Recurrent syncope due to ischemia with non-obstructive coronary artery disease: a case report.

BACKGROUND: Ischemia with non-obstructive coronary artery disease is a prevalent form of ischemic heart disease. The majority of ischemia with non-obstructive coronary artery disease cases are attributed to underlying factors such as coronary microvascular dysfunction (CMD) and/or coronary artery spasm. Ischemia with non-obstructive coronary artery disease can present with various clinical manifestations. Recurrent syncope is an atypical complaint in patients with ischemia with non-obstructive coronary artery disease. CASE PRESENTATION: This case report describes the presentation of a 58-year-old Chinese male patient who experienced repeated episodes of syncope. The syncope was found to be caused by concomitant coronary artery spasm and presumptive coronary microvascular dysfunctionc suggested by "slow flow" on coronary angiography. The patient was prescribed diltiazem sustained-release capsules, nicorandil, and atorvastatin. During the three-month follow-up conducted on our outpatient basis, the patient did not experience a recurrence of syncope. CONCLUSION: This study highlights the importance of considering ischemia with non-obstructive coronary artery disease as a potential cause of syncope in the differential diagnosis. It emphasizes the need for early diagnosis of ischemia with non-obstructive coronary artery disease to facilitate more effective management strategies.

Asymmetry of carbon sequestrations by plant and soil after forestation regulated by soil nitrogen.

Forestation is regarded as an effective strategy for increasing terrestrial carbon sequestration. However, its carbon sink potential remains uncertain due to the scarcity of large-scale sampling data and limited knowledge of the linkage between plant and soil C dynamics. Here, we conduct a large-scale survey of 163 control plots and 614 forested plots involving 25304 trees and 11700 soil samples in northern China to fill this knowledge gap. We find that forestation in northern China contributes a significant carbon sink (913.19 ± 47.58 Tg C), 74% of which is stored in biomass and 26% in soil organic carbon. Further analysis reveals that the biomass carbon sink increases initially but then decreases as soil nitrogen increases, while soil organic carbon significantly decreases in nitrogen-rich soils. These results highlight the importance of incorporating plant and soil interactions, modulated by nitrogen supply in the calculation and modelling of current and future carbon sink potential.

Exosomal miR­152­5p/ARHGAP6/ROCK axis regulates apoptosis and fibrosis in cardiomyocytes.

Acute myocardial infarction (AMI) is a fatal cardiovascular disease with a high mortality rate. The discovery of effective biomarkers is crucial for the diagnosis and treatment of AMI. In the present study, miRNA sequencing and reverse transcription-quantitative polymerase chain reaction techniques revealed that the expression of exosome derived miR-152-5p was significantly downregulated in patients with AMI compared with healthy controls. A series of functional validation experiments were then performed using H9c2 cardiomyocytes. Following transfection of the cardiomyocytes using an miR-152-5p inhibitor, immunofluorescence staining of a-smooth muscle actin revealed a marked increase in fibrosis. Western blotting revealed that the expression levels of the apoptotic protein Bax, TNF-α and collagen-associated proteins were significantly increased, whereas those of the apoptosis-inhibiting factor Bcl-2 and vascular endothelial growth factor A were significantly decreased. Furthermore, the binding of Rho GTPase-activating protein 6 (ARHGAP6) to miR-152-5p was predicted using an online database and verified using a dual-luciferase reporter gene assay. The transfection of cardiomyocytes with miR-152-5p mimics was found to inhibit the activation of ARHGAP6 and Rho-associated coiled-coil containing kinase 2 (ROCK2). These results suggest that miR-152-5p targets ARHGAP6 through the ROCK signaling pathway to inhibit AMI, which implies that miR-152-5p may be a diagnostic indicator and potential target for treatment of myocardial infarction.

Increased risk of sleep-related movement disorder in patients with Helicobacter pylori infection: A nationwide population-based study.

