Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons, leading to motor and non-motor symptoms that severely impact patients' life. This research combines the advantages of slope symbolization and phase transfer entropy (PTE) to propose the phase slope transfer entropy (PSlope-TE) algorithm. Simulation experiments verified that PSlope-TE outperformed baseline algorithms in terms of stability under varying data lengths and robustness against noise interference. Applied to electroencephalogram (EEG) signals, PSlope-TE revealed that PD patients in the OFF state exhibited stronger information transfer in the delta, theta, and gamma frequency bands compared to healthy controls(HC), particularly in the frontal motor regions. In contrast, differences between HC and PD patients in the ON state were less pronounced. Overall, the proposed algorithm assists in comprehending the effects of PD and Levodopa therapy on brain information transmission and coupling dynamics.

The gut microbiota is known to influence levodopa metabolism in the intestinal tract, primarily through the action of tyrosine decarboxylase, an enzyme encoded by the tyrosine decarboxylase gene (tyrDC). However, the effect of the abundance of the tyrDC gene on levodopa pharmacokinetics remains unclear. The aim of this study was to investigate this relationship in Parkinson’s disease (PD) patients undergoing a levodopa challenge test. Our study enrolled 12 PD patients with a good response to levodopa. Plasma levodopa pharmacokinetics were determined via liquid chromatography‒tandem mass spectrometry, while tyrDC gene abundance in faecal samples was assessed via metagenomic shotgun sequencing. A total of 12 PD patients (age: 58.00 ± 8.80 years) with an Hoehn and Yahr stage of 2.25 (2.0–3.0) and a disease duration of 8.46 ± 4.94 years were enrolled. After levodopa administration, the MDS-UPDRS-III score decreased 71.28

IntroductionVisual hallucination is a prevalent psychiatric disorder characterized by the occurrence of false visual perceptions due to misinterpretation in the brain. Individuals with Parkinson’s disease often experience both minor and complex visual hallucinations. The underlying mechanism of complex visual hallucinations in Parkinson’s patients is commonly attributed to dysfunction in the visual pathway and attention network. However, there is limited research on the mechanism of minor hallucinations.MethodsTo address this gap, we conducted an experiment involving 13 Parkinson’s patients with minor hallucinations, 13 Parkinson’s patients without hallucinations, and 13 healthy elderly individuals. We collected and analyzed EEG and MRI data. Furthermore, we utilized EEG data from abnormal brain regions to train a machine learning model to determine whether the abnormal EEG data were associated with minor hallucinations.ResultsOur findings revealed that Parkinson’s patients with minor hallucinations exhibited excessive activation of cortical excitability, an imbalanced interaction between the attention network and the default network, and disruption in the connection between these networks. These findings is similar to the mechanism observed in complex visual hallucinations. The visual reconstruction of one patient experiencing hallucinations yields results that differ from those observed in subjects without such symptoms.DiscussionThe visual reconstruction results demonstrated significant differences between Parkinson’s patients with hallucinations and healthy subjects. This suggests that visual reconstruction techniques may offer a means of evaluating hallucinations.

Objective This study aimed to elucidate brain areas mediated by oral anti-parkinsonian medicine that consistently show abnormal resting-state activation in PD and to reveal their functional connectivity profiles using meta-analytic approaches. Methods Searches of the PubMed, Web of Science databases identified 78 neuroimaging studies including PD OFF state (PD-OFF) versus (vs.) PD ON state (PD-ON) or PD-ON versus healthy controls (HCs) or PD-OFF versus HCs data. Coordinate-based meta-analysis and functional meta-analytic connectivity modeling (MACM) were performed using the activation likelihood estimation algorithm. Results Brain activation in PD-OFF vs. PD-ON was significantly changed in the right putamen and left inferior parietal lobule (IPL). Contrast analysis indicated that PD-OFF vs. HCs had more consistent activation in the right paracentral lobule, right middle frontal gyrus, right thalamus, left superior parietal lobule and right putamen, whereas PD-ON vs. HCs elicited more consistent activation in the bilateral middle temporal gyrus, left occipital gyrus, right inferior frontal gyrus and right caudate. MACM revealed coactivation of the right putamen in the direct contrast of PD-OFF vs. PD-ON. Subtraction analysis of significant coactivation clusters for PD-OFF vs. PD-ON with the medium of HCs showed effects in the sensorimotor, top-down control, and visual networks. By overlapping the MACM maps of the two analytical strategies, we demonstrated that the coactivated brain region focused on the right putamen. Conclusions The convergence of local brain regions and co-activation neural networks are involved the putamen, suggesting its potential as a specific imaging biomarker to monitor treatment efficacy. Systematic review registration [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD CRD42022304150].

