Liquid chromatography-mass spectrometry-based metabolomic profiling reveals sex differences of lipid metabolism among the elderly from Southwest China.

BACKGROUND: The sexual dimorphism represents one of the triggers of the metabolic disparities while the identification of sex-specific metabolites in the elderly has not been achieved. METHODS: A group of aged healthy population from Southwest China were recruited and clinical characteristics were collected. Fasting plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomic analyses were performed. Differentially expressed metabolites between males and females were identified from the metabolomic analysis and metabolite sets enrichment analysis was employed. RESULTS: Sixteen males and fifteen females were finally enrolled. According to clinical characteristics, no significant differences can be found except for smoking history. There were thirty-six differentially expressed metabolites between different sexes, most of which were lipids and lipid-like molecules. Twenty-three metabolites of males were increased while thirteen were decreased compared with females. The top four classes of metabolites were fatty acids and conjugates (30.6%), glycerophosphocholines (22.2%), sphingomyelins (11.1%), and flavonoids (8.3%). Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins were significantly enriched in metabolite sets enrichment analysis. CONCLUSIONS: Significant lipid metabolic differences were found between males and females among the elderly. Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins may partly account for sex differences and can be potential treatment targets for sex-specific diseases.

Serum levels of lipocalin-2 in patients with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease. Evidence has shown that lipocalin-2 (LCN2) is involved in the pathological process of PD. We aimed to explore whether serum levels of LCN2 could be a biomarker of PD. METHODS: We recruited consecutive PD patients and healthy controls (HC) in our hospital from June 2020 to July 2020. Serum LCN2 levels were detected using the LCN2 enzyme-linked immunosorbent assay (ELISA) kit. The motor section of the Unified Parkinson's Disease Rating Scale (UPDRS III) and the Hoehn and Yahr Staging Scale (H&Y) were assessed on admission to evaluate disease severity in patients with PD. Cognitive status was measured by the Montreal Cognitive Assessment (MoCA). RESULTS: We finally recruited 75 patients, including 40 PD patients and 35 HC. Serum LCN2 levels were not significantly increased in PD patients compared with HC (4.9 [- 0.7 to 18.6] vs 1.9 [- 1.5 to 16.9] ng/mL, P = 0.33). Besides, there was no significant difference in LCN2 levels between patients at early and advanced stage of PD (P = 0.75), as well as between cognitively impaired PD patients, PD patients with normal cognition, and HC (P = 0.30). Moreover, LCN2 had no correlation with disease duration (r = - 0.1, P = 0.37), UPDRS III score (r = 0.07, P = 0.65), and MoCA score (r = 0.221, P = 0.17). CONCLUSIONS: Overall, our study suggests that serum LCN2 levels may not be a biomarker for PD.

Lipid metabolic dysregulation is involved in Parkinson's disease dementia.

Dementia is very common in the late stage of patient with Parkinson's disease (PD). We aim to explore its underlying pathogenesis and identify candidate biomarkers using untargeted metabolomics analysis. Consecutive PD patients and healthy controls were recruited. Clinical data were assessed and patients were categorized into Parkinson's disease without dementia (PDND) and Parkinson's disease dementia (PDD). Fast plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomics analysis was performed. Based on the identified differentially-expressed metabolites from the metabolomics analysis, multivariate linear regression analyses and receiver operating characteristic (ROC) curves were further employed. According to the clinical data, the mean ages of PDND and PDD patients were significantly higher than those of healthy controls. The incidence of hypercholesterolemia was decreased in PDD patients. PDD patients also had lower levels of triglyceride, low-density lipoprotein cholesterol, and apolipoprotein B. There were 24 and 57 differentially expressed metabolites in PDD patients when compared with the healthy controls and PDND patients from the metabolomics analysis. Eleven lipid metabolites were simultaneously decreased between these two groups, and can be further subcategorized into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and prenol lipids. The plasma levels of the eleven metabolites were positively correlated with MMSE score and can be candidate biomarkers for PDD patients with areas under the curve ranging from 0.724 to 0.806 based on the ROC curves. Plasma lipoproteins are significantly lower in PDD patients. A panel of eleven lipid metabolites were also decreased and can be candidate biomarkers for the diagnosis of PDD patients. Lipid metabolic dysregulation is involved in the pathogenesis of Parkinson's disease dementia.