Background and purpose: Evidence increasingly suggests that Helicobacter pylori infection (HPI) is associated with movement disorders such as Parkinson's disease (PD). However, the relationship between HPI and sleep-related movement disorders (SRMD) remains unknown. This nationwide population-based study tried to demonstrate whether patients with HPI have a higher risk of developing SRMD in a general adult population. Methods: The study cohort enrolled 9,393 patients who were initially diagnosed with HPI between 2000 and 2013. Notably, 37,572 age- and sex-matched controls without prior HPI were selected as the reference. A Cox proportional hazard regression analysis was performed for multivariate adjustment. Results: Patients with HPI had a higher risk of developing SRMD (adjusted hazard ratio [HR] = 2.18, 95% confidence interval [CI] = 1.26-3.82, p < 0.01). Patients with HPI aged ≥65 years exhibited the highest risk (HR = 3.01, 95% CI = 1.90-5.30, p < 0.001), followed by patients aged 45-64 years (HR = 1.69, 95% CI = 1.26-2.90, p <0.01) and <45 years (HR = 1.49, 95% CI = 1.12-2.49, p < 0.01). Patients were most likely to develop SRMD 5 years or more after diagnosis of HPI (HR = 3.33, 95% CI = 1.97-5.89, p < 0.001). The increased risk of SRMD in male patients with HPI (HR = 2.73, 95% CI = 1.53-4.79, p < 0.001) was greater than in female patients (HR = 1.14, 95% CI = 1.04-1.65, p < 0.05). Conclusion: Patients with HPI were associated with an increased risk for SRMD, with a higher risk in men, aged ≥65 years, and diagnosed for more than 5 years.

Association of serum biomarkers with early neurologic improvement after intravenous thrombolysis in ischemic stroke.

BACKGROUND: Early neurologic improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue based on a prospective cohort. METHODS: In INTRECIS study, five centers were designed to consecutively collect blood sample from enrolled patients. The patients with ENI and without ENI were matched by propensity score matching with a ratio of 1:1. Preset 49 biomarkers were measured through microarray analysis. Enrichment of gene ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers. RESULTS: Of 358 patients, 19 patients with ENI were assigned to ENI group, while 19 matched patients without ENI were assigned to Non ENI group. A total of nine biomarkers were found different between two groups, in which serum levels of chemokine (C-C motif) ligand (CCL)-23, chemokine (C-X-C motif) ligand (CXCL)-12, insulin-like growth factor binding protein (IGFBP)-6, interleukin (IL)-5, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, plasminogen activator inhibitor (PAI)-1, platelet-derived growth factor (PDGF)-AA, suppression of tumorigenicity (ST)-2, and tumor necrosis factor (TNF)-α were higher in the ENI group, compared with those in the Non ENI group. CONCLUSIONS: We found that serum levels of CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α at admission were associated with post-thrombolytic ENI in stroke. The role of biomarkers warrants further investigation. TRIAL REGISTRATION: Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT02854592.

Effects of smoking on the prognosis of anterior circulation acute ischemic stroke with intravenous thrombolysis.

OBJECTIVE: This is a single-center retrospective analysis of the clinical data of 516 patients with acute ischemic stroke who underwent intravenous thrombolysis. This study was conducted to compare the therapeutic efficacy of smokers and non-smokers. METHODS: Univariate analysis was used to analyze and compare the clinical data of smokers and non-smokers. Multivariate analysis was used to assess risk factors affecting the 90-day modified Rankin Scale (mRS) score. RESULTS: Among the 516 patients, 235 (45.5 %) were smokers. Univariate analysis showed that smokers have a better 90-day prognosis and a lower 90-day mRS score than non-smokers. Multivariate logistic regression analysis showed that smoking is not a protective factor affecting prognosis, while baseline National Institutes of Health Stroke Scale (NIHSS) score was an independent risk factor affecting the 90-day functional outcome. Subgroup analysis did not determine a relationship between the 90-day mRS score and the smoking intensity and duration. CONCLUSION: Smoking was not associated with a good 90-day prognosis after intravenous thrombolysis (IVT) treatment. The good clinical outcome of smokers in univariate analysis was bound up with their baseline characteristics. Baseline NIHSS score was the independent risk factor that affected the 90-day outcome of AIS patients undergoing IVT.

