The neural correlates of apathy in the context of aging and brain disorders: a meta-analysis of neuroimaging studies.

Introduction: Apathy is a prevalent mood disturbance that occurs in a wide range of populations, including those with normal cognitive aging, mental disorders, neurodegenerative disorders and traumatic brain injuries. Recently, neuroimaging technologies have been employed to elucidate the neural substrates underlying brain disorders accompanying apathy. However, the consistent neural correlates of apathy across normal aging and brain disorders are still unclear. Methods: This paper first provides a brief review of the neural mechanism of apathy in healthy elderly individuals, those with mental disorders, neurodegenerative disorders, and traumatic brain injuries. Further, following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, the structural and functional neuroimaging meta-analysis using activation likelihood estimation method is performed on the apathy group with brain disorders and the healthy elderly, aiming at exploring the neural correlates of apathy. Results: The structural neuroimaging meta-analysis showed that gray matter atrophy is associated with apathy in the bilateral precentral gyrus (BA 13/6), bilateral insula (BA 47), bilateral medial frontal gyrus (BA 11), bilateral inferior frontal gyrus, left caudate (putamen) and right anterior cingulate, while the functional neuroimaging meta-analysis suggested that the functional connectivity in putamen and lateral globus pallidus is correlated with apathy. Discussion: Through the neuroimaging meta-analysis, this study has identified the potential neural locations of apathy in terms of brain structure and function, which may offer valuable pathophysiological insights for developing more effective therapeutic interventions for affected patients.

Functional Covariance Connectivity of Gray and White Matter in Olfactory-Related Brain Regions in Parkinson's Disease.

Before the onset of motor symptoms, Parkinson's disease (PD) involves dysfunction of the anterior olfactory nucleus and olfactory bulb, causing olfactory disturbance, commonly resulting in hyposmia in the early stages of PD. Accumulating evidence has shown that blood oxygen level dependent (BOLD) signals in white matter are altered by olfactory disorders and related stimuli, and the signal changes in brain white matter pathways show a certain degree of specificity, which can reflect changes of early olfactory dysfunction in Parkinson's disease. In this study, we apply the functional covariance connectivity (FCC) method to decode FCC of gray and white matter in olfactory-related brain regions in Parkinson's disease. Our results show that the dorsolateral prefrontal, anterior entorhinal cortex and fronto-orbital cortices in the gray matter have abnormal connectivity with the posterior corona radiata and superior corona radiata in white matter in patients with Parkinson's hyposmia. The functional covariance connection strength (FCS) of the right dorsolateral prefrontal cortex and white matter, and the covariance connection strength of the left superior corona radiata and gray matter function have potential diagnostic value. These results demonstrate that alterations in FCC of gray and white matter in olfactory-related brain regions can reflect the change of olfactory function in the early stages of Parkinson's disease, indicating that it could be a potential neuroimaging marker for early diagnosis.

Outcomes and risk factors of perforating and non-perforating middle cerebral artery infarctions after intravenous thrombolysis.

The clinical symptoms of perforating arteries differ, and responses to intravenous thrombolytic therapy are heterogeneous. Here, we investigated the effect of intravenous thrombolytic therapy and the related factors influencing acute perforating and non-perforating middle cerebral artery infarctions. We analyzed 320 patients with acute middle cerebral artery infarction who received alteplase thrombolysis within 4.5 h of onset at two stroke centers from January 2016 to December 2019. Outcome measures included rates of a favorable functional outcome (modified Rankin Scale scores of 0-2), distribution of modified Rankin Scale scores, intracranial hemorrhage, and symptomatic cerebral hemorrhage at 14 days, with comparisons between perforating artery and non-perforating artery cerebral infarction groups. In the perforating vessel disease group, 12 cases (17.4%) of intracranial hemorrhage occurred, with symptomatic cerebral hemorrhage in three cases (4.3%); there were no significant differences between the perforating and non-perforating vessel disease groups (all P > 0.05). In the perforating vessel disease group, the only significant prognostic factor was the National Institutes of Health Stroke Scale score before thrombolysis (Exp(B) = 1.365; 95% confidence interval [CI] 1.124-1.659; P = 0.002), and the only significant risk factor for hemorrhagic transformation was previous perforator disease (Exp(B) = 0.078; P = 0.038). Regardless of whether an acute infarction is perforating or non-perforating, intravenous thrombolytic therapy can yield a favorable outcome. Therefore, intravenous thrombolysis should be actively administered to treat perforating artery infarctions with a high risk of disability.

