Dysbiosis of oral and gut microbiota may influence ischemic stroke (IS) pathogenesis through immune and metabolic mechanisms. This study investigated microbial translocation between oral and gut niches and its functional metabolic impact in IS patients. A total of 57 individuals were analyzed, including 25 controls (FC/KC) and 32 IS patients (FS/KS). Samples were obtained from the gut and oral subgingival plaque. The microbiome analysis was performed using the PacBio platform 16 S rRNA full-length gene sequencing, while non-targeted metabolomics was used to assess intestinal metabolites. The oral cavity of IS patients harbored abundant periodontal pathogens, including Porphyromonas and Fusobacterium. Bacterial genera (such as Streptococcus, Neisseria, Ligilactobacillus, Leptotrichia, Blautia, Veillonella, and Capnocytophaga) significantly overlapped between the oral and gut niches in IS patients, suggesting mutual transfer. IS patients exhibited increased diversity and dysbiosis in their gut microbiota, characterized by a deficiency of short-chain fatty acids (SCFA)-producing bacteria (Bacteroides and Faecalibacterium), and an enrichment of opportunistic pathogens (Streptococcus and Ligilactobacillus). Metabolomic analysis revealed concomitant disturbances in microbial metabolism, marked by decreased SCFAs (butyrate) and increased levels of specific amino acids (L-tryptophan). These metabolic changes were correlated with the microbial shifts. IS is associated with distinct dysbiosis in both the oral and gut ecosystems, which are interconnected through bacterial translocation. The metabolic disruption may link microbial dysbiosis to stroke pathogenesis through the oral-gut axis.

Introduction: Primitive trigeminal artery (PTA) is a rare intracranial vascular malformation, and mechanical thrombectomy and revascularization via PTA are rarely reported. Case presentation: We reported a case of mechanical thrombectomy through PTA in a patient who presented with sudden slurred speech and had a National Institutes of Health Stroke Scale score of 12. Digital subtraction angiography of the cerebral vasculature showed PTA formation in the right internal carotid artery cavernous segment, with acute occlusion of the distal basilar artery at the PTA junction, and bilateral vertebral arteries and proximal basilar artery were underdeveloped. Therefore, we chose mechanical thrombectomy via PTA; but unfortunately, the vessel failed to recanalize. Follow-up at 1 month post-procedure indicated that the patient had passed away. We present the endovascular process and analyze and summarize the reasons for the failure to provide a reference for subsequent mechanical thrombectomy via PTA. Conclusions: PTA increases the risk of ischemic stroke and adds to the complexity of mechanical thrombectomy post-stroke. However, in certain situations, PTA can be used as a thrombectomy channel to increase the first-line possibility of timely endovascular treatment to save ischemic brain tissue.

IntroductionNeutrophil extracellular traps (NETs) provide key innate immune mechanisms, and studies have shown innate immunity and adaptive immunity are directly linked to Parkinson’s disease (PD) pathology. However, limited research has been conducted on NETs in the context of PD.MethodsA differential analysis was implemented to acquire differentially expressed genes (DEGs) between PD and control as well as between high- and low-score groups determined by a gene set variation analysis (GSVA). Then, the genes within the critical module, obtained through a weighted gene co-expression network analysis (WGCNA), were intersected with the DEGs to identify the overlapping genes. Then, five kinds of algorithms in the protein–protein interaction (PPI) were performed to identify potential biomarkers. Subsequently, a nomogram for forecasting PD probability was created. An enrichment analysis and an immune infiltration analysis were performed on the identified biomarkers. qRT-PCR was performed to validate the expression trends of three biomarkers.ResultsWe revealed 798 DEGs between PD and control groups as well as 168 DEGs between high- and low-score groups obtained by differential analyses. The pink module containing 926 genes was identified as the critical module. According to the intersection of these gene sets, a total of 43 overlapping genes were screened out. Furthermore, GPR78, CADM3, and CACNA1E were confirmed as biomarkers. Moreover, we found that biomarkers mainly participated in pathways, such as the ‘hydrogen peroxide catabolic process’, and ‘cell cycle’; five kinds of differential immune cells between PD and control groups were identified. Finally, the qRT-PCR analysis demonstrated the up-regulation of GPR78, CADM3, and CACNA1E in the PD group.DiscussionOur study authenticated GPR78, CADM3, and CACNA1E as the biomarkers associated with PD. These findings provide an original reference for the diagnosis and treatment of PD.

