Remote ischemic conditioning prevents ischemic cerebrovascular events in children with moyamoya disease: a randomized controlled trial.

BACKGROUND: Moyamoya disease (MMD) is a significant cause of childhood stroke and transient ischemic attacks (TIAs). This study aimed to assess the safety and efficacy of remote ischemic conditioning (RIC) in children with MMD. METHODS: In a single-center pilot study, 46 MMD patients aged 4 to 14 years, with no history of reconstructive surgery, were randomly assigned to receive either RIC or sham RIC treatment twice daily for a year. The primary outcome measured was the cumulative incidence of major adverse cerebrovascular events (MACEs). Secondary outcomes included ischemic stroke, recurrent TIA, hemorrhagic stroke, revascularization rates, and clinical improvement assessed using the patient global impression of change (PGIC) scale during follow-up. RIC-related adverse events were also recorded, and cerebral hemodynamics were evaluated using transcranial Doppler. RESULTS: All 46 patients completed the final follow-up (23 each in the RIC and sham RIC groups). No severe adverse events associated with RIC were observed. Kaplan-Meier analysis indicated a significant reduction in MACEs frequency after RIC treatment [log-rank test (Mantel-Cox), P = 0.021]. At 3-year follow-up, two (4.35%) patients had an ischemic stroke, four (8.70%) experienced TIAs, and two (4.35%) underwent revascularization as the qualifying MACEs. The clinical improvement rate in the RIC group was higher than the sham RIC group on the PGIC scale (65.2% vs. 26.1%, P < 0.01). No statistical difference in cerebral hemodynamics post-treatment was observed. CONCLUSIONS: RIC is a safe and effective adjunct therapy for asymptomatic children with MMD. This was largely due to the reduced incidence of ischemic cerebrovascular events.

The Negative Prognostic Role of Inflammatory Biomarkers in Patients With Chronic Cerebrospinal Venous Insufficiency.

BACKGROUND: The pathologic consequences of inflammatory responses in chronic cerebrospinal venous insufficiency (CCSVI) remains poorly understood. Hence, this study was aimed to evaluate the peripheral inflammatory biomarkers in patients with intracranial and extracranial CCSVI pathology. In addition, the relationship between inflammatory cytokine profile and CCSVI prognosis was also evaluated. METHODS: Patients diagnosed with CCSVI between July 2017 and July 2019 were included and subsequently divided into 3 groups based on the location of stenosis. The inflammatory biomarker assay included neutrophil-to-lymphocyte ratios (NLRs), platelet-to-lymphocyte ratios (PLRs), red blood cell distribution widths (RDW), C-reactive protein (CRP) levels, interleukin-6 (IL-6) levels, and neuron-specific enolase levels. Clinical outcomes were assessed using the modified Rankin Scale and Patient Global Impression of Change score. Univariate and multivariate regression analyses were performed to identify significant prognostic factors for poorer outcomes. Finally, we established a nomogram based on the multivariate regression analysis. RESULTS: We enrolled 248 patients in total, including 102 males and 146 females, with an average age of 57.85±12.28 years. Compared with patients with internal jugular vein stenosis, cerebral venous sinus stenosis (CVSS) patients were mostly younger and had been suffering from headaches and severe papilledema. Higher levels of NLR, RDW, and CRP were also observed in the CVSS group. Multivariate analysis indicated that NLR, PLR, and IL-6 were the independent prognostic factors for poor CCSVI outcomes. CONCLUSIONS: The clinical presentations and increases in NLR, PLR, IL-6, and CRP levels could be distinctly marked in patients with CVSS-related CCSVI than that in internal jugular vein stenosis-related CCSVI, indicating poor prognostic outcomes in these patients. A proinflammatory state might be associated with CCSVI pathology.

Potential Anti-Inflammatory and Anti-Coagulation Effects of One-Time Application of Remote Ischemic Conditioning in Patients With Subacute/Chronic Cerebral Arteriostenosis and Venostenosis.

