短时程脊髓电刺激治疗爆发痛合并触诱发痛的急性期带状疱疹的临床研究

目的探讨短时程脊髓电刺激(temporary spinal cord stimulation, tSCS)治疗爆发痛合并触诱发痛的急性期带状疱疹的临床疗效。方法回顾性地分析同济大学附属第十人民医院疼痛科2020年1月—2020年12月收治的52例接受tSCS治疗的爆发痛合并触诱发痛的急性期带状疱疹患者的临床资料，评估在治疗前、治疗后3d、7d、14d、3个月、6个月的总体疼痛情况(numerical rating scale, NRS)评分、(simple McGill scores, McGill)评分、爆发痛情况(发生率、NRS评分、次数以及持续时间)、触诱发痛情况(发生率、分级)、术后不良反应等；评估在治疗前、治疗后7d、3个月、6个月的睡眠时长、睡眠中醒来次数、疼痛障碍指数(pain disorder index, PDI)、功能状态评分(Karnofsky score, KPS)、抑郁症筛查量表(patient health questionnaire depression module scale, PHQ-9)和焦虑症筛查量表(generalized anxiety disorder-7 scale, GAD-7)等。结果与治疗前相比，治疗后3d、7d、14d、3个月、6个月的总体疼痛NRS评分、总体疼痛MCGILL评分、静息痛NRS评分明显降低(均P<0.001)；与治疗前相比，治疗后3d、7d、14d、3个月、6个月的的爆发痛NRS评分明显降低(均P<0.05)，治疗后14d、3个月、6个月时的爆发痛次数以及持续时间都明显降低(均P<0.05)；与治疗前比较，患者治疗后7d、14d、3个月、6个月时的触诱发痛的分级都明显降低，差异均有统计学意义(均P<0.05)；与治疗前相比，治疗后14d、3个月、6个月的PDI评分明显降低(P<0.05)；与治疗前相比，治疗后14d、3个月、6个月的PHQ-9评分和GAD-7评分都明显减少(P<0.05)，与术前的药物使用情况相比，治疗后各镇痛药使用人数普遍呈下降趋势；术中及整个随访期间未观察到严重不良事件。结论短时程脊髓电刺激对爆发痛合并触诱发痛的急性期带状疱疹具有较好的临床疗效。     

Orchestration of the circadian clock and its association with Alzheimer's disease: Role of endocannabinoid signaling

Circadian rhythms are 24-hour natural rhythms regulated by the suprachiasmatic nucleus, also known as the "master clock". The retino-hypothalamic tract entrains suprachiasmatic nucleus with photic information to synchronise endogenous circadian rhythms with the Earth’s light-dark cycle. However, despite the robustness of circadian rhythms, an unhealthy lifestyle and chronic photic disturbances cause circadian rhythm disruption in the suprachiasmatic nucleus’s TTFL loops via affecting glutamate and γ-aminobutyric acid-mediated neurotransmission in the suprachiasmatic nucleus. Recently, considerable evidence has been shown correlating CRd with the incidence of Alzheimer's disease. The present review aims to identify the existence and signalling of endocannabinoids in CRd induced Alzheimer's disease through retino-hypothalamic tract- suprachiasmatic nucleus-cortex. Immunohistochemistry has confirmed the expression of cannabinoid receptor 1 in the suprachiasmatic nucleus to modulate the circadian phases of the master clock. Literature also suggests that cannabinoids may alter activity of suprachiasmatic nucleus by influencing the activity of their major neurotransmitter γ-aminobutyric acid or by interacting indirectly with the suprachiasmatic nucleus’s two other major inputs i.e., the geniculo-hypothalamic tract-mediated release of neuropeptide Y and serotonergic inputs from the dorsal raphe nuclei. Besides, the expression of cannabinoid receptor 2 ameliorates cognitive deficits via reduction of tauopathy and microglial activation. In conclusion, endocannabinoids may be identified as a putative target for correcting CRd and decelerating Alzheimer’s disease.     

Cyanidin-3-glucoside protects against high glucose-induced injury in human nucleus pulposus cells by regulating the Nrf2/HO-1 signaling

Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway.     