Posttraumatic epilepsy (PTE) accounts for approximately 20% of structural epilepsy, and surgical intervention may be a potential treatment option for these patients. Therefore, the purpose of this meta-analysis is to evaluate the effectiveness of surgical interventions for the management of PTE. Four electronic databases (Pubmed, Embase, Scopus and Cochrane library) were searched to identify studies on surgical management of PTE. Seizures reduction rate were analyzed quantitatively in a meta-analysis. Fourteen studies involving 430 PTE patients were selected for analysis, out of which 12 reported on resective surgery (RS), 2 on vagus nerve stimulation (VNS), and 2 of the 12 RS studies reported that 14 patients underwent VNS. The seizure reduction rate for surgical interventions (both RS and VNS) was 77.1% (95% confidence interval [CI]: 69.8%-83.7%) with moderate heterogeneity (I-2 = 58.59%, P-hetero = 0.003). Subgroup analysis based on different follow-up times revealed that the seizure reduction rate was 79.4% (95% CI: 69.1%-88.2%) within 5 years and 71.9% (95% CI: 64.5%-78.8%) beyond 5 years. The seizure reduction rate for RS alone was 79.9% (95% CI: 70.3%-88.2%) with high heterogeneity (I-2 = 69.85%, P-hetero = 0.001). Subgroup analysis showed that the seizure reduction rate was 77.9% (95% CI: 66%-88.1%) within 5 years and 85.6% (95% CI: 62.4%-99.2%) beyond 5 years, with 89.9% (95% CI: 79.2%-97.5%) for temporal lobectomy and 84% (95% CI: 68.2%-95.9%) for extratemporal lobectomy. The seizure reduction rate for VNS alone was 54.5% (95% CI: 31.6%-77.4%). Surgical interventions appeared to be effective for PTE patients without severe complications, RS seemed more beneficial than VNS, while temporal lobectomy is more favorable than extratemporal resection. However, further studies with long-term follow-up data are needed to better understand the relationship between VNS and PTE.

Acute carbon monoxide (CO) poisoning survivors may experience persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS). This study evaluated the clinical features, laboratory results, acute brain lesions (ABLs) on diffusion‐weighted imaging (DWI) at presentation, and long‐term outcomes and explored differences between patients with PNS and DNS.

Context: Hypoxia-induced injury is a classic symptom of obstructive sleep apnea hypopnea syndrome (OSAHS), which is a risk factor of various diseases, such as hypertension, heart failure and stroke. However, there is no effective therapy for hypoxia-induced injury or OSAHS due to the elusive mechanism involved.Objective: This study aimed to assess the effects of paeoniflorin on hypoxia-induced injury and explore the underlying mechanism.Materials and methods: Hypoxic models of SD rats and CTX-TNA2 cells were used to assess the effect of paeoniflorin, and the expressions of hif1a, miR-210, caspase1 and GSDMD were detected using western blots and RT-PCR. Plasmid transfection was performed to explore the role of miR-210 in the effect of paeoniflorin.Results: Firstly, we confirmed that hypoxia induced severe neuronal injury and an enhancement of inflammation in the rat brain, with elevated expression of caspase1, IL1b and IL18. In addition, the results showed an activation of astrocytes and an increased level of pyroptosis under hypoxic conditions, which suggested a critical role of pyroptosis in hypoxiainduced injury of the brain. Furthermore, we found that compared with the controls, paeoniflorin treatment improved hypoxia-induced pyroptosis in astrocytes. Moreover, we detected the activation of hif1a/miR-210 signaling in the effects of paeoniflorin on astrocytes. As expected, the expression of hif1a and miR-210 was significantly upregulated in astrocytes when exposed to hypoxia, while paeoniflorin treatment reversed these enhancements. After transfection of miR-210 mimics, the attenuation of pyroptosis induced by paeoniflorin was suppressed, which was accompanied by an increase of ROS levels, as well as LDH release, indicating a critical role of miR-210 in pyroptosis in astrocytes.Conclusions: Our findings demonstrated that paeoniflorin improved hypoxia-induced pyroptosis in astrocytes via depressing hif1a/miR-210/caspase1/GSDMD signaling, providing robust evidence for the treatment of hypoxic injury and OSAHS.HighlightsHypoxia induces severe injury and inflammatory response in the rat brain;Hypoxia enhanced pyroptotic level and led to an activation of astrocytes.;Paeoniflorin alleviates hypoxia-induced pyroptosis in astrocytes;Transfection of miR-210 mimics suppressed the effects of paeoniflorin on hypoxia-induced pyroptosis in astrocytes.

Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease (AD). However, there are currently no effective drugs that can target chronic stress to prevent AD. In this study, we explored the neuroprotective effect of hydroxysafflor yellow A (HSYA) against chronic mild stress (CMS)-induced memory impairments in mice and the underlying mechanism. The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice. HSYA increased the expression of brain-derived neurotrophic factor (BDNF) and activated downstream tropomyosin-related kinase B (TrkB) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt)/mammalian target of rapamycin (mTOR) signaling. HSYA decreased the expression of regulator of calcineurin 1-1L (RCAN1-1L) that could promote the activity of glycogen synthase kinase-3β (GSK-3β). HSYA also attenuated tau phosphorylation by inhibiting the activity of GSK-3β and cyclin-dependent kinase-5 (Cdk5). Our data indicated that HSYA has protective effects against CMS-induced BDNF downregulation, tau phosphorylation and memory impairments. HSYA may be a promising therapeutic candidate for AD by targeting chronic stress.

We investigated the effects of the Chinese herb Codonopsis pilosula isolate isorhapontigenin on antioxidant factor and the PI3K/Serine/Akt signaling pathway in Parkinson's disease. This research was, therefore, carried out to explore a possible protective mechanism of isorhamnetin in Parkinson's disease. The results support that isorhapontigenin could effectively inhibit isorhapontigenin restored myeloperoxidase + induced reduction of antioxidant levels. Also, 1-Methyl-4-phenylpyridine up-regulated the expression of phosphorylated-Akt, phosphorylated-PI3K, and phosphorylated mammalian target of rapamycin, while isorhapontigenin inhibited the expression of phosphorylated-Akt, phosphorylated-PI3K, and phosphorylated- mammalian target of rapamycin. Furthermore, LY294002 improved the antioxidant effect of isorhapontigenin in PC12 cells, and insulin-like growth factor 1 inhibited the antioxidant effect of isorhapontigenin in PC12 cells. Our results support the finding that isorhamnetin enhanced the antioxidant effect induced by 1-Methyl-4-phenylpyridine in PC12 cells by suppressing the activation of the PI3K/Akt signaling pathway.

BACKGROUND:Considerable controversy exists on the association between serum vitamin D concentrations and Alzheimer disease (AD) risk. This study aimed to synthesize the association of serum vitamin D concentrations with AD in adults.METHODS:PubMed, Embase, and Cochrane library databases were searched for prospective cohort studies with data on serum vitamin D concentrations and AD risk.RESULT:The studies that reported the adjusted relative risks (RRs) with 95% confidence intervals (CIs) of AD associated with serum vitamin D concentrations were included and subjected to subgroup analyses. Six prospective cohort studies with 1607 AD cases and 21,692 individuals were included in the meta-analysis. In 4 cohort studies with information about serum vitamin D concentrations <25 and 25 to 50 nmol/L, the random effects summary estimate did not show an increased risk of AD after adjustment for the established risk factors, while 3 cohort studies reported the RRs for incident AD per standard deviation (SD) decrease in serum vitamin D concentration and the random effects summary estimate did not show an increased risk of AD after adjustment for the established risk factors.CONCLUSIONS:The current meta-analysis indicated that serum vitamin D deficiency (<25 nmol/L) or insufficiency (25-50 nmol/L) was not statistically significant and associated with the risk of AD.

