The Association of Systemic Inflammatory Response Index and Neutrophil-to-High-Density Lipoprotein Ratio Mediated by Fasting Blood Glucose with 90-Day Prognosis in Acute Ischemic Stroke Patients.

INTRODUCTION: The contribution of individual and combined inflammatory markers for the prognosis of acute ischemic stroke (AIS) remains elusive. This study investigated the effect of systemic inflammatory response index (SIRI), and neutrophil to high-density lipoprotein ratio (NHR), which is mediated by fasting blood glucose (FBG), on 90-day prognosis of patients with AIS. METHODS: In this pre-specified substudy of an observational cohort study, 2,828 patients with AIS were enrolled from the Nanjing Stroke Registry between January 2017 and July 2021. Peripheral venous blood was collected from patients fasting for at least 8 h within 24 h of admission to gather information on the following parameters: neutrophil count, lymphocyte count, monocyte count, HDL level, and fasting blood glucose level. Then, the SIRI and NHR values were calculated. Following this, the correlation among SIRI, NHR, and modified Rankin Scale (mRS) scores 90 days after onset was examined via univariate and multivariate logistic analyses. Lastly, mediation analysis was performed to examine the relationship between systematic inflammatory response and study outcomes mediated by FBG. RESULTS: SIRI and NHR were both negatively correlated with clinical outcomes (p < 0.05). Logistic regression analysis revealed that SIRI and NHR were independently associated with poor outcomes after adjusting for potential confounders. Subgroup analyses further validated these correlations. Meanwhile, mediation analysis corroborated that FBG partially mediated the associations between SIRI and a poor prognosis at 90 days (indirect effect estimate = 0.0038, bootstrap 95% CI 0.001-0.008; direct effect estimate = 0.1719, bootstrap 95% CI 0.1258-0.2179). Besides, FBG also played a mediating role between NHR and poor outcomes (indirect effect estimate = 0.0066, bootstrap 95% CI 0.002-0.120; direct effect estimate = 0.1308, bootstrap 95% CI 0.0934-0.1681). CONCLUSION: Our study demonstrated that SIRI and NHR are positively associated with poor clinical and mortality outcomes at 90 days in AIS patients, which was partially mediated by FBG.

The relationship between systemic inflammation index, systemic immune-inflammatory index, and inflammatory prognostic index and 90-day outcomes in acute ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUND AND PURPOSE: To explore the association of systemic inflammatory index (SIRI), systemic immune-inflammatory index (SII) and inflammatory prognosis index (IPI) with 90d outcomes in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. METHODS: The patients who underwent intravenous thrombolysis were enrolled in the present study from September 2019 to December 2022. According to the relevant blood indexes obtained in 24 h after admission, the corresponding values of SIRI, SII and IPI were calculated. The correlation among SIRI, SII, IPI, and admission NIHSS scores was examined by Spearman correlation analysis. ROC curve analysis was conducted to determine the optimal cut-off value of SIRI, SII, IPI, and their corresponding sensitivity and specificity to evaluate their predictive value on admission for poor prognosis. To investigate whether high SIRI, SII, and IPI were independent predictors of poor outcomes within 90 days, variables with P-value < 0.05 during univariate analysis were included in multivariate analysis. RESULTS: Compared with the good outcome group, the poor outcome group had higher SIRI, IPI, and SII. Spearman correlation analysis showed that the SIRI, IPI, and SII levels significantly correlated with the admission NIHSS score (r = 0.338, 0.356, 0.427, respectively; Ps < 0.001). Univariate analysis and Multivariate logistic regression analysis revealed high SIRI, SII, and IPI values as independent risk factors for poor 90-day prognosis (OR = 1.09, 1.003 and 7.109, respectively). CONCLUSIONS: High SIRI, IPI, and SII values are correlated with poor 90d outcomes in AIS patients undergoing intravenous thrombolysis.

Relationship between mean blood pressure during hospitalization and clinical outcome after acute ischemic stroke.

