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The aim of this study was to clarify the dynamic neural activity of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD).Using dynamic functional network connectivity (dFNC) analysis, we evaluated 41 PD patients with LID (LID group) and 34 PD patients without LID (No-LID group). Group spatial independent component analysis and sliding-window approach were employed. Moreover, we applied a k-means clustering algorithm on windowed functional connectivity (FC) matrices to identify reoccurring FC patterns (i.e., states).The optimal number of states was determined to be five, the so-called State 1, 2, 3, 4, and 5. In ON phase, compared with No-LID group, LID group occurred more frequently and dwelled longer in strongly connected State 1, characterized by strong positive connections between visual network (VIS) and sensorimotor network (SMN). When switching from OFF to ON phase, LID group occurred less frequently in State 3 and State 4. Meanwhile, LID group dwelled longer in State 2 and shorter in State 3. No-LID group occurred more frequently in State 5 and less frequently in State 3. Additionally, correlation analysis demonstrated that dyskinesia's severity was associated with frequency of occurrence and dwell time in State 2, dominated by inferior frontal cortex in cognitive executive network (CEN).Using dFNC analysis, we found that dyskinesia may be related to the dysfunctional inhibition of CEN on motor loops and excessive excitation of VIS and SMN, which provided evidence of the changes in brain dynamics associated with the occurrence of dyskinesia.

Alterations in brain function in Parkinson’s disease (PD) patients with diphasic dyskinesia have not been investigated. We aimed to explore the alterations in regional brain function. Each of 53 levodopa (LD)-treated PD patients had two resting-state functional magnetic resonance imaging (rs-fMRI) scans in the same morning, before and after taking LD. The regional homogeneity (ReHo) approach was used to reveal local synchronization changes. Two-way factorial repeated measures analysis of covariance, with group as a between-subject factor and LD effect as a within-subject factor, was performed to explore the two main effects and interaction. Interactive analysis was used to show outcomes that combined disease status and LD effect. Spearman’s correlations were used to detect associations between interactive brain regions and severity of dyskinetic symptoms, assessed by the Unified Dyskinesia Rating Scale (UDyRS) scores, along with moderation analyses. There was no significant difference in the main group effect analysis. Significantly different clusters obtained from main LD effect analysis were in left caudate nucleus and putamen. ReHo values decreased in the caudate nucleus and increased in the putamen during the ON state after taking LD. Interaction between group and LD effect was found in left medial superior frontal gyrus (mSFG), where there were the lowest ReHo values, and was negatively correlated with UDyRS scores in the diphasic dyskinetic group during the ON state. The relationship was independent of LD dose. Abnormal local synchronization in the mSFG is closely associated with the development of diphasic dyskinesia in PD patients.

Abnormal dopaminergic modulation of the cortico-basal ganglia motor loops results in the emergence of levodopa-induced dyskinesia (LID). We focused on alterations in the gray matter (GM) volume and the cortical thickness of the brain, especially in cortico-basal ganglia motor loops, in Parkinson's disease (PD) with diphasic dyskinesia. 48 PD patients with diphasic dyskinesia, 60 PD patients without dyskinesia and 48 healthy controls (HC) were included. Voxel-based morphometry (VBM) was applied to get GM images from MRI brain images. FreeSurfer was used to get cortical thickness. Distinct analyses of covariance (ANCOVA) and linear contrasts were performed for early- and late-onset PD groups. The severity of diphasic dyskinesia was evaluated by the Unified Dyskinesia Rating Scale (UDysRS). Finally, the correlations between mean volumes of clusters showing differences and the UDysRS scores were performed by Pearson's correlation. The GM volumes of precentral gyri were increased in PD patients with diphasic dyskinesia when compared with those without dyskinesia, which were positively correlated with UDysRS scores in PD patients with diphasic dyskinesia. However, there was no significant difference in cortical thickness among groups. The increased precentral gyri GM volumes might be associated with the pathogenesis and the severity of diphasic dyskinesia.

Taking the library of Shanghai Civil Aviation College as an example, this paper analyzes its space service practice, and finds that there are some problems in the space service of higher vocational college library: insuffi-cient new space area, backward space service facilities, insufficient under-standing of space service by librarians, and insufficient space service eval-uation mechanism. Based on this, this paper puts forward the counter-measures of library space service in higher vocational colleges and provides reference for other higher vocational colleges to develop space service.

