Atorvastatin enhances kainate‐induced gamma oscillations in rat hippocampal slices

Atorvastatin has been shown to affect cognitive functions in rodents and humans. However, the underlying mechanism is not fully understood. Because hippocampal gamma oscillations (γ, 20–80 Hz) are associated with cognitive functions, we studied the effect of atorvastatin on persistent kainate‐induced γ oscillation in the CA3 area of rat hippocampal slices. The involvement of NMDA receptors and multiple kinases was tested before and after administration of atorvastatin. Whole‐cell current‐clamp and voltage‐clamp recordings were made from CA3 pyramidal neurons and interneurons before and after atorvastatin application. Atorvastatin increased γ power by ~ 50% in a concentration‐dependent manner, without affecting dominant frequency. Whereas atorvastatin did not affect intrinsic properties of both pyramidal neurons and interneurons, it increased the firing frequency of interneurons but not that of pyramidal neurons. Furthermore, whereas atorvastatin did not affect synaptic current amplitude, it increased the frequency of spontaneous inhibitory post‐synaptic currents, but did not affect the frequency of spontaneous excitatory post‐synaptic currents. The atorvastatin‐induced enhancement of γ oscillations was prevented by pretreatment with the PKA inhibitor H89, the ERK inhibitor U0126, or the PI3K inhibitor wortmanin, but not by the NMDA receptor antagonist D‐AP5. Taken together, these results demonstrate that atorvastatin enhanced the kainate‐induced γ oscillation by increasing interneuron excitability, with an involvement of multiple intracellular kinase pathways. Our study suggests that the classical cholesterol‐lowering agent atorvastatin may improve cognitive functions compromised in disease, via the enhancement of hippocampal γ oscillations.     

Differences in spatial and temporal frequency interactions between central and peripheral parts of the feline area 18

The visual system demonstrates significant differences in information processing abilities between the central and peripheral parts of the visual field. Optical imaging based on intrinsic signals was used to investigate the difference in stimulus spatial and temporal frequency interactions related to receptive field eccentricity in the cat area 18. Changing either the spatial or the temporal frequency of grating stimuli had a significant impact on responses in the cortical areas corresponding to the centre of the visual field and more peripheral parts at 10 degrees eccentricity. The cortical region corresponding to the centre of the gaze was tuned to 0.4 cycles per degree (c/deg) for spatial frequency and 2 Hz for temporal frequency. In contrast, the cortical region corresponding to the periphery of the visual field was tuned to a lower spatial frequency of 0.15 c/deg and a higher temporal frequency of 4 Hz. Interestingly, when we simultaneously changed both the spatial frequency and the temporal frequency of the grating stimuli, the responses were significantly different from those estimated with an assumption of independence between the spatial and temporal frequency in the cortical region corresponding to the periphery of the visual field. However, in the cortical area corresponding to the centre of the gaze, spatial frequency showed significant independence from temporal frequency. These properties support the notion of relative specialization of visual information processing for peripheral representations in cortical areas.     

The impact of parkinson's disease on the cortical mechanisms that support auditory–motor integration for voice control

Several studies have shown sensorimotor deficits in speech processing in individuals with idiopathic Parkinson's disease (PD). The underlying neural mechanisms, however, remain poorly understood. In the present event‐related potential (ERP) study, 18 individuals with PD and 18 healthy controls were exposed to frequency‐altered feedback (FAF) while producing a sustained vowel and listening to the playback of their own voice. Behavioral results revealed that individuals with PD produced significantly larger vocal compensation for pitch feedback errors than healthy controls, and exhibited a significant positive correlation between the magnitude of their vocal responses and the variability of their unaltered vocal pitch. At the cortical level, larger P2 responses were observed for individuals with PD compared with healthy controls during active vocalization due to left‐lateralized enhanced activity in the superior and inferior frontal gyrus, premotor cortex, inferior parietal lobule, and superior temporal gyrus. These two groups did not differ, however, when they passively listened to the playback of their own voice. Individuals with PD also exhibited larger P2 responses during active vocalization when compared with passive listening due to enhanced activity in the inferior frontal gyrus, precental gyrus, postcentral gyrus, and middle temporal gyrus. This enhancement effect, however, was not observed for healthy controls. These findings provide neural evidence for the abnormal auditory–vocal integration for voice control in individuals with PD, which may be caused by their deficits in the detection and correction of errors in voice auditory feedback. Hum Brain Mapp 37:4248–4261, 2016. © 2016 Wiley Periodicals, Inc.     

