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Adaptation of the layer V supraspinal motor corticofugal projections from the primary (M1) and premotor (PM) cortices after CNS motor disorders in non-human primates: A survey. 非人灵长类中枢神经系统运动失调后,来自初级(M1)和运动前(PM)皮质的第 V 层棘上运动皮质-耳廓投射的适应性:调查。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-06-07 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0342
Eric M Rouiller

Motor commands are transmitted from the motor cortical areas to effectors mostly via the corticospinal (CS) projection. Several subcortical motor nuclei also play an important role in motor control, the subthalamic nucleus, the red nucleus, the reticular nucleus and the superior colliculus. These nuclei are influenced by motor cortical areas via respective corticofugal projections, which undergo complex adaptations after motor trauma (spinal cord/motor cortex injury) or motor disease (Parkinson), both in the absence or presence of putative treatments, as observed in adult macaque monkeys. A dominant effect was a nearly complete suppression of the corticorubral projection density and a strong downregulation of the corticoreticular projection density, with the noticeable exception in the latter case of a considerable increase of projection density following spinal cord injury, even enhanced when an anti-NogoA antibody treatment was administered. The effects were diverse and less prominent on the corticotectal and corticosubthalamic projections. The CS projection may still be the major efferent pathway through which motor adaptations can take place after motor trauma or disease. However, the parallel supraspinal motor corticofugal projections may also participate in connectional adaptations supporting the functional recovery of motor abilities, representing potential targets for future clinical strategies, such as selective electrical neurostimulations.

运动指令主要通过皮质脊髓(CS)投射从运动皮质区域传递到效应器。几个皮层下运动核也在运动控制中发挥重要作用,它们是眼下核、红核、网状核和上丘。在运动创伤(脊髓/运动皮层损伤)或运动疾病(帕金森病)后,这些核团通过各自的皮质突触受到运动皮层区域的影响,在没有或存在假定治疗的情况下,这些核团都会发生复杂的适应性变化,正如在成年猕猴身上观察到的那样。最主要的影响是皮质ubral投射密度几乎完全被抑制,皮质ticular投射密度强烈下调,但脊髓损伤后投射密度明显增加,甚至在使用抗NogoA抗体治疗后还有所增加。对皮质直节投射和皮质丘脑下投射的影响是多样的,而且不那么突出。CS投射可能仍然是运动创伤或疾病后发生运动适应的主要传出途径。然而,平行的脊髓上运动皮质-耳廓投射也可能参与连接适应,支持运动能力的功能恢复,是未来临床策略(如选择性神经电刺激)的潜在目标。
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引用次数: 0
Retraction of "Effect of C-phycocyanin on HDAC3 and miRNA-335 in Alzheimer's disease". 撤回 "C-花青素对阿尔茨海默病中 HDAC3 和 miRNA-335 的影响 "一文。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-31 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0808
Zhengyu Li, Li Gan, Si Yan, Yufang Yan, Wei Huang

[This retracts the article DOI: 10.1515/tnsci-2020-0101.].

[此文撤稿,DOI: 10.1515/tnsci-2020-0101.]。
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引用次数: 0
Suanzaoren decoction exerts its antidepressant effect via the CaMK signaling pathway. 川芎煎剂通过 CaMK 信号通路发挥抗抑郁作用。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-08 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0341
Xiaofang Zhang, Jiyuan Guo, Ce Zhang, Wenhua Wang, Shuailin Du, Xusheng Tian

Calmodulin-dependent protein kinases (CaMKs) are widely regarded as "memory molecules" due to their role in controlling numerous neuronal functions in the brain, and the CaMK signaling pathway plays a crucial role in controlling synaptic plasticity. Suanzaoren decoction (SZRD) can improve depression-like behavior and thus has potential benefits in the clinical treatment of depression; however, its mechanism of action is not fully understood. In this study, we found that key proteins in the CaMK signaling pathway were regulated by the decoction used to treat depression. The purpose of this research was to ascertain if the SZRD's therapeutic efficacy in the treatment of depression is associated with the modulation of key proteins in the CaMK signaling pathway. A rat model of depression was created by exposing the animals to chronic, unexpected, mild stress. Model rats were given intragastric administration of SZRD or fluoxetine every morning once a day. Protein and mRNA relative expression levels of CaM, CaMK I, and CaMK IV in the hippocampus were measured by Western blot, quantitative polymerase chain reaction, and immunohistochemistry in the hippocampus. Our findings demonstrated that SZRD significantly improved the mood of depressed rats. This indicates that SZRD, by modulating the CaMK signaling system, may alleviate depressive symptoms and lessen work and life-related pressures.