Change of Serum Biomarkers to Post-Thrombolytic Symptomatic Intracranial Hemorrhage in Stroke.

Background: Symptomatic intracranial hemorrhage (sICH) is a terrible complication after intravenous alteplase in stroke, and numerous biomarkers have been investigated. However, the change of biomarkers to sICH has not been well determined. Aim: To investigate the association between the change of biomarkers and sICH. Methods: This is a prospective cohort study, and patients with sICH within 24 h after thrombolysis were enrolled, while patients without sICH were matched by propensity score matching with a ratio of 1:1. The blood samples were collected before and 24 h after intravenous thrombolysis (IVT), and preset 49 serum biomarkers were measured by microarray analysis. Protein function enrichment analyses were performed to detect the association between the change of biomarkers and sICH. Results: Of consecutive 358 patients, 7 patients with sICH in 24 h were assigned to the sICH group, while 7 matched patients without any ICH were assigned to the non-sICH group. A total of 9 biomarkers were found to significantly change before vs. after thrombolysis between groups, including increased biomarkers, such as brain-derived neurotrophic factor, C-C motif chemokine ligand (CCL)-24, interleukin (IL)-6, IL-10, IL-18, and vascular endothelial growth factor, and decreased biomarkers, such as CCL-11, intercellular adhesion molecule-1, and IL-7. Conclusions: This is the first study to identify changes in serum biomarkers in patients with sICH after IVT, and found that 6 neuroinflammatory and 3 neuroprotective biomarkers may be associated with brain injury following post-thrombolytic sICH. Clinical Trial Registration: https://www.clinicaltrials.gov, identifier: NCT02854592.

Association of Serum Biomarkers With Post-Thrombolytic Symptomatic Intracranial Hemorrhage in Stroke: A Comprehensive Protein Microarray Analysis From INTRECIS Study.

BACKGROUND: Symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis is closely related to the poor outcome of stroke. AIMS: To determine the serum biomarkers associated with sICH based on the INTRECIS study. METHODS: Enrolled patients with sICH and without any ICH were matched by propensity score matching with the ratio of 1:1. Preset 49 biomarkers were measured by protein microarray analysis. Gene Ontology and Pathway Enrichment Analysis and protein-protein interaction network (PPI) were analyzed in the identified biomarkers. RESULTS: Of the consecutive 358 patients, eight patients occurred with sICH, which was assigned as an sICH group, while eight matched patients without any ICH were assigned as a Non-sICH group. A total of nine biomarkers were found significantly different between groups, among which the levels of interferon (IFN)-γ and interleukin (IL)-4 were higher, while the levels of C-reactive protein (CRP), glial cell line-derived neurotrophic factor (GDNF), insulin-like growth factor-binding protein (IGFBP)-6, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, matrix metalloprotein (MMP)-2, plasminogen activator inhibitor (PAI)-1, and platelet-derived growth factor (PDGF)-AA were lower in the sICH group compared with those in the Non-sICH group. CONCLUSIONS: Our finding indicated that baseline serum CRP, GDNF, IFN-γ, IGFBP-6, IL-4, LYVE-1, MMP-2, PAI-1, and PDGF-AA levels were associated with post-thrombolytic sICH in stroke.

miR-6718-5p and miR-4329 can be used as potential biomarkers for acute myocardial infarction.

BACKGROUND: The prevention and prognosis of the onset or recurrence of acute myocardial infarction (AMI) is a difficult problem in contemporary research. METHODS: In this study, peripheral blood samples were collected from seven patients with AMI and nine healthy adults, and exosome microRNAs (miRNAs) were extracted. The miRNA differential expression profiles of serum exosomes in patients with AMI were obtained by using the next-generation sequencing technology combined with bioinformatics analysis. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to verify the primary screening of differential exosome miRNAs to reveal the possible mechanism of their action on AMI. RESULTS: Compared with healthy individuals, 544 miRNAs were upregulated and 518 miRNAs were downregulated in AMI patients preoperatively. Among these miRNAs, we selected miR-6718 and miR-4329 for qPCR verification. The expression of miR6718 and miR-4329 in patients with myocardial infarction was significantly lower than that in normal controls.