The symptom trajectories to clinical remission in Chinese patients with unipolar major depressive disorder

There is little understanding of how unipolar major depressive disorder (UMDD) symptoms evolve in response to antidepressant treatment. The present research examined the associations between symptom trajectories and clinical remission in Chinese patients with UMDD. A total of 165 outpatients with UMDD received treatment of fluoxetine (20 mg/day) for 6 weeks and were assessed for symptom severity at weeks 1, 2, 4, and 6. We found that patients with UMDD show heterogeneity in treatment response to fluoxetine. Psychomotor retardation is a prominent symptom during the 6 weeks of assessment, and its severity at baseline is negatively associated with clinical remission.     

Therapeutic effects of lipo-prostaglandin E1 on angiogenesis and neurogenesis after ischemic stroke in rats

Previous studies have demonstrated that prostaglandin E1 (PGE1) has a neuroprotective effect on cerebral ischemia. However, it remains unknown whether PGE1 promotes angiogenesis and neurogenesis after ischemic stroke. In this study, adult male Sprague-Dawley rats were subjected to permanently distal middle cerebral artery occlusion (MCAO). Rats were treated with lipo-prostaglandin E1(lipo-PGE1, 10 μg/kg/d) or the same volume of 0.9% saline starting 24 hours after MCAO daily for 6 consecutive days. All rats were injected 5'-bromo-2'-deoxyuridine (BrdU, 50 mg/kg) intraperitoneally every 12 hours for 3 consecutive days before being sacrificed. At 7 and 14 days after MCAO or sham-operation, rats were sacrificed. Post-stroke neurological outcome, infarction volume, angiogenesis and neurogenesis were evaluated. Treatment with lipo-PGE1 significantly increased the vascular density in the peri-infarct areas at 7 and 14 days after MCAO. The lipo-PGE1 treatment significantly enhanced the proliferation and migration of endogenous neural stem cells in the ipsilateral subventricular zone. The neural stem cells associated with blood vessels closely within a neurovascular niche in lipo-PGE1-treated rats after stroke. The lipo-PGE1 treatment also significantly improved the neurological recovery after MCAO. These results indicate that treatment with lipo-PGE1 promotes post-stroke angiogenesis, neurogenesis and their interaction, which would contribute to neurological recovery after cerebral infarction. Our study provides novel experimental evidences for the neuroprotective roles of PGE1 in ischemic stroke.     

Quality of life in 188 patients with myasthenia gravis in China

Myasthenia gravis (MG) is a kind of chronic autoimmune disease which can weaken patients' motor function and, furthermore, produce negative impact on the health-related quality of life (HRQoL). The primary purpose of this research was to evaluate factors that might affect the HRQoL of MG patients. A cross-sectional clinical research was carried out including 188 successive patients with MG. Myasthenia Gravis Foundation of America (MGFA) classification and Quantitative Myasthenia Gravis (QMG) score were applied to assess the severity of the disease. The Medical Outcome Survey 36-Item Short-Form Health Survey (SF-36) was used to estimate the HRQoL. Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were utilized to measure the depression and anxiety symptom. Factors may influence the HRQoL of MG patients include age, educational level, occupation, the situation of the thymus, the type of MG and generalized myasthenia gravis (GMG), the severity of the disease and the psychological disorder. Higher QMG and HARS scores were two significant factors that can prognosticate lower Physical Composite Score (PCS) and Mental Composite Score (MCS), while older age was just a significant factor which has prognostic value for lower PCS. The results of this research may have a potential guiding significance for the clinical treatment strategy and improve the quality of life in patients with MG consequently. In addition to the treatment of physical symptoms, the psychological symptoms such as anxiety and depression should be concerned as well.     

