Humoral immunosuppression of exposure to polycyclic aromatic hydrocarbons and the roles of oxidative stress and inflammation.

Previous studies have indicated adverse health effects of exposure to polycyclic aromatic hydrocarbons (PAHs), but evidence on the association between PAH exposure and immunity is scarce and its underlying mechanism is largely unknown. This study assessed human exposure to PAHs by determining the concentrations of PAHs in serum and their metabolites in paired urine. The oxidative stress and inflammation levels were evaluated by urinary DNA damage biomarker 8-hydroxydeoxyguanosine, white blood cell counts and C-reaction protein. We investigated the relationship between PAH exposure and seven immunological components, and explored the indirect roles of oxidative stress and inflammation by mediation and moderation analysis. Multivariate regression analysis revealed that 1-hydroxynaphthalene and 2-hydroxyfluorene were negatively associated with immunoglobulin A, and 3-hydroxyphenanthrene was negatively correlated with complement component 3. Restricted cubic spline analysis demonstrated nonlinear relationships between some individual PAHs or their metabolites with immunological components. Bayesian kernel machine regression and quantile g-computation revealed significant associations of higher PAH exposure with decreased immunoglobulin G and kappa light chain levels. Phenanthrene was the compound that contributed the most to reduced immunoglobulin G. Mediation analysis demonstrated significant indirect effects of 8-hydroxydeoxyguanosine and white blood cell counts on the association between higher PAH exposure and decreased immunological components. Moderation analysis revealed that PAH exposure and decreased immunological components are significantly associated with higher levels of C-reaction protein and white blood cell counts. The results demonstrated significant immunosuppression of PAH exposure and highlighted the indirect roles of oxidative stress and inflammation. Interventions to reduce systemic inflammation may mitigate the adverse immune effects of PAH exposure.

Association between polycyclic aromatic hydrocarbon exposure and liver function: The mediating roles of inflammation and oxidative stress.

Polycyclic aromatic hydrocarbon (PAH) exposure has been associated with adverse health effects, and accumulating evidence suggests that PAH exposure may impair liver function. However, the underlying mechanisms linking PAH exposure and liver function impairment remain unclear. This study aimed to explore the association between PAH exposure and liver function biomarkers, and the mediating effects of inflammation and oxidative stress. The cross-sectional study included 155 adults and their urinary PAH metabolites (OH-PAHs) were determined, and eight liver function biomarkers were measured in paired serum samples. A comprehensive statistical analysis investigated the linear, non-linear, individual, and joint effects of the association between urinary OH-PAHs and liver function biomarkers. The results indicated significant positive associations between urinary OH-PAH concentrations and liver function biomarker levels, suggesting that PAH exposure may adversely affect liver function. 2-hydroxyfluorene was identified as the individual metabolite contributing significantly to elevated gamma-glutamyl transferase levels. Further stratification by gender revealed that this association is more pronounced in males. Moreover, we observed significant mediation effects of the oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine and the inflammatory biomarkers C-reactive protein and white blood cell count on this association. The physiological responses triggered by PAH exposure are mediated by inflammation, which serves as a link between oxidative stress, cellular injury, and elevated liver enzyme levels. The results demonstrated that increased inflammation and oxidative stress mediated the association between increased urinary OH-PAHs and elevated liver function biomarkers. The results contribute to a better understanding of the potential mechanisms underlying PAH exposure's hepatotoxic effects.

Association of co-exposure to polycyclic aromatic hydrocarbons and phthalates with oxidative stress and inflammation.