OBJECTIVE: The optimal blood pressure (BP) targets for acute ischemic stroke are unclear. We aimed to assess the relationship between Mean BP and clinical outcomes during hospitalization. MATERIALS AND METHODS: We included 649 patients with Acute ischemic stroke (AIS) from December 2020 to July 2021. BP was measured daily, and mean blood pressure was calculated. Clinical events recorded within 90 days of randomization were: recurrent ischemic stroke, symptomatic intracranial hemorrhage, and death. The modified Rankin Scale (mRS) was used to measure primary outcomes 3 months after AIS. Logistic multiple regression analysis was performed by statistical software R. RESULT: There is a nonlinear U-shaped relationship between SBP and poor outcomes. This means higher SBP and lower SBP will increase the incidence of poor outcomes. The optimal mean SBP during hospitalization was 135-150 mmHg, and patients with SBP < 135mmhg OR 2.4 [95% Cl, (1.16 ~ 4.97)], P = 0.018; and > 150mmhg OR 2.04 [95% Cl, 1.02 ~ 4.08], p = 0.045 had a higher probability of poor outcomes. CONCLUSION: Our study shows that the optimal SBP of patients with AIS during hospitalization was 135-150 mmHg. The findings suggest that the relationship between mean SBP and 3-month functional outcome after AIS was U-shaped. Both higher SBP and lower SBP lead to poor prognosis in AIS patients.

Postmenopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease: A systematic review and time-response meta-analysis.

Hormone therapy continues to be a favourable option in the management of menopausal symptomatology, but the associated risk-benefit ratios with respect to neurodegenerative diseases remain controversial. The study aim was to determine the relation between menopausal hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in human subjects. A literature search was performed in PubMed/Medline, Cochrane collaboration, and Scopus databases from onset of the database to September 2019. Random-effects model was used to estimate pooled odd ratio (OR) and 95 % confidence intervals (CI). Subgroup analysis was performed based on the type and formulation of hormone. In addition, the time-response effect of this relationship was also assessed based on duration of hormone therapy. Associations between hormone therapy and Alzheimer's disease, dementia, and Parkinson's disease in menopausal women were reported in 28 studies. Pooled results with random effect model showed a significant association between hormone therapy and Alzheimer's disease (OR 1.08, 95 % CI 1.03-1.14, I2: 69 %). This relationship was more pronounced in patients receiving the combined estrogen-progestogen formulation. Moreover, a significant non-linear time-response association between hormone therapy and Alzheimer's disease was also identified (Coef1 = 0.0477, p1<0.001; Coef2 = -0.0932, p2<0.001). Similarly, pooled analysis revealed a significant association between hormone therapy and all-cause dementia (OR 1.16, 95 % CI 1.02-1.31, I2: 19 %). Interestingly, no comparable relationship was uncovered between hormone therapy as a whole and Parkinson's disease (OR 1.14, 95 % CI 0.95-1.38, I2: 65 %); however, sub-group analysis revealed a significant relationship between the disease and progestogen (OR 3.41, 95 % CI 1.23-9.46) or combined estrogen-progestogen formulation use (OR 1.49, 95 % CI 1.34-1.65). Indeed, this association was also found to be driven by duration of exposure (Coef1 = 0.0626, p1 = 0.04). This study reveals a significant direct relationship between the use of certain hormonal therapies and Alzheimer's disease, all-cause dementia, and Parkinson's disease in menopausal women. However, the association appears to shift in direct after five years in the context of Alzheimer's disease, adding further weight to the critical window or timing hypothesis of neurodegeneration and neuroprotection.

Correlation of Cerebral White Matter Lesions with Carotid Intraplaque Neovascularization assessed by Contrast-enhanced Ultrasound.