This paper introduces the performance management method into the management of public libraries’ reading promotion activities. The literature analysis method and the empirical research method are used to study its scientific rationality to promote the enthusiasm of librarians and improve the efficiency of reading promotion activities.

This paper provides references for the space service of public libraries in China. 51 public libraries in East China were investigated in terms of space type, space facilities and space service reconstruction; the current situation of space service was analyzed and some problems were revealed. Based on the investigation, the characteristics of public libraries’ space service in East China are summarized from the perspective of space type, space service concept and space service mode. And the problems in the aspects of new space service level, space service facility construction and space service evaluation mechanism are pointed out. Through the analysis, space service strategies of public libraries in China are proposed: libraries’ overall quality should be strengthened; space service based on information technology should be promoted; users’ needs should be respected and evaluation mechanism should be developed.

Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incidence and cognitive outcomes of ICAS) is to elucidate the pathophysiology of stroke and cognitive impairment in ICAS population, comprehensively evaluating the complex interactions among life-course exposure, genomic variation, vascular risk factors, cerebrovascular burden and coexisting neurodegeneration.SICO-ICAS is a multicenter, prospective, observational cohort study. We aim to recruit 3,000 patients with symptomatic or asymptomatic ICAS (50% or occlusion) who will be followed up for ≥12 months. All participants will undergo pre-designed magnetic resonance imaging packages, blood biomarkers testing, as well as detailed cognitive domains assessment. All participants will undergo clinical visits every 6 months and telephone interviews every 3 months. The primary outcome measurement is ischemic stroke or cognitive impairment within 12 months after enrollment.This study will establish a large prospective ICAS cohort, hopefully discover new biomarkers associated with vulnerable intracranial plaques, identify subjects at high risk for incident ischemic stroke or cognitive impairment, and eventually propose a precise diagnostic and treatment strategy for ICAS population.Chinese Clinical Trials Register ChiCTR2200061938.

Background Rapid eye movement (REM) sleep behavior disorder (RBD) is one of the common nonmotor symptoms of Parkinson’s disease (PD), characterized by frequently occurring REM sleep without muscle atonia. Our aim was to explore dynamic network connection changes in PD patients with RBD. Method On the basis of RBD screening questionnaire (RBDSQ), 126 PD patients were classified into those with probable RBD symptoms (PD-pRBD) and without probable RBD (PD-npRBD). We applied independent component analysis, sliding window approach and k-means clustering methods to clarify dynamic functional connectivity alterations. Results In contrast to PD-npRBD, PD-pRBD patients were liable to engage in a brain pattern mainly marked by weaker positive couplings between visual network (VIS) and default mode network (DMN), DMN and basal ganglia network (BG), and within DMN (State IV). In addition, we discovered that both PD patients with or without pRBD had shorter dwell time and fewer occurrences in State III, characterized by positive correlations between VIS and DMN, BG and DMN, and positive within-network coupling of sensorimotor network (SMN), relative to healthy controls. Conclusions Our study suggested that the weaker positive couplings between VIS and DMN, DMN and BG, and within DMN in State IV could be involved in the pathogenesis of PD patients with probable RBD on an overall level.

In this work, the theoretical and experimental study on vibration transmission in quasi-periodic impedance layered structures built by magnetorheological (MR) fluid is conducted. Based on the MR effect of MR fluid, the quasi-periodic layered structures formed by low and high impedance layers following Fibonacci, Thue–Morse and multiperiodic sequences are constructed, respectively. These different quasi-periodic patterns can be flexibly obtained by controlling the arrangement style and magnetic field strength of electromagnets outside the MR fluid. The vibration transfer model is established based on the transfer matrix method and the trends of vibration level difference with different parameters are analyzed. Furthermore, experiments are performed to estimate the vibration transmissivity of the proposed structures. It indicates that the developed quasi-periodic impedance layered structures can exhibit greater damping effect on vibrations by appropriately increasing the magnetic field strength and thickness ratio of low to high impedance layers. Moreover, there exist quasi-periodic impedance patterns whose attenuation effect on vibration is better than that of periodic pattern in the frequency range studied in this paper (20–200 Hz). This means that the introducing of the particular quasi-periodicity increases the transmission loss of vibrations in a certain frequency range. This investigation is conducive to further expand the application of MR materials and quasi-periodic structures in the field of vibration control.