BACKGROUND: Remote ischemic conditioning (RIC) is an extremely simple, non-invasive, and cost-effective method with a neuroprotective effect. This study aimed to evaluate the immediate effects of one-time application of RIC on inflammation and coagulation in patients with chronic cerebral vascular stenosis, and compare the different effects of RIC on cerebral arteriostenosis and cerebral venostenosis. METHOD: A total of 47 patients with defined cerebral arteriostenosis (n=21) or venostenosis (n=26) were prospectively enrolled. RIC intervention was given once with 5 cycles of inflating and deflating for 5 minutes alternately. Blood was sampled 5 minutes before and after RIC for inflammatory and thrombophilia biomarkers. Differences in inflammatory and thrombotic variables at differing time points in the group were assessed using paired t tests or Wilcoxon matched-pairs signed-rank test. RESULTS: Patients with cerebral arteriostenosis had a higher level of pre-RIC neutrophil-to-lymphocyte ratio ( P =0.034), high-sensitivity C-reactive protein ( P =0.037), and fibrinogen ( P =0.002) than that with cerebral venostenosis. In the arterial group, levels of fibrinogen ( P =0.023) decreased, and interleukin-6 levels were elevated ( P =0.019) after a single RIC. Age was negatively related to interleukin-6, C-reactive protein, and fibrinogen. CONCLUSION: One-time RIC interventions may show seemingly coexisted proinflammatory and anti-coagulation effects of a single bout on patients with cerebral arteriostenosis. Older age was a negative predictor for multiple biomarkers in the cerebral arteriostensosis group. The protective effect of RIC on cerebral venostenosis patients needs to be further studied in a larger sample size.

Advancements in our understanding of circular and long non-coding RNAs in spinal cord injury.

Spinal cord injury (SCI), either from trauma or degenerative changes, can result in severe disability and impaired quality of life. Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy. Recent studies have shown that non-coding RNAs, including both long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), regulate various cellular processes in SCI. In this review, we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression. Current evidence for the roles of lncRNAs and circRNAs in neuronal cell death and glial cell activation will also be reviewed. Finally, the possibility that lncRNAs and circRNAs are novel modulators of SCI pathogenesis will be discussed.

High-Resolution Magnetic Resonance Black Blood Thrombus Imaging and Serum D-Dimer in the Confirmation of Acute Cortical Vein Thrombosis.

Cerebral cortical vein thrombosis (CCVT) is often misdiagnosed because of its non-specific diagnostic symptoms. Here, we analyzed a cohort of patients with CCVT in hopes of improving understandings and treatments of the disease. A total of 23 patients with CCVT (confirmed with high-resolution imaging), who had been diagnosed between 2017 and 2019, were enrolled in this cohort study. Baseline demographics, clinical manifestations, laboratory data, radiological findings, treatment, and outcomes were collected and analyzed. Fourteen females and nine males were enrolled (mean age: 32.7 ± 11.9 years), presenting in the acute (within 7 days, n = 9), subacute (8-30 days, n = 7), and chronic (over 1 month, n = 7) stages. Headaches (65.2%) and seizures (39.1%) were the most common symptoms. Abnormally elevated plasma D-dimers were observed in the majority of acute stage patients (87.5%). The diagnostic accuracy of contrast-enhanced magnetic resonance venography (CE-MRV) and high-resolution magnetic resonance black-blood thrombus imaging (HR-MRBTI) in detecting CCVT were 57.1 and 100.0%, respectively. All patients had good functional outcomes after 6-month of standard anticoagulation (mRS 0-1) treatment. However, four CCVT patients that had cases involving multiple veins showed symptom relief after batroxobin therapy (p = 0.030). HR-MRBTI may be a fast and accurate tool for non-invasive CCVT diagnosis. HR-MRBTI combined with D-dimer can also precisely identify the pathological stage of CCVT. Batroxobin may safely accelerate cortical venous recanalization in combination with anticoagulation. Follow-up studies with larger sample sizes are suggested to evaluate the safety and efficacy of batroxobin for treating CCVT.

Normobaric oxygen may correct chronic cerebral ischemia-mediated EEG anomalies.