Botulinum Toxin Type A for Upper Limb Spasticity in Poststroke Patients: A Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND AIM: Botulinum toxin type A is considered to be an effective antispasmodic in recent years. We assess the effectiveness of botulinum toxin type A for the treatment of poststroke spasticity in the upper extremity using a meta-analysis. METHODS: We searched several databases including PubMed, Web of Science, Embase, and Cochrane database for relevant studies, up until October 2017. All randomized controlled trials of botulinum toxin type A treat poststroke upper limb spasticity published were included. The primary outcome measure was modified ashworth score at the elbow, finger and wrist, pain score, and barthel index. RESULTS: Ten randomized controlled trials were identified and reported sufficient data for inclusion in the pooled analysis (n = 950). The results of modified ashworth score at different joints, pain score, barthel index showed no difference was found in the effectiveness of botulinum toxin type A compared with placebo in the treatment of the upper limb spasticity after stroke. But modified ashworth score at the elbow was improver in Dysport subgroups (standardized mean difference [SMD] = -.39, 95%CI = -.67 to -.10, P = .008) compared with Botox subgroups (SMD = .08, 95%CI = -.68 to .83, P = .84). CONCLUSIONS: The meta-analysis of these studies showed that the overall effectiveness of botulinum toxin type A does not seem to differ from placebo for poststroke Patients. But the meta-analysis yielded a favorable effect of Dysport compared with placebo based on 4 trials.

SIRT1: The Value of Functional Outcome, Stroke-Related Dementia, Anxiety, and Depression in Patients with Acute Ischemic Stroke.

BACKGROUND: The outcome of ischemic stroke depends on multiple factors and their function of each other. Studies have shown that Sirtuin1 (SIRT1) plays a chief role in the key procedure during ischemia/hypoxia by protecting against cellular stress and controlling the metabolic pathways. AIMS: To explore the alterations in serum SIRT1 concentrations in acute ischemic stroke (AIS) patients and the relationship between SIRT1 and poststroke dementia, anxiety, and depression. METHODS: One hundred and twenty four consecutive patients with clinically diagnosed AIS were recruited to participate in the study. Serum SIRT1 levels were measured using a commercially available ELISA equipment for SIRT1 (Cusabio, Wuhan, China). In 1 year after admission, the severity of stroke was assessed with the National Institutes of Health Stroke Scale score, and the functional outcome was measured by a modified Rankin scale, the Hamilton Anxiety Scale scores were evaluated to define patients with or without anxiety, and the Hamilton Depression Scale scores for depression. RESULTS: We found the levels of serum SIRT1 was significantly higher (P = .036) in AIS patients (.62 ± .77 ng/mL) compared with healthy control subjects (.45 ± .69 ng/mL), but not significantly higher SIRT1 concentration (.58 ± .69 versus .64 ± .81 ng/mL, P = .298) than patients in the unfavorable functional outcome group. CONCLUSIONS: There is no potential diagnostic and prognostic role of SIRT1 in AIS-related dementia, anxiety, and depression. The role of SIRT1 in AIS among human race needs to be further investigated.

Increased Serum Alkaline Phosphatase in Patients with Acute Ischemic Stroke.