Improving MRI-based analysis of brain structural changes in patients with hypertension via a privileged information learning algorithm.

Hypertension can lead to changes in the brain structure and function, and different blood pressure levels (2017ACC/AHA) have different effects on brain structure. It is important to analyze these changes by machine learning methods, and various characteristics can provide rich information for the analysis of these changes. However, multiple feature extraction involves complex data processing. How to make a single feature achieve the same diagnosis effect as multiple features do is worth of study. Kernel ridge regression (KRR) is a kind of machine learning method, which shows faster learning speed and generalization ability in classification tasks. In order to knowledge transfer, we use privileged information (PI) to transfer information of multiple types of feature to single feature. This allows only one feature type to be used during the test stage. In the process of feature fusion, we need to consider all the samples' attribution making the classifier better. In this work, we propose a multi-kernel KRR+ framework based on self-paced learning to analyze the changes of the brain structure in patients with different blood pressure levels. Specifically, one kind of a feature is taken as main feature, and other features are input into the multi-kernel KRR as PI. These two inputs are fed into the final KRR classifier together. In addition, a self-paced learning method is introduced into sample selecting to avoid training the classifier using samples with a large loss value firstly, which improves the generalization performance of the classifier. Experimental results show that the proposed method can make full use of the information of various features and achieve better classification performance. This shows self-paced learning based KRR can help analyze brain structure of patients with different blood pressure levels. The discriminative features may help clinicians to make judgments of hypertension degrees on brain MRI images.

The increase of α-synuclein and alterations of dynein in A53T transgenic and aging mouse.

The dynein protein plays a key role in the degradation pathway by attaching to targeted molecules and transporting the autophagosome to the centrosome. Aging plays an important role in the pathogenesis of Parkinson's disease (PD), but its effect on dynein is not clear. In this study we analyzed behavioral characteristics using the rod endurance test and climbing rod time test in different aged mice (3 months, 12 months, 20 months), and measured protein expression of dynein, α-synuclein, Tctex-1, and LC3 in the substantianigra of the mice by Western blot. The mRNA levels of dynein, α-synuclein, LC3 and Tctex-1 were measured by quantitative real time reverse transcription PCR, and detecting expression of dynein and α-synuclein by immunofluorescence. We found the motor functions of A53T mutant mice, in 12 months and 20 months, decreased more significantly compared with normal mice (p < 0.05). In addition, the expression of dynein, LC3-Ⅱ and Tctex-1 proteins in the substantia nigra of the two groups decreased with age. However, α-synuclein protein increased gradually with age, with significantly higher levels in the PD groups compared with age matched controls (p < 0.05). These results were confirmed by immunofluorescence. Our data demonstrates that dynein and other autophagy proteins change with age, and this is associated with increased α-synuclein. Therefore, therapeutics that prevent dynein dysfunction may offer novel treatments for PD and other autophagy related diseases.

Olfactory functional covariance connectivity in Parkinson's disease: Evidence from a Chinese population.

Introduction: Central anosmia is a potential marker of the prodrome and progression of Parkinson's disease (PD). Resting-state functional magnetic resonance imaging studies have shown that olfactory dysfunction is related to abnormal changes in central olfactory-related structures in patients with early PD. Methods: This study, which was conducted at Guanyun People's Hospital, analyzed the resting-state functional magnetic resonance data using the functional covariance connection strength method to decode the functional connectivity between the white-gray matter in a Chinese population comprising 14 patients with PD and 13 controls. Results: The following correlations were observed in patients with PD: specific gray matter areas related to smell (i.e., the brainstem, right cerebellum, right temporal fusiform cortex, bilateral superior temporal gyrus, right Insula, left frontal pole and right superior parietal lobule) had abnormal connections with white matter fiber bundles (i.e., the left posterior thalamic radiation, bilateral posterior corona radiata, bilateral superior corona radiata and right superior longitudinal fasciculus); the connection between the brainstem [region of interest (ROI) 1] and right cerebellum (ROI2) showed a strong correlation. Right posterior corona radiation (ROI11) showed a strong correlation with part 2 of the Unified Parkinson's Disease Rating Scale, and right superior longitudinal fasciculus (ROI14) showed a strong correlation with parts 1, 2, and 3 of the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr Scale. Discussion: The characteristics of olfactory-related brain networks can be potentially used as neuroimaging biomarkers for characterizing PD states. In the future, dynamic testing of olfactory function may help improve the accuracy and specificity of olfactory dysfunction in the diagnosis of neurodegenerative diseases.

