Trial of Thrombectomy 6 to 24 Hours after Stroke Due to Basilar-Artery Occlusion.

BACKGROUND: The effects and risks of endovascular thrombectomy 6 to 24 hours after stroke onset due to basilar-artery occlusion have not been extensively studied. METHODS: In a trial conducted over a 5-year period in China, we randomly assigned, in a 1:1 ratio, patients with basilar-artery stroke who presented between 6 to 24 hours after symptom onset to receive either medical therapy plus thrombectomy or medical therapy only (control). The original primary outcome, a score of 0 to 4 on the modified Rankin scale (range, 0 to 6, with a score of 0 indicating no disability, 4 moderately severe disability, and 6 death) at 90 days, was changed to a good functional status (a modified Rankin scale score of 0 to 3, with a score of 3 indicating moderate disability). Primary safety outcomes were symptomatic intracranial hemorrhage at 24 hours and 90-day mortality. RESULTS: A total of 217 patients (110 in the thrombectomy group and 107 in the control group) were included in the analysis; randomization occurred at a median of 663 minutes after symptom onset. Enrollment was halted at a prespecified interim analysis because of the superiority of thrombectomy. Thrombolysis was used in 14% of the patients in the thrombectomy group and in 21% of those in the control group. A modified Rankin scale score of 0 to 3 (primary outcome) occurred in 51 patients (46%) in the thrombectomy group and in 26 (24%) in the control group (adjusted rate ratio, 1.81; 95% confidence interval [CI], 1.26 to 2.60; P<0.001). The results for the original primary outcome of a modified Rankin scale score of 0 to 4 were 55% and 43%, respectively (adjusted rate ratio, 1.21; 95% CI, 0.95 to 1.54). Symptomatic intracranial hemorrhage occurred in 6 of 102 patients (6%) in the thrombectomy group and in 1 of 88 (1%) in the control group (risk ratio, 5.18; 95% CI, 0.64 to 42.18). Mortality at 90 days was 31% in the thrombectomy group and 42% in the control group (adjusted risk ratio, 0.75; 95% CI, 0.54 to 1.04). Procedural complications occurred in 11% of the patients who underwent thrombectomy. CONCLUSIONS: Among patients with stroke due to basilar-artery occlusion who presented 6 to 24 hours after symptom onset, thrombectomy led to a higher percentage with good functional status at 90 days than medical therapy but was associated with procedural complications and more cerebral hemorrhages. (Funded by the Chinese National Ministry of Science and Technology; BAOCHE ClinicalTrials.gov number, NCT02737189.).

The additional value of high-resolution vessel wall imaging in screening suitable chronic internal carotid artery occlusion candidates for endovascular recanalization: comparison with digital subtraction angiography.

BACKGROUND: High-resolution vessel wall imaging (HR-VWI) can provide information about exact occluded length, etiology, and the presence of intraluminal thrombus or residual cavity. PURPOSE: To investigate the extra value of HR-VWI in screening patients with chronic internal carotid artery occlusion (CICAO) for recanalization suitability in comparison with digital subtraction angiography (DSA). MATERIAL AND METHODS: We retrospectively reviewed patients who underwent endovascular recanalization with no internal carotid artery signal on magnetic resonance angiography (MRA) and whose both preoperative DSA and HR-VWI data were available. Patients were classified into type I (focal occlusion distal to ophthalmic artery), type II or III (occlusion proximal or at/distal to clinoid segment), and near-occlusion. Occlusion etiology and suitability for recanalization were analyzed both on preoperative DSA and HR-VWI. Accuracy of occlusion classification and differences in the modified Rankin scale scores between the baseline and follow-up were estimated. RESULTS: A total of 20 patients were included. With intraoperative DSA as the gold standard, we found HR-VWI could additionally show intraluminal thrombi. Preoperative DSA misclassified one near-occlusion, one type I occlusion, and one type II occlusion as type III occlusions, and one near-occlusion as a type II occlusion. Therefore, compared with the preoperative DSA, three additional cases were successfully recanalized based on HR-VWI. The accuracy of HR-VWI was higher than preoperative DSA (100% vs. 80%). Prognosis improvement of type I was significantly better than type II and near-occlusion (P<0.05). CONCLUSION: HR-VWI can identify occluded etiology, extent, and classification of CICAO. This information is potentially useful in screening candidates for endovascular recanalization and helpful to indicate prognosis.

Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China: A Real-World Nationwide Registry.

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. METHODS: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. RESULTS: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56-73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55-72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P=0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213-2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065-2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325-3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085-3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098-2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222-13.385]). CONCLUSIONS: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Concurrent Bronchial Artery and Posterior Inferior Cerebellar Artery Microcatheter Interventional Chemotherapy for Adenocarcinoma of the Lung with Solitary Cerebellar Metastasis.

BACKGROUND Lung cancer with intracranial metastasis requires concurrent treatment of the primary lung tumor and the secondary brain tumor. This study aimed to investigate the short-term clinical efficacy of concurrent bronchial artery and posterior inferior cerebellar artery microcatheter interventional chemotherapy for the treatment of adenocarcinoma of the lung with solitary cerebellar metastasis. MATERIAL AND METHODS Seventeen patients with adenocarcinoma of the lung with solitary cerebellar metastasis received concurrent microcatheter interventional chemotherapy via the bronchial artery and posterior inferior cerebellar artery. Two cycles of treatment with teniposide (VM-26), carmustine (BCNU), carboplatin (CBP), and pirarubicin (THP) were performed every four weeks. RESULTS Four patients (23.53%) achieved a complete response (CR), five patients (29.41%) achieved a partial response (PR), seven patients (41.18%) had stable disease (SD), and only one patient (5.88%) developed progressive disease (PD). The objective response rate (ORR) and disease control rate (DCR) were 52.94% (9/17) and 94.12% (16/17), respectively. Four patients (11.76%) developed grade 1/2 chemotherapy toxicity, which included three cases (8.82%) of gastrointestinal toxicity and one case (2.84%) of granulocytopenia, but no grade 3/4 toxicity was found. During microcatheter interventional chemotherapy, three patients (8.82%) developed intracranial complications, including two cases (5.88%) of cerebrovascular spasm and one case (2.94%) of cerebral edema. CONCLUSIONS In 17 patients with adenocarcinoma of the lung with solitary cerebellar metastasis, concurrent microcatheter interventional chemotherapy via the bronchial artery and posterior inferior cerebellar artery was safe and showed short-term efficacy.

Recombinant CTRP9 administration attenuates neuroinflammation via activating adiponectin receptor 1 after intracerebral hemorrhage in mice.

BACKGROUND: Neuroinflammation is a crucial factor contributing to neurological injuries after intracerebral hemorrhage (ICH). C1q/TNF-related protein 9 (CTRP9), an agonist of adiponectin receptor 1 (AdipoR1), has recently been shown to reduce inflammatory responses in systemic diseases. The objective of this study was to investigate the protective role of CTRP9 against neuroinflammation after ICH in a mouse model and to explore the contribution of adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor kappa B (NFκB) pathway in AdipoR1-mediated protection. METHODS: Adult male CD1 mice (n = 218) were randomly assigned to different groups for the study. ICH was induced via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administered intranasally at 1 h after ICH. To elucidate the underlying mechanism, AdipoR1 small interfering ribonucleic acid (siRNA) and selective phosphorylated AMPK inhibitor Dorsomorphin were administered prior to rCTRP9 treatment. Brain edema, short- and long-term neurobehavior evaluation, blood glucose level, western blot, and immunofluorescence staining were performed. RESULTS: Endogenous CTRP9 and AdipoR1 expression was increased and peaked at 24 h after ICH. AdipoR1 was expressed by microglia, neurons, and astrocytes. Administration of rCTRP9 reduced brain edema, improved short- and long-term neurological function, enhanced the expression of AdipoR1 and p-AMPK, and decreased the expression of phosphorylated NFκB and inflammatory cytokines after ICH. The protective effects of rCTRP9 were abolished by administration of AdipoR1 siRNA and Dorsomorphin. CONCLUSIONS: Our findings demonstrated that administration of rCTRP9 attenuated neuroinflammation through AdipoR1/AMPK/NFκB signaling pathway after ICH in mice, thereby reducing brain edema and improving neurological function after experimental ICH in mice. Therefore, CTRP9 may provide a potential therapeutic strategy to alleviate neuroinflammation in ICH patients.

