Normobaric Hyperoxia Combined With Endovascular Treatment Based on Temporal Gradient: A Dose-Escalation Study.

BACKGROUND: Normobaric hyperoxia (NBO) has neuroprotective effects in acute ischemic stroke. Thus, we aimed to identify the optimal NBO treatment duration combined with endovascular treatment. METHODS: This is a single-center, randomized controlled, open-label, blinded-end point dose-escalation clinical trial. Patients with acute ischemic stroke who had an indication for endovascular treatment at Tianjin Huanhu Hospital were randomly assigned to 4 groups (1:1 ratio) based on NBO therapy duration: (1) control group (1 L/min oxygen for 4 hours); (2) NBO-2h group (10 L/min for 2 hours); (3) NBO-4h group (10 L/min for 4 hours); and (4) NBO-6h group (10 L/min for 6 hours). The primary outcome was cerebral infarction volume at 72 hours after randomization using an intention-to-treat analysis model. The primary safety outcome was the 90-day mortality rate. RESULTS: Between June 2022 and September 2023, 100 patients were randomly assigned to the following groups: control group (n=25), NBO-2h group (n=25), NBO-4h group (n=25), and NBO-6h group (n=25). The 72-hour cerebral infarct volumes were 39.4±34.3 mL, 30.6±30.1 mL, 19.7±15.4 mL, and 22.6±22.4 mL, respectively (P=0.013). The NBO-4h and NBO-6h groups both showed statistically significant differences (adjusted P values: 0.011 and 0.027, respectively) compared with the control group. Compared with the control group, both the NBO-4h and NBO-6h groups showed significant differences (P<0.05) in the National Institutes of Health Stroke Scale scores at 24 hours, 72 hours, and 7 days, as well as in the change of the National Institutes of Health Stroke Scale scores from baseline to 24 hours. Additionally, there were no significant differences among the 4 groups in terms of 90-day mortality rate, symptomatic intracranial hemorrhage, early neurological deterioration, or severe adverse events. CONCLUSIONS: The effectiveness of NBO therapy was associated with oxygen administration duration. Among patients with acute ischemic stroke who underwent endovascular treatment, NBO therapy for 4 and 6 hours was found to be more effective. Larger-scale multicenter studies are needed to validate these findings. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05404373.

Dehydration in cerebral venous sinus thrombosis.

AIMS: This study aimed to unravel the dehydration status of patients with cerebral venous sinus thrombosis (CVST) to facilitate the understanding of dehydration in CVST. METHODS: This was a multicenter retrospective study and three populations were recruited, namely, patients with CVST, CVST mimics, and healthy subjects. Blood samples were obtained 1-2 days after admission to assess dehydration status. Stata 15.1 was performed for statistical analysis. RESULTS: A total of 208 patients were diagnosed with CVST, 237 with CVST mimics, and 200 healthy individuals were enrolled. The urine specific gravity (USG, 1.020 [1.014, 1.029] vs. 1.017 [1.011, 1.021]) was higher in patients with CVST than in those with mimics (all p < 0.001). The percentage of USG >1.03 was also higher in CVST (22.6%) than in its mimics (6.3%, p < 0.001). With the development of CVST, USG (acute vs. sub-acute vs. chronic, 1.022 [1.015, 1.033] vs. 1.021 [1.015, 1.031] vs. 1.019 [1.014, 1.025]) decreased. All dehydration-related markers could not differentiate CVST from its mimics and healthy populations, and they were not associated with CVST severity and prognosis (p > 0.05). CONCLUSION: High levels of USG, especially USG >1.013, were more common in patients with CVST. Dehydration-related indices could not characterize CVST and were not associated with CVST severity and prognosis.

CYP1B1 affects the integrity of the blood-brain barrier and oxidative stress in the striatum: An investigation of manganese-induced neurotoxicity.

