Investigation of vascular risk factor control and secondary prevention medication compliance in acute ischemic stroke.

Objectives: This study aimed to investigate the management of vascular risk factors, with a specific focus on understanding the various factors affecting risk factor control through an in-depth analysis of clinical data and a longitudinal follow-up of patients who have experienced ischemic strokes. Methods: A total of 1,572 participants were included in the analysis. We assessed thresholds for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin (HbA1c) levels to uncover the contextual conditions and factors affecting vascular risk factor control. Moreover, the study also scrutinized medication compliance at intervals of 3, 6, and 12 months post-onset. Logistic regression was used to adjust for confounding factors. Results: At 3, 6, and 12 months, BP,LDL, hemoglobin control targets were achieved in 50.7, 51.8, and 50.6%; 51.5, 59.4, and 50.6%; 48.1, 44.0, and 48.4%,respectively. Notably, age was associated with the achievement of BP control (odds ratio [OR], 0.96; 95% confidence intervals [CI], 0.94-0.98; p < 0.0001). Ethnic minorities (OR, 4.23; 95% CI, 1.19-15.09; p = 0.02) and individuals with coronary heart disease (OR, 0.5; 95% CI, 0.3-1.0; p = 0.05) experienced decreased BP control ratios. A previous history of stroke (OR, 1.7; 95% CI, 1.0-2.8; p = 0.03) and unrestricted alcohol consumption (OR, 3.3; 95% CI, 1.0-11.1; p = 0.05) was significantly associated with the achievement of lipid control. Furthermore, lifestyle modifications were significantly correlated with the achievement of BP control (OR, 0.19; 95% CI, 0.12-0.30; p < 0.01), blood glucose control (OR, 0.03; 95% CI, 0.01-0.08; p < 0.01), and blood lipid control (OR, 0.26; 95% CI, 0.16-0.42; p < 0.01). The absence of regular physical activity was associated with lower rates of glycemic (OR, 0.14; 95% CI, 0.06-0.36; p < 0.01) and lipid controls (OR, 0.55; 95% CI, 0.33-0.90; p = 0.01). Over time, overall medication compliance declined. Conclusion: Within the cohort of patients under medication, the compliance rate concerning vascular risk factors remains unsatisfactory. Attention should be paid to compliance with secondary prevention medications and enhance the control of vascular risk factors, as compliance emerges as the key to effective prevention.

Huanglian Jiedu decoction alleviates neurobehavioral damage in mice with chronic alcohol exposure through the RAS-RAF-MEK-ERK pathway.

Objective: Long-term alcohol consumption can cause organic damage to the brain, resulting in mental and nervous system abnormalities and intellectual impairment. Huanglian Jiedu decoction (HLJDD) is the classic representative of clearing heat and detoxifying. This study aimed to explore the effects and possible mechanisms of HLJDD on brain injury in chronic alcohol-exposed mice. Methods: The alcohol-exposed mice were treated with different doses of HLJDD to observe behavioral changes, hippocampal Aß1-42 deposition, number and ultrastructural changes of neurons in the hippocampus and prefrontal cortex, and expressions of synaptic proteins. On this basis, transcriptome sequencing was used to analyze the differentially expressed genes in different treatment groups, and functional enrichment analysis was performed. Then, WB and RT-PCR were used to verify the expression of the pathway. Results: Chronic alcohol exposure reduced body weight in mice, led to motor cognitive impairment, increased Aß1-42 in the hippocampus, decreased the number of neurons in the hippocampus and prefrontal cortex, and the expression of PSD95 and SYN in the hippocampus. HLJDD significantly improved the cognitive dysfunction of mice and alleviated the damage of the hippocampus and prefrontal cortex. Transcriptome sequencing results showed that the regulatory effects of HLJDD on chronic alcohol-exposed mice may be related to the RAS pathway. Further experiments confirmed that chronic alcohol exposure caused a significant increase in protein and gene expressions of the RAS-RAF-MEK-ERK pathway in mouse, and this activation was reversed by HLJDD. Conclusion: HLJDD may ameliorate brain damage caused by chronic alcohol exposure by regulating the RAS-RAF-MEK-ERK pathway.

Neuroprotective effects of morroniside from Cornus officinalis sieb. Et zucc against Parkinson's disease via inhibiting oxidative stress and ferroptosis.