钙调蛋白依赖性蛋白激酶(Calmodulin-dependent protein kinases,CaMKs)被广泛认为是 "记忆分子",因为它们在控制大脑中多种神经元功能方面发挥着作用,而CaMK信号通路在控制突触可塑性方面发挥着至关重要的作用。川芎煎剂(SZRD)可以改善抑郁样行为,因此在临床治疗抑郁症方面具有潜在的益处;然而,其作用机制尚未完全清楚。在本研究中,我们发现用于治疗抑郁症的煎剂调节了 CaMK 信号通路中的关键蛋白。本研究的目的是确定深海鳕鱼煎剂治疗抑郁症的疗效是否与 CaMK 信号通路中关键蛋白的调节有关。我们通过让大鼠长期处于意外的轻微压力下,建立了抑郁症大鼠模型。每天早上给模型大鼠胃内注射一次 SZRD 或氟西汀。通过Western印迹、定量聚合酶链反应和海马免疫组化法测定了海马中CaM、CaMK I和CaMK IV的蛋白和mRNA相对表达水平。我们的研究结果表明,SZRD 能明显改善抑郁大鼠的情绪。这表明,通过调节 CaMK 信号系统,SZRD 可减轻抑郁症状,减轻工作和生活压力。
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引用次数: 0
FT4-to-FT3 ratio is a novel prognostic marker in subacute combined spinal cord degeneration patients. FT4-FT3比值是亚急性合并脊髓变性患者预后的新标志。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-03 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0340
Song Luo, Xiao-Rui Wang, Li-Juan Yang, Liang-Yu Zou

Objectives: The FT4-to-FT3 ratio (FFR) variations in patients with subacute combined spinal cord degeneration (SCSD) as a potentially useful prognostic indicator are still unknown. This study aimed to investigate the changes of FFR as a potentially valuable prognostic predictor in patients with SCSD.

Methods: This study included 144 consecutive SCSD patients who received standard diagnostic and therapeutic procedures between January 2015 and December 2021 and were admitted to the Department of Neurology at the First Affiliated Hospital of Bengbu Medical University. At the time of admission, we gathered data on all patients' demographics, daily routines, previous chronic conditions, medication histories, and other clinical details. For the purpose of measuring FFR, blood samples were specifically taken within 48 h of admission. The degree of neurological impairment of patients was assessed using the functional disability scale at the time of admission. At 6 months following discharge, the Modified Rankin Scale (mRS) was used to evaluate the clinical prognosis. To evaluate the relationship between the FFR and the risks of a poor outcome (mRS > 2), univariate and multivariate logistic regression analysis was utilized. The significance of the FT4/FT3 ratio in predicting the clinical outcomes in SCSD patients 6 months after discharge was assessed using the area under curve-receiver operating characteristic (AUC-ROC).

Results: About 90 patients (62.5%) of the 144 patients had poor outcomes, while 54 (37.5%) had favorable outcomes. Higher FFR at admission was independently linked to higher odds of a poor outcome, according to a logistic analysis. With an optimized cutoff value of >2.843, the FFR exhibited the maximum accuracy for predicting a poor outcome, according to the AUC‒ROC curve (AUC 0.731, P < 0.001; sensitivity, 77.8%; specificity, 83.3%). FFR was identified as an independent predictor of poor outcomes by multivariate logistic regression (OR, 2.244; 95% CI, 1.74-2.90; P < 0.001).

Conclusions: We discovered that in patients who had a bad result 6 months after discharge, the FFR had dramatically increased at the time of admission, providing a unique prognostic marker in patients with SCSD.