AIMS: Excessive influx of manganese (Mn) into the brain across the blood-brain barrier induces neurodegeneration. CYP1B1 is involved in the metabolism of arachidonic acid (AA) that affects vascular homeostasis. We aimed to investigate the effect of brain CYP1B1 on Mn-induced neurotoxicity. METHOD: Brain Mn concentrations and α-synuclein accumulation were measured in wild-type and CYP1B1 knockout mice treated with MnCl2 (30 mg/kg) and biotin (0.2 g/kg) for 21 continuous days. Tight junctions and oxidative stress were analyzed in hCMEC/D3 and SH-SY5Y cells after the treatment with MnCl2 (200 µM) and CYP1B1-derived AA metabolites (HETEs and EETs). RESULTS: Mn exposure inhibited brain CYP1B1, and CYP1B1 deficiency increased brain Mn concentrations and accelerated α-synuclein deposition in the striatum. CYP1B1 deficiency disrupted the integrity of the blood-brain barrier (BBB) and increased the ratio of 3, 4-dihydroxyphenylacetic acid (DOPAC) to dopamine in the striatum. HETEs attenuated Mn-induced inhibition of tight junctions by activating PPARγ in endothelial cells. Additionally, EETs attenuated Mn-induced up-regulation of the KLF/MAO-B axis and down-regulation of NRF2 in neuronal cells. Biotin up-regulated brain CYP1B1 and reduced Mn-induced neurotoxicity in mice. CONCLUSIONS: Brain CYP1B1 plays a critical role in both cerebrovascular and dopamine homeostasis, which might serve as a novel therapeutic target for the prevention of Mn-induced neurotoxicity.

Clinical study of modified photodynamic therapy combined with Taohong Siwu Decoction in treating hypertrophic scar after severe burn.

OBJECTIVE: The aim of this study was to study the curative effect and the relative mechanism of modified photodynamic therapy combined with Taohong Siwu Decoction in the treatment of hyperplastic scar after severe burn, in order to provide a stable, safe and satisfactory scheme for scar repair. METHODS: Forty cases with hyperplastic scars after severe burns admitted to the plastic surgery department from May 2021 to May 2022 were divided into a control group and an observation group by means of the random number table method. The control group was treated with ordinary laser therapy combined with Taohong Siwu Decoction, while the observation group was treated with modified photodynamic therapy combined with Taohong Siwu Decoction. The Vancouver Scar Scale (VSS) was assessed in both groups, and the clinical effectiveness of both groups was compared. HE-staining was performed on the scar tissue of the same patient before and after treatment to observe the changes in the arrangement of fibroblasts. The Vascular Endothelial Growth Factor (VEGF), ß-Transforming Growth Factor (TGF-ß), and Platelet-Derived Growth Factor (PDGF) in the tissue samples of both groups were detected by quantitative real-time PCR. The patients were followed up for 6 months, and their satisfaction, side effects, and scar recurrence were observed. RESULTS: Compared with the control group, the VSS score in the observation group was lower (p < 0.05). The therapeutic effect of the observation group was superior to the control group after 3 months (p < 0.05). After 3-months of therapy, the arrangement of fibroblasts in the scar became looser in two groups, and the observation group was more looser. The VEGF, TGF-ß and PDGF levels in tissue samples of the observation group were lower than those in the control group after 3 months of treatment (p < 0.05). The satisfaction of the observation group was higher than that of the control group (p < 0.05). The adverse reactions between the two groups showed no difference (p > 0.05), while the recurrence rate was lower in the observation group (p < 0.05). CONCLUSION: Modified photodynamic therapy combined with Taohong Siwu Decoction shows remarkable efficacy in patients with hyperplastic scars after severe burns. It can improve the color, thickness, vascular distribution, and softness of the scar, and reduce the level of cytokines related to tissue repair. At the same time, it can improve patients' satisfaction with the aesthetic appearance and reduce the recurrence rate, providing a new comprehensive therapy that is safer and more effective, simple and quick, and easy to promote in the clinic.

Association between inflammatory biomarkers and venous thromboembolism: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a common thrombotic vascular disease that has a significant impact on people's well-being and quality of life. A plethora of clinical studies explore the relationship between inflammatory biomarkers and VTE but yield conflicting results. This article proposed to pool these studies to draw a more convincing conclusion. METHODS: We searched several databases for studies before April 2023. Available data was processed using Stata software (version 15.0 SE) and R (version 4.1.2). This meta-analysis has been registered in PROSPERO (CRD42022321815). The VTE in this review encompassed pulmonary embolism, deep vein thrombosis, and cerebral venous thrombosis. RESULTS: A total of 25 articles were finally involved in this study. Our results revealed that higher levels of high-sensitivity C-reactive protein (hs-CRP, MD, 0.63, 95%CI, 0.21-1.05) and C-reactive protein (CRP)> 3ug/ml (OR, 1.52, 95%CI, 1.18-1.96) might be regarded as risk factors for future VTE occurrence. The elevated levels of monocyte (MD, 0.03, 95%CI, 0.00-0.05), hs-CRP (0.85, 0.61-1.08), CRP (0.66, 0.20-1.13) and IL-6 (0.47, 0.25-0.70) might represent the previous VTE; a series of markers such as white blood cell (1.43, 0.88-1.98), neutrophil (1.79, 1.02-2.56), monocyte (0.17, 0.14-0.21), hs-CRP (3.72, 1.45-5.99), IL-6 (5.99, 4.52-7.46), platelet-lymphocyte ratio (33.1, 24.45-41.78) and neutrophil-lymphocyte ratio (1.34, 0.95-1.73) increased during the acute phase of VTE. CONCLUSIONS: In general, activated inflammatory biomarkers might not only be correlated with an increased risk of VTE, but may also give a hint of the occurrence of VTE in clinical settings.