Parkinson's disease (PD) is the second most common neurodegenera-tive disorder after Alzheimer disease accompanied by the death of dopaminergic neurons and brain nigrostriatal mitochondrial damage in the elderly population. The features of the disease include tremor, rigidity, postural instability, and motor retardation. The pathogenesis of Parkinson's disease is complex, and abnormal lipid metabolism resulting in ferroptosis due to the excessive accumulation of free radicals from oxidative stress in the substantia nigra of the brain was thought to be one of the factors causing the disease. Morroniside has been reported to have significant neuroprotective effects, although it has not been studied in PD. Therefore, this study focused on determining the neuroprotective effects of morroniside (25, 50, and 100 mg/kg) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg)-induced mice models of PD and explored 1-methyl-4-phenylpyridinium MPP+-induced ferroptosis in PC12 cells. Morroniside restored impaired motor function in the PD mice models while reducing neuronal injury. The activation of nuclear factor erythroid 2-related factor 2/antioxidant response elements (Nrf2/ARE) by morroniside promoted antioxidation, the content of reducing agent glutathione (GSH) increased, and the level of the lipid metabolite malondialdehyde (MDA) decreased. Notably, morroniside inhibited ferroptosis in substantia nigra of the brain and PC12 cells, reduced iron levels, and upregulated the expression of the iron-regulated proteins glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH-1), and ferroportin (FPN). More importantly, morroniside repaired the mitochondrial damage, restored the mitochondrial respiratory chain, and inhibited the production of reactive oxygen species (ROS). These data indicated that morroniside could activate the Nrf2/ARE signaling pathway to increase the antioxidant capacity, thereby inhibiting abnormal lipid metabolism and protecting dopaminergic neurons from ferroptosis in PD.

Biomarker of early neurological deterioration in minor stroke and proximal large vessel occlusion: A pilot study.

Background: Plasma neurofilament light chain (pNFL) represents one of the scaffolding proteins of central nervous system axonal injury. The aim of this study was to evaluate pNFL as a predictive biomarker for early neurological deterioration (END) in medically managed patients with large vessel occlusion (LVO) and mild presentation (NIHSS < 6). Methods: This retrospective study was developed from a prospectively collected stroke database, which was conducted at a large academic comprehensive stroke center in western China. Patients who first presented with acute ischemic stroke (AIS) within 24 h of symptom onset were continuously included. Stroke severity was analyzed at admission using the NIHSS score. The pNFL drawn on admission was analyzed with a novel ultrasensitive single-molecule array. Results: Thirty-nine consecutive patients were included in the analysis, and 19 (48.72%) patients experienced END. Patients who experienced END had significantly higher pNFL levels (mean, 65.20 vs. 48.28 pg/mL; P < 0.001) and larger infarct volume (mean, 15.46 vs. 9.56 mL; P < 0.001). pNFL was valuable for the prediction of END (OR, 1.170; 95% CI, 1.049-1.306; P = 0.005), even after adjusted for age and sex (OR, 1.178; 95% CI, 1.038-1.323; P = 0.006), blood sampling time, baseline NIHSS, TOAST classification, and infarct volume (OR, 1.168; 95% CI, 1.034-1.320; P = 0.012). The area under the ROC curve was 85.0% (95% CI, 0.731-0.970; P < 0.001). The sensitivity was 73.7%, and the specificity was 80%. Conclusion: END in minor stroke with LVO was distinguishable from those without END following the determination of pNFL in the blood samples within 24 h of onset. The pNFL is a promising biomarker of END in minor stroke with LVO. Clinical trial registration: ChiCTR1800020330.

High Actin Expression in Thrombus of Acute Ischemic Stroke Can Be a Biomarker of Atherothrombotic Origin Stroke.

Background: As the treatment target, the imaging information and histologic characteristics of the thrombus may differ according to the stroke subtype. This study aimed to provide the correlative study of stroke etiology with the non-contrast CT, and histological composition of retrieved clots in acute ischemic stroke (AIS). Materials and Methods: A total of 94 patients with AIS who underwent the endovascular treatment with successfully retrieved clots from January 2017 to October 2020 were enrolled in the present study. Histological analysis was performed using hematoxylin and eosin (H&E) staining and immunostaining with CD3, CD20, CD105, and actin antibodies. CT obtained at the patients' admission was to measure the attenuation and volume of all thrombus. Results: A total of 94 subjects were included in this study. Fifty-six patients were classified as cardioembolic (CE), and 38 were classified with large-artery atherosclerosis (LAA). The subjects with LAA tend to exhibit higher actin and CD105 levels, and lower Hounsfield Unit (HU) values than subjects with CE. After adjusting for confounders, the actin was positively correlated with CD105 but not with HU values. Logistics regression shows actin was valuable for the prediction of LAA (OR, 1.148; 95% CI, 1.075-1.227; p < 0.001), even adjusted for age, sex, and intervention type (OR, 1.129; 95% CI, 1.048-1.216; p = 0.001), CT density and CD105 (OR, 1.161; 95% CI, 1.056-1.277; p = 0.002). Actin levels have a strong accuracy in differentiating LAA from CE, especially combined with CT density and CD105, which yielded a sensitivity of 63.2%, a specificity of 89.3%, with the area under the curve (AUC) at 0.821 (95% CI, 0.731-0.912). Conclusion: Our findings suggest that actin's level was a major factor differentiating atherothrombotic origin strokes from the cardioembolic stroke. Clinical Trial Registration: ChiCTR2100051173.