目的:亚急性合并脊髓退行性变(SCSD)患者的FT4-FT3比值(FFR)变化作为一种潜在的有用预后指标尚不清楚。本研究旨在调查 FFR 的变化,以此作为亚急性合并脊髓变性患者潜在的有价值的预后预测指标:本研究纳入了 2015 年 1 月至 2021 年 12 月期间在蚌埠医学院第一附属医院神经内科接受标准诊断和治疗的 144 例连续 SCSD 患者。入院时,我们收集了所有患者的人口统计学资料、日常生活习惯、既往慢性病史、用药史和其他临床细节。为了测量 FFR,我们专门在入院 48 小时内采集了血液样本。入院时使用功能障碍量表评估患者的神经功能受损程度。出院后 6 个月,采用改良兰金量表(mRS)评估临床预后。为了评估 FFR 与不良预后风险(mRS > 2)之间的关系,采用了单变量和多变量逻辑回归分析。使用曲线下面积-接收者操作特征(AUC-ROC)评估了FT4/FT3比值在预测SCSD患者出院6个月后临床预后方面的意义:结果:在144名患者中,约90名患者(62.5%)预后不佳,54名患者(37.5%)预后良好。根据逻辑分析,入院时FFR越高,预后越差。根据 AUC-ROC 曲线(AUC 0.731,P <0.001;灵敏度 77.8%;特异性 83.3%),FFR 的优化截断值大于 2.843 时,预测不良预后的准确性最高。多变量逻辑回归确定 FFR 是不良预后的独立预测因子(OR,2.244;95% CI,1.74-2.90;P <0.001):我们发现,在出院 6 个月后结果不佳的患者中,入院时的 FFR 显著增加,为 SCSD 患者提供了一个独特的预后标志。
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引用次数: 0
Effect of dopamine on limbic network connectivity at rest in Parkinson's disease patients with freezing of gait. 多巴胺对伴有步态冻结的帕金森病患者静息状态下边缘网络连接的影响
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-05-02 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0336
Dione Y L Quek, Natasha Taylor, Moran Gilat, Simon J G Lewis, Kaylena A Ehgoetz Martens

Background: Freezing of gait (FOG) in Parkinson's disease (PD) has a poorly understood pathophysiology, which hinders treatment development. Recent work showed a dysfunctional fronto-striato-limbic circuitry at rest in PD freezers compared to non-freezers in the dopamine "OFF" state. While other studies found that dopaminergic replacement therapy alters functional brain organization in PD, the specific effect of dopamine medication on fronto-striato-limbic functional connectivity in freezers remains unclear.

Objective: To evaluate how dopamine therapy alters resting state functional connectivity (rsFC) of the fronto-striato-limbic circuitry in PD freezers, and whether the degree of connectivity change is related to freezing severity and anxiety.

Methods: Twenty-three PD FOG patients underwent MRI at rest (rsfMRI) in their clinically defined "OFF" and "ON" dopaminergic medication states. A seed-to-seed based analysis was performed between a priori defined limbic circuitry ROIs. Functional connectivity was compared between OFF and ON states. A secondary correlation analyses evaluated the relationship between Hospital Anxiety and Depression Scale (HADS)-Anxiety) and FOG Questionnaire with changes in rsFC from OFF to ON.

Results: PD freezers' OFF compared to ON showed increased functional coupling between the right hippocampus and right caudate nucleus, and between the left putamen and left posterior parietal cortex (PPC). A negative association was found between HADS-Anxiety and the rsFC change from OFF to ON between the left amygdala and left prefrontal cortex, and left putamen and left PPC.

Conclusion: These findings suggest that dopaminergic medication partially modulates the frontoparietal-limbic-striatal circuitry in PD freezers, and that the influence of medication on the amygdala, may be related to clinical anxiety in freezer.

背景:帕金森病(PD)步态冻结(FOG)的病理生理学尚不清楚,这阻碍了治疗方法的开发。最近的研究表明,与多巴胺 "关闭 "状态下的非冻结者相比,帕金森病冻结者在静息状态下的前三角-边缘回路功能失调。虽然其他研究发现多巴胺能替代疗法改变了帕金森病患者的大脑功能组织,但多巴胺药物对冷冻患者前三角-边缘功能连接的具体影响仍不清楚:目的:评估多巴胺治疗如何改变PD冰冻症患者前三角-边缘回路的静息状态功能连通性(rsFC),以及连通性的改变程度是否与冰冻严重程度和焦虑有关:方法:23 名 PD FOG 患者在临床定义的多巴胺能药物 "关闭 "和 "开启 "状态下接受了静息 MRI(rsfMRI)检查。在先验定义的边缘回路 ROI 之间进行了基于种子到种子的分析。比较了 "关 "和 "开 "状态之间的功能连接性。二次相关分析评估了医院焦虑和抑郁量表(HADS)-焦虑)和 FOG 问卷与 rsFC 从 OFF 到 ON 的变化之间的关系:结果发现:与开启相比,PD 冻结者的关闭状态显示右侧海马和右侧尾状核之间的功能耦合增加,而左侧丘脑和左侧后顶叶皮层(PPC)之间的功能耦合增加。结论:HADS-焦虑与左侧杏仁核和左侧前额叶皮层之间以及左侧丘脑和左侧后顶叶皮层之间的rsFC从 "关闭 "到 "开启 "的变化之间存在负相关:这些研究结果表明,多巴胺能药物部分调节了帕金森氏症冷冻患者的额顶叶-边缘-纹状体回路,而药物对杏仁核的影响可能与冷冻患者的临床焦虑有关。
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引用次数: 0
Single cocaine exposure attenuates the intrinsic excitability of CRH neurons in the ventral BNST via Sigma-1 receptors. 单次可卡因暴露可通过 Sigma-1 受体减弱腹侧 BNST CRH 神经元的内在兴奋性。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-24 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0339
Jintao Wu, Yue Zhao

