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  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 2 ( 2023-02), p. 327-336
    Abstract: Sex disparities in acute large vessel occlusion (LVO) following endovascular treatment (EVT) have been recently reported. However, there is uncertainty about the effect of sex differences on functional outcomes after EVT, particularly in an Asian population. The present study aimed to compare the clinical and safety outcomes between men and women with anterior circulation LVO treated with EVT. Methods: We analyzed data from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke: a Prospective Multicenter Registry Study) Registry, which was conducted at 111 hospitals from 26 provinces in China between November 2017 and March 2019. Men and women with anterior circulation LVO treated with EVT were matched using propensity scores. After a 1:1 propensity score matching, we compared the clinical outcomes including 90-day ordinal modified Rankin Scale distribution (primary outcome), procedure duration, successful reperfusion, symptomatic intracranial hemorrhage, and mortality. Furthermore, we explored sex modification on the primary outcome in subgroup analysis. Results: Of 1321 patients, 483 (36.6%) were women and 838 (63.4%) were men. The mean age for women and men were 68 and 62 years old, respectively. Among 578 patients identified after matching, there were no sex differences (men versus women) in 90-day ordinal modified Rankin Scale distribution (median [interquartile range], 4 [1–5] versus 3 [1–5], P =0.464), successful reperfusion (86.5% versus 91.0%, P =0.089), symptomatic intracranial hemorrhage (6.5% versus 7.9%, P =0.512), and mortality within 90 days (17.7% versus 17.0%, P =0.826). However, men had a longer median procedure duration than women (86 [52–128] versus 72 [48–110] minutes, β=14.51, [95% CI, 4.19–24.84]; P =0.006). Subgroup analysis showed that in patients with National Institutes of Health Stroke Scale score 〈 15, women tended to have a better outcome than men, whereas there was no gender effect in those with National Institutes of Health Stroke Scale score ≥15 ( P for interaction=0.032). Conclusions: Overall, this matched-control study from the ANGEL-ACT study showed similar clinical outcomes between men and women with anterior circulation LVO treated with EVT. However, in the subgroup of patients presenting with lower stroke severity (ie, National Institutes of Health Stroke Scale score 〈 15), women tended to have a better outcome than men highlighting a potential sex disparity for further investigation. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 5 ( 2022-05), p. 1580-1588
    Abstract: In patients undergoing mechanical thrombectomy (MT), adjunctive antithrombotic might improve angiographic reperfusion, reduce the risk of distal emboli and reocclusion but possibly expose patients to a higher intracranial hemorrhage risk. This study evaluated the safety and efficacy of combined MT plus eptifibatide for acute ischemic stroke. Methods: This was a propensity-matched analysis of data from 2 prospective trials in Chinese populations: the ANGEL-ACT trial (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) in 111 hospitals between November 2017 and March 2019, and the EPOCH trial (Eptifibatide in Endovascular Treatment of Acute Ischemic Stroke) in 15 hospitals between April 2019 and March 2020. The primary efficacy outcome was good outcome (modified Rankin Scale score 0–2) at 3 months. Secondary efficacy outcomes included the distribution of 3-month modified Rankin Scale scores and poor outcome (modified Rankin Scale score 5–6) and successful recanalization. The safety outcomes included any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 3-month mortality. Mixed-effects logistic regression models were used to account for within-hospital clustering in adjusted analyses. Results: Eighty-one combination arm EPOCH subjects were matched with 81 ANGEL-ACT noneptifibatide patients. Compared with the no eptifibatide group, the eptifibatide group had significantly higher rates of successful recanalization (91.3% versus 81.5%; P =0.043) and 3-month good outcomes (53.1% versus 33.3%; P =0.016). No significant difference was found in the remaining outcome measures between the 2 groups. All outcome measures of propensity score matching were consistent with mixed-effects logistic regression models in the total population. Conclusions: This matched-control study demonstrated that MT combined with eptifibatide did not raise major safety concerns and showed a trend of better efficacy outcomes compared with MT alone. Overall, eptifibatide shows potential as a periprocedural adjunctive antithrombotic therapy when combined with MT. Further randomized controlled trials of MT plus eptifibatide should be prioritized. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03844594 (EPOCH), NCT03370939 (ANGEL-ACT).
