痛情绪相关神经递质及神经环路研究进展＊

痛情绪是指因疼痛引发的情绪和情感体验，是疾病过程中最常见的一种情绪。痛情绪相关神经机制非常复杂，但主要与单胺类神经递质、神经肽和某些神经环路有关，笔者将结合目前研究现状分别从以上两方面展开，就痛情绪相关单胺类神经递质和神经肽在受体分类、脑区通路、共疾病以及各神经递质之间的联系和痛情绪相关神经环路中各个蛋白的作用机制等方面进行探讨。     

Novel Extracorporeal Dialysis Circuit to Improve the Removal Efficiency of High and Middle Molecular Weight Toxins

A new extracorporeal circuit for hemodialysis was designed with the goal of improving the middle and high molecular weight toxins removal. A recirculation pathway was added to the hemodialysis circuit and relevant pressure regulation was performed along the circuit in order to keep the ultrafiltration rate as zero. The influence of increasing the recirculation to dialysate flow rate ratio on the removal of urea, vitamin B12, and hemoglobin was investigated. This removal was also modeled by an analytical method and solved by MATLAB software. A significant increase in removal of vitamin B12 (34%) and especially hemoglobin (228%) was achieved using the recirculation flow in an adjusted hemodialysis circuit. The model showed an acceptable agreement with the experimental results which shows its applicability for prediction of different toxin removal in this circuit.     

Evolutionarily conserved and divergent functions for cell adhesion molecules in neural circuit assembly

The developing nervous system generates remarkably precise synaptic connections between neurons and their postsynaptic target cells. Numerous neural cell adhesion proteins have been identified to mediate cell recognition between synaptic partners in several model organisms. Here, I review the role of protein interactions of cell adhesion molecules in neural circuit assembly and address how these interactions are utilized to form different neural circuitries in different species. The emerging evidence suggests that the extracellular trans-interactions of cell adhesion proteins for neural wiring are evolutionarily conserved across taxa, but they are often used in different steps of circuit assembly. I also highlight how these conserved protein interactions work together as a group to specify neural connectivity.     

IN.PACT AV Access Trial: Economic Evaluation of Drug-Coated Balloon Treatment for Dysfunctional Arteriovenous Fistulae Based on 12-Month Clinical Outcomes

PurposeTo study, from a U.S. payer’s perspective, the economic consequences of drug-coated balloon (DCB) versus standard percutaneous transluminal angioplasty (PTA) use for the treatment of stenotic lesions in dysfunctional hemodialysis arteriovenous fistulae.Materials and MethodsCost differences between DCBs and PTA at year 1 and beyond were calculated via 2 methods. The first approach used the mean absolute number of trial-observed access circuit reinterventions through 12 months (0.65 ± 1.05 vs 1.05 ± 1.18 events per patient for DCBs and PTA, respectively) and projected treatment outcomes to 3 years. The second approach was based on the trial-observed access circuit primary patency rates at 12 months (53.8% vs 32.4%) and calculated the cost difference on the basis of previously published Medicare cost for patients who maintained or did not maintain primary patency. Assumptions regarding DCB device prices were tested in sensitivity analyses, and the numbers needed to treat were calculated.ResultsUsing the absolute number of access circuit reinterventions approach, the DCB strategy resulted in an estimated per-patient savings of $1,632 at 1 year and $4,263 at 3 years before considering the DCB device cost. The access circuit primary patency approach was associated with a per-patient cost savings of $2,152 at 1 year and $3,894 at 2.5 years of follow-up. At the theoretical DCB device reimbursement of $1,800, savings were $1,680 and $2,049 at 2.5 and 3 years, respectively. The one-year NNT of DCB compared to PTA was 2.48.ConclusionsEndovascular therapy for arteriovenous access stenosis with the IN.PACT AV DCB can be expected to be cost-saving if longer follow-up data confirm its clinical effectiveness.     

无抗凝连续性肾脏替代治疗体外循环装置使用时间影响因素的研究

目的探讨影响无抗凝连续性肾脏替代治疗(CRRT)体外循环装置使用时间的主要影响因素,为合理的无抗凝CRRT护理风险评估提供依据。方法对2015年7月至2018年7月首次行无抗凝CRRT合并高危出血风险的257例急慢性肾衰竭患者进行回顾性分析。结果无抗凝CRRT治疗中体外循环装置发生衰竭125例(48.64%),CRRT体外循环装置使用时间为(248.51±87.56)min。多因素Cox比例风险回归模型分析显示,4个独立影响因素与体外循环装置使用时间显著相关,分别为:治疗中血流量不畅停泵次数(HR=1.572,95%CI=1.373～1.801),静脉壶栓塞容积比(HR=1.022,95%CI=1.014～1.030),红细胞压积(HR=1.037,95%CI=1.007～1.068),CRRT治疗剂量(HR=1.336,95%CI=1.007～1.772)。结论治疗中血流量不畅停泵次数、高静脉壶栓塞容积比、高红细胞压积、高CRRT剂量是影响无抗凝CRRT体外循环装置使用时间的独立危险因素;治疗中施行周期性生理盐水冲洗并不能有效延长体外循环装置的使用时间。临床工作者应针对相关危险因素有针对性地制定干预措施,进而最大限度地降低体外循环装置衰竭的发生率,延长装置使用时间,保障医疗护理安全。     