The ventral bed nucleus of the stria terminalis (vBNST) plays a key role in cocaine addiction, especially relapse. However, the direct effects of cocaine on corticotropin-releasing hormone (CRH) neurons in the vBNST remain unclear. Here, we identify that cocaine exposure can remarkably attenuate the intrinsic excitability of CRH neurons in the vBNST in vitro. Accumulating studies reveal the crucial role of Sigma-1 receptors (Sig-1Rs) in modulating cocaine addiction. However, to the authors' best knowledge no investigations have explored the role of Sig-1Rs in the vBNST, let alone CRH neurons. Given that cocaine acts as a type of Sig-1Rs agonist, and the dramatic role of Sig-1Rs played in intrinsic excitability of neurons as well as cocaine addiction, we employ BD1063 a canonical Sig-1Rs antagonist to block the effects of cocaine, and significantly recover the excitability of CRH neurons. Together, we suggest that cocaine exposure leads to the firing rate depression of CRH neurons in the vBNST via binding to Sig-1Rs.

纹状体末端腹侧床核(vBNST)在可卡因成瘾尤其是复吸中起着关键作用。然而,可卡因对 vBNST 中促肾上腺皮质激素释放激素(CRH)神经元的直接影响仍不清楚。在这里,我们发现可卡因暴露能显著降低体外 vBNST 中 CRH 神经元的内在兴奋性。越来越多的研究揭示了 Sigma-1 受体(Sig-1Rs)在调节可卡因成瘾中的关键作用。然而,据作者所知,还没有研究探讨过 Sig-1Rs 在 vBNST 中的作用,更不用说 CRH 神经元了。鉴于可卡因是一种 Sig-1Rs 激动剂,而且 Sig-1Rs 在神经元的内在兴奋性和可卡因成瘾中发挥着重要作用,我们采用了一种典型的 Sig-1Rs 拮抗剂 BD1063 来阻断可卡因的作用,并显著恢复了 CRH 神经元的兴奋性。综上所述,我们认为暴露于可卡因会通过与 Sig-1Rs 结合导致 vBNST 中 CRH 神经元的发射率降低。
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引用次数: 0
The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling. ACE2/Ang-(1-7)/MasR轴通过激活PI3K/Akt信号转导减轻兔子心肺复苏后的脑损伤。
IF 1.8 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-11 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0334
Jing Cheng, Hong Yang, Fang Chen, Li Qiu, Fang Chen, Yanhua Du, Xiangping Meng

Background: Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR.

Method: We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting.

Results: Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR.

Conclusion: Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.