Parkinson’s disease (PD) is a highly heterogeneous neurodegenerative disorder with varying clinical subtypes. Recently, a novel classification called MNCD (Motor/Non-motor/Cognition/Dependency) has been proposed, which can also include staging based on disease severity. We aim to investigate which staging, the MNCD classification and staging or Hoehn and Yahr (H Y) staging, exhibits a stronger correlation with the 39-item Parkinson’s Disease Questionnaire (PDQ-39). In a cross-sectional study conducted at our single center, 357 PD patients were recruited. Data encompassed scores from various assessments such as the Movement Disorder Society of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts I, II, III and IV, Montreal Cognitive Assessment (MoCA), PDQ-39, and the H Y scale. The mean age of these patients was 66.4 ± 9.1 years old, and the majority (54.6

Objective To analyze relationship between autonomic nervous function and cognitive function in elderly patients with Parkinson's disease(PD).Methods A total of 130 elderly patients with PD admitted to The Affiliated Brain Hospital of Nanjing Medical University from January 2020 to December 2022 were included.Hoehn-Yahr staging was used to evaluate stage of the disease,Unified Parkinson's Disease Rating Scale Ⅲ(UPDRS Ⅲ)was used to evaluate the severity of motor disorders,Scales for Outcomes in Parkinson's Disease-Autonomic(SCOPA-AUT)was used to evaluate autonomic nervous function,Mini-Mental State Examination(MMSE)and Montreal Cognitive Assessment(MoCA)were used to evaluate cognitive function,Non-Motor Symptoms Scale(NMSS)was used to evaluate the severity of non-motor symptoms.Results According to whether the patients were accompanied by Alzheimer's disease(AD),they were divided into a group with AD(n=82)and a group without AD(n=48).The proportion of Hoehn-Yahr staging 3 to 5(x2=5.689,P=0.017),UPDRS Ⅲ score(t=21.490,P=0.000),SCOPA-AUT score(t=21.330,P=0.000),dysregulation of body temperature(x2=8.512,P=0.004),urinary dysfunction(x2=17.270,P=0.000),gastrointestinal dysfunction(x2=24.471,P=0.000),dysregulation of pupil(x2=5.299,P=0.021),cardiovascular dysfunction(x2=15.355,P=0.000)and NMSS score(t=32.309,P=0.000)in the group with AD were higher than those in the group without AD,the MMSE(t=4.730,P=0.000)and MoCA(t=6.840,P= 0.000)total scores and subtype scores(P=0.000,for all)in the group with AD were lower than those in the group without AD.Correlation analysis showed that the SCOPA-AUT score of PD patients with AD was negatively correlated with MMSE and MoCA total scores and subtype scores(P=0.000,for all).Conclusions The autonomic dysfunction of elderly PD patients with AD is more serious,and the autonomic nervous function is closely related to cognitive function.

Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. However, studies on ICH at high altitude are insufficient. We aimed to compare the initial manifestations, imaging features and short-term functional outcomes of ICH at different altitudes, and further explore the effect of altitude on the severity and prognosis of ICH. We retrospectively recruited ICH patients from January 2018 to July 2021 from two centers at different altitudes in China. Information regarding to clinical manifestations, neuroimages, and functional outcomes at discharge were collected and analyzed. Association between altitude and initial severity, neuroimages, and short-term prognosis of ICH were also investigated. A total of 724 patients with 400 lowlanders and 324 highlanders were enrolled. Compared with patients from the plain, those at high altitude were characterized by more severe preliminary manifestations (P < 0.0001), larger hematoma volume (P < 0.001) and poorer short-term functional outcome (P < 0.0001). High altitude was independently associated with dependency at discharge (adjusted P = 0.024), in-hospital mortality (adjusted P = 0.049) and gastrointestinal hemorrhage incidence (adjusted P = 0.017). ICH patients from high altitude suffered from more serious initial manifestations and worse short-term functional outcome than lowlanders. Control of blood pressure, oxygen supplementation and inhibition of inflammation may be critical for ICH at high altitude.

Growing evidence supports that depression in Parkinson's disease (PD) depends on disruptions in specific neural networks rather than regional dysfunction. According to the resting-state functional magnetic resonance imaging data, the study attempted to decipher the alterations in the topological properties of brain networks in de novo depression in PD (DPD). The study also explored the neural network basis for depressive symptoms in PD. We recruited 20 DPD, 37 non-depressed PD and 41 healthy controls (HC). The Graph theory and network-based statistical methods helped analyse the topological properties of brain functional networks and anomalous subnetworks across these groups. The relationship between altered properties and depression severity was also investigated. DPD revealed significantly reduced nodal efficiency in the left superior temporal gyrus. Additionally, DPD decreased five hubs, primarily located in the temporal-occipital cortex, and increased seven hubs, mainly distributed in the limbic cortico-basal ganglia circuit. The betweenness centrality of the left Medio Ventral Occipital Cortex was positively associated with depressive scores in DPD. In contrast to HC, DPD had a multi-connected subnetwork with significantly lower connectivity, primarily distributed in the visual, somatomotor, dorsal attention and default networks. Regional topological disruptions in the temporal-occipital region are critical in the DPD neurological mechanism. It might suggest a potential network biomarker among newly diagnosed DPD patients.

目的 分析伴发作性中枢神经系统障碍的腓骨肌萎缩症XI型(CMTX1)的临床及遗传学特点.方法 回顾性分析2021-08南京医科大学附属脑科医院收治的1例CMTX1伴发作性中枢神经系统障碍患者的临床资料及基因检测结果,并以"夏科-马里-图斯病、腓骨肌萎缩症、发作性、卒中样、CMTX1、CMTX、X-linked Charcot-Marie-Tooth connexin32、GJB1、episodic、recurrent"为关键词,检索万方数据知识服务平台、中国知网、PubMed数据库公开发表的CMTX1伴发作性中枢神经系统障碍病例.结果 共检索到中英文文献46篇,结合本病例,共纳入58例病例,重点总结中文文献报道的11例病例临床及遗传学特点.11例伴发作性中枢神经系统功能障碍的CMTX1患者在发作期临床表现为四肢无力、构音障碍、吞咽困难、头晕呕吐,发作持续时间10 min～20 h,发作后均可缓解.MRI显示以脑室白质周围对称性DWI序列高信号,T2序列异常信号最为常见,其次是胼胝体压部的异常信号.神经电生理特点是周围神经传导速度中等程度减慢.中文报道的11例基因突变位点无重复,中英文报道的58例基因突变位点仅少数重复,出现 2 次及以上的突变位点是 c.65G＞A(p.Arg22Gln)、c.425G＞A(p.Arg142Gln)、c.490C＞T(p.Arg164Trp)、c.424C＞T(p.Arg142Trp),本例患者携带 c.65G＞A(p.Arg22Gln)为文献已报道的最常见致病变异.结论 发作性中枢神经系统障碍伴脑白质病变的患者应考虑CMTX1诊断的可能,应结合家族史、详细的神经系统检查、电生理及遗传学检测进一步明确.

