Blood-Brain Barrier Permeable Photoacoustic Probe for High-Resolution Imaging of Nitric Oxide in the Living Mouse Brain.

Alternations in the brain nitric oxide (NO) homeostasis are associated with a variety of neurodegeneration diseases; therefore, high-resolution imaging of NO in the brain is essential for understanding pathophysiological processes. However, currently available NO probes are unsuitable for this purpose due to their poor ability to cross the blood-brain barrier (BBB) or to image in deep tissues with spatial resolution. Herein, we developed a photoacoustic (PA) probe with BBB crossing ability to overcome this obstacle. The probe shows a highly selective ratiometric response toward NO, which enables the probe to image NO with micron resolution in the whole brain of living mice. Using three-dimensional PA imaging, we demonstrated that the probe could be used to visualize the detailed NO distribution in varying depth cross-sections (0-8 mm) of the living Parkinson's disease (PD) mouse brain. We also investigated the therapeutic properties of natural polyphenols in the PD mouse brain using the probe as an imaging agent and suggested the potential of the probe for screening therapeutic agents. This study provides a promising imaging agent for imaging of NO in the mouse brain with high resolution. We anticipate that these findings may open up new possibilities for understanding the biological functions of NO in the brain and the development of new imaging agents for the diagnosis and treatment of brain diseases.

N6-Methyladenosine RNA modification in cerebrospinal fluid as a novel potential diagnostic biomarker for progressive multiple sclerosis.

BACKGROUND: Progressive multiple sclerosis (PMS) is an uncommon and severe subtype of MS that worsens gradually and leads to irreversible disabilities in young adults. Currently, there are no applicable or reliable biomarkers to distinguish PMS from relapsing-remitting multiple sclerosis (RRMS). Previous studies have demonstrated that dysfunction of N6-methyladenosine (m6A) RNA modification is relevant to many neurological disorders. Thus, the aim of this study was to explore the diagnostic biomarkers for PMS based on m6A regulatory genes in the cerebrospinal fluid (CSF). METHODS: Gene expression matrices were downloaded from the ArrayExpress database. Then, we identified differentially expressed m6A regulatory genes between MS and non-MS patients. MS clusters were identified by consensus clustering analysis. Next, we analyzed the correlation between clusters and clinical characteristics. The random forest (RF) algorithm was applied to select key m6A-related genes. The support vector machine (SVM) was then used to construct a diagnostic gene signature. Receiver operating characteristic (ROC) curves were plotted to evaluate the accuracy of the diagnostic model. In addition, CSF samples from MS and non-MS patients were collected and used for external validation, as evaluated by an m6A RNA Methylation Quantification Kit and by real-time quantitative polymerase chain reaction. RESULTS: The 13 central m6A RNA methylation regulators were all upregulated in MS patients when compared with non-MS patients. Consensus clustering analysis identified two clusters, both of which were significantly associated with MS subtypes. Next, we divided 61 MS patients into a training set (n = 41) and a test set (n = 20). The RF algorithm identified eight feature genes, and the SVM method was successfully applied to construct a diagnostic model. ROC curves revealed good performance. Finally, the analysis of 11 CSF samples demonstrated that RRMS samples exhibited significantly higher levels of m6A RNA methylation and higher gene expression levels of m6A-related genes than PMS samples. CONCLUSIONS: The dynamic modification of m6A RNA methylation is involved in the progression of MS and could potentially represent a novel CSF biomarker for diagnosing MS and distinguishing PMS from RRMS in the early stages of the disease.

Characterization of Myostain (MSTN) and Myogenic Differentiation Antigen (MyoD) and the Effect of Dexamethasone on Their Expression in Large-Scale Loach Paramisgurnus dabryanus.