A Novel Spectrum Contrast Mapping Method for Functional Magnetic Resonance Imaging Data Analysis.

Many studies reported that spontaneous fluctuation of the blood oxygen level-dependent signal exists in multiple frequency components and changes over time. By assuming a reliable energy contrast between low- and high-frequency bands for each voxel, we developed a novel spectrum contrast mapping (SCM) method to decode brain activity at the voxel-wise level and further validated it in designed experiments. SCM consists of the following steps: first, the time course of each given voxel is subjected to fast Fourier transformation; the corresponding spectrum is divided into low- and high-frequency bands by given reference frequency points; then, the spectral energy ratio of the low- to high-frequency bands is calculated for each given voxel. Finally, the activity decoding map is formed by the aforementioned energy contrast values of each voxel. Our experimental results demonstrate that the SCM (1) was able to characterize the energy contrast of task-related brain regions; (2) could decode brain activity at rest, as validated by the eyes-closed and eyes-open resting-state experiments; (3) was verified with test-retest validation, indicating excellent reliability with most coefficients > 0.9 across the test sessions; and (4) could locate the aberrant energy contrast regions which might reveal the brain pathology of brain diseases, such as Parkinson's disease. In summary, we demonstrated that the reliable energy contrast feature was a useful biomarker in characterizing brain states, and the corresponding SCM showed excellent brain activity-decoding performance at the individual and group levels, implying its potentially broad application in neuroscience, neuroimaging, and brain diseases.

Effects of Baduanjin Exercise on Rehabilitation of Patients With Mild to Moderate Parkinson's Disease.

OBJECTIVES: Rehabilitation, aerobic exercise, and many traditional Chinese exercises are known to significantly improve balance in patients with Parkinson's disease. Baduanjin, a traditional physical and mental exercise, has long been practiced for health care as it regulates organs, the nervous and motor systems. METHODS: We recruited 31 eligible participants. Patients underwent a 3-week Baduanjin program, including 35-min exercise daily. Scores on the Modified Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-motor Symptoms Scale (NMSS), and gait and balance tests were compared before and after the Baduanjin program. RESULTS: MDS-UPDRS-total (t = 4.669, P ≤ 0.001), MDS-UPDRS part-I (t = 5.805, P ≤ 0.001), MDS-UPDRS part-II (t = 5.234, P ≤ 0.001), MDS-UPDRS part-III (t = 3.274, P = 0.003), and NMSS (t = 4.815, P ≤ 0.001) scores significantly decreased after the 3-week intervention. Gait parameters like step (t = 2.289, P = 0.030) and cycle (t = 2.181, P = 0.038) durations also significantly improved, while Balance-check® indicators, including the total score (t = -2.147, P = 0.041) and grade (t = 3.432, P = 0.002) significantly differed before and after exercise. CONCLUSION: Baduanjin exercise shows beneficial effects for non-motor symptoms, balance, gait, and daily activities in patients with Parkinson's disease. Baduanjin can be included in the patients' family exercise, which is conducive to their rehabilitation, as well as for obtaining important social and economic benefits. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [ChiCTR-IPR-17011875].

The role of carotid stenosis ultrasound scale in the prediction of ischemic stroke.