Electrophysiological differences between upper and lower limb movements in the human subthalamic nucleus

ObjectiveFunctional processes in the brain are segregated in both the spatial and spectral domain. Motivated by findings reported at the cortical level in healthy participants we test the hypothesis in the basal ganglia of Parkinson’s disease patients that lower frequency beta band activity relates to motor circuits associated with the upper limb and higher beta frequencies with lower limb movements.MethodsWe recorded local field potentials (LFPs) from the subthalamic nucleus using segmented “directional” DBS leads, during which patients performed repetitive upper and lower limb movements. Movement-related spectral changes in the beta and gamma frequency-ranges and their spatial distributions were compared between limbs.ResultsWe found that the beta desynchronization during leg movements is characterised by a strikingly greater involvement of higher beta frequencies (24–31 Hz), regardless of whether this was contralateral or ipsilateral to the limb moved. The spatial distribution of limb-specific movement-related changes was evident at higher gamma frequencies.ConclusionLimb processing in the basal ganglia is differentially organised in the spectral and spatial domain and can be captured by directional DBS leads.SignificanceThese findings may help to refine the use of the subthalamic LFPs as a control signal for adaptive DBS and neuroprosthetic devices.     

Focal hole versus screw stimulation to prevent false negative results in detecting pedicle breaches during spinal instrumentation

ObjectiveWe describe a stimulus-evoked EMG approach to minimize false negative results in detecting pedicle breaches during lumbosacral spinal instrumentation.MethodsIn 36 patients receiving 176 lumbosacral pedicle screws, EMG threshold to nerve root activation was determined using a focal probe inserted into the pilot hole at a depth, customized to the individual patients, suitable to position the stimulating tip at the point closest to the tested nerve root. Threshold to screw stimulation was also determined.ResultsMean EMG thresholds in 161 correctly fashioned pedicle instrumentations were 7.5 mA ± 2.46 after focal hole stimulation and 21.8 mA ± 6.8 after screw stimulation. Direct comparison between both thresholds in individual pedicles showed that screw stimulation was always biased by an unpredictable leakage of the stimulating current ranging from 10 to 90%. False negative results were never observed with hole stimulation but this was not true with screw stimulation.ConclusionsFocal hole stimulation, unlike screw stimulation, approaches absolute EMG threshold as shown by the lower normal limit (2.6 mA; p < 0.05) that borders the upper limit of threshold to direct activation of the exposed root.SignificanceThe technique provides an early warning of a possible pedicle breakthrough before insertion of the more harmful, larger and threaded screw.     

角膜电刺激对糖尿病大鼠前部缺血性视神经病变模型的影响

观察并评估角膜电刺激对糖尿病大鼠前部缺血性视神经病变（AION）模型的影响。方法：实验 研究。健康雄性Sparague-Dawley大鼠40只，随机分组后抽出8只作为正常大鼠组。余下32只先予 以链脲佐菌素腹腔注射建立糖尿病大鼠模型，将造模成功的大鼠随机抽出8只作为糖尿病组，余下 24只糖尿病大鼠采用孟加拉玫瑰红联合532 nm激光方法建立AION大鼠模型。将24只造模成功的 AION大鼠随机分成3组，每组8只，分别为AION模型组，不予任何处理；电刺激组，予以角膜电刺 激（刺激参数为：电流1 mA，频率20 Hz，波宽1 ms/phase，刺激时间1 h，隔日1次，刺激2周）；假电 刺激组，电极安放位置与电刺激组相同，仅不接通电源。2周后5组大鼠进行眼底照相、光学相干断 层扫描和视觉诱发电位，然后处死，行视网膜及视神经冰冻切片，苏木精伊红染色观察。数据采用 单因素方差分析和LSD-t检验进行分析。结果：正常大鼠组视盘上半部视网膜厚度为（211±13）μm， 糖尿病大鼠组为（206±16）μm，AION模型组为（240±54）μm，假电刺激组为（216±11）μm，电刺 激组为（198±4）μm，5组视盘上半部视网膜厚度差异有统计学意义（F=2.854，P=0.038）。其中AION 模型组视盘上半部视网膜厚度高于正常组、糖尿病组、电刺激组，差异均有统计学意义（P<0.05）； 正常组与糖尿病组差异无统计学意义，AION模型组与假电刺激组未见明显差异。视觉诱发电位示 AION模型组N1潜伏期较电刺激组延长，差异有统计学意义（t=4.1，P<0.001）；AION模型组P1潜伏 期较正常组、糖尿病组、假电刺激组、电刺激组延长，差异均有统计学意义（t=4.1、2.5、2.6、3.2， P<0.05）；电刺激组N1-P1波幅大于假电刺激组，差异有统计学意义（t=4.0，P<0.001）。结论：角膜电 刺激能促进糖尿病大鼠前部缺血性视神经病变模型肿胀的视盘变薄，加速视盘水肿的消退，同时在 一定程度上改善视功能。