Myostatin (MSTN) and myogenic differentiation antigen (MyoD) play an essential role in specification and differentiation of skeletal muscle. However, the role of stress in the regulation of MyoD and MSTN has not been fully revealed and more evidence should be provided. Here, we reported the cloning and expressional analyses of MSTN and MyoD in Large-scale Loach Paramisgurnus dabryanus (hereafter PdMSTN and PdMyoD). Injecting individuals with 0, 60, 600, and 1,200 µg/kg dexamethasone (DXM) for five consecutive days resulted in a dose-dependent change of PdMSTN and PdMyoD expression. The expression of PdMSTN was upregulated with increasing DXM concentrations, while PdMyoD expression was downregulated. The changes in the expression of these genes at different time points for 10 consecutive days were studied after individuals were treated with 600 µg/kg DXM. Compared with the control group, PdMSTN expression decreased and PdMyoD expression increased before 12 h, and both PdMSTN and PdMyoD expression levels increased at 24 h, which was significantly higher than those in control group. At a prolonged treatment of 5-10 d, expression levels of PdMSTN and PdMyoD had significantly reduced. The results indicate that both PdMyoD and PdMSTN are involved in DXM-induced stress in Large-scale Loach.

Serum Levels of IL-1 ß , IL-6, TGF- ß , and MMP-9 in Patients Undergoing Carotid Artery Stenting and Regulation of MMP-9 in a New In Vitro Model of THP-1 Cells Activated by Stenting.

Inflammation plays an important role in the pathophysiological process after carotid artery stenting (CAS). Monocyte is a significant source of inflammatory cytokines in vascular remodeling. Telmisartan could reduce inflammation. In our study, we first found that, after CAS, the serum IL-1ß, IL-6, TGF-ß, and MMP-9 levels were significantly increased, but only MMP-9 level was elevated no less than 3 months. Second, we established a new in vitro model, where THP-1 monocytes were treated with the supernatants of human umbilical vein endothelial cells (HUVECs) that were scratched by pipette tips, which mimics monocytes activated by mechanical injury of stenting. The treatment enhanced THP-1 cell adhesion, migration and invasion ability, and the phosphorylation of ERK1/2 and Elk-1 and MMP-9 expression were significantly increased. THP-1 cells pretreated with PD98095 (ERK1/2 inhibitor) attenuated the phosphorylation of ERK1/2 and Elk-1 and upregulation of MMP-9, while pretreatment with telmisartan merely decreased the phosphorylation of Elk-1 and MMP-9 expression. These results suggested that IL-1ß, IL-6, TGF-ß, and MMP-9 participate in the pathophysiological process after CAS. Our new in vitro model mimics monocytes activated by stenting. MMP-9 expression could be regulated through ERK1/2/Elk-1 pathway, and the protective effects of telmisartan after stenting are partly attributed to its MMP-9 inhibition effects via suppression of Elk-1.

Active fault-tolerant control for the dual-valve hydraulic system with unknown dead-zone.

This paper proposes a method for high-performance motion control of the dual-valve hydraulic system subject to parameter and model uncertainties, unknown proportional valve dead-zone, and servo valve fault. By constructing a detailed dual-valve fault system model (DFSM), a disturbance observer-based adaptive robust fault-tolerant controller is proposed via the backstepping method. This controller integrates a model-based fault detection algorithm for real-time fault monitoring and subsequent controller reconfiguration. Additionally, the DFSM-based adaptive robust control (ARC) technique is applied to handle the unknown dead-zone problem and other nonlinearities, ensuring precise control. Once the servo valve fault occurs, a nonlinear observer estimates the fault and collaborates with the ARC to establish a reconfigured controller, thereby maintaining motion control. The effectiveness of the proposed method has been experimentally verified.

1,4-Bisvinylbenzene-Bridged BODIPY Dimers for Fluorescence Imaging in the Second Near-Infrared Window.

Herein, we report a class of 1,4-bisvinylbenzene-bridged BODIPY dimers with fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm). These dyes show excellent NIR-II fluorescence properties and can be easily functionalized to achieve good water-solubility or tumor-targeting ability. In vivo imaging results demonstrate that these dyes have high resolution and deep-penetration NIR-II imaging ability, which enable them to be used as promising NIR-II imaging agents.

A Torque Control Strategy for a Robotic Dolphin Platform Based on Angle of Attack Feedback.