INTRODUCTION: To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study. METHODS: A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared. RESULTS: There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P < 0.05). Both TSS and RI-TSS with GBF showed an inverse "S" curve relationship (R2 was 0.839 and 0.843, all P < 0.05). The AUC values of TSS-based and RI-TSS-based predictions of each endpoint were all greater than 0.7 (all P < 0.05), but the differences of the AUC values between TSS, RI-TSS, and GBF were not statistically significant (all P > 0.05). CONCLUSIONS: The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.

Effects of Blood Pressure in the Early Phase of Ischemic Stroke and Stroke Subtype on Poststroke Cognitive Impairment.

BACKGROUND AND PURPOSE: Blood pressure (BP) control in the early phase of stroke is controversial to reduce the risk of poststroke cognitive impairment (PSCI). This study was to investigate the impact of BP levels in the early phase of ischemic stroke and stroke subtype on PSCI. METHODS: Seven hundred and ninety-six patients with acute ischemic stroke were included. Cognitive function was assessed after stroke onset using the Montreal Cognitive Assessment. Patients were divided into quintiles according to systolic BP and diastolic BP levels in the early phase. Subtype analyses were according to Trial of ORG 10172 in Acute Stroke Treatment classification (infarct cause) and Oxfordshire Community Stroke Project classification (infarct location). RESULTS: After adjusting for multiple variables, the quintiles with the lowest systolic BP (Q1, 102-127 mm Hg) and with the highest systolic BP (Q5, 171-215 mm Hg) were associated with increased PSCI risk (odds ratio, 1.83; 95% confidence interval, 1.64-2.28; P=0.007 in Q1; odds ratio, 2.32; 95% confidence interval, 1.74-2.90; P<0.001 in Q5) at 3 months as compared with the middle quintile (Q3, 143-158 mm Hg). Similar association was found in diastolic BP quintiles. The analysis of cerebral infarction subtype demonstrated that both large artery atherosclerosis and total anterior circulation infarct were associated with increased risk of PSCI at 3 months after adjusting for multiple variables (large artery atherosclerosis: odds ratio, 1.42; 95% confidence interval, 1.06-1.90; P=0.031; total anterior circulation infarct: odds ratio, 1.68; 95% confidence interval, 1.32-2.15; P=0.001). CONCLUSIONS: Lower or higher BP in the early phase of ischemic stroke was correlated with increased PSCI risk at 3 months. Maintaining systolic/diastolic BP in the levels of 143 to 158/93 to 102 mm Hg might be beneficial to reduce the occurrence of PSCI. Moreover, large artery atherosclerosis subtype and total anterior circulation infarct subtype were correlated with increased PSCI risk at 3 months. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org. Unique identifier: ChiCTR-TRC-14004804.

Blood pressures immediately following ischemic strokes are associated with cerebral perfusion and neurologic function.

The optimal range of blood pressure levels in the early phase of ischemic stroke with hypertension is still controversial. Based on our stroke registry database, we explored the relationship between blood pressure levels and cerebral perfusion in the early phase of ischemic stroke with hypertension and neurofunctional recovery at 3 months after stroke. Total 732 stroke patients with hypertension were finally analyzed. Patients were divided into quintiles according to systolic blood pressure (SBP) and diastolic blood pressure (DBP) to perform multivariable logistic regression to analyze their relation with neurofunctional recovery, respectively. The cerebral perfusion levels displayed a reverse "U" shape curve with the change of blood pressure levels. Sufficient estimated cerebral blood flow (ECBF) in the early phase of ischemic stroke was associated with good neurofunctional recovery at 3 months after stroke. The best neurofunctional recovery was observed in the middle quintiles with SBP at 161 to 177 mm Hg and DBP at 103 to 114 mm Hg, respectively. So maintaining appropriate blood pressure levels in the early phase of ischemic stroke might be beneficial to cerebral perfusion and neurofunctional recovery.

Silencing of Tctex1 impairs autophagy lysosomal degradation of α-synuclein and cell viability.