Exposure to multiple environmental pollutants is ubiquitous and inevitable, but studies investigating their exposure effects on oxidative stress or inflammation have mainly been restricted to single-pollutant models. This study investigated the association of co-exposure to polycyclic aromatic hydrocarbons and phthalates with oxidative stress and inflammation. Using a cross-sectional study in adults, we measured urinary concentrations of metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) and phthalates (mPAEs), urinary oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine, and 9 inflammatory biomarkers in paired blood samples. The associations of urinary OH-PAHs and mPAEs with oxidative stress and inflammation biomarkers were evaluated by different statistical models. The Bayesian kernel machine regression and quantile g-computation was used to examine the joint effects, and increased levels of urinary concentrations of OH-PAHs and mPAEs were associated with elevated 8-hydroxy-2'-deoxyguanosine level and white blood cell counts. Exposure to polycyclic aromatic hydrocarbons contributed more significantly to inflammation, while exposure to phthalates contributed more to oxidative stress. Monoisobutyl phthalate was identified as the most significant metabolite contributing to elevated oxidative stress levels. 1-Hydroxypyrene was negatively associated with platelet, and monomethyl phthalate was significantly positively associated with interleukin 6 in multivariate linear regression. The restricted cubic spline analysis revealed non-linear patterns of 3-hydroxyfluorene with white blood cell, lymphocyte, neutrophil, and C-reactive protein. The results indicated significant associations between increased co-exposure to polycyclic aromatic hydrocarbons and phthalates with elevated oxidative stress and inflammation. Further investigation is needed to elucidate the underlying biological mechanisms and to determine the potential public health implications.

Association between polycyclic aromatic hydrocarbon exposure and blood lipid levels: the indirect effects of inflammation and oxidative stress.

Although previous studies have indicated polycyclic aromatic hydrocarbons (PAHs) as cardiovascular health risk factors, evidence linking exposure to PAHs and blood lipids is still lacking, and the mechanism remains largely unknown. In this study, we evaluated the association between human internal exposure to PAHs and blood lipid levels in adults, as well as the indirect effects of inflammation and oxidative stress. The internal exposure of PAHs was assessed by determining serum PAHs and their hydroxylated metabolites (OH-PAHs) in the paired urine samples. Multivariable linear regression results demonstrated significant positive associations of individual PAHs and OH-PAHs with blood lipid biomarkers. The Bayesian kernel machine regression model revealed positive joint effects of PAH internal exposure on the fasting blood glucose, low-density lipoprotein cholesterol, total cholesterol, and total triglyceride, as well as an increased ratio of apolipoprotein B to apolipoprotein A1. In evaluating individual effects, serum phenanthrene played the most significant role in the association of increased PAH exposure with elevated fasting blood glucose. Quantile g-computation demonstrated the significant change in the levels of apolipoprotein B, ratio of apolipoprotein B to apolipoprotein A1, low-density lipoprotein cholesterol, and total cholesterol per quartile increase in PAH internal exposure. The restricted cubic spline analysis demonstrated the non-linear relationship between individual PAHs and OH-PAHs on blood lipid biomarkers. The mediation analysis indicated that PAH exposure may affect blood lipids not directly, but rather indirectly through intermediate inflammation and oxidative stress. The results demonstrated a significant association between increased PAH exposure levels and elevated blood lipids, highlighting the indirect effects of inflammation and oxidative stress.

Factors influencing recurrence after an ischemic stroke vary by sex.

OBJECTIVES: To determine the factors that affect recurrent stroke after acute ischemic stroke, specifically between male and female groups. METHODS: We examined relative factors associated with recurrent stroke in Chinese patients with first-ever ischemic stroke. LASSO (least absolute shrinkage and selection operator) Cox regression were used to determine the predictors of recurrent stroke in the male and female groups. Next, We used Kaplan-Meier survival curves and interactions among these predictors to assess the association between relapse-related factors and recurrent stroke. RESULTS: During one year of follow-up, we documented 42 incidents of recurrent stroke in males and 15 in females. There was no significant difference in the overall recurrence rate between men and women. We finally identified three variables in males and one variable in females associated considerably with recurrent stroke by LASSO Cox regression. In females, good sleep appeared to be the most significant protective factor against recurrent stroke(hazard ratio [HR], 0.21; 95% CI, 0.08-0.57). In the male group, we found two risk factors: atherosclerotic burden (HR, 2.42; 95% CI, 1.30-4.51) and coronary heart disease (HR, 2.98; 95% CI, 1.16-7.66); and one protective factor: domestic/physical activities (HR, 0.45; 95% CI, 0.24-0.83). We also found an interaction between good sleep and domestic/physical activities in males (Pinteraction = 0.016). DISCUSSION: Our data indicate that the factors for recurrent stroke may differ by sex. Engaging in domestic/physical activities may substantially lower recurrent strokes in Chinese adult males. And good sleep in females appears to be more important in preventing stroke recurrence.