Abstract Background: Considerable controversy exists on the association between serum vitamin D concentrations and Alzheimer disease (AD) risk. This study aimed to synthesize the association of serum vitamin D concentrations with AD in adults. Methods: PubMed, Embase, and Cochrane library databases were searched for prospective cohort studies with data on serum vitamin D concentrations and AD risk. Result: The studies that reported the adjusted relative risks (RRs) with 95% confidence intervals (CIs) of AD associated with serum vitamin D concentrations were included and subjected to subgroup analyses. Six prospective cohort studies with 1607 AD cases and 21,692 individuals were included in the meta-analysis. In 4 cohort studies with information about serum vitamin D concentrations <25 and 25 to 50 nmol/L, the random effects summary estimate did not show an increased risk of AD after adjustment for the established risk factors, while 3 cohort studies reported the RRs for incident AD per standard deviation (SD) decrease in serum vitamin D concentration and the random effects summary estimate did not show an increased risk of AD after adjustment for the established risk factors. Conclusions: The current meta-analysis indicated that serum vitamin D deficiency (<25 nmol/L) or insufficiency (25–50 nmol/L) was not statistically significant and associated with the risk of AD.

Background: This study aims to explore the relation between 25(OH)D level, ambulatory arterial stiffness index (AASI), and other parameters from ambulatory blood pressure monitoring (ABPM). Methods: The study sample consisted of 102 older patients with essential hypertension. Clinical characteristics of population divided into three groups according to 25(OH)D tertile. Results: The patients in the high tertile of 25(OH)D with low body mass index (BMI) (P < 0.01), low tertile group with high low-density lipoprotein (LDL) (P < 0.05). Significant differences were in terms of Office SBP, Office PP, 24 h SBP, 24 h PP, daytime SBP, daytime PP, night-time SBP, night-time PP (P < 0.01), nocturnal dipping (P < 0.05) and ASSI (P < 0.01) among three groups. AASI showed decrease as 25(OH)D increases. Differences are significant. Correlation test showed a significant relationship of AASI with BMI (r = 0.368, P < 0.001), 24 h average SBP (r = 0.641, P < 0.001), 24 h average PP (0.66, P < 0.001), nocturnal dipping (r = -0.217, P < 0.05), 25(OH)D (r = -0.621, P < 0.001). Multivariate liner regression analysis showed that 25(OH)D (P < 0.01) and 24 h average PP (P < 0.01) were independently related to AASI. Conclusions: The relationship of AASI with BMI, 24 h average SBP, 24 h average PP, Nocturnal dipping, 25(OH)D are significant. 25(OH)D (P < 0.01) and 24 h average PP (P < 0.01) were independently related to AASI. Copyright (C) 2018, Taiwan Society of Geriatric Emergency & Critical Care Medicine. Published by Elsevier Taiwan LLC.

Objective: To explore clinical features and risk factors of delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). Methods: A total of 184 ACMP patients admitted in the Department of Neurology, The First Hospital of Lanzhou University from 2008 to 2016 were recruited as study subjects. They were randomly divided into the study group (DEACMP) and the control group (non-DEACMP). Twelve (12) indices (age, sex, coma time and JSC score, COHb, WBC, CK, CK-MB, LDH, abnormal skull CT, hospitalization time, and hyperbaric oxygen therapy) of patients in the two groups were analyzed. Results: ACMP patients in two groups, there were 114 cases with coma time of patients in the control group was 12h or less 12h, 19 patients with 13h to 24h, 11 cases with 25h to 48h, 4 cases with over 48h. 36 delayed encephalopathy cases in 184 ACMP patients were the study group. The incidence rate was 19.56%. There were 13 cases with coma time of patients in the study group was 12h or less 12h, 11 patients with 13h to 24h, 5 cases with 25h to 48h, 7 cases with over 48h. The coma time in the study group was longer. Patients in the study group compared with the control group in ratio of male and female, there were no differences in mean age and laboratory indexes (COHb concentration and WBC), data had no statistical significance (P > 0.05). According to Japan coma scale (JSC) scoring, it was found that consciousness dysfunction when admitted into hospital in the study group was worse compared with the control group. At the same time, Cranial CT in the study group showed that patients with hypoxic hypoxia brain change, which compared with the control group, the percentage was more high, differences had statistical significance (P < 0.01). According to indexes in experiment, it showed that CK, CK-MB and LDH level significantly increased in the study group compared with the control group, differences had statistical significance (P < 0.01). Compared with the control group, hospitalization time in the study group was longer and hyperbaric oxygen treatment had been prolonged. Differences between two groups had statistical significance (P < 0.01). Conclusion: DEACMP patients should particularly pay attention to strengthen clinical monitor to decrease incidence of DEACMP.