Inflammatory Markers Differentiate Cerebral Venous Sinus Thrombosis from Mimics.

Imaging tests always misdiagnose anatomical variants of cerebral sinuses as cerebral venous sinus thrombosis (CVST). Anatomical variants of cerebral sinuses are called CVST mimics. This study aimed to identify the role of inflammatory markers in differentiating CVST from mimics. A total of 146 patients diagnosed as CVST and 93 patients with mimics were recruited in this study. Receiver operating characteristic (ROC) analysis was performed to demonstrate the sensitivity and specificity of inflammatory markers for diagnosing CVST. Rank logistic regression analysis was performed to identify the association of markers to CVST severity and prognosis. CVST presented higher inflammatory reactions compared with mimics, demonstrated by the neutrophil count (5.11 [3.97-6.80] vs. 3.06 [2.34-3.86]), interleukin (IL)-6 (7.42 [3.85-14.22] vs. 2.47 [1.50-4.00]), and neutrophil-to-lymphocyte ratio (NLR; 3.19 [2.18-4.62] vs. 1.66 [1.16-2.22]). ROC analysis showed markers with area under the curve (AUC) >0.8, including IL-6 (optimal cutoff: 3.790; kappa value: 0.499), neutrophil count (3.975; 0.522), and NLR (2.070; 0.476). After propensity score matching, only IL-6 had an AUC >0.8, with an optimal cutoff of 3.060 and a kappa value of 0.636. Ranked logistic regression showed that IL-6 (odds ratio, 95% confidence interval: 1.063, 1.026-1.101; 1.029, 1.009-1.050), cerebrospinal fluid (CSF) immunoglobulin (Ig) A (0.279, 0.110-0.706; 0.398, 0.162-0.974), CSF IgM (22.399, 3.004-167.001; 9.545, 1.382-65.928), and CSF IgG (1.287, 1.124-1.473; 1.232, 1.091-1.392) were independently correlated with the baseline and follow-up mRS. In conclusion, inflammatory markers in CVST were different from those in mimics. These markers, especially IL-6, could not only differentiate CVST from its mimics, but also evaluate CVST severity and prognosis.

Clinical study of modified photodynamic therapy combined with Taohong Siwu Decoction in treating hypertrophic scar after severe burn

Abstract Objective: The aim of this study was to study the curative effect and the relative mechanism of modified photodynamic therapy combined with Taohong Siwu Decoction in the treatment of hyperplastic scar after severe burn, in order to provide a stable, safe and satisfactory scheme for scar repair. Methods: Forty cases with hyperplastic scars after severe burns admitted to the plastic surgery department from May 2021 to May 2022 were divided into a control group and an observation group by means of the random number table method. The control group was treated with ordinary laser therapy combined with Taohong Siwu Decoction, while the observation group was treated with modified photodynamic therapy combined with Taohong Siwu Decoction. The Vancouver Scar Scale (VSS) was assessed in both groups, and the clinical effectiveness of both groups was compared. HE-staining was performed on the scar tissue of the same patient before and after treatment to observe the changes in the arrangement of fibroblasts. The Vascular Endothelial Growth Factor (VEGF), β-Transforming Growth Factor (TGF-β), and Platelet-Derived Growth Factor (PDGF) in the tissue samples of both groups were detected by quantitative real-time PCR. The patients were followed up for 6 months, and their satisfaction, side effects, and scar recurrence were observed. Results: Compared with the control group, the VSS score in the observation group was lower (p < 0.05). The therapeutic effect of the observation group was superior to the control group after 3 months (p < 0.05). After 3-months of therapy, the arrangement of fibroblasts in the scar became looser in two groups, and the observation group was more looser. The VEGF, TGF-β and PDGF levels in tissue samples of the observation group were lower than those in the control group after 3 months of treatment (p < 0.05). The satisfaction of the observation group was higher than that of the control group (p < 0.05). The adverse reactions between the two groups showed no difference (p > 0.05), while the recurrence rate was lower in the observation group (p < 0.05). Conclusion: Modified photodynamic therapy combined with Taohong Siwu Decoction shows remarkable efficacy in patients with hyperplastic scars after severe burns. It can improve the color, thickness, vascular distribution, and softness of the scar, and reduce the level of cytokines related to tissue repair. At the same time, it can improve patients' satisfaction with the aesthetic appearance and reduce the recurrence rate, providing a new comprehensive therapy that is safer and more effective, simple and quick, and easy to promote in the clinic.