Bailout intracranial angioplasty or stenting following thrombectomy for acute large vessel occlusion in China (ANGEL-REBOOT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: Unsuccessful recanalisation or reocclusion after thrombectomy is associated with poor outcomes in patients with large vessel occlusion (LVO) acute ischaemic stroke (LVO-AIS). Bailout angioplasty or stenting (BAOS) could represent a promising treatment for these patients. We conducted a randomised controlled trial with the aim to investigate the safety and efficacy of BAOS following thrombectomy in patients with LVO. METHODS: ANGEL-REBOOT was an investigator-initiated, multicentre, prospective, randomised, controlled, open-label, blinded-endpoint clinical trial conducted at 36 tertiary hospitals in 19 provinces in China. Participants with LVO-AIS 24 h after symptom onset were eligible if they had unsuccessful recanalisation (expanded Thrombolysis In Cerebral Infarction score of 0-2a) or risk of reocclusion (residual stenosis >70%) after thrombectomy. Eligible patients were randomly assigned by the minimisation method in a 1:1 ratio to undergo BAOS as the intervention treatment, or to receive standard therapy (continue or terminate the thrombectomy procedure) as a control group, both open-label. In both treatment groups, tirofiban could be recommended for use during and after the procedure. The primary outcome was the change in modified Rankin Scale score at 90 days, assessed in the intention-to-treat population. Safety outcomes were compared between groups. This trial was completed and registered at ClinicalTrials.gov (NCT05122286). FINDINGS: From Dec 19, 2021, to March 17, 2023, 706 patients were screened, and 348 were enrolled, with 176 assigned to the intervention group and 172 to the control group. No patients withdrew from the trial or were lost to follow-up for the primary outcome. The median age of patients was 63 years (IQR 55-69), 258 patients (74%) were male, and 90 patients (26%) were female; all participants were Chinese. After random allocation, tirofiban was administered either intra-arterially, intravenously, or both in 334 [96%] of 348 participants. No between-group differences were observed in the primary outcome (common odds ratio 0·86 [95% CI 0·59-1·24], p=0·41). Mortality was similar between the two groups (19 [11%] of 176 vs 17 [10%] of 172), but the intervention group showed a higher risk of symptomatic intracranial haemorrhage (eight [5%] of 175 vs one [1%] of 169), parenchymal haemorrhage type 2 (six [3%] of 175 vs none in the control group), and procedure-related arterial dissection (24 [14%] of 176 vs five [3%] of 172). INTERPRETATION: Among Chinese patients with unsuccessful recanalisation or who are at risk of reocclusion after thrombectomy, BAOS did not improve clinical outcome at 90 days, and incurred more complications compared with standard therapy. The off-label use of tirofiban might have affected our results and their generalisability, but our findings do not support the addition of BAOS for such patients with LVO-AIS. FUNDING: Beijing Natural Science Foundation, National Natural Science Foundation of China, National Key R&D Program Beijing Municipal Administration of Hospitals Incubating Program, Shanghai HeartCare Medical Technology, HeMo (China) Bioengineering, Sino Medical Sciences Technology.

Efficacy and Safety of Butylphthalide in Patients With Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: DL-3-n-butylphthalide (NBP) is a drug for treating acute ischemic stroke and may play a neuroprotective role by acting on multiple active targets. The efficacy of NBP in patients with acute ischemic stroke receiving reperfusion therapy remains unknown. Objective: To assess the efficacy and safety of NBP in patients with acute ischemic stroke receiving reperfusion therapy of intravenous thrombolysis and/or endovascular treatment. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled, parallel randomized clinical trial was conducted in 59 centers in China with 90-day follow-up. Of 1236 patients with acute ischemic stroke, 1216 patients 18 years and older diagnosed with acute ischemic stroke with a National Institutes of Health Stroke Scale score ranging from 4 to 25 who could start the trial drug within 6 hours from symptom onset and received either intravenous recombinant tissue plasminogen activator (rt-PA) or endovascular treatment or intravenous rt-PA bridging to endovascular treatment were enrolled, after excluding 20 patients who declined to participate or did not meet eligibility criteria. Data were collected from July 1, 2018, to May 22, 2022. Interventions: Within 6 hours after symptom onset, patients were randomized to receive NBP or placebo in a 1:1 ratio. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) thresholds of 0 to 2 points, depending on baseline stroke severity. Results: Of 1216 enrolled patients, 827 (68.0%) were men, and the median (IQR) age was 66 (56-72) years. A total of 607 were randomly assigned to the butylphthalide group and 609 to the placebo group. A favorable functional outcome at 90 days occurred in 344 patients (56.7%) in the butylphthalide group and 268 patients (44.0%) in the placebo group (odds ratio, 1.70; 95% CI, 1.35-2.14; P < .001). Serious adverse events within 90 days occurred in 61 patients (10.1%) in the butylphthalide group and 73 patients (12.0%) in the placebo group. Conclusions and Relevance: Among patients with acute ischemic stroke receiving intravenous thrombolysis and/or endovascular treatment, NBP was associated with a higher proportion of patients achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03539445.