Functional magnetic resonance imaging (fMRI) is a convolution of latent neural activity and the hemodynamic response function (HRF). According to prior studies, the neurodegenerative process in idiopathic Parkinson's Disease (PD) interacts significantly with neuromuscular abnormalities. Although these underlying neuromuscular changes might influence the temporal characteristics of HRF and fMRI signals, relatively few studies have explored this possibility. We hypothesized that such alterations would engender changes in estimated functional connectivity (FC) in fMRI space compared to latent neural space. To test these theories, we calculated voxel-level HRFs by deconvolving resting-state fMRI data from PD patients (n = 61) and healthy controls (HC) (n = 47). Significant group differences in HRF (P < 0.05, Gaussian random field-corrected) were observed in several regions previously associated with PD. Subsequently, we focused on putamen-seed-based FC differences between the PD and HC groups using fMRI and latent neural signals. The results suggested that neglecting HRF variability may cultivate false-positive and false-negative FC group differences. Furthermore, HRF was related to dopamine receptor type 2 (DRD2) gene expression (P < 0.001, t = -7.06, false discover ratecorrected). Taken together, these findings reveal HRF variation and its possible underlying molecular mechanism in PD, and suggest that deconvolution could reduce the impact of HRF variation on FC group differences. (c) 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

Background: Presently, neurotransmitter deficits in GBA-related Parkinson's disease (GBA-PD) and relationships with cognitive impairment are poorly understood. A better understanding of neurotransmitter impairments in GBA-PD - particularly in the newly diagnosed drug-naive phase - may support developing targeted intervention strategies. We aimed to investigate patterns of neurotransmitter deficits in GBA-PD and idiopathic PD (iPD) and cognitive performance correlations.Methods: We recruited 189 newly diagnosed PD patients for GBA sequencing. Voxel-wise gray matter volume (GMV) was evaluated in a subgroup of 17 GBA-PD, 100 iPD, and 32 age-and sex-matched healthy controls (HCs). The JuSpace toolbox covering various neurotransmitter maps helped assess whether the spatial patterns of GMV alterations in GBA-PD or iPD patients (relative to HCs) were associated with specific neurotransmitter systems.Results: GBA-PD patients indicated widespread GM atrophy in the fronto-temporal-occipital region compared with HCs. GMV atrophy was spatially correlated in GBA-PD and iPD with serotonergic, dopaminergic, and acetylcholinergic pathway distributions (p < 0.05, false discovery rate corrected). Executive function and language in cognitive domains were also associated with the strength of GMV colocalization of serotonergic, dopaminergic, and acetylcholinergic circuits.Conclusions: Regional GM atrophy related to specific neurotransmitter deficits in de novo GBA-PD and iPD pa-tients could provide new insights into pathophysiological processes, facilitating potential therapeutic targets to support PD management.

目的 利用网络药理学和分子对接技术预测熟地平颤方治疗帕金森病(PD)的主要活性成分、潜在靶点及其分子作用机制.方法 借助中药系统药理学数据库与分析平台(TCMSP)和TCM@TAIWAN台湾中医药资料库、PubChem、Swiss Target Prediction平台筛选熟地平颤方中药的主要化学成分及其作用靶点,利用GeneCards和DisGeNET数据库筛选PD的相关靶点,STRING和Cytoscape软件构建共同靶点蛋白相互作用网络(PPI)及中药-活性成分-靶点网络图.通过Metascape对关键靶点进行基因本体论(GO)、DisGeNET功能富集和京都基因与基因组百科全书数据库(KEGG)通路富集分析.运用iGEMDOCK软件进行批量分子对接实验.结果 筛选出熟地平颤方29个主要活性成分,178个与PD共有的作用靶点,主要核心靶点包括AKT1、ALB、MAPK3、CASP3和APP等.GO功能和KEGG通路富集显示该方调控蛋白丝氨酸/苏氨酸及酪氨酸蛋白激酶、神经递质受体、肽链内切酶等多种分子功能,通过神经活动配体-受体相互作用、cAMP、雌激素、磷脂酶D等多种信号通路发挥治疗PD的作用.DisGeNET功能富集结果表明熟地平颤方广泛参与了认知障碍、淀粉样变性、记忆缺陷、神经痛和成瘾行为等方面的改善.分子对接结果显示羊毛甾醇、胆固醇与前列腺素G/H合酶2(PTGS2),α1-谷甾醇与白蛋白(ALB)均有较强的结合活性.结论 网络药理学和分子对接技术初步揭示了熟地平颤方通过多成分、多靶点及多通路发挥PD的治疗作用,为其进一步研究提供了参考.

