Identifying Parkinson's disease with mild cognitive impairment by using combined MR imaging and electroencephalogram.

OBJECTIVES: To analyse the changes of quantitative electroencephalogram (qEEG) and cortex structural magnetic resonance (MR) imaging in Parkinson's disease with mild cognitive impairment (PD-MCI) and to explore the "composite marker"-based machine learning model in identifying PD-MCI. METHODS: Retrospective analysis of patients with PD identified 36 PD-MCI and 35 PD with normal cognition (PD-NC). QEEG features of power spectrum and structural MR features of cortex based on surface-based morphometry (SBM) were extracted. Support vector machine (SVM) was established using combined features of structural MR and qEEG to identify PD-MCI. Feature importance evaluation algorithm of mean impact value (MIV) was established to sort the vital characteristics of qEEG and structural MR. RESULTS: Compared with PD-NC, PD-MCI showed a statistically significant difference in 5 leads and waves of qEEG and 7 cortical region features of structural MR. The SVM model based on these qEEG and structural MR features yielded an accuracy of 0.80 in the training set and had a high prediction accuracy of 0.80 in the test set (sensitivity was 0.78, specificity was 0.83, area under the receiver operating characteristic curve was 0.77), which was higher than the model built by the feature separately. QEEG features of theta wave in C3 had a marked impact on the model for classification according to the MIV algorithm. CONCLUSIONS: PD-MCI is characterized by widespread structural and EEG abnormality. "Composite markers" could be valuable for the individualized diagnosis of PD-MCI by machine learning. KEY POINTS: • Explore the brain abnormalities in Parkinson's disease with mild cognitive impairment by using the quantitative electroencephalogram and cortex structural MR simultaneously. • Multimodal features based support vector machine for identifying Parkinson's disease with mild cognitive impairment has an acceptable performance. • Theta wave in C3 is the most influential feature of qEEG and cortex structure MR imaging in identifying Parkinson's disease with mild cognitive impairment using support vector machine.

Hospital and healthcare insurance system record-based epidemiological study of myasthenia gravis in southern and northern China.

OBJECTIVE: This is the first cross-region epidemiological study of myasthenia gravis (MG) in China. We estimated the incidence, prevalence, and medical costs of MG in southern China and explored the differences between the southern and northern Chinese populations. METHODS: We collected and analyzed records from 20 hospitals in the southern city, Guangzhou, 13 hospitals in the northern city, Harbin, and two healthcare insurance systems: job based and residence based in Guangzhou during 2000-2017. RESULTS: (1) The estimated annual incidence of MG was 1.55-3.66 per 100,000, and the estimated prevalence of MG was 2.19-11.07 per 100,000 in southern China based on insurance records. (2) The proportion of hospitalized MG patients in the south-based hospital records was three times as high as that in the north-based hospital records. (3) Female MG prevalence was significantly higher than male MG prevalence in Guangzhou, while the similar gender difference in Harbin was not statistically significant due to higher variation in earlier years. (4) The average expense was $35-42 for each outpatient service and $2526-2673 for each hospitalization expense in the south. (5) Contrary to the increase of insurance-based estimate of MG prevalence, the proportion of hospitalized MG patients did not increase over the years, suggesting rising awareness and utilization of health insurance. CONCLUSIONS: The southern MG population had a significantly higher prevalence and a lower response threshold to medication than the northern MG population. These results are calling for further investigations on the genetic, cultural, and environmental variations of the Chinese MG populations between north and south.

Changes in theta activities in the left posterior temporal region, left occipital region and right frontal region related to mild cognitive impairment in Parkinson's disease patients.