Tctex1 is an important element of the dynein motor unit in mammalian cells that helps move targets along microtubules and toward the centrosome for degradation. Here, we analyzed the role of Tctex1 in the α-synuclein autophagy-lysosome degradation pathway using Tctex1-siRNA in SH-SY5Y cells. Results showed that siRNA silencing of Tctex1 suppressed cellular viability and promoted cell apoptosis. Protein and mRNA expression of Tctex1 and dynein decreased after Tctex1 knockdown, whereas α-synuclein, LC3-II, and LAMP2 increased. Consistently, fluorescence intensity of Tctex1 was weaker in siRNA-Tctex1-transfected cells, and that of α-synuclein, LC3-II, and LAMP2 was increased. Tctex1 inhibition reduced cell viability and promoted apoptosis. These results show that Tctex1 plays an important role in α-synuclein autophagic degradation and in maintaining cellular homeostasis.

Tctex1 plays a key role in the α-synuclein autophagy lysosomal degradation pathway.

Tctex1 is an important structure of dynein light chain in mammalian cells, clarifying the role of Tctex1 in α-synuclein autophagy lysosomal degradation may offer insights into the formation of Lewy bodies and neuronal death. We constructed dsRED-N1-Tctex1 overexpression, pDsRED2-N1-Tctex1(T94E) mutation and transfected into SH-SY5Y cells. Relative protein expression was measured by Western Blot and mRNA levels were measured by real-time quantitative PCR. Confocal microscopy was used to observe their sublocalizations in cells. We found that: WST assay results show that cell activity decreased after Tctex1 mutation (T94E), while Tctex1 overexpression increased cell activity. In Tctex1 mutation transfected cell lines Tctex1 and dynein protein levels decreased; α-synuclein, LC3-II and LAMP2 protein increased. However, α-synuclein, LC3-II and LAMP2 proteins were reduced in Tctex1 overexpression cell lines, with the same trend was found in mRNA levels. In Tctex1 mutation transfected cell lines Tctex1 fluorescence intensity weakened; α-synuclein, LC3-II and LAMP2 fluorescence was enhanced, while α-synuclein, LC3-II and LAMP2 weakened in Tctex1 overexpressing cells. Our results suggest that Tctex1 mutants interference lead to Tctex1 downregulation and dysfunction. Tctex1 overexpression promoted autophagy lysosome fusion and effectively degraded α-synuclein with increased cell activity. Thus, Tctex1 plays an important role in α-synuclein autophagic degradation.

Midterm Blood Pressure Variability Is Associated with Poststroke Cognitive Impairment: A Prospective Cohort Study.

OBJECTIVE: The aim of this study was to investigate the relationship between blood pressure variability (BPV) and poststroke cognitive impairment (PSCI). METHODS: Seven-hundred ninety-six patients with acute ischemic stroke were included in this study. Midterm BPV was evaluated by calculating the SD and coefficient of variation (CV, 100 × SD/mean) of systolic blood pressure (SBP) and diastolic blood pressure during the 7 days after stroke onset. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) at admission and at all follow-up visits. Patients with MoCA scores <26 were considered to have PSCI. RESULTS: The incidence of PSCI reached its peak (72%) 3 months after stroke onset and decreased to 30.3% at 12 months poststroke. After adjusting for covariables, the increase in the prevalence of PSCI at 3 months was independently associated with increases in the CV of blood pressure during the 7 days after stroke [odds ratios and 95% CI for patients in the second to fifth quintiles of SBP CV were 2.28 (1.18, 4.39), 2.33 (1.18, 4.62), 2.69 (1.31, 5.53), and 4.76 (1.95, 11.67), respectively]. Sub-analysis of the MoCA scores revealed that the patients had impairments in visuoperceptual abilities and executive functions, as well as in naming and delayed recall (p < 0.05). CONCLUSION: Midterm BPV during the early phase of acute ischemic stroke is independently associated with PSCI, especially in the visuoperceptual, executive, and delayed recall domains. CLINICAL TRIAL REGISTRATION: http://www.chictr.org.cn, identifier ChiCTR-TRC-14004804.

The Impact of Paeoniflorin on α-Synuclein Degradation Pathway.