AIMS: To explore the safety and efficacy of normobaric oxygen (NBO) on correcting chronic cerebral ischemia (CCI) and related EEG anomalies. METHODS: This prospective randomized trial (NCT03745092) enrolled 50 cases of CCI patients, which were divided into NBO (8 L/min of oxygen supplement) group and control group (room air) randomly, and also enrolled 21 healthy volunteers. Two times of 30-min EEG recordings with the interval of 45min of NBO or room air were analyzed quantitatively. RESULTS: The CCI-mediated EEG presented with two patterns of electrical activities: high-power oscillations (high-power EEG, n = 26) and paroxysmal slow activities under the normal-power background (normal-power EEG, n = 24). The fronto-central absolute power (AP) of the beta, alpha, theta, and delta in the high-power EEG was higher than that in healthy EEG (p < 0.05). The fronto-central theta/alpha, delta/alpha and (delta + theta)/(alpha + beta) ratios in the normal-power EEG were higher than those in healthy EEG (p < 0.05). The high-power EEG in NBO group had higher fronto-central AP reduction rates than those in control group (p < 0.05). NBO remarkably reduced the fronto-central theta/alpha, delta/alpha, and (delta + theta)/(alpha + beta) ratios in the normal-power EEG (p < 0.05). CONCLUSIONS: NBO rapidly ameliorates CCI-mediated EEG anomalies, including attenuation of the abnormal high-power oscillations and the paroxysmal slow activities associated with CCI.

Ruxolitinib treatment permits lower cumulative glucocorticoid dosing in children with secondary hemophagocytic lymphohistiocytosis.

BACKGROUND: This study aimed to analyze the effects of ruxolitinib on children with secondary hemophagocytic lymphohistiocytosis (HLH). METHODS: Eleven pediatric patients diagnosed with HLH and treated with ruxolitinib (ruxolitinib group: group R) between November 2017 and August 2018 were retrospectively analyzed. Eleven age-matched pediatric patients with HLH undergoing conventional treatment (control group: group C) during the same period were also analyzed. RESULTS: In group R, three patients who did not respond to methylprednisolone (MP) pulse and intravenous immunoglobulin (IVIG) therapies were treated with Ruxolitinib and their temperature decreased to normal levels. Four patients had normal temperature after conventional treatment (dexamethasone and etoposide, with or without cyclosporine A), but they had severe organ involvement, including obvious yellowing of the skin, increased liver enzyme levels and neuropsychiatric symptoms, and they were all ameliorated with ruxolitinib treatment. Four patients were relieved with ruxolitinib therapy alone. In group C, the body temperatures of eleven patients decreased to normal levels after conventional treatment. The body temperature of group R patients decreased to normal levels more rapidly than that of group C patients. The glucocorticoid dosage in group R was significantly lower than that in group C. Both groups were followed-up for 2-2.5 years. No obvious adverse drug reactions to ruxolitinib were observed during treatment and follow-up. CONCLUSION: Ruxolitinib might be an effective drug in controlling body temperature and reducing inflammation indicators. It might be a potential replacement for glucocorticoid therapy for HLH treatment in children, thereby reducing or avoiding glucocorticoid-related adverse reactions.

Clinical characteristics, inflammation and coagulation status in patients with immunological disease-related chronic cerebrospinal venous insufficiency.

BACKGROUND: Immunological disease-related chronic cerebrospinal venous insufficiency (CCSVI) is rarely reported. This study aimed to analyze clinical characteristics, inflammation, and coagulation status in patients with immunological disease-related CCSVI. METHODS: Patients with CCSVI were enrolled from 2017 to 2019 and divided into three cohorts based on their immunological disease backgrounds, including groups with confirmed autoimmune disease, with suspected/subclinical autoimmune disease, and with non-immunological etiology. Immunological, inflammatory, and thrombophilia biomarker assay in blood samples were obtained. Mann-Whitney U test or Fisher's exact test was used to compare continuous variables or categorical variables between the CCSVI patients with or without the immunological etiology. Spearman's correlation analysis was conducted among age, baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), interleukin-6 (IL-6), C-reactive protein (CRP), and neuron-specific enolase (NSE) in the three groups. RESULTS: A total of 255 consecutive patients with CCSVI were enrolled, including three subgroups: CCSVI with confirmed autoimmune disease (n=41), CCSVI with suspected/subclinical autoimmune disease (n=116) and CCSVI with non-immunological etiology (n=98). In the first subgroup, a series of 41 cases was confirmed with eight different autoimmune diseases including antiphospholipid syndrome (n=18), Sjögren's syndrome (n=8), immunoglobulin G4-related disease (n=7), Behçet's disease (n=2), autoimmune hepatitis (n=2), Wegener's granulomatosis (n=2), systemic sclerosis (n=1) and AQP4 antibody-positive neuromyelitis optica spectrum disorder (n=1). Groups with immunological etiology did not show a higher incidence of thrombophilia or increased pro-inflammatory biomarkers (e.g., neutrophil, IL-6). However, patients with non-immunological etiology had a higher baseline level of CRP. Additionally, baseline PLR was moderately correlated to NLR and CRP in CCSVI patients with non-immunological etiology and suspected/subclinical autoimmune disease. CONCLUSIONS: The formation of CCSVI may be based on the inflammatory process, facilitated by multiple risk factors, among which medical history of immunological diseases may play a significant role due to the intricate relationship between inflammation and coagulation. Moreover, CCSVI may also cause an independent inflammatory injury in venous walls, leading to focal stenosis or thrombus, without attacks from autoimmune antibodies.