Biological fish can always sense the state of water flow and regulate the angle of attack in time, so as to maintain the highest movement efficiency during periodic flapping. The biological adjustment of the caudal fin's angle of attack (AoA) depends on the contraction/relaxation of the tail muscles, accompanying the variation in tail stiffness. During an interaction with external fluid, it helps to maintain the optimal angle of attack during movement, to improve the propulsion performance. Inspired by this, this paper proposes a tail joint motion control scheme based on AoA feedback for the high-speed swimming of bionic dolphins. Firstly, the kinematic characteristics of the designed robot dolphin are analyzed, and the hardware basis is clarified. Second, aiming at the deficiency of the tail motor, which cannot effectively cooperate with the waist joint motor during high-frequency movement, a compensation model for the friction force and latex skin-restoring force is designed, and a joint angle control algorithm based on fuzzy inference is proposed to realize the tracking of the desired joint angle for the tail joint in torque mode. In addition, a tail joint closed-loop control scheme based on angle of attack feedback is proposed to improve the motion performance. Finally, experiments verify the effectiveness of the proposed motion control scheme.

Quantifying the Leaping Motion Using a Self-Propelled Bionic Robotic Dolphin Platform.

Kinematic analysis of leaping motions can provide meaningful insights into unraveling the efficient and agile propulsive mechanisms in dolphin swimming. However, undisturbed kinematic examination of live dolphins has been very scarce due to the restriction of close-up biological observation with a motion capture system. The main objective of this study is to quantify the leaping motion of a self-propelled bionic robotic dolphin using a combined numerical and experimental method. More specifically, a dynamic model was established for the hydrodynamic analysis of a changeable submerged portion, and experimental data were then employed to identify hydrodynamic parameters and validate the effectiveness. The effects of wave-making resistance were explored, indicating that there is a varying nonlinear relationship between power and speed at different depths. In addition, the wave-making resistance can be reduced significantly when swimming at a certain depth, which leads to a higher speed and less consumed power. Quantitative estimation of leaping motion is carried out, and the results suggest that with increase of the exiting velocity and angle, the maximum height of the center of mass (CM) increases as well; furthermore, a small exiting angle usually requires a much larger exiting velocity to achieve a complete exiting motion. These findings provide implications for optimizing motion performance, which is an integral part of underwater operations in complex aquatic environments.

Dynamic pruning group equivariant network for motor imagery EEG recognition.

Introduction: The decoding of the motor imaging electroencephalogram (MI-EEG) is the most critical part of the brain-computer interface (BCI) system. However, the inherent complexity of EEG signals makes it challenging to analyze and model them. Methods: In order to effectively extract and classify the features of EEG signals, a classification algorithm of motor imagery EEG signals based on dynamic pruning equal-variant group convolutional network is proposed. Group convolutional networks can learn powerful representations based on symmetric patterns, but they lack clear methods to learn meaningful relationships between them. The dynamic pruning equivariant group convolution proposed in this paper is used to enhance meaningful symmetric combinations and suppress unreasonable and misleading symmetric combinations. At the same time, a new dynamic pruning method is proposed to dynamically evaluate the importance of parameters, which can restore the pruned connections. Results and Discussion: The experimental results show that the pruning group equivariant convolution network is superior to the traditional benchmark method in the benchmark motor imagery EEG data set. This research can also be transferred to other research areas.

Natural organic-inorganic hybrid structure enabled green biomass adhesive with desirable strength, toughness and mildew resistance.

Plant based proteins are green, sustainable, and renewable materials that show the potential to replace traditional formaldehyde resin. High performance plywood adhesives exhibit high water resistance, strength, toughness, and desirable mildew resistance. Adding petrochemical-based crosslinkers is not economically viable or environmentally benign; this chemical crosslinking strategy makes the imparted high strength and toughness less attractive. Herein, a green approach based on natural organic-inorganic hybrid structure enhancement is proposed. The design of soybean meal-dialdehyde chitosan-amine modified halloysite nanotubes (SM-DACS-HNTs@N) adhesive with desirable strength and toughness enhanced by covalent bonding (Schiff base) crosslinking and toughened by surface-modified nanofillers is demonstrated. Consequently, the prepared adhesive showed a wet shear strength of 1.53 MPa and work of debonding of 389.7 mJ, which increased by 146.8 % and 276.5 %, respectively, due to the cross-linking effect of organic DACS and toughening effect of inorganic HNTs@N. The introduction of DACS and Schiff base generation enhanced the antimicrobial property of the adhesive and increased the mold resistance of the adhesive and plywood. In addition, the adhesive has good economic benefits. This research creates new opportunities for developing biomass composites with desirable performance.