The aim of this study was to investigate changes in brain activity associated with mild cognitive impairment (MCI) in a large sample of nondemented Parkinson's disease (PD) patients and its relationship with specific neuropsychological deficits. Electroencephalography (EEG) and neuropsychological assessment were performed in a sample of 135 nondemented PD patients and 44 healthy controls. All patients underwent a neuropsychological battery to assess global cognitive function. Patients were classified according to their cognitive status as PD patients with MCI (n = 61) and without MCI (n = 74). EEG data were used to analyze the relative band power parameters for the following frequency bands: delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz) and beta (13-30 Hz). In addition, relative band power parameters were compared between groups and examined for correlations with neuropsychological performance. The relative theta band powers in three regions (O1, T5 and F4) exhibited statistically significant increases in PD patients with MCI. Beta band powers also exhibited obvious decreases in five regions (T5, T6, P3, P4 and C3) in the PD-MCI group compared with the normal control group. Furthermore, correlation analyses revealed that attention, visuospatial and executive functions were associated with theta power in local regions, mainly in the frontal region (F4). The present study demonstrated that changes in brain activities limited to distinct cognitive domains, especially the theta power in the frontal region, could serve as an electrophysiological marker of cognitive impairment in nondemented PD patients.

The patterns of EEG changes in early-onset Parkinson's disease patients.

The aim of this study was to investigate the patterns of brain activity changes in early-onset Parkinson's disease (EOPD) patients and its relationship with the severity of disease and motor deterioration. Electroencephalography (EEG) was performed in a sample of 52 nondemented EOPD patients and 20 healthy controls with similar age. All patients underwent a battery to assess PD severity and motor deterioration. The EEG data were rated by visual and quantitative analyses with the grant total EEG (GTE) score and NicoletOne Software. The parameters of relative band power and coherences for various frequency bands were calculated. In addition, all parameters were compared between groups and examined for correlations with the severity of disease and motor deterioration. The GTE score and two subscores including "Diffuse Slow Waves" and "Frequency of Rhythmic Background Activity" of EOPD increased comparing to control group. The relative beta band powers in seven regions (O1,O2,T5,T6,P3,P4 and C3) indicated significant decreases in EOPD patients and obvious increases in interhemispheric beta coherences were observed in the midtemporal area and frontal area (T3T4 and F3F4). Furthermore, correlation analyses revealed that longer duration was associated with the subscore of "background wave frequency". The beta frequency bands in the right posterior temporal (T6) showed negative relationship with the modified Hoehn-Yahr grading scores. This study is the first to depict the patterns of EEG changes in EOPD patients without dementia and offer a better understanding of the pathophysiological mechanisms underlying and prognostic purposes in EOPD. Some of these changes could serve as useful biomarkers in the study of EOPD.

Differential diagnosis value of sympathetic skin response and cutaneous silent period on early-stage multiple system atrophy and Parkinson disease.

PURPOSE: Early differentiation between Parkinson's disease (PD) and Multiple system atrophy (MSA), particularly the parkinsonian subtypes (MSA-P), is challenging due to similar clinical symptoms. We aimed to evaluate Sympathetic skin response (SSR) and Cutaneous silent period (CSP) parameters in patients with MSA-P and PD to identify possible biomarkers that could distinguish the two groups of patients in early stage. METHODS: 22 individuals with early-stage MSA-P, 29 with early-stage PD, and 28 healthy controls were recruited from Guangdong Provincial People's Hospital. Demographic data was collected for all participants. Their SSR and CSP were evaluated using clinical electromyography equipment. Data were compared between different groups. The diagnostic accuracy of SSR and CSP parameters was calculated using the ROC curve. Logistic regression was used to produce an integration model to enhance diagnostic utility. RESULTS: Foot amplitude, CSP end latency and duration distinguished MSA-P from PD with the area under the curve (AUC) 0.770, 0.806, and 0.776, respectively. Foot and hand SSR amplitude distinguished PD from HC with the AUC 0.871 and 0.768, respectively. Foot SSR amplitude, hand SSR amplitude, and CSP end latency distinguished MSA-P from HC with the AUC 0.964, 0.872, and 0.812, respectively. The combination of SSR and CSP parameters differentiation between MSA-P and PD, PD and HC with the AUC 0.829 and 0.879, respectively. CONCLUSIONS: Analysis of SSR and CSP parameters showed excellent diagnostic accuracy in discriminating patients with early-stage MSA-P from HC and good diagnostic accuracy in discriminating patients with MSA-P from PD with early stages.

The high frequency and clinical feature of seronegative myasthenia gravis in Southern China.