PURPOSE: Carotid atherosclerotic plaque is closely associated with cerebral white matter lesions (WMLs), while intraplaque neovascularization (IPN) contributes significantly to arterial remodeling and plaque vulnerability. In this study, we aim to evaluate the correlation of carotid IPN with cerebral WMLs. METHODS: The presence of IPN and WMLs were assessed by contrast-enhanced ultrasound (CEUS) and MRI respectively. IPN was evaluated utilizing semi-quantification visual grading scale and WMLs was divided according to Fazekas grading scale. We investigated the baseline data, Fazekas grades, and IPN grades among 269 participants. We explored the influences of each variable on Fazekas grades using ordinal logistic regression and evaluated the relationship between IPN grades and WMLs Fazekas grades. RESULTS: Increased age (OR: 1.06, P<0.001), hypertension (OR: 2.17, P=0.002), cerebral infarction (OR: 1.74, P=0.046), and elevated carotid IPN grading were significantly associated with aggravated Fazekas grades (grade 2 or 3). To be specific, people having grade 3, 2, and 1 carotid IPN were 25.84 (P<0.001), 10.64 (P<0.001), and 5.96 (P=0.010) times as likely to have elevated Fazekas grades compared with those who having grade 0 carotid IPN. CONCLUSION: Increased carotid IPN is independently correlated with aggravated cerebral WMLs.

Isolated hypoglossal nerve palsy from internal carotid artery dissection related to PKD-1 gene mutation.

BACKGROUND: Internal carotid artery dissection has been well recognized as a major cause of ischaemic stroke in young and middle-aged adults. However, internal carotid artery dissection induced hypoglossal nerve palsy has been seldom reported and may be difficult to diagnose in time for treatment; even angiography sometimes misses potential dissection, especially when obvious lumen geometry changing is absent. CASE PRESENTATION: We report a 42-year-old man who presented with isolated hypoglossal nerve palsy. High-resolution MRI showed the aetiological dissected internal carotid artery. In addition, a potential genetic structural defect of the arterial wall was suggested due to an exon region mutation in the polycystic-kidney-disease type 1 gene. CONCLUSIONS: Hypoglossal nerve palsy is a rare manifestations of carotid dissection. High-resolution MRI may provide useful information about the vascular wall to assist in the diagnosis of dissection. High-throughput sequencing might be useful to identify potential cerebrovascular-related gene mutation, especially in young individuals with an undetermined aetiology.

Recurrent risk of ischemic stroke due to Vertebrobasilar Dolichoectasia.

BACKGROUND: Patients with vertebrobasilar dolichoectasia usually have persistent hemodynamic abnormalities, and therefore, may bear an increased risk of stroke. This study aimed to identify risk factors for stroke recurrence in patients with vertebrobasilar dolichoectasia. METHODS: Patients with acute ischemic stroke were screened and evaluated for eligibility. Enrolled patients were followed via scheduled clinical visits or telephone interviews. Ischemic stroke recurrence was proposed with clinical symptoms and confirmed with cranial Magnetic Resonance Imaging or Computerized Tomography scans. Baseline characteristics and vascular geometry were compared between patients with and without stroke recurrence. Significant parameters were introduced into COX proportional hazard model to detect possible predictors of stroke recurrence. RESULTS: A total of 115 stroke patients with vertebrobasilar dolichoectasia were enrolled, of which 22 (19.1%) had recurrence during 22 ± 6 months follow-up. Basilar artery diameter ≥ 5.3 mm (HR = 4.744; 95% CI, 1.718-13.097; P = 0.003), diffuse intracranial dolichoectasia (HR = 3.603; 95% CI, 1.367-9.496; P = 0.010) and ischemic heart disease history (HR = 4.095; 95% CI, 1.221-13.740; P = 0.022) had increased risk of recurrence. CONCLUSIONS: Stroke patients with vertebrobasilar dolichoectasia may have a high risk of recurrence. Larger basilar artery diameter or diffuse intracranial dolichoectasia may increase the risk of recurrence.

Mean Platelet Volume as a Predictor for Restenosis After Carotid Angioplasty and Stenting.