Trans-omics analyses revealed key epigenetic genes associated with overall survival in secondary progressive multiple sclerosis.

BACKGROUND: Secondary progressive multiple sclerosis (SPMS) is the second most common presentation of multiple sclerosis (MS) and is characterized by a gradually deteriorating disease with or without relapses. Approximately 80% of patients with relapsing-remitting MS (RRMS) develop SPMS within 20 years. Epidemiological investigations have revealed an average 7-year life expectancy decrease (more severe in progressive subtypes) in patients with MS. Studies have focused on the neurodegenerative pathogenesis of SPMS; and epigenetic changes have been associated with disease progression in neurodegenerative disorders. However, the evidence for the association between epigenetic changes and SPMS is scarce. Thus, in this study we aimed to identify the key epigenetic genes in SPMS. METHODS: We downloaded DNA methylation and gene expression matrices from the Gene Expression Omnibus (GEO) database. We used bioinformatic analyses to identify key epigenetic genes associated with overall survival (OS) in patients with SPMS. RESULTS: We found 49 differentially methylated positions (DMPs) between the SPMS and control GSE40360 datasets. We used the wANNOVAR server to obtain 64 methylated genes. We merged the gene expression datasets (GSE131282 and GSE135511) in the NetworkAnalyst platform and found 12,442 differentially-expressed genes (DEGs) between SPMS and controls using the Fisher's method, fixed effect model, Vote counting, and direct merging methods. Moreover, we identified 21 epigenetic genes (all hyper-methylated) after an integrating analysis of DMPs and DEGs of patients with SPMS. We established an epigenetic gene signature associated with the OS of patients with SPMS including six hyper-methylated genes (ITGA6, PPP1R16B, RNF126, ABHD8, FOXK1, and SLC6A19) based on the LASSO-Cox method. The calculated individual risk scores were associated with Oss, and we divided patients into high- and low-risk groups on the basis of the mean cut-off value. The six key epigenetic genes were significantly associated with gender, disease duration, and age at death via Spearman correlation analyses. In addition, survival analyses revealed a significant OS difference between high- and low-risk groups. The ROC curves indicated good performance for this predictive model. CONCLUSION: We identified 21 hyper-methylated genes in patients with SPMS via an integrated analysis of DNA methylation and gene expression datasets. We identified a six-epigenetic gene signature that predicts the individual OS with good accuracy. These results indicated that epigenetic modifications play a vital role in the disease progression of SPMS.

Bioinformatic Analysis of Coexpressed Differentially Expressed Genes and Potential Targets for Intracerebral and Subarachnoid Hemorrhage.

BACKGROUND: Secondary brain injury following intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is life threatening, and effective therapeutic strategies are lacking. This study aimed to understand the molecular pathogenesis of ICH- or SAH-induced secondary brain injury and provide insights regarding potential therapeutic options. METHODS: Original data of tissue microarray studies were downloaded from the Gene Expression Omnibus database. We identified the differentially expressed genes (DEGs) for each disease and common DEGs between ICH and SAH. Functional enrichment analyses were then analyzed, and a protein-protein interaction network was constructed to strictly select hub genes. Additionally, immune infiltration analyses were used to identify the common differently distributed cells in both diseases. Finally, animal model microarrays were used for external validation. RESULTS: We identified 158 common DEGs. The common DEGs were significantly enriched in cytotoxicity and inflammation pathways. The top 10 hub genes were then filtered through the protein-protein interaction networks. Moreover, natural regulatory T, T helper 17, and dendritic cells and monocytes and macrophages were identified as common differentially distributed immune cells. Additionally, target microRNAs and related drugs of hub genes were predicted. CONCLUSIONS: This study identified a variety of key genes and their respective molecular functions involved in both ICH and SAH for better understanding of the cytotoxic and inflammatory pathogenesis of secondary brain injury. The predicted targeted microRNAs and related drugs of hub genes not only could provide insights into the novel therapeutic strategies, but also could aid in future studies and drug discovery.