Tanshinone­IIA inhibits myocardial infarct via decreasing of the mitochondrial apoptotic signaling pathway in myocardiocytes.

Myocardial ischemia triggers an inflammatory reaction and oxidative stress that increases apoptosis of myocardiocytes. It has been evidenced that tanshinone­IIA (Tan­IIA) protects against heart failure post­myocardial infarction via inhibition of the apoptotic pathway. The purpose of the present study was to investigate the therapeutic effect of Tan­IIA in a rat model of myocardial ischemia, and explore the possible mechanism of Tan­IIA in myocardiocytes. The rat model of myocardial ischemia was established by left anterior descending coronary artery and rats received treatment with either Tan­IIA (10 mg/kg) or PBS for 20 days continuously. The cardiac function in the experimental rat model was detected using the Sequoia 512 echocardiography system on day 21. The cell viability of myocardiocytes was assessed by CCK­8 assay. Apoptosis of myocardiocytes and myocardial tissue was evaluated by TUNEL assay. The infarct size of the myocardial ischemia rat was determined through 2,3,5­triphenyltetrazolium chloride (TTC) and Evan blue double staining assay. The expression levels of apoptotic factors were assessed by immunohistochemistry, western blotting and immunofluorescence. The results demonstrated that Tan­IIA reduced myocardial infarct size and improved the myocardial function in myocardial ischemia rats. Compared with PBS, Tan­IIA treatment decreased myocardial tissue apoptosis and the expression levels of caspase­3, Cyto c and Apaf­1 in myocardial tissue. Tan­IIA increased the viability of impaired myocardiocytes, inhibited apoptosis of impaired myocardiocytes and increased Bcl­2 and Bak expression in myocardiocytes. In addition, Tan­IIA increased Bim and CHOP, decreased TBARS, ROS and H2O2 production, decreased ATF4 and IRE1α expression, and reduced intracellular calcium and oxidative stress in myocardiocytes. Furthermore, caspase­3 overexpression blocked Tan­IIA­decreased apoptosis of myocardiocytes. In conclusion, the data in the present study indicated that Tan­IIA improved myocardial infarct and apoptosis via the endoplasmic reticulum stress­dependent pathway and mitochondrial apoptotic signaling pathway.

Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer.

Tumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

Effectiveness of intravenous r-tPA versus UK for acute ischaemic stroke: a nationwide prospective Chinese registry study.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (r-tPA) and urokinase (UK) are both recommended for the treatment of acute ischaemic stroke (AIS) in China, but with few comparative outcome data being available. We aimed to compare the outcomes of these two thrombolytic agents for the treatment of patients within 4.5 hours of onset of AIS in routine clinical practice in China. METHODS: A pre-planned, prospective, nationwide, multicentre, real-world registry of consecutive patients with AIS (age ≥18 years) who received r-tPA or UK within 4.5 hours of symptom onset according to local decision-making and guideline recommendations during 2017-2019. The primary effectiveness outcome was the proportion of patients with an excellent functional outcome (defined by modified Rankin scale scores 0 to 1) at 90 days. The key safety endpoint was symptomatic intracranial haemorrhage according to standard definitions. Multivariable logistic regression was used for comparative analysis, with adjustment according to propensity scores to ensure balance in baseline characteristics. RESULTS: Overall, 4130 patients with AIS were registered but 320 had incomplete or missing data, leaving 3810 with available data for analysis of whom 2666 received r-tPA (median dose 0.88 (IQR 0.78-0.90) mg/kg) and 1144 received UK (1.71 (1.43-2.00)×104 international unit per kilogram). There were several significant intergroup differences in patient characteristics: r-tPA patients were more educated, had less history of stroke, lower systolic blood pressure, greater neurological impairment and shorter treatment times from symptom onset than UK patients. However, in adjusted analysis, the frequency of excellent outcome (OR 1.18, 95% CI 1.00 to 1.40, p=0.052) and symptomatic intracranial haemorrhage (OR 0.70, 95% CI 0.33 to 1.47, p=0.344) were similar between groups. CONCLUSIONS: UK may be as effective and carry a similar safety profile as r-tPA in treating mild to moderate AIS within guidelines in China. REGISTRATION: http://www.clinicaltrials.gov. unique identifier: NCT02854592.