Normobaric Hyperoxia Combined With Endovascular Treatment for Patients With Acute Ischemic Stroke: A Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVES: To investigate the safety and efficacy of normobaric hyperoxia (NBO) combined with endovascular treatment (EVT) in patients with acute ischemic stroke (AIS). METHODS: In this single-center, proof-of-concept, assessor-blinded, randomized, controlled pilot study, patients with AIS in the acute anterior circulation with large vessel occlusion who had an indication for EVT were randomly assigned to the EVT group or the NBO + EVT group. The NBO + EVT group was given 100% oxygen through a face mask initiated before vascular recanalization (10L/min for 4 hours), while the EVT group was given room air. The primary endpoint was infarct volume measured by MRI within 24-48 hours after randomization. RESULTS: A total of 231 patients were screened, and 86 patients were randomized into a ratio of 1:1 (EVT group, n = 43; NBO + EVT group, n = 43). The median infarction volume of the NBO + EVT group at 24-48 hours after randomization was significantly smaller than that of the EVT group (median 20.1 vs 37.7 mL, p < 0.01). The median mRS score at 90 days was 2 for the NBO + EVT group when compared with 3 for the EVT group (adjusted value 1.8, 95% CI 1.3-4.2; p = 0.038). Compared with the EVT group, the NBO + EVT group had a lower incidence of symptomatic intracranial hemorrhagic (7% vs 12%), mortality (9% vs 16%), and adverse events (33% vs 42%); however, such a difference was not statistically significant. DISCUSSION: NBO in combination with EVT seems to be a safe and feasible treatment strategy that could significantly reduce infarct volume, improve short-term neurobehavioral test score, and enhance clinical outcomes at 90 days when compared with EVT alone in patients with AIS. These observations need to be further confirmed by a large, multicenter, randomized clinical trial. CLINICAL TRIALS REGISTRATION: NCT03620370. CLASSIFICATION OF EVIDENCE: This pilot study provides Class I evidence that NBO combined with standard EVT decreases infarction volume in patients with acute anterior circulation stroke.

Inflammation in Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) is a rare form of cerebrovascular disease that impairs people's wellbeing and quality of life. Inflammation is considered to play an important role in CVT initiation and progression. Several studies have reported the important role of leukocytes, proinflammatory cytokines, and adherence molecules in the CVT-related inflammatory process. Moreover, inflammatory factors exacerbate CVT-induced brain tissue injury leading to poor prognosis. Based on clinical observations, emerging evidence shows that peripheral blood inflammatory biomarkers-especially neutrophil-to-lymphocyte ratio (NLR) and lymphocyte count-are correlated with CVT [mean difference (MD) (95%CI), 0.74 (0.11, 1.38), p = 0.02 and -0.29 (-0.51, -0.06), p = 0.01, respectively]. Moreover, increased NLR and systemic immune-inflammation index (SII) portend poor patient outcomes. Evidence accumulated since the outbreak of coronavirus disease-19 (COVID-19) indicates that COVID-19 infection and COVID-19 vaccine can induce CVT through inflammatory reactions. Given the poor understanding of the association between inflammation and CVT, many conundrums remain unsolved. Further investigations are needed to elucidate the exact relationship between inflammation and CVT in the future.

Anatomic Asymmetry of Transverse Sinus May Be Irrelevant to the Prognosis of Intracerebral Hemorrhage.