背景:复苏患者死亡的主要原因是心脏骤停/心肺复苏(CA/CPR)后的脑损伤。血管紧张素转换酶 2(ACE2)/血管紧张素(Ang)-(1-7)/Mas 受体(MasR)轴对脑损伤有益处。因此,我们研究了 ACE2/Ang-(1-7)/MasR 轴在 CA/CPR 后脑损伤中的作用:方法:我们共使用了 76 只雄性新西兰兔,其中 10 只接受了假手术,66 只接受了 CA/CPR。通过评估血清中神经元特异性烯醇化酶和 S100 钙结合蛋白 B 的水平以及神经功能缺损评分来确定神经功能。对大脑含水量进行了估算。海马神经元凋亡通过末端脱氧核苷酸转移酶 dUTP 缺口标记法进行评估。各种基因的表达水平通过酶联免疫吸附试验和免疫印迹法进行测定:结果:Ang-(1-7)(MasR激活剂)可减轻CA/CPR诱导的神经功能缺损、脑水肿和神经元损伤,而A779(MasR拮抗剂)则具有相反的作用。ACE2/Ang-(1-7)/MasR的刺激使ACE/Ang II/AT1R轴失活,并激活了PI3K/Akt信号转导。抑制 PI3K/Akt 信号可抑制 Ang-(1-7) 介导的对 CA/CPR 后脑损伤的保护作用:总之,ACE2/Ang-(1-7)/MasR 轴通过激活 PI3K/Akt 信号,减轻海马神经元凋亡,从而减轻 CA/CPR 引起的脑损伤。
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引用次数: 0
Trehalose improves the movement ability of AβarcDrosophila by restoring the damaged mitochondria. 通过恢复受损的线粒体,树胶糖提高了 AβarcDrosophila 的运动能力。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-10 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0338
Liangxian Li, Zhiheng Huang, Mingli Wu, Xia Li, Bo Xiao, Dong Yao, Biwen Mo

Background: The deposition of Aβ42 has been regarded as one of the important pathological features of Alzheimer's disease (AD). However, drug development for Aβ42 toxicity has been progressed slowly.

Objective: Our aim was to introduce the effect and related mechanism of trehalose on an Aβarc (arctic mutant Aβ42) Drosophila AD model.

Methods: The human Aβarc was expressed in Drosophila to construct the AD model. Trehalose was added to the culture vial. The movement ability was determined by detecting climbing ability and flight ability. Enzyme-linked immunosorbent assay was used to detect the levels of Aβarc, ATP, and lactate. Electron microscopy assay, mitochondrial membrane potential assay, and mitochondrial respiration assay were used to assess the mitochondrial structure and function.

Results: Trehalose strongly improved the movement ability of Aβarc Drosophila in a concentration gradient-dependent manner. Furthermore, trehalose increased the content of ATP and decreased the content of Aβarc and lactate both in the brain and thorax of Aβarc Drosophila. More importantly, the mitochondrial structure and function were greatly improved by trehalose treatment in Aβarc Drosophila.

Conclusion: Trehalose improves movement ability at least partly by reducing the Aβarc level and restoring the mitochondrial structure and function in Aβarc Drosophila.