Visual hallucinations are a common non-motor symptom in Parkinson's disease (PD) patients, and the mechanism of their occurrence is still unclear. Damage of visual neural pathway is one of the main explanations for Parkinson's hallucination which will cause changes in the Visual Neural Information Flow, resulting in patients processing visual information differently than healthy people. This study aimed at investigating the abnormalities of bottom-up and top-down visual information flow in patients with PD. Eight patients with PD with hallucinations and eight healthy controls were selected. EEG data in the resting state were collected and analyzed for abnormalities in visual information flow in combination with spectral and brain network analysis. Compared with healthy controls, EEG data from PD patients showed enhanced activity in theta ( $\theta$ ) and alpha ( $\alpha$ ) bands associated with top-down information flow and reduced activity in gamma ( $\gamma$ ) band associated with bottom-up information flow, generating the accumulation and dissemination of disorderly information flow. The imbalance of visual information flow may be one of the main causes of visual hallucinations in PD patients.

目的 评估β-淀粉样蛋白(Aβ)42、Aβ40、α-突触核蛋白(α-syn)及p-tau181蛋白对早期初诊帕金森病轻度认知功能障碍(PD-MCI)的诊断价值.方法 利用超灵敏单分子阵列技术方法(SiMoA)检测2018年7月至2021年5月至南京脑科医院门诊就诊的23例早期初诊PD认知功能正常患者(PD-NC组)、32例早期初诊PD-MCI患者(PD-MCI组)及21名健康对照者(NC组)血浆中的Aβ42、Aβ40、α-syn及p-tau181蛋白浓度并计算Aβ42/Aβ40、Aβ42/α-syn及Aβ40/α-syn比值,分析上述指标在各组间的差异、与各认知域的相关性及对诊断PD-MCI的敏感性和特异性.结果 PD-NC组、PD-MCI组及NC组间血浆Aβ42、Aβ40、α-syn、p-tau181蛋白浓度及Aβ42/α-syn、Aβ40/α-syn比值的差异无统计学意义.但PD-MCI相较于PD-NC组Aβ42/Aβ40比值明显下降(0.069±0.012 vs.0.079±0.001,P<0.05).Aβ42/Aβ40比值诊断PD-MCI的敏感性为82.6％,特异性为62.5％.Aβ42/Aβ40比值与PD认知功能损害的特定认知领域如视空间与执行功能(r=0.274,P=0.043)及语言认知领域(r=0.322,P=0.016)存在显著相关性.结论 Aβ42/Aβ40比值可用来诊断早期PD-MCI患者,且与特定认知域损害有关,具有一定的临床辅助诊断价值.

BackgroundDepression is one of the most prevalent and disturbing non-motor symptoms in Parkinson’s disease (PD), with few dynamic functional connectivity (dFC) features measured in previous studies. Our aim was to investigate the alterations of the dynamics in de novo patients with PD with depression (dPD).MethodsWe performed dFC analysis on the data of resting-state functional MRI from 21 de novo dPD, 34 de novo patients with PD without depression (ndPD), and 43 healthy controls (HCs). Group independent component analysis, a sliding window approach, followed by k-means clustering were conducted to assess functional connectivity states (which represented highly structured connectivity patterns reoccurring over time) and temporal properties for comparison between groups. We further performed dynamic graph-theoretical analysis to examine the variability of topological metrics.ResultsFour distinct functional connectivity states were clustered via dFC analysis. Compared to patients with ndPD and HCs, patients with dPD showed increased fractional time and mean dwell time in state 2, characterized by default mode network (DMN)-dominated and cognitive executive network (CEN)-disconnected patterns. Besides, compared to HCs, patients with dPD and patients with ndPD both showed weaker dynamic connectivity within the sensorimotor network (SMN) in state 4, a regionally densely connected state. We additionally observed that patients with dPD presented less variability in the local efficiency of the network.ConclusionsOur study demonstrated that altered network connection over time, mainly involving the DMN and CEN, with abnormal dynamic graph properties, may contribute to the presence of depression in patients with PD.