BACKGROUND: We investigate the probable effect of anatomic asymmetry of transverse sinus (TS) on the outcomes of acute intracerebral hemorrhage (ICH), to provide reference for customized treatment. METHODS: Consecutive patients with imaging-confirmed acute ICH were enrolled from October 2015 through October 2019, and divided into 2 groups: symmetrical and unilateral (left or right) slender TS groups, based on the status of TS in imaging maps. Brain computed tomography (CT) maps of all patients at baseline and half-month post-ICH were obtained, and the volumes of hematoma and the perihematomal edemas (PHE), as well as the modified Rankin Scale (mRS) scores at the month-3 post-ICH between the 2 groups were assessed and analyzed. RESULTS: A total of 46 eligible patients entered into final analysis, including 18 cases in the slender TS group (14 cases involved the left side while 4 cases involved the right side), and 28 cases in the symmetrical TS group. The mRS scores, hematoma absorption rates, and the residual volumes of PHE of all patients in the 2 groups at half-month post-ICH showed no statistical significance (all P >0.05), and all of the items mentioned above were related to the hematoma volume at baseline (all P <0.001). At the month-3 follow-up post-ICH, the mRS scores between the 2 groups showed no statistical significance as well ( P =0.551). CONCLUSIONS: Anatomic asymmetry of TS may not affect the prognosis of PHE and clinical outcome after ICH.

Clinical Features of Coexisting Anti-NMDAR and MOG Antibody-Associated Encephalitis: A Systematic Review and Meta-Analysis.

Coexisting anti-NMDAR and MOG antibody (anti-NMDAR-IgG+/MOG-IgG+)-associated encephalitis have garnered great attention. This study aimed to perform a secondary analysis to determine the clinical features of this disease. We searched several databases for related publications published prior to April 2021. A pooled analysis was conducted with the fixed-effects model using the Mante-Haenszel method (I 2 ≤ 50%), or the random-effects model computed by the DerSimonian-Laird method (I 2 > 50%). Stata software (version 15.0 SE) was used for the analyses. Nine observational studies and 16 case reports (58 cases with anti-NMDAR-IgG+/MOG-IgG+, 21.0 [8.5, 29.0] years, male 58.6%) were included. The incidences (95%CI) of anti-NMDAR-IgG+/MOG-IgG+ in the patients with serum MOG-IgG+ and CSF anti-NMDAR-IgG+ were 0.09 (0.02-0.19) and 0.07 (0.01-0.19), respectively. The median [IQR] of CSF anti-NMDAR antibody titer was 32 [10, 100], and the serum anti-MOG antibody titer was 100 [32, 320]. The prominent clinical symptoms were encephalitic manifestations, including seizures (56.9%) and abnormal behavior (51.7%), rather than demyelinating manifestations, such as speech disorder (34.5%) and optic neuritis (27.6%). Relapse occurred in 63.4% of anti-NMDAR-IgG+/MOG-IgG+ patients, in whom 50.0% of cases relapsed with encephalitic manifestations, and 53.8% relapsed with demyelinating manifestations. The common MRI changes were in the cortex or subcortex (70.7%) and brainstem (31.0%). 31.3% of patients presented with unilateral cerebral cortical encephalitis with epilepsy and 12.5% displayed bilateral frontal cerebral cortex encephalitis. Anti-NMDAR-IgG+/MOG-IgG+ patients showed more frequent mental behavior (OR, 95%CI, 68.38, 1.36-3,434.37), involuntary movement (57.86, 2.53-1,325.11), sleep disorders (195.00, 7.07-5,380.15), and leptomeninge lesions (7.32, 1.81-29.58), and less frequent optic neuritis (0.27, 0.09-0.83) compared to anti-NMDAR-IgG-/MOG-IgG+ patients and presented more common relapse (5.63, 1.75-18.09), preceding infection (2.69, 1.03-7.02), subcortical lesions (116.60, 4.89-2,782.09), basal ganglia lesions (68.14, 2.99-1,554.27), brainstem lesions (24.09, 1.01-574.81), and spinal cord lesions (24.09, 1.01-574.81) compared to anti-NMDAR-IgG+/MOG-IgG-. In conclusion, anti-NMDAR-IgG+/MOG-IgG+ was rarely observed, but the incidence rate of relapse was very high. The overall symptoms seemed to be similar to those of NMDAR encephalitis.

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.

Pathogenesis and Management in Cerebrovenous Outflow Disorders.