BACKGROUND: Stroke is one of the most common causes of disability and death. Higher alkaline phosphatase (ALP) levels have been associated with poor functional outcomes and mortality in previous studies. We investigated alterations in serum ALP concentrations and functional outcomes in patients with acute ischemic stroke (AIS). METHODS: Patients with first-ever AIS were recruited to participate in the study. Serum ALP levels were measured using a Cobas Integra 400 Plus automatic biochemical analyzer, and severity of stroke was evaluated using the National Institutes of Health Stroke Scale (NIHSS) score on admission. Functional outcome was measured using the modified Rankin scale 1 year after admission. RESULTS: Serum ALP concentration was increased in patients with AIS (81.75 ± 20.49 versus 69.93 ± 16.12 U/L, P = .000) and the optimal ALP cutoff point for diagnosing patients with AIS was 81.50 U/L, with a sensitivity of 49.5% and specificity of 78.9%. However, there was no significant correlation between ALP and NIHSS scores (r = .170, P = .085) and ALP was not significantly different between favorable and unfavorable functional outcomes (81.76 ± .60 versus 81.70 ± 20.54 U/L, P = .802). CONCLUSIONS: Serum ALP concentration, which was increased in patients with AIS, might represent a low-potency biomarker for the diagnosis of AIS. However, this was not significantly correlated with NIHSS scores or the functional outcome after 1 year.

Decreased serum proNGF concentration in patients with Parkinson's disease.

Parkinson's disease (PD), a progressive and age-related neurodegenerative condition, is a common neurodegenerative disorder. However, no validated biomarkers for PD have been identified to date. Accumulating evidence supports the role of proNGF-p75NTR-sortilin signaling in the neurodegeneration and pathogenesis of PD. The aim of our study was to investigate alterations in serum proNGF concentrations in PD patients and related anxiety. Seventy-seven consecutive PD patients and 39 healthy controls were enrolled, and clinical data were collected. Modified Hoehn-Yahr Staging Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and Hamilton Anxiety (HAMA) Scale scores were assessed upon admission. Serum proNGF concentration was compared between that of PD patients and healthy controls. Pearson correlation coefficients were determined to explore the relationship between proNGF concentration and UPDRS, Hoehn-Yahr, and HAMA scores. Received operating characteristic (ROC) curves and proNGF optimal cutoff point were used to distinguish PD and related anxiety. The median concentration of proNGF was significantly lower (p = 0.000) in PD patients (94.91 ng/L, range 85.92-118.06 ng/L) compared with that of healthy controls (106.67 ng/L, range 102.39-122.06 ng/L). The optimal proNGF cutoff point for distinguishing PD patients was 102.29 ng/L, and the sensitivity and specificity values were 87.0 and 100%, respectively. proNGF concentration positively correlated with UPDRS (r = 0.281, p = 0.013), Hoehn-Yahr (r = 0.260, p = 0.023), and HAMA (r = 0.276, p = 0.015) scores. Our results indicate that serum proNGF concentration may represent a biomarker for PD and its role in the pathogenesis of PD thus warrants further investigation.

Divergent Urinary Metabolic Phenotypes between Major Depressive Disorder and Bipolar Disorder Identified by a Combined GC-MS and NMR Spectroscopic Metabonomic Approach.

Bipolar disorder (BD) is a complex debilitating mental disorder that is often misdiagnosed as major depressive disorder (MDD). Therefore, a large percentage of BD subjects are incorrectly treated with antidepressants in clinical practice. To address this challenge, objective laboratory-based tests are needed to discriminate BD from MDD patients. Here, a combined gas chromatography-mass spectrometry (GC-MS)-based and nuclear magnetic resonance (NMR) spectroscopic-based metabonomic approach was performed to profile urine samples from 76 MDD and 43 BD subjects (training set) to identify the differential metabolites. Samples from 126 healthy controls were included as metabolic controls. A candidate biomarker panel was identified by further analyzing these differential metabolites. A testing set of, 50 MDD and 28 BD subjects was then used to independently validate the diagnostic efficacy of the identified panel using an area under the receiver operating characteristic curve (AUC). A total of 20 differential metabolites responsible for the discrimination between MDD and BD subjects were identified. A panel consisting of six candidate urinary metabolite biomarkers (propionate, formate, (R*,S*)2,3-dihydroxybutanoic acid, 2,4-dihydroxypyrimidine, phenylalanine, and ß-alanine) was identified. This panel could distinguish BD from MDD subjects with an AUC of 0.913 and 0.896 in the training and testing sets, respectively. These results reveal divergent urinary metabolic phenotypes between MDD and BD. The identified urinary biomarkers can aid in the future development of an objective laboratory-based diagnostic test for distinguishing BD from MDD patients.