Prognostic factors for acute vertebrobasilar artery occlusion-reperfusion: a multicenter retrospective cohort study.

BACKGROUND: This study aimed to analyze the long-term prognostic factors in acute vertebrobasilar artery occlusion (VBAO) patients treated with endovascular treatment (EVT). METHODS: This study was performed using the acute posterior circulation ischemic stroke registry database from 21 stroke centers in 18 cities in China and retrospectively included consecutive patients aged 18 years or older with an acute, symptomatic, radiologically confirmed VBAO who were treated with EVT between December 2015 and December 2018. Favorable clinical outcomes were evaluated by machine-learning methods. A clinical signature was constructed in the training cohort using the least absolute shrinkage and selection operator regression and was validated in the validation cohort. RESULTS: From 28 potential factors, 7 variables were independent prognostic factors and were included in the model: Modified Thrombolysis in Cerebral Infarction (M) [odds ratio (OR): 2.900; 95% confidence interval [CI]: 1.566-5.370], age (A) (OR, 0.977; 95% CI: 0.961-0.993), National Institutes of Health Stroke Scale (N) (13-27 vs. ≤12: OR, 0.491; 95% CI: 0.275-0.876; ≥28 vs. ≤12: OR, 0.148; 95% CI: 0.076-0.289), atrial fibrillation (A) (OR, 2.383; 95% CI: 1.444-3.933), Glasgow Coma Scale (G) (OR, 2.339; 95% CI: 1.383-3.957), endovascular stent-retriever thrombectomy (E) (stent-retriever vs. aspiration: OR, 0.375; 95% CI: 0.156-0.902), and estimated time of onset of the occlusion to groin puncture (Time) (OR, 0.950; 95% CI: 0.909-0.993) (abbreviated as MANAGE Time). In the internal validation set, this model was well calibrated with good discrimination [C-index (95% CI)=0.790 (0.755-0.826)]. A calculator based on the model can be found online ( http://ody-wong.shinyapps.io/1yearFCO/ ). CONCLUSION: Our results indicate that optimizing for EVT, along with specific risk stratification, may improve long-term prognosis. However, a larger prospective study is needed to confirm the findings.

An Empirical Study on the Influence of Smart Home Interface Design on the Interaction Performance of the Elderly.

The concept of the smart home has been widely recognized and accepted, but the differentiated characteristics of elderly smart products in terms of demand and use are becoming more and more prominent. The lack of an efficient navigation design of the smart product interface increases the cognitive burden of elderly users, and how to better meet the needs of the elderly with smart products gradually becomes the focus of attention. This study was conducted for the elderly group, using the scenario-based design method to analyze the needs of elderly users, combining the research results of scenario theory with the smart home interaction design research method, focusing on how to make the style of interface navigation, sliding layout and button size more suitable for the cognitive behavior of elderly users. The purpose of this research is to realize an age-friendly smart home interaction design in terms of functional design and interface design. The experiment is divided into two stages: in stage 1, two different layouts and operation methods are commonly used for the age-friendly smart home interface: up and down sliding and left and right sliding; in stage 2, the functional buttons are square, where 4 styles are selected, and the side lengths are set to 10 mm, 12 mm, 15 mm, 18 mm and 22 mm. The sliding and retrieval test and retrieval and click test results show that for different sliding layout methods, the interactive performance and subjective evaluation of the interface with the up-and-down sliding layout are better. Among all functional button styles, the interaction performance and subjective evaluation of the simple button style with lines are the best. Among the function keys with a size of 10-22 mm, the interaction performance is better from 12 mm to 18 mm. The conclusion of the better interface data information obtained from this experiment improves the rationality of the age-friendly smart home interface and makes the smart home interface better for the age-friendly scenario.