Background Traditional measures of static functional connectivity may not completely reflect the dynamic neural activity of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). This study was aimed to investigate the dynamic changes of large-scale functional network connectivity in the temporal domain in PD patients with and without LID. Methods Using dynamic functional network connectivity (dFNC) analysis, we evaluated 41 PD patients with LID (LID group) and 34 PD patients without LID (No-LID group), on and off their levodopa medications. Group spatial independent component analysis, sliding-window approach and k-means clusters were employed. Results In OFF phase, we found no differences between PD subgroups in temporal properties. In ON phase, compared than No-LID group, LID group occurred more frequently and dwelled longer in strongly connected State 1, characterized by strong connections between visual network (VIS) and other networks. When switching from OFF to ON phase, LID group occurred more frequently and dwelled longer in State 2 and occurred less frequently and dwelled shorter in State 3 (both states were strongly connected), while No-LID group occurred more frequently and dwelled longer in State 5 (weakly connected). Additionally, correlation analysis further demonstrated that the severity of dyskinesia was only associated with frequency of occurrence and dwell time in State 2, dominated by inferior frontal cortex in cognitive executive network (CEN), strongly connecting with sensorimotor network (SMN) and VIS. Conclusions Using dFNC analysis, we found that compared to those without LID, PD patients with LID may be involved in the superexcitation of VIS, as well as interconnections between CEN and SMN, VIS, having impact on inhibition of motor circuits. The dFNC analysis might provide new insights into the neural mechanisms of LID in PD.

Levodopa-induced dyskinesias are common motor complication of Parkinson’s disease after 4–6 years of treatment. The hallmarks of dyskinesias include unilateral onset and the tendency to appear on the more affected body sides. There is a growing literature documenting the lateralization abnormalities are associated with the emergence of dyskinesias. Our investigation aimed to explore interhemispheric functional and its corresponding morphological asymmetry. A total of 22 dyskinetic patients, 23 nondyskinetic patients, and 26 controls were enrolled. Resting-state functional magnetic resonance imaging scans were performed twice before and after dopaminergic medication. Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer were employed to assess the synchronicity of functional connectivity and structural alternations between hemispheres. During OFF state, dyskinetic patients showed desynchronization of inferior frontal cortex (IFC) when compared to nondyskinetic patients. And during ON state, dyskinetic patients showed desynchronization of IFC and pre-supplementary motor area (pre-SMA) when compared to nondyskinetic patients. However, there was no corresponding significant asymmetries in cortical thickness. Moreover, the degree of desynchronization of IFC and pre-SMA in dyskinetic pateients during ON state were negatively correlated with the Abnormal Involuntary Movement Scale (AIMS) scores. Notably, among patients who showed asymmetrical dyskinesias, there was a significant negative correlation between VMHC values of IFC and dyskinesias symptom asymmetry. Our findings suggested that uncoordinated inhibitory control over motor circuits may underlie the neural mechanisms of dyskinesias in Parkinson’s disease and be related to its severity and lateralization.

Accumulating evidence suggests that iron metabolism may be involved in the pathophysiology of Parkinson's disease (PD), and particularly in motor phenotype. This investigation aimed to examine plasma iron metabolism related indicators in patients with tremor-dominant phenotype of PD and determine less invasive, potential markers from plasma, which could partially reflect pathophysiological mechanisms of the brain. Seventy-six PD patients were recruited and thirty-three of them were classified into the tremor-dominant PD (TD-PD) group and forty-three into the non-tremor dominant PD (NT-PD) group, as determined by clinical characteristics. Plasma iron, ceruloplasmin, transferrin and ferritin levels were measured using Beckman Coulter AU biochemical assays, immune transmission turbidimetry method, scatter turbidimetry method and chemiluminescence method, respectively. Spearman's correlation analysis and multiple linear regression analysis were used for further study. Compared to healthy controls, TD-PD patients exhibited lower plasma iron level (p = 0.006) and higher transferrin level (p 0.001). Plasma transferrin level was much higher in the TD-PD as compared to NT-PD (p = 0.003). Furthermore, plasma transferrin level was positively correlated with the severity of tremor in TD-PD (r = 0.358, p = 0.041). Multiple linear regression further demonstrated significant associations of plasma transferrin level with severity of tremor in TD-PD (regression coefficient = 0.253, P = 0.016), independently from other confounding factors. The elevated plasma transferrin level, combining with decreased plasma iron level might be given considerable weight in the recognition of parkinsonian tremor.