Activation of AdipoR1 with rCTRP9 Preserves BBB Integrity through the APPL1/AMPK/Nrf2 Signaling Pathway in ICH Mice.

BACKGROUND: The disruption of the blood brain barrier (BBB) is the key factor leading to neurological impairment after intracerebral hemorrhage (ICH) injury. Adiponectin receptor 1 (AdipoR1) has an important effect contributing to the integrity of BBB. As a homologue of adiponectin, recombinant C1q/TNF-related protein 9 (rCTRP9) has neuroprotective effect in cerebrovascular diseases. The aim of this study was to investigate the protective effect of AdipoR1 activation with rCTRP9 on BBB integrity after ICH injury and the potential mechanisms. METHODS: 177 male mice were subjected in this study. ICH was induced by injecting collagenase into the right basal ganglia. rCTRP9 was treated intranasally at 1 hour after ICH. Selective siRNA was administered prior to ICH. Western blot, immunofluorescence staining, neurobehavioral tests, and BBB permeability were evaluated. RESULTS: ICH increased the expression of endogenous AdipoR1 and CTRP9. Administration of rCTRP9 ameliorated neurological deficits and reduced the BBB permeability at 24 hours in ICH mice. Furthermore, rCTRP9 promoted the expression of AdipoR1, APPL1, p-AMPK, Nrf2, and tight junctional proteins. The intervention of specific siRNA of AdipoR1, APPL1, and p-AMPK reversed the protective effects of rCTRP9. CONCLUSIONS: Activation of AdipoR1 with rCTRP9 improved neurological functions and preserved BBB integrity through the APPL1/AMPK/Nrf2 signaling pathway in ICH mice. Therefore, CTRP9 could serve as a promising therapeutic method to alleviate BBB injury following ICH in patients.

Addition of Aß42 to Total Cerebral Small Vessel Disease Score Improves the Prediction for Cognitive Impairment in Cerebral Small Vessel Disease Patients.

PURPOSE: To investigate the associations between concentrations of Aß40 and Aß42 and vascular cognitive impairment (VCI) in cerebral small vessel disease (CSVD) patients and evaluate the value of combination of levels of Aß40 or Aß42 and the total CSVD score in predicting VCI. PATIENTS AND METHODS: A total of 199 CSVD patients were divided into VCI group and non-VCI group according to the criteria of VCI. Demographic data, MRI markers of CSVD, blood pressure, vascular risk factors, laboratory markers, and serum Aß40 and Aß42 concentration were collected. Univariate analysis was performed with the Student's t-test, Mann-Whitney U-test or Chi-square test. Variables with P<0.10 in univariate analysis were then included in multivariate analysis that used a backward stepwise logistic regression model. The predictive values were assessed with receiver operating characteristic (ROC) curve. RESULTS: VCI was determined in 112 CSVD patients (56.3%). Hyperlipidemia (OR: 1.618, 95% CI: 1.265-3.049), the total CSVD score (OR: 1.414, 95% CI: 1.213-2.278) and serum Aß42 concentration (OR: 1.401, 95% CI: 1.212-1.946) were independent risk factors for VCI in CSVD patients with adjustment for age, education years, diabetes and fasting blood-glucose (FBG). The area under curves (AUCs) were 0.640 (SE: 0.040, 95% CI: 0.563-0.718), 0.733 (SE: 0.035, 95% CI: 0.664-0.802) and 0.827 (SE: 0.030, 95% CI: 0.768-0.887), respectively, for the total CSVD score, serum Aß42 concentration and their combination applied in predicting VCI in CSVD patients. Z test demonstrated that the AUC of combination prediction was significantly higher than individual prediction (0.827 vs 0.640, Z=3.740, P<0.001; 0.827 vs 0.733, Z=2.039, P=0.021). CONCLUSION: Combination of Aß42 and total CSVD score could significantly elevate the predictive value of cognitive impairment in CSVD patients.