Objective:To investigate the characteristics and evolution of mild motor symptoms (MMS) in patients with prodromal Parkinson′s disease (pPD).Methods:Based on the pPD cohort screened by Parkinson′s Disease Prodromal Clinical Assessment Scale in Nanjing community from July 2018 to December 2020, the clinical data of 30 patients with pPD who completed the baseline assessment and were followed up for at least 1 year were analyzed. According to the Unified Parkinson Diease Rating Scale Ⅲ (UPDRS-Ⅲ) score, the patients were divided into MMS group (UPDRS-Ⅲ score>3) and non-MMS group (NMMS group, UPDRS-Ⅲ score≤3). The differences and evolution characteristics of clinical characteristics between the 2 groups were compared. Multivariate linear regression was used to analyze the risk factors of motor symptom progression in pPD patients.Results:Among the 30 patients with pPD, 7 of 23 patients in the MMS group were converted to PD at the end of follow-up, 1 of 7 patients in the NMMS group were converted to PD at the end of follow-up. The UPDRS-Ⅲ score [10.00 (7.00, 17.00)], Montreal Cognitive Assessment Scale (MoCA) score [25.50 (24.75, 28.00)] and the Hamilton Anxiety Scale (HAMA) score [9.00 (5.00, 13.00)] at the end of follow-up of pPD patients were significantly higher than those at baseline [7.00 (4.00, 12.00), 24.00 (22.75, 25.25) and 8.00 (2.00, 11.00)], and the differences were statistically significant ( Z=-3.505, P<0.001; Z=-2.956, P=0.003; Z=-2.427, P=0.015).Subgroup analysis showed that UPDRS-Ⅲ score [11.00 (7.00, 18.00)], MoCA score [25.00 (24.00, 27.00)] and HAMA score [ 9.00 (6.00, 15.00)] at the end of follow-up in the MMS group were higher than those at baseline [8.00 (6.00, 12.00), 24.00 (22.00, 25.00) and 9.00 (3.00, 11.00)], and the difference was statistically significant (Z=-2.768, P=0.006; Z=-2.457, P=0.014; Z=-2.250, P=0.024). The Non-Motor Symptoms Questionnaire score at the end of follow-up in the MMS group (8.96±5.20) was significantly lower than that in the baseline (11.04±4.41), and the difference was statistically significant ( t=2.441, P=0.023).There was no significant difference in Mini-Mental State Examination (MMSE), Hamilton Depression Scale (HAMD), Rapid Eyes Movement Sleep Behavior Disorder Questionnaire-Hong Kong (RBDQ-HK) and Sniffin′ sticks olfactory test score at the end of follow-up in the MMS group. Only UPDRS-Ⅲ score in the NMMS group was increased at the end of follow-up [7.00 (5.00, 8.00)] compared with the baseline [4.00 (1.00, 4.00)], and the difference was statistically significant ( Z=-2.375, P=0.018). There was no significant difference in MoCA, MMSE, HAMA, HAMD, RBDQ-HK, and Sniffin′ sticks olfactory test score between the NMMS group and the baseline at the end of follow-up. Conclusion:The clinical conversion rate of pPD patients with MMS is high,and screening of this population should be paid attention.

BackgroundPatients with Parkinson’s disease (PD) experience a decline in verbal fluency (VF) immediately after undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN). This phenomenon is thought to be related to surgical microlesions.PurposeWe investigated the alterations in interhemispheric functional connectivity after STN-DBS in PD patients. We also evaluated the correlation between these changes and decreased VF scores.MethodOverall, 30 patients with PD were enrolled in the study. Resting-state functional magnetic resonance imaging scans were performed twice, once before and once after DBS, in PD patients. Voxel-mirrored homotopic connectivity (VMHC) was applied in order to evaluate the synchronicity of functional connectivity between the hemispheres.ResultAfter undergoing STN-DBS, PD patients demonstrated reduced VMHC value in the posterior cerebellum lobe, angular gyrus, precuneus/posterior cingulate gyrus (PCC), supramarginal gyrus, superior frontal gyrus (SFG) (medial and dorsolateral) and middle frontal gyrus (MFG). In addition, we observed a significant positive correlation between the altered VMHC value in the SFG and MFG and the change of phonemic VF scores.ConclusionPD patients demonstrated an interhemispheric coordination disorder in the prefrontal cortex, cerebellum, supramarginal gyrus and DMN after undergoing STN-DBS. The positive correlation between reduced VMHC value in the SFG and MFG and the changes of VF scores provides a novel understanding with regard to the decline of VF after DBS.

