Serum metabolomics analysis combined with network pharmacology reveals possible mechanisms of postoperative cognitive dysfunction in the treatment of Mongolian medicine Eerdun Wurile basic formula.

This study analyzed the endogenous metabolites and metabolic pathways in the serum of Sprague-Dawley (SD) rats gavaged with the Eerdun Wurile basic formula (EWB) using metabolomics methods and network pharmacology to explore the possible mechanism of action of the EWB in improving postoperative cognitive dysfunction (POCD). SD rats were divided into the basic formula group, which received the EWB, and the control group, which received equal amounts of distilled water. The blood was collected from the abdominal aorta and analyzed for metabolite profiles using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Network pharmacology predicts the targets of the differential metabolites and disease targets; takes the intersection and constructs a "metabolite-disease-target" network; and performs protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 56 metabolites were selected for significant differences between the groups, mainly affecting amphetamine addiction, alcoholism, and regulation of lipolysis in adipocytes. A total of 177 potential targets for differential metabolite action in POCD were selected. The PI3K-Akt pathway, the HIF-1 pathway, and the FoxO pathway were in key positions. The studies have shown that EWB could improve POCD through multicomponents, multitargets, and multipathways, providing new possibilities and reference values for the treatment of POCD.

Atmospheric saccharides over the East China Sea: Assessment of the contribution of sea-land emission and the aging of levoglucosan.

A one-year observation of aerosols on a remote island was conducted and saccharides were applied to reveal the behaviors of organic aerosol in the East China Sea (ECS). The seasonal fluctuations of total saccharides were relatively small, with annual mean concentration of 64.82 ± 26.88 ng/m3, contributing 10.20 % and 4.90 % to WSOC and OC, respectively. However, the individual species showed significant seasonal variations due to the differences in both the emission sources and the influencing factors between marine and terrestrial areas. Anhydrosugars was the highest species and showed little diurnal variation in air mass from land areas. Primary sugars and primary sugar alcohols showed higher concentrations in blooming spring and summer and were higher in daytime than nighttime due to intense biogenic emissions both in marine and mainland areas. Accordingly, secondary sugar alcohols showed obvious different diurnal variation with ratios of day/night reducing to 0.86 in summer but even increasing to 1.53 in winter, attributing to the additional impact of secondary transmission process. Source appointment suggested that biomass burning emission (36.41 %) and biogenic emission (43.17 %) were the main causes of organic aerosol, while anthropogenic related secondary process and sea salt injection accounted for 13.57 % and 6.85 %, respectively. We further elucidate that the biomass burning emission might be underestimated, as levoglucosan undergoes degradation processes in the atmosphere, which are affected by various atmospheric physicochemical factors, and the degradation degree is particularly severe in remote areas like the oceans. In addition, significantly low ratio of levoglucosan to mannosan (L/M) occurred in air mass from marine area, indicating that levoglucosan was likely be more fully aged after hovering over a large-scale of oceanic area.

The Novel Biomarkers-Based HALP (Hemoglobin, Albumin, Lymphocyte and Platelet)-Prognostic Model for Acute and Subacute Patients with Cerebral Venous Sinus Thrombosis: A Retrospective Cohort Study.

AIM: Increasing evidences suggest that HALP is an independent predictor of prognosis in patients with inflammation. However, the relationship between HALP and prognosis in patients with cerebral venous sinus thrombosis (CVST) has not been studied. In this study, we aimed to evaluate the prognosis values of HALP in acute or subacute CVST and explore the new prognostic model for CVST. METHODS: Consecutive patients who were diagnosed as having acute and subacute CVST were retrospectively investigated. We determined the patients' functional outcomes by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to assess the relationship between factors and poor functional outcomes. The area under the ROC curve (AUC) was estimated to evaluate the ability of markers and models in predicting clinical prognosis. The prognostic model was presented as nomogram. In addition, the decision curve analysis (DCA) was used to analyze the benefit of this model. Furthermore, survival curves were described by the Kaplan-Meier analysis. RESULTS: A total of 270 patients were included of which 31 had poor outcome. Multivariable logistic regression analysis demonstrated HALP (OR=0.978, 95%CI: 0.958-0.999, P=0.039) was a protective predictor of outcome. The AUC of HALP was 0.749 (95% CI: 0.633-0.865, P=0.044). DCA demonstrated that this model significantly improved risk prediction at threshold probabilities of CVST at 0 to 85% compared to ISCVT-RS scores. Patients with higher HALP (P=0.006) presented higher overall survival rates. CONCLUSION: HALP may be a potential protective marker in acute and subacute CVST patients. The new prognostic model with HALP had potentially better value for acute and subacute CVST patients.