背景:Aβ42 的沉积一直被认为是阿尔茨海默病(AD)的重要病理特征之一。然而,针对 Aβ42 毒性的药物开发进展缓慢:我们的目的是介绍三卤糖对 Aβarc(北极突变体 Aβ42)果蝇 AD 模型的影响及相关机制:方法:在果蝇中表达人Aβarc,构建AD模型。方法:在果蝇体内表达人 Aβarc 以构建 AD 模型。通过检测爬行能力和飞行能力来确定果蝇的运动能力。酶联免疫吸附试验检测 Aβarc、ATP 和乳酸的水平。电镜检测、线粒体膜电位检测和线粒体呼吸检测用于评估线粒体结构和功能:结果:在浓度梯度依赖性作用下,曲哈洛糖能显著提高 Aβarc 果蝇的运动能力。此外,在 Aβarc 果蝇的大脑和胸部,三卤糖都能增加 ATP 的含量,降低 Aβarc 和乳酸的含量。更重要的是,经曲阿露糖处理的 Aβarc 果蝇的线粒体结构和功能得到了极大改善:结论:通过降低 Aβarc 水平和恢复 Aβarc 果蝇的线粒体结构和功能,树胶糖至少部分改善了果蝇的运动能力。
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引用次数: 0
Association between FOXP3 polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population. 中国北方汉族人群中 FOXP3 多态性和表达与神经脊髓炎视谱系障碍风险之间的关系
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-04-05 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0337
Jing Liu, Gaoning Wang, Jiahe Yang, Yulin Wang, Ruoyi Guo, Bin Li
<p><strong>Background: </strong>Forkhead box P3 (<i>FOXP3</i>) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between <i>FOXP3</i> polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population.</p><p><strong>Materials and methods: </strong>We genotyped single nucleotide polymorphisms at loci of the <i>FOXP3</i> gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of <i>FOXP3</i> in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups.</p><p><strong>Results: </strong>The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, <i>p</i> = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, <i>p</i> = 0.038). The proportions of the three genotypes of rs2232365 (<i>p</i> = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of <i>FOXP3</i> was markedly greater in the NMOSD group than in the control group (<i>p</i> = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (<i>p</i> = 0.004 and 0.007, respectively).</p><p><strong>Conclusion: </strong><i>FOXP3</i> polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of <i>FOXP3</i> rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. <i>FOXP3</i> mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decr
背景:叉头盒 P3(FOXP3)在自身免疫性疾病的发病机制中起着关键作用。在本研究中,我们对三个单核苷酸多态性(即 rs2232365、rs3761548 和 rs3761549)进行了基因分型,以确定中国北方汉族人群中 FOXP3 多态性与神经脊髓炎视谱系障碍(NMOSD)易感性之间的关系:采用多重 SNaPshot 技术对 136 名 NMOSD 患者和 224 名健康受试者的 FOXP3 基因位点(rs2232365、rs3761548 和 rs3761549136)进行单核苷酸多态性基因分型。使用 qPCR 分析了 63 名 NMOSD 患者和 35 名健康受试者外周血单核细胞中 FOXP3 的 mRNA 表达水平。非参数检验用于检测不同组间的 FOXP3 mRNA 表达:结果:rs2232365中G的小等位基因频率(MAF)在NMOSD组明显低于对照组(几率比[OR] = 0.57,95%置信区间[95% CI]:0.41-0.79, p = 0.001).利用遗传(共显性、显性和隐性)模型和单倍型分析,rs2232365中G的MAF与该人群的NMOSD保护相关。此外,单倍型分析表明,单倍型 GCT 以及 rs2232365、rs3761548 和 rs3761549 等位基因可预测对 NMOSD 的保护作用(OR = 0.63,95% CI = 0.41-0.97,p = 0.038)。rs2232365 的三种基因型比例(p = 0.001)在中重度组(残疾状况扩展量表(EDSS)≥ 3 分)和轻度组(EDSS < 3 分)之间没有显著差异。显然,在 rs2232365 患者中,中重度组中 AA 基因型患者的比例(64.3%)明显高于轻度组(36.4%)。然而,在 rs2232365 患者中,GG 基因型患者的比例(15.2%)在轻度组明显高于中重度组(2.9%)。在 NMOSD 组中,FOXP3 的 mRNA 表达明显高于对照组(p = 0.001)。然而,急性非治疗期患者的FOXP3 mRNA表达量低于健康对照组和缓解组患者(p = 0.004和0.007):结论:FOXP3多态性和单倍型与中国汉族人群的NMOSD易感性有关。FOXP3 rs2232365的小等位基因G和单倍型GCT与NMOSD的保护相关。GG 基因型可降低 NMOSD 的严重程度,而 AA 基因型则与中度至重度 NMOSD 有关。与健康对照组相比,NMOSD 患者的 FOXP3 mRNA 表达量更高。然而,与健康对照组相比,急性非治疗期患者的 FOXP3 mRNA 表达减少。
{"title":"Association between <i>FOXP3</i> polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.","authors":"Jing Liu, Gaoning Wang, Jiahe Yang, Yulin Wang, Ruoyi Guo, Bin Li","doi":"10.1515/tnsci-2022-0337","DOIUrl":"https://doi.org/10.1515/tnsci-2022-0337","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Forkhead box P3 (&lt;i&gt;FOXP3&lt;/i&gt;) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between &lt;i&gt;FOXP3&lt;/i&gt; polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;We genotyped single nucleotide polymorphisms at loci of the &lt;i&gt;FOXP3&lt;/i&gt; gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of &lt;i&gt;FOXP3&lt;/i&gt; in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, &lt;i&gt;p&lt;/i&gt; = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, &lt;i&gt;p&lt;/i&gt; = 0.038). The proportions of the three genotypes of rs2232365 (&lt;i&gt;p&lt;/i&gt; = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS &lt; 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of &lt;i&gt;FOXP3&lt;/i&gt; was markedly greater in the NMOSD group than in the control group (&lt;i&gt;p&lt;/i&gt; = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (&lt;i&gt;p&lt;/i&gt; = 0.004 and 0.007, respectively).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;&lt;i&gt;FOXP3&lt;/i&gt; polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of &lt;i&gt;FOXP3&lt;/i&gt; rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. &lt;i&gt;FOXP3&lt;/i&gt; mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decr","PeriodicalId":23227,"journal":{"name":"Translational Neuroscience","volume":"15 1","pages":"20220337"},"PeriodicalIF":2.1,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10998649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative analysis of CRASH and IMPACT in predicting the outcome of 340 patients with traumatic brain injury. CRASH 和 IMPACT 预测 340 名脑外伤患者预后的比较分析。
IF 2.1 4区 医学 Q4 NEUROSCIENCES Pub Date : 2024-03-22 eCollection Date: 2024-01-01 DOI: 10.1515/tnsci-2022-0327
Tingting An, Zibei Dong, Xiangyang Li, Yifan Ma, Jie Jin, Liqing Li, Lanjuan Xu