BACKGROUND AND PURPOSE: Platelet aggregation plays a vital role in the development of in-stent restenosis (ISR) after carotid angioplasty and stenting (CAS). Mean platelet volume (MPV) has been suggested as an index of platelet reactivity. This study aimed to investigate the association between MPV and ISR in CAS patients. METHODS: A total of 261 patients with CAS were enrolled. MPV was measured before CAS procedure. Digital subtraction angiography, computed tomographic angiography, or duplex ultrasonography was performed at 6 months and annually after the procedure. ISR was defined as ≥50% stenosis in the treated lesion. Cox regression was used to identify predictors of ISR after CAS. RESULTS: Of the 261 patients with CAS, 46 (17.6%) were determined with ISR during a mean follow-up of 12.1±16.1 months (range, 2.1-120.7). On multivariate analysis, baseline MPV >10.1 fL (hazard ratio, 3.20; 95% confidence interval, 1.28-8.03), lesion length (hazard ratio, 1.05; 95% confidence interval, 1.02-1.08), residual stenosis (hazard ratio, 1.07; 95% confidence interval, 1.05-1.10), and baseline glucose (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02) were associated with ISR. CONCLUSIONS: Elevated MPV may be associated with ISR after CAS. Patients with high preprocedural MPV may benefit from an intensified antiplatelet therapy after CAS.

Argatroban for preventing occlusion and restenosis after extracranial artery stenting.

BACKGROUND/AIMS: Restenosis following extracranial artery stenting is a limitation that affects long-term outcomes. Effective and satisfying pharmacological strategies in preventing restenosis have not been established. This study aimed to evaluate whether argatroban, a direct thrombin inhibitor, could reduce the risk of in-stent restenosis after extracranial artery stenting. METHODS: One hundred and fourteen patients hospitalized between August 2010 and August 2011 were enrolled. Patients were randomly assigned to argatroban (n = 58) and blank control groups (n = 56). The patients in the argatroban arm were treated with 10 mg of intravenous argatroban twice daily 2 days before and 3 days after the stenting procedures. Patients were followed for 12 months after the procedure. During follow-up, restenosis and target revascularization were analyzed. Recurrent cerebrovascular and cardiovascular events and deaths were also compared between the groups. RESULTS: One patient in the stenting group withdrew immediately after the procedure due to unsuccessful stenting. Restenosis occurred in 4 patients (7.4%) in the argatroban group and in 11 patients (21.6%) in the control group during the 6- to 9-month angiographic follow-up period (p = 0.032). Nine months after the procedures, argatroban-treated patients had a trend towards a lower incidence of target revascularization compared with the controls (5.4 vs. 13.7%, p = 0.188). No major bleeding events or other adverse events occurred in the argatroban group. CONCLUSION: This pilot clinical trial is the first that uses argatroban to prevent restenosis in ischemic cerebrovascular disease, and suggests that intravenous administration of argatroban is effective and safe in preventing restenosis after extracranial artery stenting. Larger randomized controlled clinical trials are warranted.

Diffusion Tensor Imaging as a Tool to Evaluate the Cognitive Function of Patients With Vascular Dementia: A Meta-Analysis.

BACKGROUND: Vascular dementia (VaD) is the most common type of dementia secondary to Alzheimer's disease. The pathologic mechanism of VaD is complex, and VaD still lacks a more objective diagnosis and evaluation method. Diffusion tensor imaging (DTI) can better detect the organizational structure and functional characteristics compared with any other diagnosis methods. Therefore, DTI has broad application in evaluating the severity and prognosis of VaD. This study aimed to assess the value of DTI in evaluating the cognitive function of patients with VaD. METHODS: Authors searched Pubmed, Embase, and Cochrane Library, using the search terms, such as "diffusion tensor imaging," "DTI," "Vascular Dementia," "Arteriosclerotic Dementia," "Cognition," and "Cognitive." A voxel-based meta-analysis combined with quality statistics was performed, using the anisotropic effect-size version of the signed differential mapping method. RESULTS: A total of 8 case-control studies were included in this meta-analysis. The sample size of patients ranged from 35 to 60, including 166 patients in the VaD group and 177 healthy individuals. The DTI imaging of the brain tissue of VaD patients was significantly different from that of healthy individuals. CONCLUSIONS: DTI imaging of the brain tissue of VaD patients was clearly different from that of healthy controls. Therefore it may be feasible to use DTI imaging as a diagnostic method for VaD.