Nonsteroidal anti-inflammatory drugs versus corticosteroid for treatment of shoulder pain: a systematic review and meta-analysis.

OBJECTIVE: To compare the treatment efficacy between corticosteroid injection and nonsteroidal anti-inflammatory drugs (NSAIDs) for patients with shoulder pain. DATA SOURCES: PubMed and EMBASE databases were searched from inception to January 2014. Reference lists of the retrieved studies were additionally scrutinized. STUDY SELECTION: Randomized controlled trials (RCTs) comparing corticosteroid injection with NSAIDs for treatment of shoulder pain were included. The primary outcome was remission, and the secondary outcomes were pain relief and improvement of range of active abduction. Study selection was conducted by 2 researchers independently. Any disagreements were solved by discussion and confirmed by the third reviewer. DATA EXTRACTION: Two reviewers independently conducted data extraction and the quality assessment. Data regarding patients, intervention, control, and outcomes were extracted from the included trials. DATA SYNTHESIS: Six high-quality RCTs of 267 patients meeting the inclusion criteria were included. For an outcome of remission, NSAIDs were less effective than corticosteroid in 4 or 6 weeks (relative risk, .64; 95% confidence interval, .45-.92). NSAIDs did not significantly differ with corticosteroid in pain relief and improvement of range of active abduction. CONCLUSIONS: Current meta-analysis suggests that NSAIDs are less effective than corticosteroid in achieving remission in patients with shoulder pain at 4 or 6 weeks after treatment. Considering the limited number of studies and small size of each trial, the results should be interpreted with caution, and more high-quality RCTs are encouraged.

Increased serum SGLT2 and its potential diagnostic and prognostic value in patients with acute ischemic stroke.

BACKGROUND: Recently acquired data suggests that sodium-glucose cotransporter-2 (SGLT2) may be a therapeutic target for cerebral ischemia. The specific impact of SGLT2 in acute ischemic stroke (AIS) remains unknown. We aimed to explore the levels of SGLT2 in AIS patients and its association with functional prognosis. METHODS: In this study, 132 AIS patients and 44 healthy controls were recruited prospectively to determine serum SGLT2 levels. Logistic regression analysis was employed to assess the association between serum SGLT2 level and stroke risk as well as 3-month outcome. Receiver operating characteristic (ROC) curves were utilized to evaluate predictive values for blood biomarkers. RESULTS: Serum SGLT2 levels were significantly higher (P =.000) in AIS patients (47.1 (interquartile range [IQR]: 42.4-50.9) ng/mL) than healthy controls (35.7 (IQR: 28.6-39.5) ng/mL). The optimal SGLT2 cutoff point for diagnosing AIS was 39.55 ng/mL, with a sensitivity of 90.2 % and specificity of 77.3 %. Serum levels of SGLT2 were negatively correlated with the onset time of AIS (linear fit R2 = 0.056, P =.006), but were not associated with National Institutes of Health Stroke Scale (NIHSS) scores (r = 0.007, P >.05) and lesion volume (r = -0.151, P >.05). SGLT2 was not remarkably different between patients with unfavorable and favorable outcomes (46.7 (IQR: 41.9-49.6) ng/mL vs 47.6 (IQR: 42.5-51.9) ng/mL; P =.321). CONCLUSIONS: The serum SGLT2 concentration may be a potential biomarker for the diagnosis of AIS. However, it does not exhibit any association with disease severity or functional prognosis.

Wernicke encephalopathy induced by glucose infusion: A case report and literature review.