In keeping with its status as one of the major causes of disability and mortality worldwide, brain damage induced by cerebral arterial disease has been the subject of several decades of scientific investigation, which has resulted in a vastly improved understanding of its pathogenesis. Brain injury mediated by venous etiologies, however, such as cerebral, jugular, and vertebral venous outflow disturbance, have been largely ignored by clinicians. Unfortunately, this inattention is not proportional to the severity of cerebral venous diseases, as the impact they exact on the quality of life of affected patients may be no less than that of arterial diseases. This is evident in disease sequelae such as cerebral venous thrombosis (CVT)-mediated visual impairment, epilepsy, and intracranial hypertension; and the long-term unbearable head noise, tinnitus, headache, dizziness, sleeping disorder, and even severe intracranial hypertension induced by non-thrombotic cerebral venous sinus (CVS) stenosis and/or internal jugular venous (IJV) stenosis. In addition, the vertebral venous system (VVS), a large volume, valveless vascular network that stretches from the brain to the pelvis, provides a conduit for diffuse transmission of tumors, infections, or emboli, with potentially devastating clinical consequences. Moreover, the lack of specific features and focal neurologic signs seen with arterial etiologies render cerebral venous disease prone to both to misdiagnoses and missed diagnoses. It is therefore imperative that awareness be raised, and that as comprehensive an understanding as possible of these issues be cultivated. In this review, we attempt to facilitate these goals by systematically summarizing recent advances in the diagnosis and treatment of these entities, including CVT, CVS stenosis, and IJV stenosis, with the aim of providing a valid, practical reference for clinicians.

Safety and efficacy of normobaric oxygenation on rescuing acute intracerebral hemorrhage-mediated brain damage-a protocol of randomized controlled trial.

BACKGROUND: All of the existing medication and surgical therapies currently cannot completely inhibit intracerebral hemorrhage (ICH)-mediated brain damage, resulting in disability in different degrees in the involved patients. Normobaric oxygenation (NBO) was reported attenuating ischemic brain injury. Herein, we aimed to explore the safety and efficacy of NBO on rescuing the damaged brain tissues secondary to acute ICH, especially those in the perihematoma area being threatened by ischemia and hypoxia. METHODS: A total of 150 patients confirmed as acute spontaneous ICH by computed tomography (CT) within 6 h after symptoms onset, will enroll in this study after signing the informed consent, and enter into the NBO group or control group randomly according to a random number. In the NBO group, patients will inhale high-flow oxygen (8 L/min, 1 h each time for 6 cycles daily) and intake low-flow oxygen (2 L/min) in intermittent periods by mask for a total of 7 days. While in the control group, patients will breathe in only low-flow oxygen (2 L/min) by mask for 7 consecutive days. Computed tomography and perfusion (CT/CTP) will be used to evaluate cerebral perfusion status and brain edema. CT and CTP maps in the two groups at baseline and day 7 and 14 after NBO or low-flow oxygen control will be compared. The primary endpoint is mRS at both Day14 post-ICH and the end of the 3rd month follow-up. The secondary endpoints include NIHSS and plasma biomarkers at baseline and Day-1, 7, and 14 after treatment, as well as the NIHSS at the end of the 3rd month post-ICH and the incidence of bleeding recurrence and the mortalities within 3 months post-ICH. DISCUSSION: This study will provide preliminary clinical evidence about the safety and efficacy of NBO on correcting acute ICH and explore some mechanisms accordingly, to offer reference for larger clinical trials in the future. TRIAL REGISTRATION: ClinicalTrials.gov NCT04144868 . Retrospectively registered on October 29, 2019.

Cerebral venous sinus stenosis should not be neglected when cerebral artery stenosis is confirmed: a case report.

PURPOSE: Cerebral venous sinus stenosis (CVSS) is easily neglected in clinical setting due to its nonspecific symptoms. In patients with cerebral arterial stenosis (CAS), the symptoms caused by CVSS are often mistakenly thought of being attributed to CAS. In this case, we aimed to highlight the clinical manifestations and treatment strategies of CVSS comorbid with CAS. MATERIALS AND METHODS: We present an 83-year-old female who complained a series of nonspecific and non-focal neurological deficits such as tinnitus, head noise, dizziness, etc. She was initially diagnosed as CAS and underwent anti-CAS medication orally for over 2 years, whereas her symptoms were still aggravating. RESULTS: Magnetic resonance venography (MRV) and magnetic resonance imaging (MRI) displayed severe stenoses at bilateral sigmoid-transverse sinus conjunctions, and thus, the patient underwent intravenous stenting finally. Her aforementioned symptoms significantly attenuated after venous stenting and even disappeared gradually at 3-month, 6-month and 1-year follow-up. CONCLUSIONS: This paper revealed that cerebral venous outflow disturbance should not be overlooked when the nonspecific and non-focal neurological deficits could not be explained by cerebral artery disease. For this arteriovenous condition, intravenous stenting may be a feasible and effective way for symptoms relieving.