Schaftoside improves cerebral ischemia-reperfusion injury by enhancing autophagy and reducing apoptosis and inflammation through the AMPK/mTOR pathway.

BACKGROUND: As a flavonoid compound, schaftoside (SS) possesses a wide range of pharmaceutical activities. Nonetheless, it is unclear whether SS has a neuroprotective effect in cerebral ischemia-reperfusion injury (CI/RI). OBJECTIVES: To examine the neuroprotective effect of SS in CI/RI and explore the underlying mechanism. MATERIAL AND METHODS: An in vivo middle cerebral artery occlusion (MCAO) was used to simulate CI/RI in rats. Oxygen glucose deprivation/reperfusion (OGD/R) of HT22 cells was used to establish a cellular model of CI/RI in vitro. Pathological changes were evaluated with hematoxylin and eosin (H&E) staining, apoptosis was measured using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and flow cytometry, and inflammatory factors were assessed using enzyme-linked immunosorbent assay (ELISA). Protein expression was detected using western blot or immunofluorescence. RESULTS: Our results indicated that SS attenuated CI/RI by improving neurologic deficits and reducing brain edema. Moreover, SS treatment blocked apoptosis and inflammation and enhanced autophagy in MCAO rats. Schaftoside was found to amplify the activation of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway induced by MCAO. Similarly, SS pretreatment increased cell viability and autophagy, and reduced apoptosis and inflammation in OGD/R-induced HT22 cells. The OGD/R enlarges the p-AMPK/AMPK ratio while restricting the p-mTOR/mTOR ratio, and it was found that SS further enhanced the effect of OGD/R on the AMPK/mTOR pathway. Rapamycin promoted the effect of SS on OGD/R-induced HT22 cells, while compound C produced the opposite results. Mechanistically, SS promoted autophagy and reduced apoptosis and inflammation through the regulation of the AMPK/mTOR signaling pathway. CONCLUSIONS: The obtained results showed that SS protected against CI/RI through an autophagy-mediated AMPK/mTOR pathway when accessed in vitro and in vivo.

High-Performance Fe-Based Prussian Blue Cathode Material for Enhancing the Activity of Low-Spin Fe by Cu Doping.

Iron-based Prussian blue (FeHCF) has great application potential in the large-scale production of sodium-ion (Na+) batteries because of its high theoretical capacity and abundant Fe ore resources. However, the Fe(CN)6 vacancies and crystal water seriously affect the electrochemical performance. Herein, a Cu-doped FeHCF (Cu-FeHCF) cathode material is successfully prepared directly by a coprecipitation method. After Cu doping, the monoclinic structure and the quasi-cubic morphology are retained, but the electrochemical performance is significantly improved. In addition to few Fe(CN)6 vacancies and low crystal water, the improved performance is also related to the enhanced electrochemical activity of low-spin Fe and the stabilizing effect of Cu on the crystal structure. Moreover, Cu doping also controls the side reaction to a certain extent. As a result, after Cu doping, the initial discharge capacity is enhanced from 107.9 to 127.4 mA h g-1 at 100 mA g-1, especially the capacities contributed by low-spin Fe increase from 30.0, 21.7, and 16.7 mA h g-1 to 48.8, 45.4, and 43.7 mA h g-1 for the first three cycles, respectively. Even at 2 A g-1, Cu-FeHCF still has a promising initial capacity of 82.3 mA h g-1 and only a 0.047% capacity decay rate for each cycle over 500 cycles. Therefore, Cu-FeHCF shows excellent application potential in the field of Na+ energy storage batteries.

Synergistic Modification of Fe-Based Prussian Blue Cathode Material Based on Structural Regulation and Surface Engineering.