Seasonal source identification and formation processes of marine particulate water soluble organic nitrogen over an offshore island in the East China Sea.

Water soluble organic nitrogen (WSON) had great influences on the aerosol chemistry, hygroscopicity, marine primary productivity, as well as nitrogen biogeochemical cycles. Aerosol sampling was conducted over an offshore island in the East China Sea in four seasons of 2019, aiming to reveal the seasonal sources and secondary formation processes of marine WSON. The annual mean WSON concentration reached 1.05 ± 1.72 µg/m3 with a mean WSON/WSTN fraction of 27 %. In spring, WSON was associated with combustion emissions. The liquid-phase reaction of NH3/NH4+ with VOCs was a potential secondary formation process of WSON. In summer, WSON was mainly formed through the gaseous phase oxidation of marine biogenic precursors. In autumn, WSON showed miscellaneous sources from agricultural activities, biomass burning, and fossil fuel combustion. In addition to the contribution from primary urea, WSON could be also affected by the oxidation of biological proteinaceous matters. This explained the highest WSON concentrations and WSON/WSOC ratios in autumn. In winter, WSON was probably emitted from sea spray aerosols via the bubble-bursting processes. This study indicated that the sources of WSON over the coastal waters in the East China Sea were quite diverse, highlighting the need of more detailed characterization of marine WSON at the molecular level.

A Nomogram That Includes Neutrophils and High-Density Lipoprotein Cholesterol Can Predict the Prognosis of Acute Ischaemic Stroke.

Lipids are implicated in inflammatory responses affecting acute ischaemic stroke prognosis. Therefore, we aimed to develop a predictive model that considers neutrophils and high-density lipoprotein cholesterol to predict its prognosis. This prospective study enrolled patients with acute ischaemic stroke within 24 h of onset between January 2015 and December 2017. The main outcome was a modified Rankin Scale score ≥3 at the 90th day of follow-up. Patients were divided into training and testing sets. The training set was divided into four states according to the median of neutrophils and high-density lipoprotein cholesterol levels in all patients. Through binary logistic regression analysis, the relationship between factors and prognosis was determined. A nomogram based on the results was developed; its predictive value was evaluated through internal and external validations. Altogether, 1,090 patients were enrolled with 872 (80%) and 218 (20%) in the training and testing sets, respectively. In the training set, the major outcomes occurred in 24 (10.4%), 24 (11.6%), 37 (17.2%), and 49 (22.3%) in states 1-4, respectively (P = 0.002). Validation of calibration and decision curve analyses showed that the nomogram showed better performance. The internal and external testing set receiver operating characteristics verified the predictive value [area under the curve = 0.794 (0.753-0.834), P < 0.001, and area under the curve = 0.973 (0.954-0.992), P < 0.001, respectively]. A nomogram that includes neutrophils and high-density lipoprotein cholesterol can predict the prognosis of acute ischaemic stroke, thus providing us with an effective visualization tool.

Stroke and Myocardial Infarction: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Stroke and myocardial infarction (MI) are associated with each other, as demonstrated in observational studies. However, it is unclear whether this relationship is causal, and the purpose of this study was to explore the bidirectional causality between stroke and MI. METHODS: Causality between stroke and MI was assessed using two-sample Mendelian randomization (MR). All genetic instruments related to stroke (40,585 cases; 406,111 controls) and MI (43,676 cases; 128,199 controls) were derived from large published genome-wide association study. The MR analysis was calculated with inverse-variance weighting, MR-Egger, weighted mode, weighted median, and simple mode methods, and sensitivity analyses are used to detect the heterogeneity or pleiotropy. RESULTS: Genetically predicted large-artery stroke (LAS) was causally related to higher odds of MI (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 1.06-1.20, p = 1.0×10-4), and the causal effect of LAS on MI was significantly weakened (OR = 1.09, 95% CI: 1.02-1.17, p = 0.017) after excluding the multipotent single-nucleotide polymorphisms (SNPs). MI phenotypes were genetically correlated with all ischemic strokes (OR = 1.15, 95% CI: 1.03-1.28, p = 0.013) and LAS (OR = 1.39, 95% CI: 1.14-1.71, p = 0.001); but a causal effect of MI on all ischemic strokes (OR = 1.00, 95% CI: 0.95-1.28, p = 0.219) and LAS (OR = 1.26, 95% CI: 0.93-1.69, p = 0.130) was not observed after excluding the multipotent SNPs. CONCLUSION: This MR analysis provides evidence to support the causal effect of LAS subtype on MI, and some factors act as confiding factors whereas others may act as mediators.