Objectives In this study, the alterations of structural topological properties in Parkinson's disease (PD) patients with levodopa-induced dyskinesias (LIDs) were explored using white matter structural network connectome derived from diffusion tensor imaging (DTI). Methods 21 dyskinetic PD patients, 21 non-dyskinetic PD patients and 25 healthy controls were studied in global and nodal topological properties of structural networks after controlling age, gender and education. Afterwards, post hoc analyses were performed to explore further differences. Finally, multiple linear regression analysis was employed to test the associations between significant different properties and the severity of dyskinesias in PD. Results Dyskinetic PD patients exhibited significant increased global efficiency, local efficiency, clustering coefficient, but decreased shortest path length compared with the non-dyskinetic. Additionally, increased nodal efficiency in bilateral inferior frontal gyrus (IFG), right putamen, right thalamus, and decreased nodal shortest path length in bilateral IFG and right thalamus, were discovered in dyskinetic PD in comparison with non-dyskinetic PD. Notably, a negative correlation between the Abnormal Involuntary Movement Scale (AIMS) scores and shortest path length of whole-brain network was found in PD with LIDs. Conclusions Our results indicated excessively optimized topological organization of whole-brain structural connectome in PD patients with LIDs. These findings also illustrated that excessively strengthened basal ganglia-thalamocortical nodal structural connections played an important role in the presence of LIDs.

The α-synuclein (SNCA) gene is thought to be involved in levels of α-synuclein and influence the susceptibility for the development of Parkinson’s disease (PD). The aim of the present study is to explore the association among SNCA rs1193074 polymorphism, spontaneous brain activity and clinical symptoms in PD patients. 62 PD patients and 47 healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. Also blood sample of each participant was genotyped for rs11931074 polymorphism (PD: TT = 19, GT = 32, GG = 11; HC: TT = 10, GT = 25, GG = 12) and then examined to ascertain the influence of different genotypes on regional brain activity with amplitude low-frequency fluctuation analysis (ALFF). Furthermore, we evaluated the relationship among genotypes, interactive brain region and clinical symptoms in PD. Compared with HC subjects, PD patients showed decreased ALFF values in right lingual gyrus and increased ALFF values in right cerebellum posterior lobe. Significant interaction of ‘‘groups × genotypes’’ was found in the right angular gyrus, where there were higher ALFF values in TT genotype than in GT or GG genotype in the PD group and there was a contrary trend in the HC group. And further Spearman’s correlative analyses revealed that ALFF values in right angular gyrus were negatively associated with unified Parkinson’s disease rating scale (UPDRS) III score in PD-TT genotype. Our study shows for the first time that SNCA rs11931074 polymorphism might modulate brain functional alterations and correlate with motor symptoms in Chinese PD patients.

More and more evidence suggests that dopamine receptor D3 gene (DRD3) plays an important role in the clinical manifestations and the treatment of Parkinson’s disease (PD). DRD3 Ser9Gly polymorphism is the most frequently studied variant point. Our aim was to investigate the potential effect of DRD3 Ser9Gly polymorphism on modulating resting-state brain function and associative clinical manifestations in PD patients. We consecutively recruited 61 idiopathic PD patients and 47 healthy controls (HC) who were evaluated by clinical scales, genotyped for variant Ser9Gly in DRD3, and underwent resting-state functional magnetic resonance imaging. Based on DRD3 Ser9Gly polymorphism, PD patients and HCs were divided into four subgroups. Then, two-way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions of PD and DRD3 Ser9Gly polymorphism on the brain function via amplitude of low-frequency fluctuations (ALFF) approach. The association between DRD3 Ser9Gly-modulated significantly different brain regions, and clinical manifestations were detected by Spearman’s correlations. PD patients exhibited decreased ALFF values in the right inferior occipital gyrus, lingual gyrus, and fusiform gyrus. A significant difference in the interaction of “groups × genotypes” was observed in the right medial frontal gyrus. The ALFF value of the cluster showing significant interactions was positively correlated with HAMD-17 scores (r=0.489, p=0.011) and anhedonia scores (r=0.512, p=0.008) in PD patients with the Ser/Gly or Gly/Gly genotypes. Therefore, D3 gene Ser9Gly polymorphism might be associated with the severity of depression characterized by anhedonia in PD patients.