Downregulation of MiR-218-5p Protects Against Oxygen-Glucose Deprivation/Reperfusion-Induced Injuries of PC12 Cells via Upregulating N-myc Downstream Regulated Gene 4 (NDRG4).

BACKGROUND Cerebral ischemia is a major player of acute ischemic stroke (AIS) and mainly caused by blood vessels obstruction-induced reduced blood flow. Furthermore, miR-218-5p level was elevated in patients with AIS compared with controls. The present study investigated the biochemical mechanisms underlying the role of miR-218-5p in AIS in vitro. MATERIAL AND METHODS PC12 cells were chosen to establish oxidative-glucose deprivation/re-oxygenation (OGD/R) injury model. The interaction between miR-218-5p and N-myc downstream regulated gene 4 (NDRG4) was evaluated by Luciferase reporter assay. The levels of NDRG4, endothelial nitric oxide synthase (eNOS) and protein related to cell apoptosis were quantitatively analyzed with real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting. Inflammatory cytokines, myeloperoxidase (MPO) and oxidative stress status were measured using specific commercial assay kits. Further, the cells apoptosis was analyzed with flow cytometry assay. RESULTS MiR-218-5p level was notably increased in OGD/R injured PC12 cells and directly targeted NDRG4. MiR-218-5p inhibitor significantly inhibited inflammatory cytokines release, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1ß (IL-1ß), and monocyte chemotactic protein 1 (MCP-1). In addition, miR-218-5p downregulation ameliorated nitric oxide (NO) and eNOS levels and suppressed the inducible nitric oxide synthase (iNOS) expression and cell apoptosis. However, NDRG4 silencing abolished all corrective effects of miR-218-5p inhibitor in OGD/R injured PC12 cells. CONCLUSIONS Downregulation of miR-218-5p protect against OGDR-induced injuries of PC12 cells through reducing inflammatory cytokines secretion, oxidative stress status, apoptosis rate and maintenance of endovascular homeostasis via upregulating NDRG4. MiR-218-5p may serve as a novel effective biomarker to monitor AIS progression.

Increased Legumain/Smad3 expression in atherosclerotic plaque of rat thoracic aorta.

OBJECTIVES: The purpose of this study was to investigate the role of legumain in the formation and stability of atherosclerotic plaque, as well as to explore the association between legumain with Smad3 pathway in a rat atherosclerosis model. METHODS: Rat with thoracic aorta atherosclerosis was established and received treatment with statin (n = 15 each) or controls (n = 10). Serum level of legumain was determined by enzyme-linked immunosorbent assay. Legumain and Smad3 aortic expression levels were assessed by immunohistochemistry and fluorescence microscopy. Protein and mRNA levels were analyzed using Western blot analysis and reverse transcriptase coupled polymerase chain reaction, respectively. RESULTS: The atherosclerotic group showed higher serum legumain level than control and statin group. Expression of legumain and Smad3 in macrophages and foam cells was increased in atherosclerotic group compared to control and statin group. The protein and mRNA levels of legumain and Smad3 were significantly attenuated by statin treatment (p < 0.05). For all groups, legumain expression was correlated linearly with Smad3 at mRNA (coefficient: 0.94) and protein (coefficient: 097) level. CONCLUSIONS: Legumain and Smad3 expression is highly expressed in mainly atherosclerotic plaque macrophages and linearly related, which is attenuated by statin therapy, suggesting legumain a potential Smad3 pathway-related marker of atherosclerosis.

Role of IL-37 in Cardiovascular Disease Inflammation.