The antiphospholipid syndrome may induce non-thrombotic internal jugular vein stenosis: two cases report.

BACKGROUND: Antiphospholipid syndrome (APS) is associated with a high incidence of thrombotic events, either arterial thrombosis or venous thrombosis. However, APS-related non-thrombotic venous stenosis is rarely reported. CASE PRESENTATION: This study described two cases of young women with APS-related internal jugular vein stenosis (IJVS) and reviewed current literature on this issue, including clinical features, diagnosis, and treatment. CONCLUSIONS: IJVS is a rather rare complication of APS. Two cases were reported for the first time that high titer of antiphospholipid antibodies (aPL) might mediate direct vessel wall damage and further induce venous stenosis despite long-term standardized anticoagulation to prevent thrombus formation. Therefore, dynamic monitoring of autoantibodies and concomitant use of anticoagulants and corticosteroids may be necessary to the management of APS and its complications.

Normobaric oxygen therapy attenuates hyperglycolysis in ischemic stroke.

Normobaric oxygen therapy has gained attention as a simple and convenient means of achieving neuroprotection against the pathogenic cascade initiated by acute ischemic stroke. The mechanisms underlying the neuroprotective efficacy of normobaric oxygen therapy, however, have not been fully elucidated. It is hypothesized that cerebral hyperglycolysis is involved in the neuroprotection of normobaric oxygen therapy against ischemic stroke. In this study, Sprague-Dawley rats were subjected to either 2-hour middle cerebral artery occlusion followed by 3- or 24-hour reperfusion or to a permanent middle cerebral artery occlusion event. At 2 hours after the onset of ischemia, all rats received either 95% oxygen normobaric oxygen therapy for 3 hours or room air. Compared with room air, normobaric oxygen therapy significantly reduced the infarct volume, neurological deficits, and reactive oxygen species and increased the production of adenosine triphosphate in ischemic rats. These changes were associated with reduced transcriptional and translational levels of the hyperglycolytic enzymes glucose transporter 1 and 3, phosphofructokinase 1, and lactate dehydrogenase. In addition, normobaric oxygen therapy significantly reduced adenosine monophosphate-activated protein kinase mRNA expression and phosphorylated adenosine monophosphate-activated protein kinase protein expression. These findings suggest that normobaric oxygen therapy can reduce hyperglycolysis through modulating the adenosine monophosphate-activated protein kinase signaling pathway and alleviating oxidative injury, thereby exhibiting neuroprotective effects in ischemic stroke. This study was approved by the Institutional Animal Investigation Committee of Capital Medical University (approval No. AEEI-2018-033) on August 13, 2018.

Cyclosporine-A-Induced Intracranial Thrombotic Complications: Systematic Review and Cases Report.

This study reported two cases of intracranial thrombotic events of aplastic anemia (AA) under therapy with cyclosporine-A (CsA) and reviewed both drug-induced cerebral venous thrombosis (CVT) and CsA-related thrombotic events systematically. We searched PubMed Central (PMC) and EMBASE up to Sep 2019 for publications on drug-induced CVT and Cs-A-induced thrombotic events. Medical subject headings and Emtree headings were used with the following keywords: "cyclosporine-A" and "cerebral venous thrombosis OR cerebral vein thrombosis" and "stroke OR Brain Ischemia OR Brain Infarction OR cerebral infarction OR intracerebral hemorrhage OR intracranial hemorrhage." We found that CsA might be a significant risk factor in inducing not only CVT but also cerebral arterial thrombosis in patients with AA.