Clinical effect of repetitive transcranial magnetic stimulation on dysphagia due to stroke.

BACKGROUND: Repetitive transcranial magnetic stimulation (rT) could change the excitability of the cerebral cortex, and control the neurotransmitter release, with the therapeutic effect depending on stimulation intensity and position. In this study, we used 3 Hz rTMS to stimulate the pharyngeal cortical area of the lesioned hemisphere and to explore its clinical significance in the treatment of dysphagia after acute cerebral infarction. METHODS: A total of 61 in-patients with acute dysphagia caused by cerebral infarction hospitalized in the department of neurology of our hospital were included in this study and were assigned into the control and rTMS group. Patients in the control group only accepted the basic treatment of rehabilitation training, while patients in the rTMS group received additional rTMS (3 Hz) stimulation. The levels of the water swallowing test (WST) 14 days before and after the treatment of rTMS (3 Hz) would be recorded. RESULTS: After different therapies in two groups, 9 patients of the control group showed excellent curative effect, with a recovery rate of 31.0%. However, in the rTMS group, the swallowing function of 21 patients was significantly improved, with a recovery rate of 65.6%. Comparison results showed that the recovery rate of the rTMS group was much better than the control group (P < 0.05), indicating an effective therapeutic effect of 3 Hz rTMS on patients with dysphagia after acute cerebral infarction. CONCLUSION: Stimulating the target cortical representation areas of pharyngeal of the lesioned hemisphere with cerebral infarction by the rTMS (3 Hz) could improve the patients' function.

Bioinformatic identification of potential biomarkers and therapeutic targets in carotid atherosclerosis and vascular dementia.

Background: Vascular disease is the second most common cause of dementia. The prevalence of vascular dementia (VaD) has increased over the past decade. However, there are no licensed treatments for this disease. Carotid atherosclerosis (CAS) is highly prevalent and is the main cause of ischemic stroke and VaD. We studied co-expressed genes to understand the relationships between CAS and VaD and further reveal the potential biomarkers and therapeutic targets of CAS and VaD. Methods: CAS and VaD differentially expressed genes (DEGs) were identified through bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE43292 and GSE122063, respectively. Furthermore, a variety of target prediction methods and network analysis approaches were used to assess the protein-protein interaction (PPI) networks, the Gene Ontology (GO) terms, and the pathway enrichment for DEGs, and the top 7 hub genes, coupled with corresponding predicted miRNAs involved in CAS and VaD, were assessed as well. Result: A total of 60 upregulated DEGs and 159 downregulated DEGs were identified, of which the top 7 hub genes with a high degree of connectivity were selected. Overexpression of these hub genes was associated with CAS and VaD. Finally, the top 7 hub genes were coupled with corresponding predicted miRNAs. hsa-miR-567 and hsa-miR-4652-5p may be significantly associated with CAS and VaD.

Pinellia ternata attenuates carotid artery intimal hyperplasia and increases endothelial progenitor cell activity via the PI3K/Akt signalling pathway in wire-injured rats.