Inflammation is closely related to the pathogenesis and prognosis of cardiovascular disease (CVD). Interleukin-37 (IL-37), an anti-inflammatory IL-1 family cytokine, shifts cytokine expression from pro- to anti-inflammation via regulation of macrophage polarization and lipid metabolism. In macrophages, IL-37 functions through both intracellular and extracellular pathways to regulate the activity of NF-kB and PTEN as well as the expression of cytokines, including IL-1ß, IL-6, and IL-10. Moreover, IL-37 levels are increased in the serum of patients with heart failure, atherosclerosis, and acute coronary syndrome with no evidence of anti-inflammatory effects. However, transgenic overexpression of IL-37 improves cardiac infarct and attenuates atherosclerosis plaque expansion. Hence, it is worthwhile to investigate the precise mechanism and role of IL-37 in the pathogenesis of CVD, which may provide deeper understanding of the inflammatory response in this context. This review summarizes the regulatory role of IL-37 in systematic inflammation induced by CVD and highlights recent advancements in the clinical application of IL-37 as a therapeutic agent or biomarker for diagnosis of CVD.

Increased risk of sleep apnoea among primary headache disorders: a nationwide population-based longitudinal study.

BACKGROUND: Primary headache disorders (PHDs) are associated with sleep problems. It is suggested that headache and sleep disorder share anatomical and physiological characteristics. We hypothesised that patients with PHDs were exposed to a great risk for developing sleep apnoea (SA). METHODS: In this retrospective longitudinal study, the data obtained from the Longitudinal Health Insurance Database in Taiwan were analysed. The study included 1346 patients with PHDs who were initially diagnosed and 5348 patients who were randomly selected and age/sex matched with the study group as controls. PHDs, SA, comorbidities and other confounding factors were defined based on International Classification of Diseases, Ninth Revision, Clinical Modification. Cox proportional hazards regressions were employed to examine adjusted HRs after adjusting with confounding factors. RESULTS: Our data revealed that patients with PHDs had a higher risk (HR 2.17, 95% CI 1.259 to 3.739, p<0.05) to develop SA compared with matched cohorts, whereas patients with migraine exhibited a high risk (HR 2.553, 95% CI 1.460 to 4.395, p<0.01). The results showed that patients with PHDs aged 18-44 exhibited highest risk of developing SA. In addition, males with PHDs exhibited an HR 3.159 (95% CI 1.479 to 6.749, p<0.01) for developing SA, respectively. The impact of PHDs on SA risk was progressively increased by various follow-up time intervals. CONCLUSION: Our results suggest that PHDs are linked to an increased risk for SA with sex-dependent and time-dependent characteristics.

Repetitive intrathecal injection of human NMO-IgG with complement exacerbates disease severity with NMO pathology in experimental allergic encephalomyelitis mice.

Neuromyelitis optica (NMO) is recognized as a different CNS autoimmune disease from multiple sclerosis (MS). Whether NMO-IgG contributes directly to the pathogenesis of NMO or is just a serologic marker of autoimmune responses of the disease needs to be clarified. We created MOG-induced experimental autoimmune encephalomyelitis (EAE) mice by passively transferring NMO-IgG to model the pathogenic findings in NMO patients. The mice were divided into three groups and administered intrathecal PBS, human complement with IgG from normal subjects, or IgG from AQP4(+) patients on days 8 and 11 after immunization. The EAE scores of EAE mice with intrathecal NMO-IgG injection were significantly elevated 14 days post-immunization. All of the mice were sacrificed for brain and spinal cord pathology analysis on day 21 post-immunization. Compared to mice given normal human IgG, EAE mice injected with NMO-IgG had markedly decreased AQP4 and glial fibrillary acidic protein (GFAP) expression and fluorescent intensity in the brain and spinal cord but more scattered deposition of complement (C9neo). Thus, our studies not only support the pathogenic role of NMO-IgG with complement in NMO disease but also provide a platform for the development of future therapeutics.

Patterns of gray matter alterations in migraine and restless legs syndrome.