Introduction: Wernicke encephalopathy (WE) is a potentially fatal condition caused by thiamine (vitamin B1) deficiency. Chronic alcoholism is the most common cause of WE; however, other conditions responsible for thiamine deficiency should also be considered. Case Report: We report the case of a 64-year-old woman with a history of diabetes who presented with confusion and apathy. Magnetic resonance imaging of the brain showed T2 hyperintensities involving dorsolateral medulla oblongata, tegmentum of the pons, vermis of the cerebellum, periaqueductal region, and the bilateral mammillary bodies. She had a history of intravenous glucose administration before her mental symptoms developed. On suspicion of WE, she was treated with a high dose of thiamine empirically. Her clinical condition improved rapidly in 2 weeks. Conclusion: Endogenous thiamine stores can be rapidly depleted in the case of enhanced glucose oxidation. Patients who receive glucose should also be prescribed thiamine to avoid inducing or exacerbating WE.

Correlation Between Oncostatin M and Acute Ischemic Stroke: A Case-Control Study.

BACKGROUND: The expression of oncostatin M (OSM) has been studied in various diseases related to inflammatory response, but its implementation in acute ischemic stroke (AIS) remains to be explored.  Objective: The objective of this study is to assess the correlation between serum OSM expression and various aspects of AIS in a clinical setting. MATERIALS AND METHOD: A single-centered case-control study was performed in the First Affiliate Hospital of Chongqing Medical University from October 2020 to March 2021. A total of 134 patients were enrolled in the AIS group and 34 healthy individuals were enrolled in the control group. Physical examinations were performed and venous blood samples were collected. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum OSM. Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, National Institutes of Health Stroke Scale (NIHSS) score, magnetic resonance imaging (MRI) scan, and modified Rankin scale (mRS) were used to assess the classification, etiology, severity, and prognosis of the AIS group. Assessments were done to analyze serum OSM expression based on sensitivity, etiology, severity, prognosis, and several risk factors of AIS. Regression models, correlation, and sensitivity tests were performed to explore the correlation of OSM expression with various aspects of AIS. RESULTS: There was a statistically significant elevation of serum OSM expression in the AIS group (P<0.001). All AIS subgroups showed elevation in OSM level and statistically significant results were reflected in three subgroups. The area under the curve to differentiate AIS patients and control by serum OSM level was 0.747 (P<0.001), with the optimal cut-off value showing sensitivity at 58.82% and specificity at 75.37%. The elevation of serum OSM expression was proportional with severity, not proportional to the volume of infarct, and less elevated in the favorable outcome group. Serum OSM correlation with several risk factors of AIS was statistically significant in age, low-density lipoprotein, non-high-density lipoprotein, prothrombin time, and systolic blood pressure. CONCLUSION: Serum OSM was expressed differently in correlation with various aspects of AIS. Our findings supported the initial hypothesis that OSM is correlated with various aspects of AIS in humans.

Sex difference in cerebral atherosclerotic stenosis in Chinese asymptomatic subjects.

Background and purpose: Sex difference in cerebral atherosclerosis has been noted in previous studies, but the precise characteristics remain incompletely elucidated. This study aims to identify the sex difference in patients with asymptomatic cerebrovascular stenosis. Materials and methods: The image and clinical data of 1305 consecutive patients who had head and neck computed tomography angiography (CTA) were collected. Fifty hundred and seventy-three patients (287 males) with asymptomatic atherosclerotic stenosis in cerebral arteries were finally included. The stenosis number, distribution, severity and their changes with age were analyzed and compared between males and females. Simple linear regression was used to assess the change in lesions with age. Results: A total of 2097 stenoses were identified in 573 patients, males had more stenoses than females (3 [2, 5] vs 3 [2, 4], p=0.015). The number of stenoses in extracranial arteries was much higher in males (p = 0.001). Females had higher percentage of stenosis in anterior (89.6% vs 85.9%, p = 0.012) and intracranial arteries (63.3% vs 57.1%, p = 0.004) than males. Males had higher percentage of moderate-severe stenosis (5.1% vs 3.2%, p = 0.026). Age (OR = 1.67; 95% CI 1.24-2.25; p < 0.001) and hypertension (OR = 2.53; 95% CI 1.24-5.15; p = 0.01) were associated with moderate-severe stenosis. In patients over 50 years old, the number of stenoses increased by 1.03 per 10 years (p < 0.001), with 0.72 more stenoses in males (p = 0.003). Conclusions: Cerebral atherosclerotic stenosis was different between sexes regarding the distribution, severity and the change pattern with age, which underline the sex specific management in patients with cerebral atherosclerosis.