Cervical spondylotic internal jugular venous compression syndrome.

AIMS: This study aimed to identify the clinical profiles of cervical spondylosis-related internal jugular vein stenosis (IJVS) comprehensively. METHODS: A total of 46 patients, who were diagnosed as IJVS induced by cervical spondylotic compression were recruited. The clinical manifestations and imaging features of IJVS were presented particularly in this study. RESULTS: Vascular stenosis was present in 69 out of the 92 internal jugular veins, in which, 50.7% (35/69) of the stenotic vessels were compressed by the transverse process of C1, and 44.9% (31/69) by the transverse process of C1 combined with the styloid process. The transverse process of C1 compression was more common in unilateral IJVS (69.6% vs 41.3%, P = 0.027) while the transverse process of C1 combined with the styloid process compression had a higher propensity to occur in bilateral IJVS (52.2% vs 30.4%, P = 0.087). A representative case underwent the resection of the elongated left lateral mass of C1 and styloid process. His symptoms were ameliorated obviously at 6-month follow-up. CONCLUSIONS: This study proposes cervical spondylotic internal jugular venous compression syndrome as a brand-new cervical spondylotic subtype. A better understanding of this disease entity can be of great relevance to clinicians in making a proper diagnosis.

Remote ischemic conditioning for the treatment of ischemic moyamoya disease.

AIMS: This study investigated the safety and efficacy of remote ischemic conditioning (RIC) on ameliorating the sequelae of ischemic moyamoya disease (iMMD). METHODS: A total of 30 iMMD patients underwent long-term RIC and were followed up at 0.5, 1, and 2 years for clinical outcomes, including frequency of stroke recurrence, Patient Global Impression of Change (PGIC) scale, peak systolic velocities (PSV), and cerebral perfusion. RESULTS: During the whole RIC treatment process, no RIC-related adverse event occurred. Only one of 30 patients suffered a onetime infarction (3.3%), and the ratios of acceptable PGIC were 88.2%, 64.3%, and 92.3% at 0.5, 1, and 2 years follow-up. Kaplan-Meier analysis showed the frequency of stroke recurrence was significantly reduced after RIC (P = .013). The frequency of TIA per week was 1.1 (0.6, 2.8) prior to RIC and 0.1 (0.0, 0.5) post-RIC (P < .01). Compared to baseline, PSV values were significantly reduced after RIC treatment (P = .002 at 0.5, P = .331 at 1, and P = .006 at 2 years). In patients undergoing perfusion studies, 75% obtained improvement on followed-up SPECT and 95% on followed-up PET maps. CONCLUSIONS: Remote ischemic conditioning may be beneficial on controlling iMMD-induced ischemic events, relieving symptoms, and improving cerebral perfusion, without incidence of complications in this case series.

Baseline Red Blood Cell Distribution Width as a Predictor of Stroke Occurrence and Outcome: A Comprehensive Meta-Analysis of 31 Studies.

Background: Red blood cell distribution width (RDW) may be a potential biomarker of inflammation in patients with stroke. Elevated RDW is associated with higher incidence of stroke, unfavorable functional outcome, and increased mortality, although results are inconsistent in the reported literature. This study aims to evaluate the predictive power of RDW regarding stroke occurrence and outcome. Methods: A thorough literature search was conducted utilizing the PubMed Central (PMC) and EMBASE databases to identify studies up to May 2019. Data from these studies were pooled, and combined odds ratios/risk ratios (ORs/RRs) were estimated for the risk of stroke, functional outcome, and mortality. A subgroup analysis was also performed to explore heterogeneity in terms of population status, demographic factors (age, gender distribution, and country), and vascular risk factors (hypertension, diabetes mellitus, and current smoking). Results: A total of 31 studies with 3,487,896 patients were included in the analysis. Elevated RDW was found to be a risk factor in ischemic stroke (OR/RR 1.528; 95% confidence interval [CI] = 1.372-1.703), whereas combined OR in subarachnoid hemorrhage (SAH) was not statistically significant (OR/RR 1.835; 95% CI = 0.888-3.792). Elevated RDW posed increased risk in populations with conventionally higher risk of stroke, such as atrial fibrillation (AF) (OR/RR 1.292; 95% CI = 1.107-1.508) and diabetes mellitus (OR/RR 2.101; 95% CI = 1.488-2.968), and in community cohorts (OR/RR 1.245; 95% CI = 1.216-1.275). In addition, higher RDW was associated with unfavorable functional outcome, either at discharge (OR/RR 1.220; 95% CI = 1.070-1.39) or at 90 days (OR/RR 1.277; 95% CI = 1.155-1.413). Higher mortality was found in patients with increased RDW (OR/RR 1.278; 95% CI = 1.221-1.337), independent of demographic factors (age, gender distribution, and country). Conclusions: Baseline RDW should be integrated into clinical practice as a predictor of ischemic stroke occurrence and outcome. Future studies should also explore the dynamic change of RDW in post-stroke patients to evaluate the clinical significance of RDW and its impact on the inflammatory state of ischemic stroke.