The Fe-based Prussian blue (Fe-PB) composite is considered as one of the most potential cathode materials for sodium-ion batteries because of its abundant iron resources and high theoretical capacity. However, the crystal water and vacancy in the Fe-PB structure will lead to poor capacity and cycle stability. In this work, a Cu-modified Fe-PB composite (FeCu-PB@CuO) is successfully prepared through regulating the Fe-PB structure by Cu doping and engineering the surface by CuO coating. The density functional theory calculation results confirm that Cu preferentially replaces FeHS in the Fe-PB lattice and Cu doping reduces the bandgap. Our experiment results reveal that CuO coating can provide more active sites, inhibit side reactions, and potentially enhance the activity of FeHS. Due to the synergistic effect of Cu doping and CuO coating, FeCu-PB@CuO has a considerable initial discharge capacity of 123.5 mAh g-1 at 0.1 A g-1. In particular, at 2 A g-1, it delivers an impressive initial capacity of 84.3 mAh g-1, and the capacity decreasing rate of each cycle is only 0.02% over 1500 cycles. Therefore, the synergistic modification strategy of metal ion doping and metal oxide coating has tremendous application potential and can be extended to other electrode materials.

Intranasal ginsenoside Rb1 targets the brain and ameliorates cerebral ischemia/reperfusion injury in rats.

Ginsenoside Rb1 (GRb1) has been shown to benefit many central nervous system (CNS) disorders, including stroke. However, its bioavailability is low after oral administration due to poor absorption. Intranasal administration has been considered as an effective method for central nervous system drug delivery for its brain-targeting effect. Here, whether intranasal GRb1 could ameliorate cerebral ischemia/reperfusion injury was investigated. First, the concentration of GRb1 in brain tissues and plasma after intranasal and intravenous delivery was calculated using HPLC-MS/MS methods in male Sprague-Dawley rats (250±10 g). Intranasal GRb1 was considered brain-targeting if the value of the drug targeting index (DTI) was greater than 1. Rats were subjected to 1.5 h middle cerebral artery occlusion (MCAO) and were killed 24 h after reperfusion. The neuroprotective effects were measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Nissl staining. Immunoblotting of LC3 and Beclin 1, crucial autophagy-related proteins, was used to monitor the state of autophagy. With a local bioavailability of 10.28-32.48% and DTI of 7.35-23.22 in different brain regions, intranasal GRb1 was determined to be brain-targeting. Less infarct volume and more intact neuronal structure were observed in the GRb1 group. GRb1 also restored the elevation of LC3 and Beclin 1. Our work suggests that intranasal GRb1 exerts brain-targeting effects and that a single dose of intranasal GRb1 immediately after MCAO ameliorates ischemia/reperfusion insult. Autophagy is involved in these beneficial effects.

[Plasma homocysteine levels in ischemic stroke patients with obstructive sleep apnea].

OBJECTIVE: To investigate the association of plasma homocysteine and OSA (obstructive sleep apnea) syndrome in ischemic stroke (IS). METHODS: A total of 92 male IS patients were classified by apnea hypopnea index (AHI) into 2 groups: non-OSA group (AHI < 5/h) and OSA group (AHI > or = 5). All patients were tested for plasma homocysteine when polysomnography was finished at (14 +/- 2) d after the onset of IS. RESULTS: The mean level of homocysteine was significantly higher in the OSA group than that in the non-OSA group (17 +/- 5 vs 11 +/- 3 micromol/L, P < 0.01). Pearson correlation analysis revealed a positive correlation between the homocysteine level and the severity of AHI (r = 0.482, P < 0.01). Further multiple linear regression analysis showed that AHI and folate were independent predictors of homocysteine level (R2 = 0.553, P < 0.01, beta for AHI = 0.671, beta for folate = -0.256). CONCLUSION: The severity of OSA is significantly associated with an elevated level of homocysteine in IS patients. And this association is independent of other causative factors of an elevated level of homocysteine.

Neuroprotective effect of Umbelliferone against Cerebral ischemia/Reperfusion induced neurological deficits: in-vivo and in-silico studies.