The disturbance of lipid metabolism is correlated with neuropsychiatric symptoms in patients with Parkinson's disease.

OBJECTIVE: We aimed to identify the detailed relationships between serum lipid levels and neuropsychiatric symptoms in patients with Parkinson's disease (PD). METHODS: Consecutive PD patients and healthy controls were recruited and demographic data were collected. The disease stages of PD patients were assessed using Hoehn-Yahr scale while neuropsychiatric symptoms were determined using Hamilton depression rating scale (HAMD), Hamilton anxiety rating scale (HAMA), and mini-mental state examination scale. Fast serum samples were obtained and the serum levels of lipids were identified. Linear regression analyses and correlation analyses were performed to explore the relationships between serum lipid levels and neuropsychiatric symptoms. RESULTS: The serum levels of triglyceride had significantly decreased while the levels of HDL-c and lipoprotein a had increased in PD patients. Linear regression analyses confirmed that the levels of triglyceride were mainly correlated with age and HAMA score, the levels of HDL-c were correlated with disease duration and gender, and the levels of lipoprotein a were correlated with HAMD score. Correlation analyses further confirmed that the levels of triglyceride were negatively correlated with HAMA score when the levels of lipoprotein a were negatively correlated with HAMD score. CONCLUSIONS: Lipid metabolism is significantly correlated with neuropsychiatric disorders in PD patients.

Metabolomics profiling reveals altered lipid metabolism and identifies a panel of lipid metabolites as biomarkers for Parkinson's disease related anxiety disorder.

OBJECTIVES: Anxiety disorder is a common non-motor symptom in patient with Parkinson's disease (PD). We aimed to explore its pathogenesis and identify plasma biomarkers using untargeted metabolomics analysis. METHODS: Consecutive PD patients and healthy controls were recruited. Clinical data were assessed and patients with Parkinson's disease related anxiety disorder (PDA) were recognized. Fast plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomics analysis was performed. Based on the differentially expressed metabolites from the above metabolomics analysis, correlation analyses and receiver operating characteristic curves (ROC) were further employed. RESULTS: According to the clinical data, PDA patients had lower plasma levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and apolipoprotein B. There were thirty-nine differentially expressed metabolites in PDA patients when compared with the other two groups from the metabolomics analysis, respectively. Fourteen lipid metabolites were simultaneously altered between these two groups, and all of them were significantly decreased. They can be further subcategorized into fatty acyls, glycerolipids, sterol lipids, sphingolipids, and prenol lipids. The plasma levels of thirteen metabolites were negatively correlated with HAMA scores except 10-oxo-nonadecanoic acid. Based on the ROC curves, the fourteen lipid metabolites can be diagnostic biomarkers for PDA patients separately and the areas under the curve of the fourteen lipid metabolites ranged from 0.681 to 0.798. CONCLUSIONS: Significantly lower plasma lipoproteins can be found in PDA patients. A panel of fourteen lipid metabolites were also significantly decreased and can be clinical biomarkers for the diagnosis of PDA patients.

Integrated Metabolomics and Proteomics Analysis Reveals Plasma Lipid Metabolic Disturbance in Patients With Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disease in the elderly with a pathogenesis that remains unclear. We aimed to explore its pathogenesis through plasma integrated metabolomics and proteomics analysis. The clinical data of consecutively recruited PD patients and healthy controls were assessed. Fasting plasma samples were obtained and analyzed using metabolomics and proteomics methods. After that, differentially expressed metabolites and proteins were identified for further bioinformatics analysis. No significant difference was found in the clinical data between these two groups. Eighty-three metabolites were differentially expressed in PD patients identified by metabolomics analysis. These metabolites were predominately lipid and lipid-like molecules (63%), among which 25% were sphingolipids. The sphingolipid metabolism pathway was enriched and tended to be activated in the following KEGG pathway analysis. According to the proteomics analysis, forty proteins were identified to be differentially expressed, seven of which were apolipoproteins. Furthermore, five of the six top ranking Gene Ontology terms from cellular components and eleven of the other fourteen Gene Ontology terms from biological processes were directly associated with lipid metabolism. In KEGG pathway analysis, the five enriched pathways were also significantly related with lipid metabolism (p < 0.05). Overall, Parkinson's disease is associated with plasma lipid metabolic disturbance, including an activated sphingolipid metabolism and decreased apolipoproteins.