Clinical Significance of Baseline Neutrophil-to-Lymphocyte Ratio in Patients With Ischemic Stroke or Hemorrhagic Stroke: An Updated Meta-Analysis.

Background and purpose: Stroke is a leading cause of death and acquired disability in adults today. Inflammation plays an important role in the pathophysiology of stroke. The peripheral neutrophil-to-lymphocyte ratio (NLR) is an important global inflammatory indicator becoming more mainstream in stroke care. This meta-analysis aims to evaluate the relationship between the baseline NLR and acute ischemic and hemorrhagic stroke, as well as define the clinical significance of NLR in subtypes of ischemic stroke. Methods: This meta-analysis was registered in PROSPERO with the number CRD42018105305. We went through relevant articles from PubMed Central (PMC) and EMBASE. Prospective and retrospective studies were included if related to baseline NLR levels prior to treatment in patients with ischemic or hemorrhagic stroke. Studies were identified up until April 2019. The cutoff value for NLR and the sources of odds ratios (ORs)/risk ratios (RRs) were measured. Modified Rankin Scale (mRS) was used to investigate the outcomes during clinical follow-up. Predefined criteria were used to evaluate the risk of bias in eligible studies. P-values < 0.05 were considered statistically significant. STATA version 14.0 (STATA, College Station, TX) was used in all statistical analyses. Results: Thirty-seven studies with 43,979 individuals were included in the final analysis. Higher NLR levels were correlated with increased risk of ischemic stroke (ORs/RRs = 1.609; 95% CI = 1.283-2.019), unfavorable functional outcome at 3 months (ORs/RRs = 1.851; 95% CI = 1.325-2.584), and increased mortality in patients with ischemic stroke (ORs/RRs = 1.068; 95% CI = 1.027-1.111). While in terms of hemorrhagic stroke (including SAH and ICH), elevated NLR levels only had deleterious effects on mortality (ORs/RRs = 1.080; 95% CI = 1.018-1.146). Conclusions: Baseline NLR level is a promising predictor of the clinical outcomes in both ischemic and hemorrhagic stroke. In addition, elevated NLR is also associated with a high risk of ischemic stroke occurrence. However, future studies are needed to demonstrate the underlying mechanisms and further explain this association.

Potential predictors for mental stress-induced myocardial ischemia in patients with coronary artery disease.

BACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is closely associated with adverse cardiac events in patients with coronary artery disease (CAD) and we aimed to determine whether biomarkers and blood pressure could be potential predictors of MSIMI. METHODS: This study enrolled 82 patients with documented CAD between June 1, 2017 and November 9, 2017. Patient blood samples were obtained at resting period and at the end of mental arithmetic. Then, patients were assigned to MSIMI positive group and MSIMI negative group. The main statistical methods included linear regression, receiver operating characteristic (ROC) curves, and logistic regression. RESULTS: Patients with CAD with MSIMI had significantly greater median resting N-terminal pro-brain natriuretic peptide (NT-proBNP, 141.02 [45.85-202.76] pg/mL vs. 57.95 [27.06-117.64] pg/mL; Z = -2.23, P = 0.03) and mean systolic blood pressure (SBP) (145.56 ±â€Š16.87 mmHg vs. 134.92 ±â€Š18.16 mmHg, Z = -2.13, P = 0.04) when compared with those without MSIMI. After 5-min mental stress task, those who developed MSIMI presented higher elevation of median post-stressor high sensitivity cardiac troponin I (hs-cTnI, 0.020 [0.009-0.100] ng/mL vs. 0.009 [0.009-0.010] ng/mL; Z = -2.45, P = 0.01), post-stressor NT-proBNP (138.96 [39.93-201.56] pg/mL vs. 61.55 [25.66-86.50] pg/mL; Z = -2.15, P = 0.03) compared with those without MSIMI. Using the ROC curves, and after the adjustment for basic characteristics, the multiple logistic regression analysis showed that patients presenting a post-stressor hs-cTnI ≥ 0.015 ng/mL had seven-fold increase in the risk of developing MSIMI (odds ratio [OR]: 7.09; 95% confidence interval [CI]: 1.65-30.48; P = 0.009), a rest NT-proBNP ≥ 80.51 pg/mL had nearly eight-fold increase (OR: 7.85; 95% CI: 1.51-40.82; P = 0.014), a post-stressor NT-proBNP ≥ 98.80 pg/mL had 35-fold increase (OR: 34.96; 95% CI: 3.72-328.50; P = 0.002), a rest SBP ≥ 129.50 mmHg had 11-fold increase (OR: 11.42; 95% CI: 1.21-108.17; P = 0.034). CONCLUSIONS: The present study shows that CAD patients with higher hs-cTnI level, and/or greater NT-proBNP and/or SBP are at higher risk of suffering from MSIMI when compared with those without MSIMI, indicating that hs-cTnI, NT-proBNP, SBP might be potential predictors of MSIMI.

Predicting asymptomatic coronary artery stenosis by aortic arch plaque in acute ischemic cerebrovascular disease: beyond the cervicocephalic atherosclerosis?

BACKGROUND: Asymptomatic coronary artery stenosis (ACAS) ≥50% is common in patients with acute ischemic cerebrovascular disease (AICVD), which portends a poor cardiovascular and cerebrovascular prognosis. Identifying ACAS ≥50% early may optimize the clinical management and improve the outcomes of these high-risk AICVD patients. This study aimed to investigate whether aortic arch plaque (AAP), an early atherosclerotic manifestation of brain blood-supplying arteries, could be a predictor for ACAS ≥50% in AICVD. METHODS: In this cross-sectional study, atherosclerosis of the coronary and brain blood-supplying arteries was simultaneously evaluated using one-step computed tomography angiography (CTA) in AICVD patients without coronary artery disease history. The patients were divided into ACAS ≥50% and non-ACAS ≥50% groups according to whether CTA showed stenosis ≥50% in at least one coronary arterial segment. The AAP characteristics of CTA were depicted from aspects of thickness, extent, and complexity. RESULTS: Among 118 analyzed patients with AICVD, 29/118 (24.6%) patients had ACAS ≥50%, while AAPs were observed in 86/118 (72.9%) patients. Increased AAP thickness per millimeter (adjusted odds ratio [OR]: 1.56, 95% confidence interval [CI]: 1.18-2.05), severe-extent AAP (adjusted OR: 13.66, 95% CI: 2.33-80.15), and presence of complex AAP (adjusted OR: 7.27, 95% CI: 2.30-23.03) were associated with ACAS ≥50% among patients with AICVD, independently of clinical demographics and cervicocephalic atherosclerotic stenosis. The combination of AAP thickness, extent, and complexity predicted ACAS ≥50% with an area under the receiver-operating characteristic curve of 0.78 (95% CI: 0.70-0.85, P < 0.001). All three AAP characteristics provided additional predictive power beyond cervical and intracranial atherosclerotic stenosis for ACAS ≥50% in AICVD (all P < 0.05). CONCLUSIONS: Thicker, severe-extent, and complex AAP were significant markers of the concomitant ACAS ≥50% in AICVD, possibly superior to the indicative value of cervical and intracranial atherosclerotic stenosis. As an integral part of atherosclerosis of brain blood-supplying arteries, AAP should not be overlooked in predicting ACAS ≥50% for patients with AICVD.

Batroxobin in combination with anticoagulation may promote venous sinus recanalization in cerebral venous thrombosis: A real-world experience.