Inflammatory pathway is the significant marker of neuro-inflammation and plays a significant role in the expansion of cerebral ischemia/reperfusion injury. Umbelliferone (UF), 7-hydroxy coumarin, has been already proved for its anti-inflammatory and anti-oxidative effects against ischemic brain injury in the rodent model, but its underlying pharmacological mechanism for neuro-protection remain unclear. In this study, we try to explore the neuro-protective effect of umbelliferone against ischemia/Reperfusion induced neurological deficits in rats and explore the underlying mechanism. Inserting thread into the middle cerebral artery was used to induce the ischemic stroke model. The rats were treated with the umbelliferone (5, 10 and 20 mg/kg) for 14 days prior to the ischemic stroke. At the end of the experimental study, brain infarction volume, neurological score, brain edema, pro-inflammatory cytokines, inflammatory mediator were estimated in the region of brain and serum. The mRNA expression of Toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88), Fas and FasL were also estimated at the end of the study. Dose dependently treatment of umbelliferone down-regulated the neurological score, brain infarction, inflammatory mediator (TNF-α, IL-1ß, IL-6, COX-2, NF-kB and PGE2) in the serum and brain tissue as compared to I/R induced control group rats. Umbelliferone also reduced the expression of TRL4, MyD88, Fas and FasL as compared to I/R control group rats. Umbelliferone also decreased the level of nuclear factor kappa B (NF-kB) compared to MACO control group rats. Collectively, the obtained result showed that the umbelliferone protected the brain against the ischemic injury in the rats through the inhibition of inflammatory pathway.Communicated by Ramaswamy H. Sarma.

The relationship between intracranial arterial dolichoectasia and intracranial atherosclerosis.

OBJECTIVE: We aimed to investigate the relationship between intracranial arterial dolichoectasia (IADE) and intracranial atherosclerosis (ICAS). METHODS: Patients with acute ischemic stroke were screened via the Nanjing Stroke Registry Program. Patients were diagnosed with IADE (diameter, height of bifurcation, and laterality of basilar artery) based on magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) results. Intracranial atherosclerosis was defined as a ≥50 % diameter reduction in internal carotid artery, middle cerebral artery, posterior cerebral artery, or anterior cerebral artery on MRA, computed tomography angiography, or digital subtraction angiography. We also evaluated the presence and degree of white matter changes and lacuna infarctions on MRI. RESULTS: Of the 469 enrolled patients, 61 (13 %) had IADE. Patients with IADE were older (64.1 ± 9.9 vs. 59.6 ± 11.4 years, P = 0.004) and had a higher prevalence of hypertension (78.7 % vs. 61.0 %, P = 0.008) than patients without IADE. Patients with ICAS were older (62.6±10.5 vs 58.1±11.6 years, P < 0.001), had higher prevalence of hypertension (72.9 % vs. 55.0 %, P < 0.001) and a previous history of stroke (21.6 % vs. 9.2 %, P < 0.001), had higher levels of serum low-density lipoprotein cholesterol (2.57±0.82 vs. 2.31±0.86mmol/l P = 0.002), and had high counts of white blood cells (7.90±3.29 vs 7.10±2.44, P = 0.004). No association was detected between IADE and extracranial carotid atherosclerosis [odds ratio (OR)=0.618; 95 % confidence interval (CI), 0.280-1.367; P = 0.235]. After adjusting for age, sex, hypertension, and ischemic heart disease, patients with IADE had a lower ICAS rate than that in those without IADE (OR 0.417, 95 % CI, 0.213-0.816, P = 0.011). Unlike patients with ICAS, patients with IADE were more likely to have infratentorial stroke lesions (OR=2.952, 95 % CI, 1.207-7.223, P = 0.018), multi-lacuna (OR=2.142, 95 % CI, 1.158-3.964, P = 0.015), and white matter changes (OR = 2.782; 95 % CI, 1.522-5.085, P = 0.001). CONCLUSIONS: IADE was associated with advanced age, hypertension, multi-lacuna, and white matter changes but was not associated with ICAS.

Analysis of miRNA and mRNA expression in the dysregulation of insulin secretion in MIN6 cells exposed to microcystin-leucine-arginine.