Plasma Neurofilament Light Chain Is Associated with Cognitive Impairment after Posterior Circulation Stroke.

Background: Neurofilament light chain (NfL) is a biomarker for large-caliber axonal degeneration in the subcortex. The purpose of this research was to examine the relationship between plasma neurofilament light chain (pNfL) and cognitive impairment following a posterior circulation stroke. Methods: Patients over the age of 18 with their first-ever acute ischemic stroke (AIS) of the posterior cerebral circulation within 24 h of symptom onset were included from July 1, 2017, to December 31, 2019. Blood samples were collected within 48 h after the stroke. The Montreal Cognitive Assessment (MOCA) (MOCA < 26) was adopted to define poststroke cognitive impairment (PSCI) 90 days after stroke onset. Results: A total of 264 patients were analyzed in this research 101 (38.30%) patients were clinically diagnosed with PSCI. The PNfL concentration was significantly higher in the PSCI group compared with the non-PSCI group (p < 0.001). The pNfL concentration (OR 1.044; p < 0.001) remained to be a significant predictor for PSCI after a multivariable logistic regression analysis, even after adjusting for factors including age, sex, education background (OR 1.044; p < 0.001), baseline NIHSS, infarct volume, and TOAST classification (OR 1.035; p < 0.001). The diagnostic efficacy of pNfL concentration for PSCI was then explored with a ROC analysis. The optimum pNfL concentration threshold was 38.12 pg/ml, with a sensitivity of 78.20%, a specificity of 66.9%, and an AUC of 0.782 (p < 0.001). Conclusion: This research showed that pNfL concentration, independent of established conventional risk factors, could predict the cognitive impairment in 90 days following posterior circulation stroke.

Leukoencephalopathy hypomyelination with brainstem and spinal cord involvement and leg spasticity caused by DARS1 mutations.

Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL), caused by aspartyl-tRNA synthetase (DARS1) gene mutations, is extremely rare, with only a few cases reported worldwide; thus, reports on HBSL treatment are few. In this review, we summarized the clinical manifestations, imaging features, treatment methods, and gene mutations responsible for HBSL based on relevant studies and cases.

Safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy individuals: protocol for a systematic review and meta-analysis.

INTRODUCTION: COVID-19 has spread with high morbidity and mortality worldwide. Many inactivated SARS-CoV-2 vaccines are being tested at various clinical trial stages for the control and prevention of COVID-19. We aim to comprehensively and objectively evaluate the safety and immunogenicity of inactivated SARS-CoV-2 vaccines in healthy individuals through a systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS AND ANALYSIS: We will search electronic databases of PubMed, the Cochrane Library, Web of Science and EMBASE for RCTs from inception to 31 December 2021. We will also search conference abstracts, reference lists, and grey literature of all available records. Two reviewers will independently screen and extract information from the literature. Bias and the quality of included studies will be evaluated with the risk-bias assessment tool provided by the Cochrane Collaboration. Statistical analysis will be performed using Cochrane's Review Manager (RevMan), V.5.3. ETHICS AND DISSEMINATION: Ethics approval and patient informed consent are not required because we will be including published literature only. The findings of this research will be disseminated in a peer-reviewed journal and likely through other scientific events such as conferences, seminars and symposia. PROSPERO REGISTRATION NUMBER: CRD42021266285.

Plasma Neurofilament Light Chain as a Predictive Biomarker for Post-stroke Cognitive Impairment: A Prospective Cohort Study.