BACKGROUND:The mechanisms of hyperhomocysteinemia (HHcy) and hyperuricemia (HUA) that promote atherosclerosis were seldom explored and always indefinite. Therefore, we will discuss some new reviews about the role of HHcy and HUA in the pathogenesis of atherosclerosis.METHODS:This study was conducted by reading a lot of literature, including basic research and clinical application research.RESULTS:HHcy is known as an independent risk factor for atherosclerosis. Possible mechanisms for the association between homocysteine and atherosclerosis include stimulating smooth muscle cell growth, reducing endothelial cell growth and endothelial cell relaxation, and decreasing synthesis of high-density lipoprotein. HUA causes endothelial dysfunction and thereby increases oxidative stress, inducing vascular smooth muscle cell proliferation and reducing endothelial nitric oxide bioavailability. HUA plays a role in the development and pathogenesis of metabolic syndrome, hypertension, stroke, and atherosclerosis.CONCLUSIONS:Accelerated atherosclerosis may be a consequence of the combined effect of HHcy and HUA.

Traumatic brain injury (TBI) is the predominant cause of mortality in young adults and children living in China. TBI induces inflammatory responses; in addition, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 are important pro-inflammatory cytokines. Considering the observation that Hsp-70 overexpression can exert neuroprotection, identifying a drug that is able to induce the upregulation of Hsp70 has the potential to be a promising therapy for the treatment of neurological diseases. Thus, the present study assessed the clinical effectiveness of an anticancer drug and Hsp70 activator, 17-allylamino-demethoxygeldanamycin (17-AAG), to evaluate its potential as a treatment for patients with TBI. The aim of present study was to determine the neuroprotective effects of 17-AAG following trauma and to investigate the underlying mechanisms of action. To establish rat models, rats were subjected to a controlled cortical impact injury and randomly divided into vehicle or 17-AAG groups. In the 17-AAG group, rats were administered with an intraperitoneal injection of 17-AAG (80 mg/kg) immediately following the establishment of TBI. The motor function was measured using Neurologic Severity Score, and neuronal death was evaluated using immunofluorescence. The expression levels of GLT-1, Bcl-2 and Hsp-70 were detected by western blot analysis and the expression levels of inflammatory cytokines were quantified using ELISA. The present study determined that 17-AAG significantly reduced brain edema and motor neurological deficits (P<0.05), in addition to increasing neuronal survival. The aforementioned findings are associated with a downregulation of the expression levels of pro-inflammatory cytokines TNF-α, IL-1β and IL-6. Conversely, no significant changes of glutamate transporter-1 expression were observed. The present results suggest that 17-AAG treatment may provide a neuroprotective effect by reducing inflammation following TBI.

Homocysteine (Hcy) could induce amyloid β (Aβ) accumulation, synaptic dysfunction, and memory impairment as seen in Alzheimer disease (AD), the most prevalent neurodegenerative disorder, which affects more than 25 million people worldwide. Here we investigated the protective effect of hydroxysafflor yellow A (HSYA) on Hcy-induced Aβ accumulation, synaptic dysfunction, and learning and memory deficits. Rats were randomly divided into four groups: Control group, which received normal saline (NS); Hcy group, which received a daily vena caudalis injection of Hcy (400 μg/kg per day); Hcy+HSYA group, which received the same amount of Hcy plus 6 mg/kg per day HSYA intraperitoneally; and HSYA group, which received 6 mg/kg per day HSYA intraperitoneally for 2 weeks. Results showed that simultaneous supplementation of HSYA significantly attenuated Aβ accumulation, improved synaptic function, and reversed Hcy-induced cognitive impairment. Our data suggest that HSYA might be a promising therapeutic candidate for attenuating Hcy-induced AD-like pathological and behavioral deficits.