Discovery of BODIPY J-aggregates with absorption maxima beyond 1200 nm for biophotonics.

Organic dyes with absorption maxima in the second near-infrared window (NIR-II; 1000 to 1700 nm) are of great interest in biophotonics. However, because of the lack of appropriate molecular scaffolds, current research in this field is limited to cyanine dyes, and developing NIR-II-absorbing organic dyes for biophotonics remains an immense challenge. Here, we rationally designed an ethenylene-bridged BODIPY scaffold featuring excellent J-aggregation capabilities and revealed that the bridging ethylene unit is crucial for intermolecular J-coupling regulation. By integrating the electron-donating groups into the scaffold, we obtained a BODIPY dye, BisBDP2, with a J-aggregate absorption maximum of around 1300 nm. BisBDP2 J-aggregates show excellent photothermal performance, including intense photoacoustic response, and a high photothermal conversion efficiency value of 63%. In vivo results demonstrate the potential of J-aggregates for photoacoustic imaging and photothermal ablation of deep-seated tumors. This study will speed up the exploration of NIR-II-absorbing J-aggregates for future biophotonic applications.

Non-aneurysm subarachnoid hemorrhage in young adults.

OBJECTIVE: The incidence of subarachnoid hemorrhage (SAH) in the young is increasing recently. Among the young patients, some of them do not have detectable aneurysms, so the cause of the disease may be non-aneurysmal. In this study, we analyzed some clinical cases of subarachnoid hemorrhage in young adults and discussed the possible causes other than present aneurysm and arteriovenous malformation (AVM). METHODS: We reviewed 11 patients with SAH below 45 years of age enrolled in our hospital from January 2007 to June 2008. Their clinical characteristics, imaging examination results were analyzed in details: nine patients were found with no obvious cause for their hemorrhage. Four of them were followed up for 1 year and the other three were followed up for half a year. We telephoned the seven patients to gain the information on their recovery by questionnaire. RESULTS: With an average onset age of 38 years old, all patients had similar symptoms and onset behavior according to their clinical characteristics. Based on the imaging results, two had confirmed vascular malformation; the other nine did not present detectable aneurysm or AVM, but with different morphological changes of their cerebral arteries. By 1-year or half-year follow-up, the seven patients were found to have good recovery. CONCLUSION: Pathological changes of cerebral vessels due to smoking, genetic, or as an early version of formation of aneurysm, might be contributed to SAH in the young. Repeated angiogram is necessary for young patients to confirm the cause of SAH.

Analysis on death-associated factors of patients with subarachnoid hemorrhage during hospitalization.

OBJECTIVE: The prognosis of patients with high-clinical-score subarachnoid hemorrhage remains poor, with early high mortality rate. Therefore, to predict the early outcome of patients after subarachnoid hemorrhage, several clinical factors were hypothesized to be related to death during hospitalization. METHODS: Eighty-nine cases after subarachnoid hemorrhage, divided into two groups (① death group; ② survival group) according to their clinical situations during hospitalization, were studied. Twelve factors, including gender, hypertension, intracranial aneurysm, cerebral vascular spasm, hydrocephalus and conscious disturbance during hospitalization, smoking, age, WFNS (World Federation of Neurological Surgeons) scale, Fisher grade, white blood cell count and blood glucose level at admission, were analyzed by using Chi-square test, t test, and Logistic multiple regression analysis. RESULTS: The results of single-factor analysis indicated that ruptured intracranial aneurysm, conscious disturbance, increasing age, high WFNS scale, high Fisher grade, increasing white blood cell count and blood glucose level were statistically significant different between the two groups.The logistic analysis results showed that ruptured intracranial aneurysm (odds ratio [OR], 9.253; 95% confidence interval [CI], 0.617-98.263), high WFNS score (OR, 2.105; 95% CI, 1.275-5.204) and increasing white blood cell count (OR, 1.397; 95% CI 1.062-2.013) were the independent risk factors associated with death during hospitalization for patients with subarachnoid hemorrhage. CONCLUSIONS: Increased white blood cell count may indicate poor outcomes for patients during hospitalization, even early death.