BACKGROUND: Plasma neurofilaments light chain (pNfL) is a marker of axonal injury. The purpose of this study was to examine the role of pNfL as a predictive biomarker for post-stroke cognitive impairment (PSCI). METHODS: A prospective single-center observational cohort study was conducted at the General Hospital of Western Theater Command between July 1, 2017 and December 31, 2019. Consecutive patients ≥18 years with first-ever acute ischemic stroke (AIS) of anterior circulation within 24 h of symptom onset were included. PSCI was defined by the Montreal Cognitive Assessment (MOCA) (MOCA < 26) at 90 days after stroke onset. RESULTS: A total of 1,694 patients [male, 893 (52.70%); median age, 64 (16) years] were enrolled in the cohort analysis, and 1,029 (60.70%) were diagnosed with PSCI. Patients with PSCI had significantly higher pNfL [median (IQR), 55.96 (36.13) vs. 35.73 (17.57) pg/ml; P < 0.001] than Non-PSCI. pNfL was valuable for the prediction of PSCI (OR 1.044, 95% CI 1.038-1.049, P < 0.001) after a logistic regression analysis, even after adjusting for conventional risk factors including age, sex, education level, NIHSS, TOAST classification, and infarction volume (OR 1.041, 95% CI 1.034-1.047, P < 0.001). The optimal cutoff value of the pNfL concentration was 46.12 pg/ml, which yielded a sensitivity of 71.0% and a specificity of 81.5%, with the area under the curve (AUC) at 0.785 (95% CI 0.762-0.808, P < 0.001). CONCLUSION: This prospective cohort study showed that the pNfL concentration within 48 h of onset was an independent risk factor for PSCI 90 days after an anterior circulation stroke, even after being adjusted for potential influencing factors regarded as clinically relevant. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR1800020330.

A Highly Symmetric Bimetallic-Tetracarboxylate Framework: Two-Step Crystallization and Gas Separation Properties.

A novel noninterpenetrated MOF (NbU-2, NbU denotes Ningbo University) based on an enneanuclear bimetallic cluster was synthesized by postsynthetic uptake of Ni(II) ions of a sodium-based framework via two-step crystallization. This result demonstrated that the hydrolysis of metal ions in the step-by-step synthesis process is controllable and provided a new method for synthesizing high-nuclear metal cluster-based MOF materials. Note that the activated NbU-2 displays relatively high CO2/N2 selectivity, which was proved by breakthrough experiments of CO2/N2 mixtures.

Pore Space Partitioning of Metal-Organic Framework for C2H x Separation from Methane.

To develop efficient adsorbent materials for C2H x separation from methane, herein, we design a new 3-D framework (NbU-5) using the pore space partition strategy: Zn2(O2CR)4 paddlewheel units connect tetra-carboxylic linkers to build a primary framework, and 4,4-bipyridine, which acts as a pore-partitioning agent, has been successfully inserted into the cage of the primary framework. Remarkably, NbU-5 exhibits excellent C2H2/CH4 and C2H6/CH4 selectivity, which is proved by breakthrough experiments.

Heterometallic Strategy for Enhancing the Dynamic Separation of C2H2/CO2: A Linear Pentanuclear Cluster-Based Metal-Organic Framework.

A family of heterometallic NbU-3-Mn/MIII compounds were synthesized through postsynthetic exchange of MIII ions of a pentanuclear MnII-based metal-organic framework (NbU-3-Mn, where NbU denotes Ningbo University) for enhancing the gas-separation performance. Significantly, NbU-3-Mn/Fe has a C2H2/CO2 separation selectivity similar to that of NbU-3-Mn but exhibits enhanced dynamic separation of C2H2/CO2, which was proven by breakthrough experiments.

Metal-Organic Framework Containing Planar Metal-Binding Sites: Efficiently and Cost-Effectively Enhancing the Kinetic Separation of C2H2/C2H4.

One of the emerging problems plaguing the chemical industry today is the efficient and cost-effective separation of C2 hydrocarbons. In order to help address this problem, we report a new material, NbU-1, constructed by extremely cheap starting materials. The special structural characteristics of NbU-1 such as the planar, mixed-valence copper clusters and Lewis-basic adsorption channels enforce interactions with acetylene molecules that lead to the highest kinetic separation efficiency for C2H2/C2H4. Via DFT-D calculations, it is indicated that C2H2 molecules are adsorbed onto the two adjacent Cu(I) centers, but not the usual single open metal sites of Cu centers. The reported results not only provide information for a deep investigation into the separation mechanism but also offer an alternative strategy for preparing cost-effective materials that can perform highly efficient separations of light hydrocarbons.