Cephalotaxus sinensis seeds can’t germinate even in the appropriate environment. However, numerous studies have showed that cold stratification and gibberellin acid (GA) can break the seed dormancy and promote seed germination effectively. To investigate the effect of cold stratification and different concentrations of exogenous GA3 on dormancy breaking in seeds of Cephalotaxus sinensis, we monitored germination rates and changes in soluble sugar, starch, amylase, soluble protein, free amino acid during cold stratification. The results showed that seeds stratified for 5 months germinated to 12.7%, while those disposed with 200, 400, 600 mg/L of GA3 germinated to 29.2%, 21.7%, and 18.4%, respectively. Free amino acid content was enhanced significantly, whereas soluble sugar content decreased during 45 days and then increased constantly. Additionally, the main reserves such as starch, protein decreased significantly during cold stratification, and cold stratification induced increases in the activities of α-amylase, (α + β)-amylase. The preliminary results show that the combination of GA3 and cold stratification has better effect to break seed dormancy.

In many wild species, seeds are dormancy at maturity and will not germinate even under favorable environment conditions. Dormancy is a complex trail that is determined by many factors. Some studies have shown that cold stratification and the application of gibberellic acid (GA) can break seed dormancy and promote seed germination. The present study investigated the causes of plant dormancy and the effect of cold stratification and different concentrations of exogenous GA3 in regulating Cephalotaxus sinensis seed germination. Results showed that C. Sinensis seeds have good water permeability, which suggested that seed coats were not the main cause that inhibited the seed germination. There were germination inhibitions in all parts of seeds, and the order of inhibitory effect was: testa < endosperm (embryo), which indicated that existence of germination inhibitions was the main reason causing seed dormancy. Endogenous GAs and IAA (indole-3-acetic acid) content increased, while ABA (abscisic acid) content decreased over the experiments. ZR (zeatin riboside) content decreased in the early phase of cold stratification, but rebounded by the end of the experimental period. The changes of endogenous hormone indicated that GA, IAA and ZR played a positive role in seed germination, whereas ABA was associated with seed dormancy. Besides, the relative ratio of GA/ABA, IAA/ABA and ZR/ABA may play a more important role than their absolute level during the seed development.

Background: More and more evidence suggests that dopamine receptor D3 gene (DRD3) plays an important role in the clinical manifestations and the treatment of Parkinson's disease (PD). DRD3 Ser9Gly polymorphism is the most frequently studied variant point. Our aim was to investigate the potential effect of DRD3 Ser9Gly polymorphism on modulating resting-state brain function and associative clinical manifestations in PD patients. Methods: We consecutively recruited 61 idiopathic PD patients and 47 healthy controls (HC) who were evaluated by clinical scales, genotyped for variant Ser9Gly in DRD3 and underwent resting-state functional magnetic resonance imaging. Based on DRD3 Ser9Gly polymorphism, PD patients and HCs were divided into four subgroups. Then, two-way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions of PD and DRD3 Ser9Gly polymorphism on the brain function via amplitude of low-frequency fluctuations (ALFF) approach. The association between DRD3 Ser9Gly-modulated significantly different brain regions and clinical manifestations was detected by Spearman's correlations. Findings: PD patients exhibited decreased ALFF values in right inferior occipital gyrus, lingual gyrus and fusiform gyrus. A significant difference in the interaction of "groups × genotypes" was observed in right medial frontal gyrus. The ALFF value of the cluster showing significant interactions was positive correlated with HAMD-17 scores (r=0.489, p=0.011) in PD patients with the Ser/Gly or Gly/Gly genotypes. Interpretation: D3 gene Ser9Gly polymorphism might be associated with depression severity in PD patients. Funding Statement: This work was supported by the National Natural Science Foundation of China (No.81671258), the Science and Technology Project of Jiangsu Provincial Commission of Health and Family Planning (No.H201602), the Natural science foundation of Jiangsu Province (No.BK20141494), the Jiangsu Provincial Personnel Department “the Great of Six Talented Man Peak” Project (No.2014-WSN-013), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and the Science and Technology Project of Jiangsu Bureau of Traditional Chinese Medicine (No.YB2015163). Declaration of Interests: The authors declare "none". Ethics Approval Statement: This study was approved by the ethics committee of the First Affiliated Hospital of Nanjing Medical University and all participants provided us with written informed consent before participating in the experiment.