Valproate Sodium Protects Blood Brain Barrier Integrity in Intracerebral Hemorrhage Mice.

Valproate sodium (VPA) is a traditional antiepileptic drug with a neuroprotective role in cerebrovascular disease. After intracerebral hemorrhage (ICH), mechanical compression by hematoma, neuroinflammation, oxidative stress, and cytotoxicity of hematoma lysates caused the destruction of the blood brain barrier (BBB). Targeting BBB is a major therapeutic method for patients with ICH. The purpose of the present study was to explore the role of VPA in preserving BBB integrity in the ICH model and investigate the underlying molecular mechanisms. One hundred and thirty-six adult male CD1 mice were randomly divided into five groups in the study. Mice subjected to ICH were administered intraperitoneally with VPA at 3, 24, and 48 h post-ICH, respectively. Neurobehavioral assessments, BBB permeability, Evans blue fluorescence, hematoma volume, and protein expression were evaluated. The administration of VPA reduced BBB permeability and improved the neurobehavior significantly post-ICH. VPA administration significantly decreased the expression of phosphorylated nuclear factor-kappa B (p-NFκB), matrix metalloproteinases 9 (MMP9), tumor necrosis factorα (TNFα), and interleukin-6 (IL-6), while it enhanced the expression of claudin 5 and occludin in the brain. In conclusion, VPA administration maintained the integrity of BBB after experimental ICH, thus reducing brain edema and improving the neurological outcomes. Therefore, VPA administration might be a new therapeutic method to protect BBB integrity for patients with ICH.

Corrigendum: An Overview of Managements in Meningiomas.

[This corrects the article DOI: 10.3389/fonc.2020.01523.].

An Overview of Managements in Meningiomas.

Meningioma is the most frequent primary tumor of the central nervous system. Important advances have been achieved in the treatment of meningioma in recent decades. Although most meningiomas are benign and have a good prognosis after surgery, clinicians often face challenges when the morphology of the tumor is complicated or the tumor is close to vital brain structures. At present, the longstanding treatment strategies of meningioma are mainly surgery and radiotherapy. The effectiveness of systemic therapy, such as chemotherapy or targeted therapy, has not been confirmed by big data series, and some clinical trials are still in progress. In this review, we summarize current treatment strategies and future research directions for meningiomas.

Association between expression of HOTAIR and invasiveness of gliomas, and its predictive value.

BACKGROUND: Hox transcript antisense intergenic RNA (HOTAIR) is upregulated and associated with a poor prognosis in many cancer types. Besides, it is involved in the invasion and metastasis of non-small-cell lung cancer and nasopharyngeal carcinoma. OBJECTIVES: The aim of this study was to investigate the association between the expression of HOTAIR and the grades of gliomas, and to explore its possible mechanism, as well as to evaluate the value of HOTAIR applied in predicting the grades of gliomas. MATERIAL AND METHODS: A total of 123 patients undergoing glioma surgeries were enrolled. Patients with grade I and grade II-IV tumors were regarded as the control group (n = 36) and the case group (n = 87), respectively. The expression of HOTAIR, matrix metalloproteinase 7 (MMP-7), matrix metalloproteinase 9 (MMP-9), and vascular endothelial growth factor (VEGF) was detected with quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in glioma tissues and then compared between grade I and grades II-IV. The correlation between the relative expression of HOTAIR and that of MMP-7, MMP-9 and VEGF was analyzed. Multivariate analysis was performed to identify independent risk factors. Receiver operating characteristic (ROC) curve was employed to evaluate the predictive value. RESULTS: The relative expression of HOTAIR, MMP-7, MMP-9, and VEGF was lower in glioma tissues of grade I than in the case of grades II-IV, and the relative expression of HOTAIR was positively correlated with the relative expression of MMP-7, MMP-9 and VEGF. Multivariate analysis showed that the relative expression of HOTAIR was independently associated with the grades of gliomas, but the relative expression of MMP-7, MMP-9 and VEGF was not. Besides, multivariate analysis showed that the expression level of HOTAIR >0.40 was an independent risk factor for grades II-IV after classifying the relative expression of HOTAIR, and ROC analysis showed that the expression level of HOTAIR >0.40 had a moderate value when applied in predicting grades II-IV. CONCLUSIONS: Hox transcript antisense intergenic RNA might promote the invasion of gliomas through upregulating the expression of MMP-7, MMP-9 and VEGF, and the expression level of HOTAIR >0.40 had a moderate value when applied in predicting grades II-IV.