Normobaric Oxygen May Ameliorate Cerebral Venous Outflow Disturbance-Related Neurological Symptoms.

Cerebral venous outflow disturbance (CVOD) has begun to garner the attention of researches owing to a series of clinical symptoms that impose a significant impact on people's quality of life. Herein, we aimed to investigate whether normobaric oxygen (NBO) can ameliorate CVOD-induced neurological symptoms. This was one part of the prospective trial registered in ClinicalTrials.gov (NCT03373292). A total of 37 CVOD patients were divided into the NBO group (5-8 L/min of oxygen inhalation, 1 h per time, 3 times daily, n = 19) and the control group (without oxygen inhalation, n = 18) randomly. The assessments were performed at admission, 1-week hospitalization, and 6-month follow-up. Quantitative electroencephalogram (qEEG) data were recorded prior to and post 1 h of NBO in some patients. R software was used for data analysis. No NBO-related adverse events were observed during the whole NBO intervention process. The 1-week Patient Global Impression of Change (PGIC) scale showed that the symptom improvement occurred in nine patients in the NBO group (47.4%) while none in the control group (p = 0.001). NBO could improve headache evaluated with visual analog scale (pre-NBO vs. post-NBO: 4.70 ± 2.16 vs. 2.90 ± 2.03, p = 0.024) and Headache Impact Test-6 (53.40 ± 12.15 vs. 50.30 ± 13.04, p = 0.041). As for 6-month PGIC follow-up, eight out of 14 cases (57.1%) in the NBO group reported improvement, while only one out of 12 patients in the control group replied mild improvement (p = 0.014). The qEEG revealed that NBO reduced the ratio of theta to alpha power (0.65 ± 0.38 vs. 0.56 ± 0.35, p = 0.030) over the fronto-central electrodes. To sum up, NBO may be a safe and effective approach to attenuate CVOD-related symptoms (especially for headache) by brain functional improvement resulting from increasing oxygen supply to the brain tissues.

Clinical Classification and Collateral Circulation in Chronic Cerebrospinal Venous Insufficiency.

Background: As an indispensable part of the cerebral venous system, the extracranial cerebrospinal venous system is not fully recognized. This study aimed to analyze the clinical classification and imaging characteristics of chronic cerebrospinal venous insufficiency (CCSVI) quantitatively. Methods: A total of 128 patients, who were diagnosed as CCSVI by jugular ultrasound and contrast-enhanced magnetic resonance venography (CE-MRV), were enrolled from May 2018 through May 2019. For the patients with possible extraluminal compression, computed tomography venography (CTV) was applied to estimate the degree of internal jugular venous stenosis (IJVS) and rank the vertebral venous collateral circulation. Results: The causes of extraluminal compression induced IJVS included osseous compression (78.95%), carotid artery (24.21%), sternocleidomastoid muscle (5.79%), swollen lymph node (1.05%), and unknown reasons (5.26%). The subtypes of non-compression CCSVI included the high jugular bulb (77.27%), fenestration of the internal jugular vein (IJV) (7.27%), internal jugular phlebectasia (2.73%), tortuous IJV (0.91%), IJV thrombosis (14.55%), and elongated venous valves with/without erythrocyte aggregation (13.64%). For extraluminal compression induced IJVS, the ratio of severe vertebral venous expansion was higher in the severe IJVS group than that in the mild IJVS group (p < 0.001). The IJVS degree was higher in the severe vertebral venous expansion group than in the mild vertebral venous expansion group (p < 0.001). Conclusions: A multimodal diagnostic system is necessary to improve the diagnostic accuracy of CCSVI. The vertebral venous system is an important collateral circulation for CCSVI, which may be a promising indicator for evaluating IJVS degree.

Arterial spin labeling-MR may be an alternative to SPECT for evaluating cerebral perfusion in patients with unilateral middle cerebral artery stenosis.