Paeoniflorin (PF) is the major active ingredient in the traditional Chinese medicine Radix. It plays a neuroprotective role by regulating autophagy and the ubiquitin-proteasome degradation pathway. In this study, we found PF significantly reduced cell damage caused by MPP+, returning cells to normal state. Cell viability significantly improved after 24 h exposure to RAPA and PF in the MPP+ group (all P < 0.01). CAT and SOD activities were significantly decreased after PF and RAPA treatment, compared with MPP+ (P < 0.001). In addition, MPP+ activated both LC3-II and E1; RAPA increased LC3-II but inhibited E1. PF significantly upregulated both LC3-II (autophagy) and E1 (ubiquitin-proteasome pathway) expression (P < 0.001), promoted degradation of α-synuclein, and reduced cell damage. We show MPP+ enhanced immunofluorescence signal of intracellular α-synuclein and LC3. Fluorescence intensity of α-synuclein decreased after PF treatment. In conclusion, these data show PF reversed the decline of proteasome activity caused by MPP+ and significantly upregulated both autophagy and ubiquitin-proteasome pathways, promoted the degradation of α-synuclein, and reduced cell damage. These findings suggest PF is a potential therapeutic medicine for neurodegenerative diseases.

The E3 ubiquitin ligase seven in absentia homolog 1 may be a potential new therapeutic target for Parkinson's disease.

In this study, we investigated the effect of an antibody against E3 ubiquitin ligase seven in absentia homolog 1 (SIAH-1) in PC12 cells. 1-Methyl-4-phenylpyridinium (MPP(+)) treatment increased α-synuclein, E1 and SIAH-1 protein levels in PC12 cells, and it reduced cell viability; however, there was no significant change in light chain 3 expression. Treatment with an SIAH-1 antibody decreased mRNA expression levels of α-synuclein, light chain 3 and SIAH-1, but increased E1 mRNA expression. It also increased cell viability. Combined treatment with MPP(+) and rapamycin reduced SIAH-1 and α-synuclein levels. Treatment with SIAH-1 antibody alone diminished α-synuclein immunoreactivity in PC12 cells, and reduced the colocalization of α-synuclein and light chain 3. These findings suggest that the SIAH-1 antibody reduces the monoubiquitination and aggregation of α-synuclein, promoting its degradation by the ubiquitin-proteasome pathway. Consequently, SIAH-1 may be a potential new therapeutic target for Parkinson's disease.

Prestroke glycemic status is associated with the functional outcome in spontaneous intracerebral hemorrhage.

Admission hyperglycemia is thought to be related to poor neurological function and high mortality in patients with spontaneous intracerebral hemorrhage (sICH). However, it is not known whether prestroke glycemic status affects functional outcome of sICH. The study was aimed to disclose the association between prestroke glycemic status and outcome in patients with sICH. The study included 288 patients with sICH. Prestroke glycemic status was represented by hemoglobin A1c (HbA1c) values measured the next day after admission. Correlations between HbA1c and age, hematoma volume, NIHSS, and mRS were analyzed using Spearman's correlation analysis. Patients were categorized into two groups according to hematoma volume (≤25 mL or >25 mL), mRS values (≤2 or >2), or hematoma location (lobar hematoma or deep hematoma). Logistic regression analyses were used to determine the relative independent risk factors for hematoma volume, hematoma location, and mRS values. In patients with sICH, HbA1c was significantly correlated with hematoma volume, NIHSS, and mRS. High HbA1c levels were independently associated with large hematoma volume, deep ICH, and poor outcome. When patients were stratified by history of diabetes, the predictive effect of HbA1c on outcomes was only observed in patients with diabetes. Admission glucose was also related to hematoma volume, but failed to predict outcome. Although both admission glucose and HbA1c independently predicted hematoma volume in patients with sICH, HbA1c alone could serve as a better predictor of poor outcome in diabetic patients after sICH.

Silencing of SIAH1 in SH-SY5Y affects α-synuclein degradation pathway.