Heart Failure and Ischemic Stroke: A Bidirectional and Multivariable Mendelian Randomization Study.

Background: Heart failure (HF) is a potential cause of ischemic stroke (IS), and previous studies have reported an association between HF and IS. This study aimed to analyze the causal link between HF and IS using bidirectional and multivariable Mendelian randomization (MR) studies. Methods: Genetic variants significantly associated with HF and IS were selected in the MR analysis from two large genome-wide association studies. Bidirectional and multivariable MR analyses were performed to evaluate the effect of HF on IS or the effect of IS on HF. Results: Two-sample MR analysis showed causal effects of HF on IS of all causes [odds ratio (OR) = 1.555, 95% confidence interval (CI): 1.343-1.799, p = 3.35 × 10-9] and large artery atherosclerosis stroke (LAS) (OR = 1.678, 95% CI: 1.044-2.696, p = 3.03 × 10-5), while there was a suggestive effect of HF on cardioembolic stroke (CES) (OR = 3.355, 95% CI: 1.031-10.919, p = 0.044). Genetically predicted HF was not associated with small artery occlusion stroke. Bidirectional MR analysis showed causal effects of IS of all causes (OR = 1.211, 95% CI: 1.040-1.410, p = 0.014) and CES (OR = 1.277, 95% CI: 1.213-1.344, p = 6.73 × 10-21) on HF, while there were no causal effects of LAS on HF. Conclusion: This MR analysis provided evidence of the causal links between genetically predicted HF and IS. Subgroup analysis highlighted the causal or suggestive relationship between genetically predicted HF and LAS or CES. The potential causal links need further investigation with genetic information about other ancestries or etiologies of HF.

Decoding the Transcriptional Response to Ischemic Stroke in Obese and Non-obese Mice Brain.

BACKGROUND: Ischemic Stroke (IS) is a serious cerebrovascular disease, which leads to irreversible damage or death of brain cells. Effective control of stroke risk factors can effectively reduce the incidence of IS. However, there was an "obesity paradox" about the relationship between obesity and the prognosis of IS, in which obesity would not bring worse outcomes than non-obese IS patients. OBJECTIVE: Herein, we aimed to investigate the transcriptional response to IS in obese and nonobese mice brain via RNA-Seq technology. The datasets of obese and non-obese mice with/without IS were obtained from the Gene Expression Omnibus (GEO) database. METHODS: Differentially expressed genes (DEGs) between Control and Obesity (DEGsObesity) and between Obesity and Obese-Stroke (DEGsObese-Stroke) were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Protein-Protein Interaction (PPI) network analysis were performed to predict the function of DEGs. 28 and 109 DEGs were screened in DEGsObesity and DEGsObese-Stroke, respectively. RESULTS: Significantly, in the top 10 key-genes of DEGsObese-Stroke (Tnf, Lgals3, Serpinb2, Ly6c2, Chil3, Clec4e, Mmp3, Mefv, Spn, Tlr8), Tnf and Mefv were involved in the NOD-like receptor signaling pathway, which was consistent with KEGG pathway enrichment results. And Chil3, as a mononuclear cell marker, was significantly elevated in Obese-Stroke compared with Stroke, suggesting mononuclear cell, rather than other peripheral immune cells, infiltrated into the brain of Obese-stroke. CONCLUSION: Hence, we concluded that obesity could affect the brain microenvironment at the transcriptome level and Stroke after obesity could lead to more changes in NOD-like receptor signaling pathway and monocyte infiltration, compared with non-obese Stroke.

The Association Between Serum Apelin-13 and the Prognosis of Acute Ischemic Stroke.