Two forms of short-interval intracortical inhibition in human motor cortex

BackgroundPulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction.ObjectivesTo investigate whether SICI evaluated with AP and PA conditioning stimuli (CS_PA and CS_AP) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TS_PA).MethodsUsing two superimposed TMS coils, CS_PA and CS_AP were applied at interstimulus intervals (ISI) of 1–5 ms before a TS_PA, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICI_CSPA3 and SICI_CSAP3) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICI_CSPA2), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICI_CSPA3 and SICI_CSAP3.ResultsCS_AP produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CS_AP and CS_PA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICI_CSPA3 or SICI_CSAP3 with other forms of inhibition led to quite different results: SICI_CSPA3 interacted in complex ways with CBI, SAI and SICI_CSPA2, whereas the effect of SICI_CSAP3 appeared to be quite independent of them. Although SICI_CSPA and SICI_CSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICI_CSAP was disinhibited much earlier following the imperative signal than SICI_CSPA.ConclusionsSICI_CSPA appears to activate a different inhibitory pathway to that activated by SICI_CSAP. The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.     

A comprehensive knowledge base of synaptic electrophysiology in the rodent hippocampal formation

The cellular and synaptic architecture of the rodent hippocampus has been described in thousands of peer‐reviewed publications. However, no human‐ or machine‐readable public catalog of synaptic electrophysiology data exists for this or any other neural system. Harnessing state‐of‐the‐art information technology, we have developed a cloud‐based toolset for identifying empirical evidence from the scientific literature pertaining to synaptic electrophysiology, for extracting the experimental data of interest, and for linking each entry to relevant text or figure excerpts. Mining more than 1,200 published journal articles, we have identified eight different signal modalities quantified by 90 different methods to measure synaptic amplitude, kinetics, and plasticity in hippocampal neurons. We have designed a data structure that both reflects the differences and maintains the existing relations among experimental modalities. Moreover, we mapped every annotated experiment to identified potential connections, that is, specific pairs of presynaptic and postsynaptic neuron types. To this aim, we leveraged Hippocampome.org , an open‐access knowledge base of morphologically, electrophysiologically, and molecularly characterized neuron types in the rodent hippocampal formation. Specifically, we have implemented a computational pipeline to systematically translate neuron type properties into formal queries in order to find all compatible potential connections. With this system, we have collected nearly 40,000 synaptic data entities covering 88% of the 3,120 potential connections in Hippocampome.org . Correcting membrane potentials with respect to liquid junction potentials significantly reduced the difference between theoretical and experimental reversal potentials, thereby enabling the accurate conversion of all synaptic amplitudes to conductance. This data set allows for large‐scale hypothesis testing of the general rules governing synaptic signals. To illustrate these applications, we confirmed several expected correlations between synaptic measurements and their covariates while suggesting previously unreported ones. We release all data open‐source at Hippocampome.org in order to further research across disciplines.     

Depletion of microglia in developing cortical circuits reveals its critical role in glutamatergic synapse development,functional connectivity,and critical period plasticity

Microglia populate the early developing brain and mediate pruning of the central synapses. Yet, little is known on their functional significance in shaping the developing cortical circuits. We hypothesize that the developing cortical circuits require microglia for proper circuit maturation and connectivity, and as such, ablation of microglia during the cortical critical period may result in a long-lasting circuit abnormality. We administered PLX3397, a colony-stimulating factor 1 receptor inhibitor, to mice starting at postnatal day 14 and through P28, which depletes >75% of microglia in the visual cortex (VC). This treatment largely covers the critical period (P19-32) of VC maturation and plasticity. Patch clamp recording in VC layer 2/3 (L2/3) and L5 neurons revealed increased mEPSC frequency and reduced amplitude, and decreased AMPA/NMDA current ratio, indicative of altered synapse maturation. Increased spine density was observed in these neurons, potentially reflecting impaired synapse pruning. In addition, VC intracortical circuit functional connectivity, assessed by laser scanning photostimulation combined with glutamate uncaging, was dramatically altered. Using two photon longitudinal dendritic spine imaging, we confirmed that spine elimination/pruning was diminished during VC critical period when microglia were depleted. Reduced spine pruning thus may account for increased spine density and disrupted connectivity of VC circuits. Lastly, using single-unit recording combined with monocular deprivation, we found that ocular dominance plasticity in the VC was obliterated during the critical period as a result of microglia depletion. These data establish a critical role of microglia in developmental cortical synapse pruning, maturation, functional connectivity, and critical period plasticity.