Anti-acetylcholine receptor antibodies (anti-AChR-Ab) are responsible for the failure of neuromuscular junction in myasthenia gravis (MG). Some anti-AChR-Ab-seronegative MG patients have anti-muscle-specific tyrosine kinase antibodies (anti-MuSk-Ab). Here, the anti-AChR-Ab was tested in 250 MG outpatients from Southern China. While anti-MuSk-Ab was tested in 66 patients who had no anti-AChR-Ab in blood serum, but none of them was positive. The antibodies were measured by a radioimmunoprecipitation assay. The frequency of anti-AChR-Ab was 51.2 %. The percentage of anti-AChR-Ab in ocular type was lower than generalized type (44.9 vs. 66.2 %, P = 0.002). Seronegative MG was characterized by a lower percentage of thymoma than seropositive patients (P = 0.013). It seemed to be less severe in seronegative MG than seropositive MG in these 250 patients. In ocular type, seronegative MG mainly manifesting blepharoptosis but seldom diplopia or eyeball fixation related to ocular movement disability (P = 0.016). While in generalized type, seronegative MG was characterized by a lower percentage of bulbar muscle involvements than seropositive patients (P = 0.005). Logistic regression analysis revealed that bulbar weakness was affected by the existence of anti-AChR antibodies (OR = 3.524, P = 0.015). Besides, seronegative MG tended to be characterized by a lower percentage of neck extensor involvement, but this did not reach significance. The percentage of anti-AChR antibodies was much lower than other countries. Seronegative MG has characteristic clinical features that are different from features of the remaining seropositive MG. This emphasises the predictive value of anti-AChR antibodies analysis in MG patients.

Simulation on electrical field distribution and fiber falls in melt electrospinning.

Electrospinning is now a typical way of direct and consecutive producing nanofibers. In order to comprehensively understand the change of fiber chains in falling process of electrospinning, the article import dissipative particle dynamics (DPD) mesoscale simulation method into electrospinning study. In current work, an electrical force formula is proposed after simulation of the distribution of electrostatic field in electrospinning using Finite Element Method. Then, various electrostatic force, temperature and viscosity in electrospinning system are qualitatively simulated by DPD simulation. Results showed that the falling velocity of fiber increased with the increase of electrostatic force. It was found that the lower the polymer viscosity, the quicker the fiber falls. And the diameter of fiber significantly increased with augment of viscosity. Both of above are agree with experimental results. We also found that the falling velocity of fiber is in contrast with length of polymer chains, which has not been found in experiments.

Recent Advances in Cardiac Patches: Materials, Preparations, and Properties.

Cardiac patches are biomaterials that can be used for transplantation and repair of damaged myocardium by combining seed cells with the ability to form cardiomyocytes and suitable scaffold materials. On the one hand, they provide temporary support to the infarcted area, and on the other hand, they repair the damaged myocardium by delivering cells or bioactive factors to integrate with the host, which have gradually become a hot research topic in recent years. This paper summarizes the structural properties of natural myocardium and reviews the recent research progress of cardiac patches, including the seed cells and scaffold materials used in patch preparation, as well as the main methods of scaffold preparation and the structure properties of various scaffolds. In addition, a comprehensive analysis of the problems faced in the clinical implementation of cardiac patches is presented. Finally, we look forward to the development of cardiac patches and point out that precisely tunable anisotropic tissue engineering scaffolds close to natural myocardial tissue will become an important direction for future research.

[Analysis of prognostic factors and efficacy of plasmapheresis in the treatment of myasthenia crisis].

OBJECTIVE: To examine the prognostic factors and efficacy of myasthenia gravis (MG) in crisis on plasmapheresis and detect the reasons for ineffective plasmapheresis. METHODS: The investigators analyzed a total of 69 MG patients in crisis on plasmapheresis by case control study. Gender, age at onset of myasthenic symptoms, duration between the onset of crisis and plasmapheresis, pre-therapeutic use of glucocorticoids, pulmonary infections, other complications, nutritional status, history of thymectomy in 48 hours before crisis, thymic pathology, combined intravenous immunoglobulin (IVIG) and total sessions of plasmapheresis were measured retrospectively. RESULTS: Univariate analysis showed that pulmonary infections (P = 0.000, OR = 29.250), history of thymectomy in 48 hours before crisis (P = 0.046, OR = 0.267), combined intravenous immunoglobulin (P = 0.003, OR = 0.136) and total sessions of plasmapheresis (P = 0.022, OR = 0.498) were all influencing factors of plasmapheresis. However the analysis of multivariate logistic regression revealed that pulmonary infections (P = 0.000, OR = 23.600) was an independent risk factor and combined intravenous immunoglobulin (P = 0.047, OR = 0.192) was an independent protection factor of plasmapheresis. CONCLUSION: Plasmapheresis is ineffective in MG crisis with pulmonary infections. Control of pulmonary infections and combined intravenous immunoglobulin can improve the response to plasmapheresis in patients with MG crisis.