While a number of studies have reported an association between apelin-13 and ischemic stroke, few have verified its clinical effect. We investigated the prognostic value of serum apelin-13 levels in patients with acute ischemic stroke (AIS). We prospectively recruited 244 AIS patients within 24 h after stroke onset, and 167 healthy controls. We assessed the serum apelin-13 levels using ELISA, and the severity of AIS using the National Institutes of Health Stroke Scale (NIHSS). The primary outcomes included death or major disability (modified Rankin Scale score, 3-6) and major disability (modified Rankin Scale score, 3-5). Secondary outcomes included recurrent stroke and combined events (all-cause death, or cardiovascular and cerebrovascular events). We found that the serum apelin-13 levels in the patients (38.63 ng/mL (interquartile range [IQR], 29.86-50.99)) were lower than those in the healthy controls (42.50 ng/mL [IQR, 31.25-59.17]) (P = 0.017). Patients with a NIHSS score ≤ 3 had higher apelin-13 levels than those with a NIHSS score > 3 (P = 0.048). At the 3-month follow-up, multivariate logistic regression analysis indicated an association between apelin-13 and death or major disability (OR 0.31; 95% CI 0.11-0.86; P = 0.024) and major disability (OR 0.32; 95% CI 0.11-0.90; P = 0.030). At the 1-year follow-up, the patients with high apelin-13 levels showed a lower incidence of stroke and combined events (Log-rank test P < 0.05). Our findings indicate that serum apelin-13 may be a potential prognostic biomarker for AIS.

Changes of Metabolites in Acute Ischemic Stroke and Its Subtypes.

Existing techniques have many limitations in the diagnosis and classification of ischemic stroke (IS). Considering this, we used metabolomics to screen for potential biomarkers of IS and its subtypes and to explore the underlying related pathophysiological mechanisms. Serum samples from 99 patients with acute ischemic stroke (AIS) [the AIS subtypes included 49 patients with large artery atherosclerosis (LAA) and 50 patients with small artery occlusion (SAO)] and 50 matched healthy controls (HCs) were analyzed by non-targeted metabolomics based on liquid chromatography-mass spectrometry. A multivariate statistical analysis was performed to identify potential biomarkers. There were 18 significantly different metabolites, such as oleic acid, linoleic acid, arachidonic acid, L-glutamine, L-arginine, and L-proline, between patients with AIS and HCs. These different metabolites are closely related to many metabolic pathways, such as fatty acid metabolism and amino acid metabolism. There were also differences in metabolic profiling between the LAA and SAO groups. There were eight different metabolites, including L-pipecolic acid, 1-Methylhistidine, PE, LysoPE, and LysoPC, which affected glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, histidine metabolism, and lysine degradation. Our study effectively identified the metabolic profiles of IS and its subtypes. The different metabolites between LAA and SAO may be potential biomarkers in the context of clinical diagnosis. These results highlight the potential of metabolomics to reveal new pathways for IS subtypes and provide a new avenue to explore the pathophysiological mechanisms underlying IS and its subtypes.

The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score Is Associated With Poor Outcome of Acute Ischemic Stroke.

Background: The combined index of hemoglobin, albumin, lymphocyte, and platelet (HALP) is considered a novel score to reflect systemic inflammation and nutritional status. This study aimed to investigate the association between HALP score and poor outcome in patients with acute ischemic stroke (AIS). Methods: Consecutive AIS patients within 24 h after onset were prospectively enrolled. Poor outcome was a combination of a new stroke event (ischemic and hemorrhagic) and all-cause death within 90 days and 1 year. The association between HALP score and poor outcome was analyzed using Cox proportional hazards. Results: A total of 1,337 patients were included. Overall, 60 (4.5%) and 118 (8.8%) patients experienced poor outcome within 90 days and 1 year, respectively. Patients in the highest tertile of HALP score had a lower risk of poor outcome within 90 days and 1 year (hazard ratio: 0.25 and 0.42; 95% confidence intervals: 0.11-0.57 and 0.25-0.69, P for trend <0.01 for all) compared with those in the lowest tertile after adjusting relevant confounding factors. Adding HALP score to the conventional risk factors improved prediction of poor outcome in patients with AIS within 90 days and 1 year (net reclassification index, 48.38 and 28.95%; integrated discrimination improvement, 1.51 and 1.51%; P < 0.05 for all). Conclusions: Increased HALP score was associated with a decreased risk of recurrent stroke and death within 90 days and 1 year after stroke onset, suggesting that HALP score may serve as a powerful indicator for AIS.