makes them particularly well-suited assays for the investigation of basic neurobiological processes as well as drug discovery and screening in disease models.     

Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus

Alzheimer’s disease is a neurodegenerative disease affecting the aging population. A key neuropathological feature of the disease is the over-production of amyloid-beta and the deposition of amyloid-beta plaques in brain regions of the afflicted individuals. Throughout the years scientists have generated numerous Alzheimer’s disease mouse models that attempt to replicate the amyloid-beta pathology. Unfortunately, the mouse models only selectively mimic the disease features. Neuronal death, a prominent effect in the brains of Alzheimer’s disease patients, is noticeably lacking in these mice. Hence, we and others have employed a method of directly infusing soluble oligomeric species of amyloid-beta - forms of amyloid-beta that have been proven to be most toxic to neurons - stereotaxically into the brain. In this report we utilize male C57BL/6J mice to document this surgical technique of increasing amyloid-beta levels in a select brain region. The infusion target is the dentate gyrus of the hippocampus because this brain structure, along with the basal forebrain that is connected by the cholinergic circuit, represents one of the areas of degeneration in the disease. The results of elevating amyloid-beta in the dentate gyrus via stereotaxic infusion reveal increases in neuron loss in the dentate gyrus within 1 week, while there is a concomitant increase in cell death and cholinergic neuron loss in the vertical limb of the diagonal band of Broca of the basal forebrain. These effects are observed up to 2 weeks. Our data suggests that the current amyloid-beta infusion model provides an alternative mouse model to address region specific neuron death in a short-term basis. The advantage of this model is that amyloid-beta can be elevated in a spatial and temporal manner.