[Mediation of cellular immune response by TP5 in pathogenesis of myasthenia gravis].

OBJECTIVE: To evaluate the effects of TP5 upon the production of IFN-gamma and different T cell subsets by human peripheral blood mononuclear cells (PBMCs) from patients with myasthenia gravis (MG) and to provide experimental rationales for TP5 in clinical therapy of MG. METHODS: PBMCs were isolated from peripheral blood of MG individuals and cultured with anti-CD3. The level of IFN-gamma in culture supernatants was examined by ELISA. The subsets and frequency of IFN-gamma-producing cells were examined at a single-cell level by flow cytometry. RESULTS: After PBMCs stimulation with anti-CD3 and TP5 (300 microg/ml), the level of IFN-gamma expression was significantly inhibited (P(child) = 0.0001, P(adult) = 0.01); and the level of IFN-gamma expression from normal adult and child controls was also significantly inhibited (P(child) = 0.009, P(adult) = 0.0001). In addition, the inhibition of TP5 on the production of IFN-gamma by PBMCs from MG children was lower compared with normal child control. But as compared with normal adult control, the inhibition of TP5 showed no significant difference in MG adults (P(adult) = 0.481). TP5 inhibited the expression of IFN-gamma by CD8+ T cell and CD4+ T cell. CONCLUSION: TP5 can inhibit the response of cellular immune by decreasing the production of IFN-gamma in MG consequence display that the level of IFN-gamma significant decreased with the addition of TP5 and anti-CD3. But after considering the age, the level of IFN-gamma in MG children was no as much inhibited as normal child. TP5 inhibits the expression of IFN-gamma by CD8+ T and CD4+ T cells.

[Expression of regulatory T cells in thymus of myasthenia gravis patients].

OBJECTIVE: To investigate the in situ expression of regulatory T cells (Tregs) in thymus and its significance for myasthenia gravis (MG). METHODS: Thirty nine MG patients who had not accepted immunosuppressive therapy before thymectomy were recruited as study group and 19 patients undergoing cardiosurgery as control. There was no significant statistical difference in age and gender between the two groups (P > 0.05). The location and proportion of Tregs in thymus were analyzed using indirect immunofluorescence double labeling immunohistochemistry and image analysis software. RESULTS: (1) Tregs were all located in medulla zone of thymus in control and MG groups. (2) Cells of germinal center had a high expression of CD25 and a low expression of CD4. It indicates that a majority of germinal center cells were B cells. (3) There were fewer Tregs around germinal center. (4) There was no statistical significant difference in absolute number of Tregs between the two groups (P > 0.05). But the proportion of Tregs was higher in control group (P < 0.05). CONCLUSION: The proportion of thymus Tregs decreases in MG so as to weaken the function of immuno-regulation and suppression. This is probably a precipitating factor of MG.

[Thymopentin 5 in treatment of relapse after extended thymectomy: a randomized comparative clinical trial of 135 patients with myasthenia gravis].