Administration of rCTRP9 Attenuates Neuronal Apoptosis Through AdipoR1/PI3K/Akt Signaling Pathway after ICH in Mice.

Targeting neuronal apoptosis after intracerebral hemorrhage (ICH) may be an important therapeutic strategy for ICH patients. Emerging evidence indicates that C1q/TNF-Related Protein 9 (CTRP9), a newly discovered adiponectin receptor agonist, exerts neuroprotection in cerebrovascular disease. The aim of this study was to investigate the anti-apoptotic role of CTRP9 after experimental ICH and to explore the underlying molecular mechanisms. ICH was induced in mice via intrastriatal injection of bacterial collagenase. Recombinant CTRP9 (rCTRP9) was administrated intranasally at 1 h after ICH. To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were administered prior to rCTRP9 treatment. Western blots, neurofunctional assessments, immunofluorescence staining, and Fluoro-Jade C (FJC) staining experiments were performed. Administration of rCTRP9 significantly improved both short- and long-term neurofunctional behavior after ICH. RCTRP9 treatment significantly increased the expression of AdipoR1, PI3 K, p-Akt, and Bcl-2, while at the same time was found to decrease the expression of Bax in the brain, which was reversed by inhibition of AdipoR1 and PI3 K. The neuroprotective effect of rCTRP9 after ICH was mediated by attenuation of neuronal apoptosis via the AdipoR1/PI3K/Akt signaling pathway; therefore, rCTRP9 should be further evaluated as a potential therapeutic agent for ICH patients.

Association of Cardioembolism and Intracranial Arterial Stenosis with Outcomes of Mechanical Thrombectomy in Acute Ischemic Stroke.

OBJECTIVE: To estimate the association of different etiologies of cardioembolism (CE), intracranial arterial stenosis (ICAS), or the combination of these conditions with outcomes of mechanical thrombectomy in acute ischemic stroke. METHODS: Data from the intervention group of the Endovascular therapy for Acute ischemic Stroke Trial (EAST) were analyzed. In 140 patients, the presence of CE, ICAS, neither CE nor ICAS, or both conditions was assessed. The primary outcome was a favorable outcome at 90 days (modified Rankin Scale score 0-2); secondary outcomes included successful reperfusion (modified Thrombolysis In Cerebral Infarction grade 2b-3), symptomatic intracerebral hemorrhage, and 90-day mortality. RESULTS: Of 140 patients, 47 had neither CE nor ICAS, 35 had ICAS but not CE, 46 had CE but not ICAS, and 12 had both CE and ICAS. The rate of favorable outcome was 67.1% in the no CE and no ICAS group, 74.3% in the ICAS without CE group, 41.3% in the CE without ICAS group, and 33.3% in the CE and ICAS group. The CE and ICAS group had poor outcomes (odds ratio = 0.20 after adjusting for age, sex, and National Institutes of Health Stroke Scale score; 95% confidence interval, 0.04-0.95; P = 0.043). No significant differences were observed in secondary outcomes. CONCLUSIONS: The presence of both CE and ICAS was associated with poor outcome in patients with anterior circulation large-vessel occlusion treated with endovascular thrombectomy. Future studies are warranted to further explore this association.

Trends in stroke incidence among elderly low-income residents of rural China: a population-based study from 1992 to 2016.

In China, >70% of stroke deaths occur in people aged ≥65 years. However, trends in the stroke incidence among elderly people are unclear. We aimed to determine trends in the stroke incidence among elderly people in rural China. This was a population-based surveillance study conducted in Tianjin, China. Stroke events and all deaths were registered annually. Trends and annual proportion of change in incidence of first-ever stroke were evaluated from 1992 to 2016. The age-standardized incidence of first-ever stroke increased annually by 3.7% overall in elderly people (2.7% for men; 5.0% for women; all P<0.05). However, from 2008 to 2016, there was no significant change in the trends of stroke incidence among elderly people, across gender and subtypes. The proportion of elderly patients with first-ever stroke decreased by 1.1% annually. In contrast to young patients, annual changes in the incidence of stroke tended to be slight in elderly patients (3.7% vs. 9.5%) with greater increase in female patients than those in male patients (2.7% vs. 10.3% for men; 5.0% vs. 8.9% for women). Thus, the control of risk factors for stroke among elderly people is crucial, especially among older women, to reduce the burden of stroke in China.