CONTEXT: Clinically, Pinellia ternata (Thunb.) Breit. (Araceae) (PT) has been widely used in the treatment of atherosclerosis and hyperlipidaemia, but the underlying mechanisms are still not clearly understood. OBJECTIVE: This research was conducted to confirm the mechanism by which PT affects carotid artery intimal hyperplasia. MATERIALS AND METHODS: An intestinal hyperplasia Sprague-Dawley rat model was established by carotid artery injury. The rats were randomly divided into five groups (n = 8): sham, model, PT (with daily intragastric administration of 10 g/mL/kg PT tubers water extract), PT+LY294002 (with intraperitoneal injection of 50 mg/kg LY294002 + 10 g/mL/kg PT) and endothelial progenitor cells (EPCs) (with injection of 5 × 105/cells), and treated for 4 or 8 weeks. RESULTS: HE staining showed that PT attenuated intimal hyperplasia. RT-PCR, Western blotting and immunohistochemistry showed that PT increased the expression of vascular endothelial growth factor (VEGF) and eNOS in the atherosclerotic carotid artery. PT increased the Dil-acLDL+/FITC-UEA-1+ population (from 0.41 ± 0.085% to 0.60 ± 0.092%) in the blood, decreased TCHO, TG, LDL-C, IL-6 and TNF-α levels, and increased HDL-C and IL-10 levels in the blood. However, these changes were reversed by the PI3K/Akt pathway inhibitor LY294002. DISCUSSION AND CONCLUSIONS: PT can be developed as an atherosclerosis and carotid intimal hyperplasia treatment drug. Therefore, further study will focus on the effects of PT on intimal hyperplasia in wire-injured atherosclerosis patients and explore in depth some other relevant molecular mechanisms.

Effect of Huoxiang Zhengqi Pill on Early Neurological Deterioration in Patients with Acute Ischemic Stroke Undergoing Recanalization Therapy and Predictive Effect of Essen Score.

Early neurologic deterioration (END) in the acute phase of ischemic stroke is a serious clinical event, which is closely related to poor prognosis. Therefore, it is important to identify presentation features that predict END and take relevant treatment measures, as they could help to prevent the deterioration of high-risk patients. The prospective intervention study was carried out from January 2018 to December 2019. We included consecutive patients hospitalized for acute ischemic stroke (AIS) within 6 hours of onset. Patients were randomly assigned (1 : 1) to recanalization therapy plus Huoxiang Zhengqi Pill (HXZQ) (intervention group) or standard recanalization therapy alone (control group). The primary outcome was the development of END according to predefined criteria within the first 1 week of stroke onset. Poisson regression was used to identify predictors for END. Of the 155 patients enrolled in the study (age, 63 ± 11 years; 28.4% female), 20 (12.9%) developed END. Univariate analysis showed that the use of HXZQ and Essen stroke risk score (ESRS) (low risk group) were protective factors for END, while advanced age was a risk factor for END. However, in multivariate analysis, only ESRS (OR, 0.232; 95%CI, 0.058-0.928; P=0.039) and the use of HXZQ (OR, 0.297; 95%CI, 0.096-0.917; P=0.035) were statistically significant. ESRS can be used as the prediction factor of END. HXZQ has small side effects and wide indication. It could be used in the treatment of AIS.

Advanced Glycated End Products Alter Neutrophil Effect on Regulation of CD4+ T Cell Differentiation Through Induction of Myeloperoxidase and Neutrophil Elastase Activities.

CD4+ T cell subset imbalance plays an important role in the development of diabetic complications. Neutrophils have recently been known as the regulator of CD4+ T cell differentiation. However, whether neutrophils affect CD4+ T cell population in diabetes is still elusive. In this study, we investigated the effect of neutrophils stimulated with advanced glycated end products (AGEs), the marker of diabetes, on CD4+ T cell differentiation and its underlying mechanism. Our data showed that the cultural medium of healthy adult neutrophils treated with AGEs increased expressions of both Th1 (IFN-γ) and Th17 (IL-17) phenotypes and the transcription factors of Th1 (Tbet) and Th17 (RORγt) in naive CD4+T cells and CD4+CD25+FoxP3+ (Treg) T cells in vitro. Next, we found that AGEs induced the generations of myeloperoxidase (MPO) and neutrophil elastase (NE) in neutrophils; inhibition of MPO or NE attenuated the effect of AGE-stimulated neutrophils on CD4+ T cell bias. Furthermore, receptor for AGEs (RAGE) inhibitor interrupted AGE-induced MPO and NE expressions, but MPO and NE inhibitions did not change AGE-increased RAGE gene expression. These results suggested that AGEs drive the effect of neutrophils on CD4+ T cell differentiation into pro-inflammatory program through inducing MPO and NE productions in neutrophils, which is mediated by AGE-RAGE interaction.