Seven in absentia homolog (SIAH) is a ubiquitin ligase that monoubiquitinates α-synuclein. Lewy bodies are characteristically rich in monoubiquitinated α-synuclein. We aimed to determine the effect of siRNA-SIAH1 on α-synuclein autophagy and UPS degradation in SH-SY5Y. SIAH1 expression was measured with real-time quantitative PCR and Western Blot. Cell proliferation was measured by CCK-8 assay; cell apoptosis assayed by flow cytometry. Relative protein expressions were measured by Western Blot. mRNA levels of relative protein were measured by real-time quantitative PCR. The expression of α-synuclein, LC3-II and SIAH1 were observed by confocal microscopy. We found: (1) Transfection efficiency of SIAH1-siRNA into SH-SY5 measured approximately 89% by flow cytometry. (2) siRNA silencing of SIAH1 promoted cellular proliferation and suppressed apoptosis. (3) Protein and mRNA expression of α-synuclein, LC3-II and p53 decreased after SIAH1 knockdown. E1 protein and mRNA levels increased after SIAH1 siRNA. These data show silencing SIAH1 increased cell proliferation and inhibited apoptosis in SH-SY5Y neuroblastoma cells. SIAH1 knockdown enhanced the clearance of non-aggregated α-synuclein by UPS. SIAH1 is a potential target for treatment of Parkinson's disease.

A comparison of rt-PA thrombolysis guidelines between China and the USA: are changes needed?

BACKGROUND AND PURPOSE: Thrombolytic treatment criteria vary significantly between China and the USA. We reviewed current intravenous (IV) thrombolytic therapy practices in China and the USA to determine the most appropriate. METHODS: We conducted a systematic review of studies that used IV recombinant tissue plasminogen activator (rt-PA) therapy in China and the USA published between January 1950 and April 2012. RESULTS: Literature search identified 17 American and 9 Chinese studies with a total of 2545 subjects. We found a significantly lower mortality rate in the US data compared with China (8% versus 13%; Chi-square  =  24.412, P < 0.001). Our meta-regression analysis uncovered significant factors influencing mortality including male sex, hypertension, high cholesterol, smoking, and onset to treatment time (all P < 0.05). There were significantly more favorable outcomes in China than in the USA (61% versus 49%, Chi-square  =  19.159, P < 0.001). No prior history of stroke and shorter onset to IV time were also significantly associated with a favorable outcome (P < 0.05). CONCLUSIONS: Onset to IV time is critical for reducing mortality and improving favorable outcomes. We suggest Chinese acute ischemic stroke treatment guidelines be revised to include an increase in the age limit of 80 years, removing contraindications such as a history of previous sever heart, liver, and kidney dysfunction, and placing more emphasis on physician expertise.

Proxies of cognitive reserve and their effects on neuropsychological performance in patients with mild cognitive impairment.

Cognitive reserve (CR) modulates the relationship between clinical and pathological phenotypes by restricting the negative effect of cerebral lesions on cognition, according to the CR hypothesis. In this study, we evaluated 18 healthy subjects and 21 patients with mild cognitive impairment (MCI) using conventional MRI, magnetic resonance spectroscopy (MRS), the Mini-Mental State Examination (MMSE), the Wechsler Memory Scale (WMS), and the Montreal Cognitive Assessment (MoCA). The MMSE, WMS and MoCA assessments were repeated 1year later. The MRS analysis results showed that the N-acetyl-aspartate peak area (NAA; t=5.122, P<0.001) and the NAA/creatine (Cr), NAA/myo-inositol (mI) and NAA/choline (Cho) ratios were significantly changed in patients with MCI compared with the control subjects (all P<0.01). The MoCA was significantly related to the NAA/Cho ratio (R=0.443), the NAA/Cr ratio (R=0.533), and the NAA peak area (R=0.814; all P<0.05), but was unrelated to the NAA/mI ratio (R=0.400, P=0.072). We found that the hippocampal volume was significantly correlated with the MoCA, WMS and MMSE (R=0.704, 0.677, 0.542 respectively; all P<0.05). Education level had a positive effect on changes in the MoCA, MMSE, and WMS 1year later. We believe that MoCA and WMS results, MRI hippocampal volume and other related indicators (NAA peak area, NAA/Cr ratio, NAA/mI ratio, and NAA/Cho ratio) may reflect the degree of CR capacity, and that the number of years of education can significantly affect the changes in cognitive function in patients with MCI. Therefore, increasing levels of education and life skills training can help increase CR, reduce the risk of MCI, and slow down the appearance of clinical manifestations and clinical progress in patients with MCI.