目的 探讨初诊帕金森病(PD)患者非运动症状(NMS)的特点及其性别差异.方法 选取首次就诊的PD患者203例(男性102例,女性101例)及正常对照者255例(男性110例,女性145例),收集入组对象的临床资料并采用简易智能评估量表(MMSE)、蒙特利尔认知评估量表(MoCA)、汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、帕金森病睡眠量表(PDSS)、统一PD评分量表(UPDRS)第Ⅲ部分及Hoehn-Yahr(H-Y)分期对PD患者进行评估.应用NMS问卷筛查量表(NMSQ)评定其非运动症状,比较不同性别的NMS的特点.采用多因素线性回归分析PD患者NMDQ总分的影响因素.结果 98.5％的PD患者均存在至少一项NMS,其中以记忆力下降(67.5％)、情绪低落(49.8％)最为常见.PD组NMS的总分及9个分域得分均显著高于对照组(均P<0.05).PD组女性兴趣减退、情绪低落、焦虑及出汗增多的比率显著高于同组男性,而吞咽困难的比率显著降低(均P<0.05).正常对照组(HC组)女性出汗增多的比率显著高于同组男性,记忆力下降的比率显著降低(均P<0.05).PD男性及女性患者的NMS总分均受HAMD和PDSS影响(均P<0.05),而男性更易受病程影响(β=0.181,P=0.032).结论 PD初诊患者的非运动症状发生率明显高于正常人且具有性别差异.

Background and objective Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson’s disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). Methods A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG ( n = 100) or placebo ( n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. Results After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (− 1.43 scores [− 2.50, − 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (− 3.56 scores [− 5.77, − 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. Conclusion ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432

目的:基于系统药理学和相关研究文献分析预测滋肾平颤方加减治疗帕金森病伴抑郁(DPD)的主要活性成份、潜在作用靶点及分子作用机制.方法:借助中药系统药理学数据库与分析平台(TCMSP)、TCM@TAIWAN台湾中医药资料库、PubChem、Swiss ADME、Swiss Target Prediction平台筛选滋肾平颤方加减中的主要化学成份及其作用靶点,利用GeneCards和DisGeNET数据库筛选DPD的相关靶点,采用STRING和Cytoscape软件构建共同靶点蛋白相互作用(PPI)网络及中药-活性成份网络图.通过DAVID数据库对关键靶点进行GO功能富集和KEGG通路富集分析,同时查阅滋肾平颤方相关研究文献并进行归纳、整理和分析.结果:共筛选出滋肾平颤方加减主要活性成份82个,作用靶点143个,其中36个是与DPD共有的核心靶点.GO功能富集分析显示生物过程主要包括RNA聚合酶II启动子转录的正调控、对药物的反应和蛋白质自磷酸化;细胞组分主要有质膜、质膜的组成部分以及细胞膜;分子功能涵盖了蛋白质结合、ATP结合以及可识别蛋白结合等.KEGG通路富集分析揭示滋肾平颤方加减中生物活性化合物主要通过神经活性配体-受体相互作用、Rap1、cAMP等信号通路发挥抗DPD的作用.结论:通过系统药理学结合文献收集分析,滋肾平颤方加减可能通过槲皮素、山奈酚和去氢骆驼蓬碱等关键成份,作用于AKT1、EGFR和DRD2等核心靶点,通过神经活性配体-受体相互作用、Rap1和cAMP等信号通路发挥治疗DPD的作用.