Gamma-hydroxybutyrate (GHB) for narcolepsy in adults: an updated systematic review and meta-analysis.

BACKGROUND: Narcolepsy is a chronic and debilitating sleep disorder characterized by cataplexy and excessive daytime sleeping. Gamma-hydroxybutyrate (GHB) has been widely used to treat narcolepsy, and new findings have been published in recent years. OBJECTIVE: A meta-analysis was conducted to assess the efficacy and tolerability of GHB treatment in adults with narcolepsy. METHODS: A systematic search of PubMed, Cochrane, Embase, Web of Science, and clinical-trials.gov from inception to June 2018 was performed. Change in daily diaries and polysomnographic data of narcoleptic patients were defined as the efficacy outcomes. The tolerability and acceptability outcomes were the rates of adverse events and dropping out for adverse effects or other reasons. RESULTS: Fifteen randomized controlled trials involving 2104 participants were identified. GHB was found to improve cataplexy attacks (P = 0.001), subjective daytime sleepiness (P < 0.0001), daytime sleep latency (P < 0.0001), inadvertent naps/sleep attacks (P < 0.00001), effective rates (Clinical Global Impression of change) (P < 0.00001), hypnagogic hallucinations (P = 0.004), sleep paralysis (P = 0.004), stage 1 sleep (P = 0.04), slow wave sleep (P = 0.003), REM sleep (P = 0.0006), sleep shifts (P = 0.005), nocturnal awakenings (P = 0.004), quality of nocturnal sleep (P < 0.00001), chin muscle activity, and quality of life, but had no effect on stage 2 sleep (P = 0.88). GHB was less well tolerated than placebo because of side effects that occurred in a dose-dependent fashion (RR = 6.08; 95% CI = 2.18 to 16.97; P = 0.0006). CONCLUSIONS: GHB was effective in improving narcolepsy-cataplexy and related symptoms in adults but was less well tolerated than placebo because of dose-dependent side effects.

Objective diagnosis of post-stroke depression using NMR-based plasma metabonomics.

Background: Post-stroke depression (PSD) is a frequent and serious complication of stroke. However, the underlying molecular basis of PSD remains largely unknown, and no empirical laboratory tests were available to diagnose this disorder. Materials and methods: A proton nuclear magnetic resonance (1H NMR)-based metabonomic approach was employed to profile plasma samples from 32 PSD, 35 stroke patients and 35 healthy comparison subjects (the training set) in order to identify metabolite biomarkers for PSD. Then, 10 PSD, 11 stroke patients and 11 healthy comparison subjects (test set) were used to validate the diagnostic performance of these biomarkers. Results: The multivariate statistical analysis demonstrated that PSD group was significantly distinguishable from non-PSD groups (non-depression stroke patients and healthy comparison group). Five plasma metabolites (phenylalanine, tyrosine, 1-methylhistidine, 3-methylhistidine and LDL CH3-(CH2)n-) were identified responsible for distinguishing PSD from non-PSD subjects. These metabolites were mainly involved in neurotransmitter metabolism and oxidative stress. The biomarker panel composing of these metabolites was capable of distinguishing test samples with a sensitivity of 100.0% and a specificity of 95.5%. Conclusion: Our findings suggest that plasma disturbances of neurotransmitter levels and oxidative stress were implicated in the onset of PSD; these disturbed metabolites biomarkers facilitate to the development of diagnostic tool for PSD.