Clinical analysis of electrolyte imbalance in thalamic hemorrhage patients within 24 h after admission.

We have observed that patients with thalamic hemorrhage are more likely to have electrolyte disturbances than those with non-thalamic hemorrhage. Here, we are attempting to provide some comprehensive information on electrolyte disturbances in patients with thalamic hemorrhage. Retrospectively, 67 patients with thalamic hemorrhage (TH group) and 256 with non-thalamic hemorrhage (N-TH group) were found from computer tomography images. Electrolytes of these patients were tested within 24 h after hospitalization. Chi-square test was used to compare the incidence of electrolyte imbalance. Serum K+ levels were found to be abnormal in 37.31% of the patients in the TH group and 24.21% in the N-TH group, and the difference was significant (p<0.05). Such a difference was also observed for the levels of serum Na+ and Cl+. Incidences of abnormal serum K+ (p<0.05), Na+ (p<0.01) and Cl(-) (p<0.01) levels were different among thalamic hemorrhage, basal ganglia area hemorrhage and lobar hemorrhage patients. In the TH group, the mortality of patients with electrolyte disturbances (42.50%) was higher than that of patients with normal electrolyte levels (14.81%, p<0.05). The incidence of electrolyte imbalance is higher in patients with thalamic hemorrhage than in those with non-thalamic hemorrhage. The reason may be partly related to the location of the hemorrhage. Electrolyte disturbance may contribute to the higher mortality of patients with thalamic hemorrhage.

Characteristics of pulse pressure parameters in acute intracerebral hemorrhage patients.

We explored the features of changes in pulse pressure (PP) in patients with intracerebral hemorrhage (ICH). Two hundred one patients with ICH were admitted to our hospital from January 2008 to August 2009. Meanwhile, another 201 people matching in age and gender with these patients were assigned as controls. Blood Pressures (BP) were collected within the first 24 h after admission. PP was calculated from the BP readings. The mean of PPs was compared via T-test. The distributed frequency of the PP level was analyzed using the chi-square test. PPs in the ICH group were higher than those of the controls (P<0.001). Chi-square test showed a significant difference in distribution ratios of PP (P<0.01) between the ICH and control group. The largest PP range in the ICH group was from 80 to 99 mmHg, which accounted for 33.3%; PP of the control group was from 40 to 49 mmHg (30.3%). The PP level in the 40-89-year-old case group was higher than that in the 40-89-year-old control group. PP increased with age. Our investigation indicates that higher PP is correlated with acute ICH and that PP is important in predicting the risk of ICH.

Effects of early serum glucose levels on prognosis of patients with acute intracerebral hemorrhage.

Studies have indicated that hyperglycemia might cause cerebral damage to patients after acute intracerebral hemorrhage (ICH). But systematic studies on the effects of diabetes, stress hyperglycemia and normal serum glucose level on the prognosis of ICH patients are insufficient. It is essential to explore the prognosis among them. According to their serum glucose level within 24 h, 189 patients with ICH were divided into three groups: diabetes (group A), stress hyperglycemia (group B) and normal serum glucose (group C). The activity of daily living ability of patients was evaluated by Barthel index at 30 days after admission. The data analysis was done using cumulative logit model and rank sum test. Significant differences were observed in prognosis between group A and group C (OR: 0.056; CI: 0.022-0.143; p<0.0001), B and C (OR: 0.081; CI: 0.039-0.167; p<0.0001), respectively; there was no significant difference between A and B (p>0.05). No difference was found between A and B in the early serum glucose level, but significant differences were observed between A and C, and between B and C. Early hyperglycemia may worsen the prognosis of ICH patients, though patients with diabetes or stress hyperglycemia after ICH may have similar outcomes when early serum glucose levels fluctuate within the same range.