OBJECTIVE: To investigate the effect of thymopentin 5 (TP5) combined with immunosuppressive agents in treatment of relapse after extended thymectomy in patients with myasthenia gravis (MG). METHODS: One hundred thirty-five MG patients who were to undergo extended thymectomy, 62 adults and 73 children, were randomly assigned to 2 groups: non-TP5 group (n = 60) treated with intramuscular injection of prednisone + pyridostigmine daily for 3 months as a basic treatment, and TP5 group (n = 73), treated with prednisone + pyridostigmine + TP5 for 3 months. Follow-up was conducted for more than 1 year. RESULTS: The remission rates of children in the TP5 group at different time points were all markedly higher than those in the non-TP5 group, and the remission rates of children in the TP5 group during the period of 2 months to 2 years after thymectomy were all significantly higher (all P < 0.05). And the remission rates of the adults of the TP5 group during the period of 6 months to 2 years after thymectomy were all significantly higher than those of the non-TP5 group (all P < 0.05). In the pediatric cases the withdrawal rate of the TP5 group was significantly higher, and the relapse rate was significantly lower than those of the non-TP5 group. No side effect developed during the follow-up. CONCLUSION: TP5 is effective in reducing relapse and has a higher drug withdrawal rate, especially among children.

[The role of CD4+ CD25+ T cells in the mechanism of myasthenia gravis in children and adults].

OBJECTIVE: To investigate the role of CD4+CD25+ regulatory T cells in the mechanism of myasthenia gravis (MG) in children and adults. METHODS: Peripheral blood samples were collected from 13 MG patients, 5 being aged > 14 and 8 being aged

[Correlation between pathogenesis of myasthenia gravis and thymus mature dendritic cells].

OBJECTIVE: To investigate the correlation between onset of myasthenia gravis (MG) and the changes of the number and distribution of thymus mature dendritic cells (mDC). METHODS: The specimens of thymus were obtained during operation from 39 MG patients who hadn't received immunosuppressive therapy before thymectomy and 19 sex- and age-matched patients who underwent cardiosurgery as controls. Immunohistochemistry with antibody against DC-LAMP, specific surface marker of DC, was used to examine the number and distribution of thymus mDCs. RESULTS: (1) mDCs were restricted in the medulla and cortex-medulla junctional zone of thymus in the control group; while were irregularly distributed in the cortex, medulla, and stroma in the MG group. (2) mDCs presented a roughly uniform distribution in the medulla of thymus in the control group, while clustering distribution was more often in the MG group, especially dense around the germinal center. (3) The relative ratio and numbers of mDCs per average field of vision in the positive areas of the MG group were (10.9% +/- 2.2%) and (50 +/- 9), both significantly higher than those of the control group [(8.5% +/- 1.5%) and (41 +/- 7) respectively, both P < 0.05]. CONCLUSION: The number and ratio of the thymus mDCs in MG are high, high, and the distribution abnormal. mDC actively may be actively involved in the pathogenesis of MG.

[Prognostic factors related to recurrence after extended thymectomy in patients with myasthenia gravis].

OBJECTIVE: To identify the recurrence-related factors in patients with myasthenia gravis (MG) after extended thymectomy. METHODS: Followed up was conducted on 271 MG patients, 127 males and 146 females, aged 31 (4-57), who underwent extended thymectomy for 18-84 months. Post-operational pathological examination showed 32 cases of thymoma and 239 cases of diseases other than thymoma. After operation the patients were treated with pyridostigmine only or combined with adrenocortical hormone. The relevant factors of the 135 patients with relapse were evaluated: sex, Osserman classification, age while being operated on, duration of preoperative period, pathologic type of thymus, use of steroid before operation, infection after operation, whether only taking anticholinesterase drugs after operation, use of steroid immediately after operation, stopping medicine or decreasing the dose of medicine within 1-3 months after remission of symptoms. RESULTS: COX univariate analysis revealed that failure to take steroid immediately after operation (OR = 2.914, P = 0.000), infection after operation (OR = 3.441, P = 0.000), only taking anticholinesterase drugs after operation (OR = 5.947, P = 0.000), and immediately stopping medicine use or decreasing the dose of medicine within 1-3 months after the remission of symptoms (OR = 2.242, P = 0.000) were prognostic factors for postoperative recurrence. On the other hand, multivariate logistic regression analysis revealed that infection after operation (OR = 47.63, P = 0.000), only taking anticholinesterase drugs after operation (OR = 62.38, P = 0.000), and stopping medicine or decreasing the dose of medicine 1-3 months after remission of symptoms (OR = 32.76, P = 0.000) were independent influencing factors of recurrence after operation. CONCLUSION: Post-operative infection, only taking pyridostigmine, and stopping medicine too early are independent factors of postoperative relapse. Regular treatment and timely use of adrenocortical hormone decrease the recurrence after operation.