Objectives: Migraine and restless legs syndrome (RLS) are often comorbid and share elements of pathology; however, their neuroanatomical underpinnings are poorly understood. This study aimed to identify patterns of gray matter volume (GMV) alteration specific to and common among patients with RLS, migraine, and comorbid migraine and RLS. Methods: High-resolution T1-weighted images were acquired from 116 subjects: 27 RLS patients, 22 migraine patients, 22 patients with comorbid migraine and RLS, and 45 healthy controls. Direct group comparisons and conjunction analysis were first used to localize the distinct and shared neural signatures of migraine and RLS. We also investigated whether the shared neural signature could be replicated in an additional comorbid migraine/RLS group. Results: Compared with healthy controls, migraine patients showed GMV changes in the lateral occipital cortex, cerebellum, frontal pole, and middle frontal gyrus (MFG), and RLS patients showed GMV changes in the thalamus, middle temporal gyrus, anterior cingulate cortex, insular cortex, and MFG. In migraine, compared with RLS, GMV differences were found in the precuneus, lateral occipital and occipital fusiform cortex, superior frontal and precentral gyri, and cerebellum. Conjunction analyses for these disorders showed altered GMV in the MFG, also found in patients with comorbid migraine and RLS. The GMV of the MFG also correlated with sleep quality in patients with comorbid migraine and RLS. Interpretation: Migraine and RLS are characterized by shared and distinctive neuroanatomical characteristics, with a specific role of the MFG. These findings may be related to shared pathophysiology of these two distinct disorders.

Age-specific and gender-dependent impact of primary headache disorders on dementia risk: Population-based longitudinal study.

Dementia is a global burden of public health. Headache disorders are the third most common cause of disability worldwide and common problems in the elderly population. Few studies focused on the relationship between primary headache disorders (PHDs) and cognitive status, and the results remain controversial. The aim of this countrywide, population-based, retrospective study was to investigate potential association between PHDs and dementia risk.We enrolled 1346 cases with PHDs to match the 5384 individuals by age, gender and co-morbidities. The definition of PHDs, dementia, and risk factors of dementia was identified according to The International Classification of Diseases, Ninth Revision, Clinical Modification. Cox regression was administered for estimating hazard ratios (HR) for dementia.During more than 5 years of follow-up, PHDs individuals had 1.52 times (P <.05) greater risk to develop all dementia compared with individuals without PHDs. Elderly (aged ≥65 years) patients with PHDs displayed significantly higher risk to develop all dementia (P <.01) and non-Alzheimer non-vascular dementia (NAVD) P <.01). Female PHDs individuals were at higher risk of suffering from all dementia (P <.05) and NAVD (P <.05). The influence of PHDs on all dementia was highest in the first 2 years of observation.The results indicated PHDs are linked to a temporarily increased risk for dementia, mainly NAVD, with age-specific and gender-dependent characteristics.

Endothelial stem cells attenuate cardiac apoptosis via downregulating cardiac microRNA-146a in a rat model of coronary heart disease.

Coronary artery disease (CAD) is one of the main causes of hospitalization worldwide and has high morbidity. It has previously been demonstrated that stem cells serve an important role in improving myocardial function. MicroRNA (miRNA)-146a downregulation has been reported to inhibit vascular smooth muscle cell apoptosis in a rat model of coronary heart disease. The aim of the present study was to investigate the mechanisms underlying the effects of endothelial stem cell (ESC)-derived paracrine factors and cardiac miRNAs in CAD. Acute myocardial infarction was induced in 20 rats. Autologous ESCs (n=10; experimental group) or PBS (n=10; control group) were injected in the border zone. Reverse transcription-quantitative polymerase chain reaction, ELISA and immunohistochemistry assays were performed to analyze the therapeutic effects of ESCs in rats with coronary heart disease rats. Serum interleukin (IL)-1, IL-17 and tumor necrosis factor-α were reduced in the experimental group compared with control rats, as was the number of circulating proatherogenic cells. The results demonstrated that ESC transplantation markedly downregulated miRNA-146a expression and decreased apoptosis in the myocardium compared with the control group. Rats in the experimental group also had higher levels of vascular endothelial growth factor compared with the control group. In addition, it was demonstrated that miRNA-146 knockdown reduced cardiac apoptosis and increased VEGF expression. Furthermore, the infarct area in the border zone or rats with CAD was reduced in the experimental group compared with the control group. In conclusion, these results suggest that ESC transplantation may improve cardiac function via downregulating miR-146a, which may be have potential as a treatment for CAD.