Microcystin -leucine-arginine (MC-LR), produced by freshwater cyanobacteria, is a potential pancreatic ß-cell toxin. In this study, the function of the mouse pancreatic ß-cell line, MIN6, was evaluated after MC-LR exposure, and the underlying molecular mechanisms were explored. Exposure to MC-LR for 24 h was found to inhibit cell viability and impair insulin secretion. Such findings indicate that ß-cell function would be impaired following MC-LR treatment. The microarray results revealed altered miRNA and mRNA expression profiles that might be responsible for the abnormal function of MIN6 cells. Further, miRNA-gene network analysis demonstrated that miR-29b-3p, miR-6967-5p, miR-3473, miR-7061-5p, Xkr4, Tmem178b, Scp2, Ypel2, and Kcnj11 are key miRNAs and genes in the MC-LR-induced MIN6-cell toxicity. The altered expression levels of several miRNAs (e.g., miR-320-5p, miR-770-5p, miR-99a-3p, and miR-375-5p) and genes (e.g., Pklr and Gpd2) involved in insulin secretion or the onset of diabetes were also identified in MIN6 cells after treatment with MC-LR. Collectively, these findings provide evidence of the toxic effects of MC-LR on ß-cells and the underlying molecular mechanisms of its glycometabolism toxicity. MCs may thus possibly play an important role in the development of diabetes mellitus in humans.

Effects of brain-derived neurotrophic factor on local inflammation in experimental stroke of rat.

This study was aimed to investigate whether brain-derived neurotrophic factor (BDNF) can modulate local cerebral inflammation in ischemic stroke. Rats were subjected to ischemia by occluding the right middle cerebral artery (MCAO) for 2 hours. Rats were randomized as control, BDNF, and antibody groups. The local inflammation was evaluated on cellular, cytokine, and transcription factor levels with immunofluorescence, enzyme-linked immunosorbent assay, real-time qPCR, and electrophoretic mobility shift assay, respectively. Exogenous BDNF significantly improved motor-sensory, sensorimotor function, and vestibulomotor function, while BDNF did not decrease the infarct volume. Exogenous BDNF increased the number of both activated and phagocytotic microglia in brain. BDNF upregulated interleukin10 and its mRNA expression, while downregulated tumor necrosis factor α and its mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B. BDNF antibody, which blocked the activity of endogenous BDNF, showed the opposite effect of exogenous BDNF. Our data indicated that BDNF may modulate local inflammation in ischemic brain tissues on the cellular, cytokine, and transcription factor levels.

The correlation between novel peripheral blood cell ratios and 90-day mortality in patients with acute ischemic stroke.

BACKGROUND: We aimed to investigate the correlation between the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), platelet-to-white blood cell ratio (PWR) and 90-day mortality in patients with acute ischemic stroke (AIS). METHODS: We retrospectively included 633 patients with AIS from January 2017 to May 2018. The correlation between each indicator and the degree of neurologic deficit was assessed. Kaplan-Meier survival curves based on blood cell ratios were used to analyze the 90-day survival rate of patients with AIS. RESULTS: A total of 663 patients with AIS were enrolled, of which 24 (3.6%) experienced recurrence and 13 (2.0%) died. NLR>3.23 (odds ratio; OR = 2.236; 95% confidence interval [CI], 1.472-3.397; P<0.001), PNR<31.14 (OR = 0.471; 95% CI, 0.297-0.749; P = 0.001), and PWR<20.62 (OR = 0.498; 95% CI, 0.309-0.800; P = 0.004) were associated with an unfavorable 90-day prognosis. NLR>3.23, PWR<20.62, and PNR<31.14 were associated with an increased risk of 90-day mortality. CONCLUSION: PNR, PWR, and NLR were associated with the 90-day mortality of patients with AIS. Patients with high NLRs or low PWRs and PNRs may have a greater risk of mortality than other patients. These clinical indicators may help clinicians judge unfavorable prognosis early and implement the appropriate interventions.