OBJECTIVE: Cerebral blood flow (CBF) mapping of single-photon emission tomography (SPECT) is considered a gold standard for evaluating cerebral perfusion. However, invasiveness, high costs and strict technical requirements can limit its clinical use. We aimed to evaluate the concordance of CBF maps obtained from SPECT and pseudo-continuous arterial spin labeling magnetic resonance (PCASL-MR) imaging for evaluating cerebral perfusion. METHODS: PCASL-MR/SPECT-CBF maps were obtained from 16 eligible patients with unilateral middle cerebral artery stenosis (MCAS). Three slices (basal ganglia, semi-oval center and cerebellum) on both PCASL-MR and SPECT maps were divided into different regions of interest (ROIs) according to the ASPECT criterion, arterial territories, and cerebral hemispheres, respectively. The concordance of the two types of CBF maps and the specificity and sensitivity of PCASL-MR imaging on predicting regional hypoperfusion were calculated. RESULTS: A total of 448 ROIs were divided according to the ASPECT criterion, 192 ROIs partitioned in accordance with arterial territories, and 96 ROIs delineated based on cerebral hemispheres were analyzed. PCASL-MR imaging exhibited 83.78% to 100% sensitivity, 90.19% to 95.83% specificity for detection of hypoperfusion. Qualitative analyses revealed a strong concordance between PCASL-MR and SPECT on reflecting regional cerebral hypoperfusion (Kappa coefficient = 0.662-0.920, p < 0.01). Semi-quantitative analysis by ΔCBF revealed moderate consistency (Spearman correlation coefficient = 0.610-0.571). CONCLUSIONS: Our findings suggest that PCASL-MR may be a promising non-invasive, inexpensive alternative to SPECT for evaluating cerebral perfusion accurately in patients with symptomatic MCAS.

MicroRNA-182 Suppresses Malignant Melanoma Proliferation by Targeting RECK.

BACKGROUND: MicroRNAs (miRNAs) function as important post-transcriptional regulators involved in a wide range of biological behaviors. MicroRNA-182 (miR-182) has been shown to play a critical role in tumor pathogenesis. The present study aimed to investigate the role of miR-182 in malignant melanoma. METHODS: MTT assay was performed to measure the viabilities of cancer cells. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the mRNA and protein expression, respectively. Moreover, the miRNA target genes were validated with luciferase activity assay. RESULTS: In the current study, we found that the expression of miR-182 was significantly up-regulated in malignant melanoma tissues compared to the adjacent non-cancer tissues. MMT assay showed that down-regulation of miR-182 suppressed the proliferation of malignant melanoma cell line. By contrast, over-expression of miR-182 promoted the growth of malignant melanoma cells. In addition, the reversion-inducing cysteinerich protein with Kazal motifs (RECK) was down-expressed in human malignant melanoma tissues. Moreover, poor expression of miR-182 led to an increase in RECK expression, whereas over-expression of miR-182 reduced RECK levels in malignant melanoma cells. The luciferase reporter assay showed that RECK was a direct target of miR-182. CONCLUSIONS: These findings demonstrated that miR-182 inhibited malignant melanoma cell proliferation via RECK, providing a novel target for the molecular treatment of malignant melanoma.

Prognosis and risk factors for reocclusion after mechanical thrombectomy.

OBJECTIVE: This study evaluates reocclusion prognostic outcomes and explores reocclusion risk factors after mechanical thrombectomy (MT) in Chinese stroke patients. METHODS: Altogether, 614 patients with AIS with successful recanalization after MT were recruited in this study and divided into the reocclusion and the non-reocclusion group depending on the 24-h imaging results after MT. Differences between the two groups were compared including 24-h and 7-day National Institutes of Health Stroke Scale (NIHSS) scores, 90-day modified Rankin scale(mRS) scores, good prognosis (mRS:0-2) rates, incidence of intracranial hemorrhage, and 90-day mortality. RESULTS: Forty-four (7.2%) patients experienced reocclusion within 24 h. Compared with the non-reocclusion group, patients in the reocclusion group had higher 24-h (15 vs. 13) and 7-day (15 vs. 9) NIHSS scores, 90-day mRS scores (4 vs. 3), and 90-day mortality rates (34.1% vs. 18.6%); lower rates of good prognosis (13.6% vs. 9.3%); and a higher incidence of early neurological deterioration (36.4% vs. 14.7%). Age, internal carotid artery occlusion (ICA), intravenous thrombolysis (IVT), number of thrombectomy passes, stent implantation, and levels of D-dimer (adjusted odds ratio and 95% confidence interval: 0.97, 0.94-0.99; 2.40, 1.10-5.23; 2.21, 1.05-4.66; 2.60, 1.04-6.47; 0.25, 0.09-0.67; and 1.06, 1.01-1.12, respectively) were independently associated with 24-h reocclusion. INTERPRETATION: The prognosis of reocclusion after MT was poor. Timely evaluation of these factors including age, D-dimer, ICA occlusion, IVT, number of passes, and stent implantation and appropriate intervention could reduce the incidence of reocclusion for Chinese stroke patients.