AIMS: The objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black-blood thrombus imaging (MRBTI) in patients with cerebral venous thrombosis (CVT) who underwent batroxobin treatment in combination with anticoagulation. METHODS: A total of 31 CVT patients were enrolled in this real-world registry study. The patients were divided into batroxobin (n = 21) and control groups (n = 10). In addition to the same standard anticoagulation as in the control group, patients in the batroxobin group underwent intravenous batroxobin for a total of three times. RESULTS: In the batroxobin group compared with the control group, we found better odds of recanalization degree [adjusted OR (95%CI) of 8.10 (1.61-40.7)] and segment-stenosis attenuation [adjusted OR (95%CI) of 4.48 (1.69-11.9)] with batroxobin treatment. We further noted a higher ratio of patients with the attenuation of stenosis [adjusted OR (95%CI) of 26.4 (1.10-635)]; as well as a higher ratio of segments with stenosis reversion [adjusted OR (95%CI) of 4.52 (1.48-13.8)]. However, neurological deficits between the two groups showed no statistical difference at 90-day follow-up (P > 0.05). CONCLUSIONS: Batroxobin may promote venous sinus recanalization and attenuate CVT-induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit.

PM2.5 induces liver fibrosis via triggering ROS-mediated mitophagy.

BACKGROUND: The increasing epidemic of fine particulate matter (PM2.5) is a serious threat to human health. It induces the occurrence of liver fibrosis, but its molecular mechanism is not yet clear. The molecular mechanisms of PM2.5 inducing liver fibrosis were investigated in this study. METHODS: The cell viability of LX-2 cells and primary hepatic stellate cells (HSCs) was detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vitro enzyme-linked immune sorbent assay (ELISA) kits were used to detect the concentrations of antioxidant enzymes and reactive oxygen species (ROS). The mitochondrial transmembrane potential (MTP) was determined by JC-1 dye. Knockdown of Parkin was carried out by Parkin-specific siRNA transfection. Relative mRNA and protein expressions were evaluated by qRT-PCR, Western blotting, and immunofluorescence analysis. RESULTS: PM2.5 activated LX-2 cells and primary HSCs, inducing the liver fibrosis along with down-regulation of the gelatinases MMP-2, and up-regulation of myofibroblast markers collagen type I and α-SMA. The levels of ROS and reactive nitrogen species (RNS), as well as the lipid peroxidation marker malondialdehyde (MDA) were significantly up-regulated in LX-2 cells and primary HSCs treated with PM2.5. Also, the enzymatic antioxidants levels were disturbed by PM2.5. Furthermore, PM2.5 decreased the MTP, releasing cytochrome c from the mitochondria to the cytosol. The dynamics of mitochondria were regulated by PM2.5 via facilitating mitochondrial fission. The excess ROS induced by PM2.5 triggered the mitophagy by activating PINK1/Parkin pathway, and inhibition of mitophagy induced by PM2.5 diminished the liver fibrosis. CONCLUSION: PM2.5 may induce mitophagy via activating PINK1/Parking signal pathway by increasing ROS, thereby activating HSCs and causing liver fibrosis.

Understanding jugular venous outflow disturbance.

Extracranial venous abnormalities, especially jugular venous outflow disturbance, were originally viewed as nonpathological phenomena due to a lack of realization and exploration of their feature and clinical significance. The etiology and pathogenesis are still unclear, whereas a couple of causal factors have been conjectured. The clinical presentation of this condition is highly variable, ranging from insidious to symptomatic, such as headaches, dizziness, pulsatile tinnitus, visual impairment, sleep disturbance, and neck discomfort or pain. Standard diagnostic criteria are not available, and current diagnosis largely depends on a combinatory use of imaging modalities. Although few researches have been conducted to gain evidence-based therapeutic approach, several recent advances indicate that intravenous angioplasty in combination with stenting implantation may be a safe and efficient way to restore normal blood circulation, alleviate the discomfort symptoms, and enhance patients' quality of life. In addition, surgical removal of structures that constrain the internal jugular vein may serve as an alternative or adjunctive management when endovascular intervention is not feasible. Notably, discussion on every aspect of this newly recognized disease entity is in the infant stage and efforts with more rigorous designed, randomized controlled studies in attempt to identify the pathophysiology, diagnostic criteria, and effective approaches to its treatment will provide a profound insight into this issue.