Subarachnoid hemorrhage in old patients in Chongqing China.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a disorder with high mortality in central nervous system, especially in old population. Misdiagnosis and poor outcome frequently occur in old patients with SAH. This research is to investigate the demographic characteristics, clinical features, neuroimaging data, and the outcome of the old patients (≥60 of age) with SAH. METHODS: The data was from both neurosurgical and neurology departments of two hospitals in Chongqing, China, from October 2007 to March 2009. One hundred and seventy eight patients were enrolled and divided into two groups: the elderly group (≥60 of age) and the non-elderly group (≥18 but <60 of age). The condition on admission was assessed by Hunt-Hess grade (H-H) and the Glasgow scales of coma (GCS). Findings on computerized tomography (CT) were measured by Fisher grades. The outcome after 3 months was evaluated by the modified Rankin Scale (mRS). Statistic analysis was managed by Chi-square test and t-test. FINDINGS: Compared to the non-elderly group, the clinical conditions on admission in the elderly group was worse, with lower average scores of GCS, higher Fisher grades, systolic blood pressure, and percentage of the H-H IV and V. Some preexisting medical conditions with the old such as arterial hypertension, pulmonary diseases, and diabetes mellitus were worsening. During the clinical course, the elderly group had the following characteristics: the incidence of rebleeding, asymptomatic vasospasm, hydrocephalus, and other severe medical complications were all higher, while the percentage of early surgery was lower. The outcome after 3 months was poorer in the elderly. CONCLUSIONS: It is indicated that the elderly patients with SAH have poorer clinical conditions, much lower ratio of early surgery and higher incidence of rebleeding. Together, these factors contribute to a poorer short-term outcome after SAH.

Serum Cystatin C as a Potential Predictor of the Severity of Multiple System Atrophy With Predominant Cerebellar Ataxia: A Case-Control Study in Chinese Population.

Objective: Multiple system atrophy (MSA) is a serious neurodegenerative disease that is charactered by progressive neurological disability. The aim of this study was to investigate the correlation of serum oxidant factors with the severity of MSA. Methods: A total of 52 MSA patients and 52 age- and gender- matched healthy subjects were retrospectively enrolled in this study. Enzymatic colorimetric methods were used to assay the concentrations of uric acid (UA), serum creatinine (Scr), blood urea nitrogen (BUN), and cystatin C (Cys-C). Disease severity was evaluated by the Unified Multiple System Atrophy Rating Scale (UMSARS). The disease progression rate was defined by the change in UMSARS-IV (global disability score, GDS) over a 1-year period. Results: Comparisons between the two groups revealed that there were no significant differences in terms of serum Scr (70.81 ± 13.88 vs. 70.92 ± 14.19 µmol/L, p = 0.967). However, the serum levels of the other three biomarkers were significantly higher in the MSA patients (UA: 325.31 ± 84.92 vs. 291.19 ± 64.14 µmol/L, p = 0.023; BUN: 5.68 ± 1.67 vs. 4.60 ± 1.24 mmol/L, p < 0.001; Cys-C: 0.96 ± 0.15 vs. 0.89 ± 0.14 mg/L, p = 0.024). In addition, Pearson correlation analyses revealed that only serum Cys-C was significantly correlated to GDS (r = 0.281, p = 0.044). Subgroup analysis further demonstrated that serum Cys-C was the only factor that was positively associated with the disease severity in patients with MSA and predominant cerebellar ataxia (MSA-C) (r = 0.444, p = 0.018); there was no significant association in MSA patients with predominant Parkinsonism (MSA-P) (r = 0.118, p = 0.582). MSA-C patients with severe disability were shown to express higher serum levels of Cys-C than patients with mild disability (1.03 ± 0.13 vs. 0.88 ± 0.12 mg/L, p = 0.009). Finally, Kaplan-Meier plots revealed a significant difference in the 5-year probability of survival from severe disability between MSA-C patients with high- and low-concentrations of serum Cys-C (Log-rank test: X2 = 4.154, p = 0.042). ROC curve analysis confirmed that serum Cys-C exhibits good performance as a biomarker (AUC = 0.847). Conclusion: Our research indicated that oxidative stress plays a vital role in MSA. Serum Cys-C represents a potential prognostic biomarker to evaluate the severity of disease in patients with MSA-C.