[Burden of disease for stroke attributable to ambient PM_(2.5) exposure in China 1990-2019].

OBJECTIVE: To analyze the trend of disease burden of stroke attributable to ambient PM_(2.5) exposure among Chinese residents from 1990 to 2019. METHODS: On the basis of the data of global burden of disease study 2019(GBD 2019) in China, the burden of stroke attributable to the ambient PM_(2.5) exposure in China from 1990 to 2019 were analyzed using the number and rate of deaths, disability adjusted life year(DALY), DALY rate and its standardized rate and estimated annual percentage change(EAPC). RESULTS: In 2019, 24.7% of stroke deaths among people aged 15 years and above in China were due to ambient PM_(2.5) exposure. Compared with 1990, in China the number of stroke deaths and mortality attributable to ambient PM_(2.5) exposure increased to 541 800 and 39.08/100 000, respectively in 2019, and the attributable DALY and DALY rates increased by 2.07% and 1.56%, respectively, in 2019. And the attributable DALY and DALY in males were higher than those in females, and they were all increasing with aging. The attributed standardized mortality and DALY rates in China were higher than those of the global and different socio-demographic index(SDI) regions, and showed an increasing trend, with EAPCs of 1.11(95% CI 0.47-1.75) and 1.11(95% CI 0.53-1.69), respectively. CONCLUSION: The burden of stroke disease due to ambient PM_(2.5) exposure is heavy in China, with differences in gender and age, and is higher than those of the global and different SDI regions.

Activation of FAK/Rac1/Cdc42-GTPase signaling ameliorates impaired microglial migration response to Aß42 in triggering receptor expressed on myeloid cells 2 loss-of-function murine models.

Mutation of Triggering receptor expressed on myeloid cells 2 (TREM2) impairs the response of microglia to amyloid-ß (Aß) pathology in Alzheimer's disease (AD), although the mechanism governing TREM2-regulated microglia recruitment to Aß plaques remains unresolved. Here, we confirm that TREM2 mutation attenuates microglial migration. Then, using Trem2-/- mice and an R47H variant mouse model for AD generated for this study, we show that TREM2 deficiency or the AD-associated R47H mutation results in inhibition of FAK and Rac1/Cdc42-GTPase signaling critical for cell migration. Intriguingly, treatment with CN04, a Rac1/Cdc42-GTPase activator, partially enhances microglial migration in response to oligomeric Aß42 in Trem2-/- or R47H microglia both in vitro and in vivo. Our study shows that the dysfunction of microglial migration in the AD-associated TREM2 R47H variant is caused by FAK/Rac1/Cdc42 signaling disruption, and that activation of this signaling ameliorates impaired microglial migration response to Aß42 , suggesting a therapeutic target for R47H-bearing patients with high risk of AD.

Silencing MicroRNA-155 Attenuates Kainic Acid-Induced Seizure by Inhibiting Microglia Activation.

OBJECTIVE(S): Neuroinflammation is an important contributor to the development of seizures and epilepsy. Micro-RNA-155 (miR-155) plays a critical role in immunity and -inflammation. This study aims to explore the function of miR-155 and miR-155-mediated inflammation in epilepsy. METHODS: About 8-week-old male C57BL/6 mice were administered an intraperitoneal injection (i.p.) of kainic acid (KA) (15 mg/kg) or saline. The mice in the KA group developing acute seizure were further subjected to intracerebroventricular injection (i.c.v.) of antagomir negative control (NC) or miR-155 antagomir. Animal behavior was observed according to Racine's scale, and electroencephalographs were recorded. Primary microglia were cultured and treated with antagomir NC or antagomir. Whole-cell electrophysiological recording was conducted to detect the spontaneous EPSCs and IPSCs in the neurons treated with different conditioned medium from those microglia. miR-155 were detected by qRT-PCR in those models, as well as in the brain or blood from epileptic patients and healthy controls. RESULTS: miR-155 was abundantly expressed in glial cells compared with neurons, and its expression was markedly elevated in the brain of epilepsy patients and KA-induced seizure mice. Silencing miR-155 attenuated KA-induced seizure, abnormal electroencephalography, proinflammatory cytokine expression, and microglia morphology change. Moreover, conditioned media from KA-treated microglia impaired neuron excitability, whereas conditioned media from KA and miR-155 antagomir co-treated microglia had no such effects. Finally, miR-155 levels were significantly higher in the blood of epilepsy patients than those of healthy controls. CONCLUSION(S): These findings demonstrate that aberrant upregulation of miR-155 contributes to epileptogenesis through inducing microglia neuroinflammation.

High Stress Hyperglycemia Ratio Predicts Poor Outcome after Mechanical Thrombectomy for Ischemic Stroke.