Background: Both the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) and the Corticosteroid randomization after significant head injury (CRASH) models are globally acknowledged prognostic algorithms for assessing traumatic brain injury (TBI) outcomes. The aim of this study is to externalize the validation process and juxtapose the prognostic accuracy of the CRASH and IMPACT models in moderate-to-severe TBI patients in the Chinese population.

Methods: We conducted a retrospective study encompassing a cohort of 340 adult TBI patients (aged > 18 years), presenting with Glasgow Coma Scale (GCS) scores ranging from 3 to 12. The data were accrued over 2 years (2020-2022). The primary endpoints were 14-day mortality rates and 6-month Glasgow Outcome Scale (GOS) scores. Analytical metrics, including the area under the receiver operating characteristic curve for discrimination and the Brier score for predictive precision were employed to quantitatively evaluate the model performance.

Results: Mortality rates at the 14-day and 6-month intervals, as well as the 6-month unfavorable GOS outcomes, were established to be 22.06, 40.29, and 65.59%, respectively. The IMPACT models had area under the curves (AUCs) of 0.873, 0.912, and 0.927 for the 6-month unfavorable GOS outcomes, with respective Brier scores of 0.14, 0.12, and 0.11. On the other hand, the AUCs associated with the six-month mortality were 0.883, 0.909, and 0.912, and the corresponding Brier scores were 0.15, 0.14, and 0.13, respectively. The CRASH models exhibited AUCs of 0.862 and 0.878 for the 6-month adverse outcomes, with uniform Brier scores of 0.18. The 14-day mortality rates had AUCs of 0.867 and 0.87, and corresponding Brier scores of 0.21 and 0.22, respectively.

Conclusion: Both the CRASH and IMPACT algorithms offer reliable prognostic estimations for patients suffering from craniocerebral injuries. However, compared to the CRASH model, the IMPACT model has superior predictive accuracy, albeit at the cost of increased computational intricacy.

背景:国际临床试验预后与分析使命(IMPACT)模型和重度颅脑损伤后皮质类固醇随机化(CRASH)模型都是全球公认的评估创伤性脑损伤(TBI)预后的算法。本研究旨在将验证过程外部化,并比较 CRASH 模型和 IMPACT 模型在中国人群中度至重度 TBI 患者中的预后准确性:我们进行了一项回顾性研究,研究对象包括 340 名成年 TBI 患者(年龄大于 18 岁),格拉斯哥昏迷量表(GCS)评分范围为 3 到 12 分。数据收集历时两年(2020-2022 年)。主要终点为14天死亡率和6个月格拉斯哥结果量表(GOS)评分。分析指标包括用于判别的接收者操作特征曲线下面积和用于预测精度的布赖尔评分,用于定量评估模型的性能:14天和6个月的死亡率以及6个月的不利GOS结果分别为22.06%、40.29%和65.59%。对于 6 个月的不利 GOS 结果,IMPACT 模型的曲线下面积(AUC)分别为 0.873、0.912 和 0.927,布赖尔评分分别为 0.14、0.12 和 0.11。另一方面,与 6 个月死亡率相关的 AUC 分别为 0.883、0.909 和 0.912,相应的 Brier 评分分别为 0.15、0.14 和 0.13。CRASH 模型对 6 个月不良结局的 AUC 分别为 0.862 和 0.878,Brier 评分统一为 0.18。14天死亡率的AUC分别为0.867和0.87,相应的Brier评分分别为0.21和0.22:结论:CRASH 和 IMPACT 算法都能为颅脑损伤患者提供可靠的预后评估。不过,与 CRASH 模型相比,IMPACT 模型的预测准确性更高,但代价是计算复杂度增加。
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Translational Neuroscience
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