Early neurological deterioration in acute ischemic stroke: A propensity score analysis.

BACKGROUND: To investigate whether endovascular therapy (EVT) was one of the factors influencing the incidence of early neurological deterioration (END) in patients with acute ischemic stroke (AIS) as compared with intravenous thrombolysis alone. METHODS: This study was based on our single-center's database that included information on stroke patients hospitalised between January 2012 and September 2015. A total of 220 patients who underwent EVT after IV rt-PA, EVT or IV rt-PA alone. To reduce the lack of randomization, we conducted a propensity score analysis using the SPSS custom dialog. After matching was completed, the 2 groups (with END versus non-END) were compared between matched groups. Variables with a p value ≤ 0.1 by univariate analysis were candidates for inclusion in logistic regression analysis. RESULTS: Of 220 acute ischemic strokes attended, 213 patients were included (62.0%, 23.0% and 15.0% with circulation occlusion in the anterior, posterior and both branches, respectively). END was detected in 68 patients (31.9%). Multivariable analysis showed that END was positively associated with glucose level (OR, 1.40; 95%CI, 1.10-1.79; p = 0.007), uric acid level (OR, 1.01; 95% CI, 1.00-1.02; p = 0.026) and treatment methods (EVT: OR, 3.87; 95% CI, 1.32-11.35; p = 0.014). However, there was significant difference in baseline data (NIHSS and INR) between EVT group and non-EVT group. CONCLUSION: Our findings suggest that hyperglycemia, hyperuricemia and EVT may be independently associated with END in AIS, even after controlling for possible confound factors. Further studies are warranted to confirm these results.

[Risk factors for recurrence of large atherosclerotic cerebral infarction].

OBJECTIVE: To explore the risk factors for recurrence of large atherosclerotic cerebral infarction in first?episode patients. METHODS: The consecutive patients with acute cerebral infarction diagnosed in the Department of Neurology were screened for large atherosclerotic cerebral infarction by CTA/MRA examination, and all the confirmed patients were followed up for 1 year. The patients were divided into recurrent ischemic stroke group and non?recurrent group according to occurrence of cerebrovascular events during the follow?up. RESULTS: A total of 256 eligible patients were included in this study, and all of them completed the follow?up. During the 1?year follow?up, 30 (11.7%) patients had ischemic cerebrovascular stroke events. Univariate analysis showed significant differences in alcohol drinking (P=0.028), smoking (P=0.007), high?density lipoprotein cholesterol (HDL; P=0.045), ischemic heart disease (P=0.002), antihypertensive agents (P=0.036) and statin use (P=0.016) between the recurrent group and non?recurrent group. Cox regression analysis showed that irregular use of statins (RR=0.410, P=0.043), smoking (RR=2.253, P=0.043), HDL (RR=0.327, P=0.029), and ischemic heart disease (RR=8.566, P<0.001) were correlated with recurrent ischemic stroke. CONCLUSION: The first?episode patients with irregular use of statins, low HDL levels, smoking and ischemic heart disease are at higher risks for having ischemic stroke recurrence.

[Relationship between masseter muscle electromyographic activities and the position of the mandible].

OBJECTIVE: To investigate the changes in electromyographic activities of the temporal and masseter muscles at different positions of the mandible. METHODS: Twenty orthodontic patients with Angle Class II malocclusion and mandibular retrusion (ANB<6°) aged 10-14 years were enrolled in this study. All the patients were treated with Forsus fixed functional appliance combined with MBT straight-wire appliance. The electromyographic activities of the temporal (T) and masseter (M) muscles before, during and after functional treatment were evaluated by assessing the average integrated electromyogram (EMG) and T/M ratio at clenching status in different mandibular positions. RESULTS: After functional forward positioning of the mandible, the electromyographic activities of the temporal and masseter muscles decreased and T/M ratio increased significance at the clenching status (P<0.05). CONCLUSION: The appliance insertion and activation is associated with a decreased EMG activity of the temporal and masseter muscles, and the T/M ratio is correlated to the position of the mandible.