Wnt/β‐catenin signaling mediates the seizure‐facilitating effect of postischemic reactive astrocytes after pentylenetetrazole‐kindling

Ischemia not only leads to tissue damage, but also induces seizures, which in turn worsens the outcome of ischemia. Recent studies have revealed the impaired homeostatic functions of reactive astrocytes, which were thought to facilitate the development of seizures. However, how this phenotype of reactive astrocytes is regulated remains unclear. Here, using pentylenetetrazole (PTZ)‐kindling model, we investigated the roles of reactive astrocytes and their intracellular Wnt/β‐catenin signaling in the ischemia‐increased seizure susceptibility. Our data showed that somatosensory cortical ischemia significantly increased the susceptibility to PTZ‐induced seizure. Genetic ablation of Nestin‐positive reactive astrocytes significantly decreased the incidence and severity of seizures. By using a Wnt signaling reporter mice line Topgal mice, we found that Wnt/β‐catenin signaling was upregulated in reactive astrocytes after ischemia. Depletion of β‐catenin in reactive astrocytes significantly decreased the susceptibility of seizures and the expression of c‐Fos induced by PTZ in the ischemic cortex. Overexpression of β‐catenin in reactive astrocytes, in contrast, significantly increased seizure susceptibility and the expression of c‐Fos. Furthermore, the expression of aquaporin‐4 (AQP‐4) and inwardly rectifying K⁺ channel 4.1 (Kir4.1), two molecules reportedly associated with seizure development, was oppositely affected in reactive astrocytes with β‐catenin depletion or overexpression. Taken together, these data indicated that astrocytic Wnt/β‐catenin signaling accounts, at least partially, for the ischemia‐increased seizure susceptibility. Inhibiting Wnt/β‐catenin signaling may be utilized in the future for preventing postischemic seizures. GLIA 2016;64:1083–1091     

应用自行研制的运动模体研究呼吸状态改变对立体定向门控放疗的影响

目的 评价患者呼吸状态的改变对实时位置监测系统(RPM)引导下自由呼吸立体定向门控放疗影响。方法 通过自行研制运动模体模拟患者治疗过程中出现基线偏移,呼吸频率改变,呼气末延时、吸气末延时,以及不规则呼吸情况,并分析三维适形、固定野动态调强、单弧旋转调强3组计划各状态变化与模体中心小球位置(L)及电离室受照剂量的相关性。结果 自研模体的摆位重复性和测量稳定性良好。L与基线偏移呈现正相关(r=0.99,P＜0.01)。基线偏移小于摆位误差时,剂量变化在4%以内,相对较小,超出后受照剂量快速下降并呈现负相关(r= -0.95,P＜0.01),偏移超出与不超出摆位误差时所测得的受照剂量,差异具有统计学意义(Z= -3.06,P<0.01)。3组计划受基线偏移的影响率差异无统计学意义(P>0.05)。呼吸频率改变对 L 和剂量影响较小。吸气末延迟和呼气末延迟都导致3组计划剂量下降,最大达-1.74%,同时吸气末延迟相对呼气末延迟影响更大,差异具有统计学意义(Z= -2.67,P<0.01),但延迟时间长短对剂量的影响率没有明显相关性(P＞0.05),3组计划受波形改变的影响率差异无统计学意义(P＞0.05)。不规则呼吸对剂量影响较大,3组计划重复测量6次受照剂量分别为三维适形(709.68±180.00)cGy;固定野动态调强(751.40±127.16)cGy;单弧旋转调强(750.00±185.60)cGy,均小于处方剂量,一致性欠佳。结论 患者呼吸状态改变会导致剂量下降,基线偏移超出摆位误差阈值或者波形变异较大出现不规则呼吸时更甚,且与放疗技术不相关。     

胸部爆炸伤紧急救治临床指南（2022年）

胸部爆炸伤是现代战伤和恐怖袭击中最常见的损伤类型之一,也是爆炸伤中致死率最高的伤类之一,大部分严重胸部爆炸伤患者死于受伤早期和院前转运途中,故对其紧急救治特别重要。目前普遍存在治疗不规范、疗效差异大等问题,且临床上缺乏胸部爆炸伤救治规范。中华医学会创伤学分会遵循科学性、实用性和先进性的原则,针对胸部爆炸伤的分型、院前急...