OBJECTIVE: The present study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and outcome at 3 months after mechanical thrombectomy (MT) for acute occlusion in the anterior circulation. METHODS: Data from 160 consecutive patients with large vessel occlusion in the anterior circulation who underwent MT from May 2013 to March 2018 were retrospectively reviewed. SHR was calculated as the fasting glucose concentration divided by the estimated average glucose concentration (derived from the glycosylated hemoglobin level). Patients were dichotomized into 2 groups in accordance with the median SHR. Univariate and multivariate analyses were used to identify predictors of functional outcome. Good and poor outcomes were defined as modified Rankin Scale scores of 0-2 and 3-6, respectively. RESULTS: patients with unfavorable outcome had significantly higher levels of SHR than those with favorable outcome (median in SHR = 1.02 versus .84, P = .000). The median SHR was .96. Univariate analysis showed that significantly more patients with a poor outcome had SHR ≥ .96 compared with those with a good outcome (65.2% versus 31.0%, P = .000). After adjusting for potential covariates, Increased SHR (odds ratio [OR] 6.97, 95% confidence intervals [CI] 1.22-39.65, P = .029, for continuous SHR levels) and SHR ≥ .96 (OR 3.12, 95% CI 1.39-6.96, P = .006) remained independent predictors of poor outcome. CONCLUSIONS: Increased SHR is strongly correlated with poor outcome at 3 months after MT for proximal artery occlusion in the anterior circulation.

Protective Role of L-3-n-Butylphthalide in Cognitive Function and Dysthymic Disorders in Mouse With Chronic Epilepsy.

Epilepsy is a common neurological disease with recurrent seizures and neurobehavioral comorbidities, including cognitive impairment and psychiatric disorders. Recent studies suggest that L-3-n-butylphthalide (NBP), an extract from the seeds of Apium graveolens Linn. (Chinese celery), ameliorates cognitive dysfunction in ischemia and/or Alzheimer's disease animal models. However, little is known about the role of NBP in epilepsy and the associated comorbidities. Here, using a pilocarpine-induced chronic epileptic mouse model, we found that NBP supplement not only alleviated seizure severity and abnormal electroencephalogram, but also rescued cognitive and emotional impairments in these epileptic mice. The possible underlying mechanisms may be associated with the protective role of NBP in reducing neuronal loss and in restoring the expression of neural synaptic proteins such as postsynaptic density protein 95 (PSD95) and glutamic acid decarboxylase 65/67 (GAD65/67). In addition, NBP treatment increased the transcription of neuroprotective factors, brain-derived neurotrophic factor and Klotho. These findings suggest that NBP treatment may be a potential strategy for ameliorating epileptogenesis and the comorbidities of cognitive and psychological impairments.

Research on Acute Toxicity and Pharmacodynamics of Jinyulian Oral Solution.

A research on Jinyulian Oral Solution was conducted and the objectives were to discover its possible acute toxicity and antibacterial effects when used in vitro and in vivo. Regarding the acute toxicity test, Kunming mice were fed a maximum amount of the solution as their stomachs could hold, i.e., 40 mL kg(-1). To ascertain the minimum inhibitory concentration (MIC) of the solution, two types of germs, i.e., Staphylococcus aureus and Escherichia coli, were selected and tube dilution method was adopted. An antibacterial experimental model relying on animals' body was developed for the researchers to observe the solution's antibacterial effects. Test results showed that no abnormalities were discovered within 14 days after the initial date of testing and the mice grew as normal when fed with an amount of the solution 250 times of a normal clinical doze (In this case a man was assumed to weigh 60 kg.) and that the solution demonstrated obvious antibacterial effects on the two types of selected germs. The respective measured MIC50 and MIC90 values of the two germs were 3.2, 12.8, 6.4, and 25.6 mg L(-1). Therefore, it is reasonable to conclude that Jinyulian Oral Solution possesses no acute toxicity but obvious antibacterial effects on the two before-mentioned germs.

Influence of cleaning process on the laser-induced damage threshold of substrates.

The cleaning process of optical substrates plays an important role during the manufacture of high-power laser coatings. Two kinds of substrates, fused silica and BK7 glass, and two cleaning processes, called process 1 and process 2 having different surfactant solutions and different ultrasonic cleaning parameters, are adopted to compare the influence of the ultrasonic cleaning technique on the substrates. The evaluation standards of the cleaning results include contaminant-removal efficiency, weak absorption, and laser-induced damage threshold of the substrates. For both fused silica and BK7, process 2 is more efficient than process 1. Because acid and alkaline solutions can increase the roughness of BK7, process 2 is unsuitable for BK7 glass cleaning. The parameters of the cleaning protocol should be changed depending on the material of the optical components and the type of contamination.

Contact between submicrometer silica spheres.

Recently, the scope of the investigation of the deformation mechanism extended to the micrometer and submicrometer regimes. The sphere-substrate contact method was usually used because it is rather difficult to make two micrometer or submicrometer spheres contact each other precisely. Here, we used the sphere-sphere contact method via a novel, simple process to investigate the deformation of spheres. The silica particle size ranges from 400 to 900 nm. Traditionally, the harder the particle, the smaller both the contact radius and the adhesion force. Therefore, it is widely accepted that silica particles should undergo elastic deformation, but we found that silica particles underwent plastic deformation rather than elastic deformation because of van der Waals interaction. The contact radii were observed by scanning electron microscopy (SEM).

[Determination of hedychenone in Hedychium yunnanense].

OBJECTIVE: To establish an HPLC method for determination of hedychenone in Hedychium yunnanense. METHOD: C18 Chromatographic column was used, acetonitrile-water (9:1) as mobile phase, at flow rate of 1.0 mL x min(-1): The wavelength for detection was 235 nm. RESULT: The linear range of hedychenone was 5.92-29.6 microg x mL(-1)(r = 0.9999). The average recovery was 99.0%, RSD of precision was less than 2%. CONCLUSION: The method is simple, effective and feasible, and can be used to evaluate the quality of the herb.