Antibacterial and anticancer PDMS surface for mammalian cell growth using the Chinese herb extract paeonol(4-methoxy-2-hydroxyacetophenone).

Polydimethylsiloxane (PDMS) is widely used as a cell culture platform to produce micro- and nano-technology based microdevices. However, the native PDMS surface is not suitable for cell adhesion and is always subject to bacterial pollution and cancer cell invasion. Coating the PDMS surface with antibacterial or anticancer materials often causes considerable harm to the non-cancer mammalian cells on it. We have developed a method to fabricate a biocompatible PDMS surface which not only promotes non-cancer mammalian cell growth but also has antibacterial and anticancer activities, by coating the PDMS surface with a Chinese herb extract, paeonol. Coating changes the wettability and the elemental composition of the PDMS surface. Molecular dynamic simulation indicates that the absorption of paeonol onto the PDMS surface is an energy favourable process. The paeonol-coated PDMS surface exhibits good antibacterial activity against both Gram-positive and Gram-negative bacteria. Moreover considerable antibacterial activity is maintained after the coated surface is rinsed or incubated in water. The coated PDMS surface inhibits bacterial growth on the contact surface and promotes non-cancer mammalian cell growth with low cell toxicity; meanwhile the growth of cancer cells is significantly inhibited. Our study will potentially guide PDMS surface modification approaches to produce biomedical devices.

Sex Differences in Prevalence of and Risk Factors for Carotid Plaque among Adults: A Population-based Cross-Sectional Study in Rural China.

Although the associations between carotid plaque and cardiovascular disease risk factors have been identified in previous studies, there is limited information on sex-related differences in factors associated with the development of carotid plaque. We aimed to determine sex differences in the prevalence of carotid plaque and associated risk factors in rural China. A total of 3,789 subjects aged ≥45 years without history of stroke or cardiovascular disease were recruited to the study. B-mode ultrasonography was performed to determine the presence of carotid plaque. The mean age of male subjects was greater than that of female subjects. In addition, there was a higher prevalence of carotid plaque in men than in women (50.1% vs. 35.5%; P < 0.001) irrespective of age group, education level, and presence of risk factors. Older age, hypertension, diabetes mellitus, and high concentrations of low-density lipoprotein cholesterol were pronouncedly associated with the risk of carotid plaque in both men and women. These findings suggest that it is vital for physicians to be aware that conventional risk factors and other related factors are of equal importance among rural residents in China; patients should thus be treated accordingly so that reduce the burden of stroke and cardiovascular disease.

Endovascular therapy for Acute ischemic Stroke Trial (EAST): study protocol for a prospective, multicentre control trial in China.

BACKGROUND AND PURPOSE: 5 recent trials have shown the benefit of endovascular treatment for acute ischaemic stroke (AIS) due to large vessel occlusion of the anterior circulation. This study aims to evaluate the safety and efficacy of Solitaire thrombectomy in patients with moderate-to-severe stroke in the Chinese population, which has a high prevalence of intracranial atherosclerosis. METHODS AND ANALYSIS: This multicentre prospective control study will involve 17 stroke centres in China, and plans to recruit 150 patients in the intervention group, and 150 patients in the medical group, in which patients meet enrolment criteria but refuse intervention. Patients with AIS due to large vessel occlusion indicated for treatment with Solitaire stent retriever within 12 hours of symptom onset, and who meet the inclusion and exclusion criteria, will be enrolled in this study. The primary efficacy endpoint is functional independence as defined by a modified Rankin Scale (mRS) score ≤2 at 90 days or by functional improvement as defined by mRS, using shift analysis. The procedural efficacy endpoint is arterial recanalisation of the occluded target vessel measured by a modified Thrombolysis in Cerebral Infarction (mTICI) score equal or superior to 2b right following the use of the study device. The primary safety endpoint is symptomatic intracranial haemorrhage (sICH) within 24±3 hours postprocedure. ETHICS AND DISSEMINATION: The protocol was approved by the Ethics Committee at the coordinating centre and by the local Institutional Review Board of each participating centre. TRIAL REGISTRATION NUMBER: NCT02350283.