Characteristics of gray matter morphological change in Parkinson's disease patients with semantic abstract reasoning deficits.

BACKGROUND: Semantic abstract reasoning(SAR) is an important executive domain that is involved in semantic information processing and enables one to make sense of the attributes of objects, facts and concepts in the world. We sought to investigate whether Parkinson's disease subjects(PDs) have difficulty in SAR and to examine the associated pattern of gray matter morphological changes. METHODS: Eighty-six PDs and 30 healthy controls were enrolled. PDs were grouped into PD subjects with Similarities preservation(PDSP, n = 62) and PD subjects with Similarities impairment(PDSI, n = 24)according to their performance on the Similarities subtest of the Wechsler Adult Intelligence Scale. Brain structural images were captured with a 3T MRI scanner. Surface-based investigation of cortical thickness and automated segmentation of deep gray matter were conducted using FreeSurfer software. RESULTS: PDs performed notably worse on the Similarities test than controls(F = 13.56, P < 0.001).In the PDSI group, cortical thinning associated with Similarities scores was found in the left superior frontal, left superior parietal and left rostral middle frontal regions. Notable atrophy of the bilateral hippocampi was observed, but only the right hippocampus volume was positively correlated with the Similarities scores of the PDSI group. DISCUSSION: PDs have difficulty in SAR, and this limitation may be associated with impaired conceptual abstraction and generalization along with semantic memory deficits. Cortical thinning in the left frontal and parietal regions and atrophy in the right hippocampus may explain these impairments among Chinese PDs.

[Synthesis, characterization and fluorescence property of an unsymmetrical Schiff base and its copper complex].

An unsymmetrical tetradentate Schiff base ligand (H2L) was synthesized using 5-chloro-2-hydroxybenzophenone, o-phenylenediamine and salicylaldehyde. A solid complex of this ligand CuL was prepared and characterized by elemental analyses, IR spectra, UV spectra, TG-DTG and molar conductance. Possible structure of this complex was proposed. The fluorescence property of the ligand and complex was also studied. The result indicates that the Schiff base reagent exhibits a maximum of fluorescence emission spectrum at 385 nm. At pH 9.62, the copper complex of this reagent can cause fluorescence quenching of the reagent.

[Clinical value of the immune parameters in patients with myasthenia gravis].

OBJECTIVE: To evaluate the clinical value of the indices, including IgG, IgA, IgM, CD3, CD4 and CD8. METHODS: Detect CD3, CD4, CD8 by flow cytometry and detect IgG, IgA, IgM by turbidimetric method. We analyzed clinical features according to different classification of immune index, and changes of the level of these immune indices before and after treatment. RESULT: The level of IgG, IgA in patients with generalized MG was higher than that of ocular MG (P < 0.05). The ratio of CD4 to CD8 was classified into 3 groups: low (118 cases), high (60 cases), normal (68 cases). Likewise, the level of IgG, IgA, IgM was classified into 4 groups: low (156 cases), high (65 cases), disorder (31 cases), normal (67 cases). There was no statistically significance on changes of level of these immune indices before and after treatment. There was no statistically significance on clinical materials among different groups. In the low group of humoral immunity, the remission ratio of the patients with the treatment of gamma globulin was higher than that of patients without gamma globulin (95.2%, 28.8%, respectively. P < 0.01). CONCLUSION: The immune indices of IgG, IgA, IgM, CD3, CD4, CD8 seemed to be irrelevant to severity of disease and prognosis. To some extent, these immune indices can be reference in the aspect of treatment.

[Electrospinning technology in tissue engineering scaffolds].

Tissue engineering technology provides a new method to repair ill tissue and worn-out organs. In tissue engineering, scaffolds play an important role in supporting cell growth, inducing tissue regeneration, controlling tissue structure and releasing active factor. In the last decade, electrospinning technology developed rapidly and opened vast application fields for scaffolds. In this review, we summarized the technological conditions of electrospinning for scaffolds, the study of electrospun fiber scaffolds applied in tissue cell cultivation, and some new directions of electrospinning technology for scaffolds. We also addressed development directions of electrospinning research for scaffolds.