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 5 ( 2021-05), p. 1589-1600
    Abstract: A recent randomized controlled trial DIRECT-MT (Direct Intra-Arterial Thrombectomy to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals) compared the safety and efficacy of mechanical thrombectomy (MT) versus combined intravenous thrombolysis (IVT) and MT for acute large vessel occlusion. The current study utilized a prospective, nationwide registry to validate the results of the DIRECT-MT trial in a real-world practice setting. Methods: Subjects were selected from a prospective cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals from 26 provinces in China (ANGEL-ACT registry [Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke]) between November 2017 and March 2019. All patients eligible for IVT and receiving MT were reviewed and then grouped according to whether prior IVT or not (MT and combined IVT+MT). After a 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale, successful recanalization, door-to-puncture time, symptomatic intracranial hemorrhage, and intraprocedural embolization were compared. Results: A total of 1026 patients, 600 in the MT group and 426 in the combined group, were included. Among 788 patients identified after matching, there were no significant differences in the 90-day modified Rankin Scale (median, 3 versus 3 points; P =0.82) and successful recanalization (86.6% versus 89.3%; P =0.23) between the two groups; however, patients of the MT group had a shorter door-to-puncture time (median, 112 versus 136 minutes; β=−45.02 [95% CI, −68.31 to −21.74]), lower rates of symptomatic intracranial hemorrhage (5.5% versus 10.1%; odds ratio, 0.52 [95% CI, 0.30–0.91] ), and embolization (4.6% versus 8.1%; odds ratio, 0.54 [95% CI, 0.30–0.98]) than those of the combined group. Conclusions: This matched-control study largely confirmed the findings of the DIRECT-MT trial in a real-world practice setting, suggesting that MT may carry similar effectiveness to combined IVT+MT for acute large vessel occlusion patients, despite MT alone seems to be associated with a shorter in-hospital delay until procedure, lower risks of symptomatic intracranial hemorrhage, and embolization. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 6 ( 2022-06), p. 1984-1992
    Abstract: The role of stroke etiology subtype in patients with acute large vessel occlusion on the occurrence of hemorrhagic transformation (HT) after endovascular treatment is poorly studied, and which factors mediate their relationship remains largely unknown. We utilized nationwide registry data to explore the association of stroke subtype (cardioembolism versus large artery atherosclerosis) with HT and to identify the possible mediators. Methods: A total of 1015 subjects were selected from the ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke)—a prospective consecutive cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals in China between November 2017 and March 2019—and divided into large artery atherosclerosis (n=538) and cardioembolism (n=477) according to the Trial of ORG 10172 in Acute Stroke Treatment criteria. The types of HT included any intracerebral hemorrhage (ICH), parenchymal hematoma, and symptomatic ICH within 24 hours after endovascular treatment. The association between stroke subtype and HT was analyzed using a logistic regression model. Mediation analysis was done to assess how much of the effect of stroke subtype on HT was mediated through the identified mediators. Results: Stroke subtype (cardioembolism versus large artery atherosclerosis) was associated with increased risk of any ICH (29.8% versus 16.5%; odds ratio, 2.03 [95% CI, 1.22–3.36]), parenchymal hematoma (14.3% versus 5.4%; odds ratio, 2.90 [95% CI, 1.38–6.13] ), and symptomatic ICH (9.9% versus 4.7%; odds ratio, 2.59 [95% CI, 1.09–6.16]) after adjustment for potential confounders. The more thrombectomy passes in cardioembolism patients had a significant mediation effect on the association of stroke subtype with increased risk of HT (any ICH, 15.9%; parenchymal hematoma, 13.4%; symptomatic ICH, 14.2%, respectively). Conclusions: Stroke subtype is an independent risk factor for HT within 24 hours following endovascular treatment among acute large vessel occlusion patients. Mediation analyses propose that stroke subtype contributes to HT partly through thrombectomy pass, suggesting a possible pathomechanistic link. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 1467823-8
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  • 5
    In: BMC Neurology, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: The effect of atrial fibrillation (AF) on outcomes of endovascular treatment (EVT) for acute ischemic stroke (AIS) is controversial. This study aimed to investigate the association of AF with outcomes after EVT in AIS patients. Methods Subjects were selected from ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) - a prospective consecutive cohort of AIS patients undergoing EVT at 111 hospitals in China between November 2017 and March 2019, and then grouped according to having a history of AF or not. After 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale (mRS) score, successful recanalization after final attempt, symptomatic intracranial hemorrhage (ICH) within 24 h, and death within 90 days were compared. Results A total of 1755 patients, 550 with AF and 1205 without AF, were included. Among 407 pairs of patients identified after matching, no significant differences were found in the mRS score (median: 3 vs. 3 points; P  = 0.29), successful recanalization (87.2 vs. 85.3%; P  = 0.42), symptomatic ICH (9. 4 vs. 9.1%; P  = 0.86) and death (16.3 vs. 18.4%; P  = 0.44) between patients with and without AF. Conclusion The findings of this matched-control study show comparable outcomes of EVT in Chinese AIS patients with and without AF, which do not support withholding EVT in patients with both AIS and AF. Trial registration NCT03370939 First registration date: 28/09/2017 First posted date: 13/12/2017
    Type of Medium: Online Resource
    ISSN: 1471-2377
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041347-6
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  • 6
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 4 ( 2021-04), p. 1203-1212
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1467823-8
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  • 7
    In: Journal of Advanced Research, Elsevier BV, Vol. 43 ( 2023-01), p. 147-161
    Type of Medium: Online Resource
    ISSN: 2090-1232
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2541849-X
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  • 8
    In: Microbiome, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2023-11-17)
    Abstract: Parkinson’s disease (PD) is a common chronic neurological disorder with a high risk of disability and no cure. Periodontitis is an infectious bacterial disease occurring in periodontal supporting tissues. Studies have shown that periodontitis is closely related to PD. However, direct evidence of the effect of periodontitis on PD is lacking. Here, we demonstrated that ligature-induced periodontitis with application of subgingival plaque (LIP-SP) exacerbated motor dysfunction, microglial activation, and dopaminergic neuron loss in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. Results The 16S rRNA gene sequencing revealed that LIP-SP induced oral and gut dysbiosis. Particularly, Veillonella parvula ( V. parvula ) and Streptococcus mutans ( S. mutans ) from oral ligatures were increased in the fecal samples of MPTP + LIP-SP treated mice. We further demonstrated that V. parvula and S. mutans played crucial roles in LIP-SP mediated exacerbation of motor dysfunction and neurodegeneration in PD mice. V. parvula and S. mutans caused microglial activation in the brain, as well as T helper 1 (Th1) cells infiltration in the brain, cervical lymph nodes, ileum and colon in PD mice. Moreover, we observed a protective effect of IFNγ neutralization on dopaminergic neurons in V. parvula- and S. mutans- treated PD mice. Conclusions Our study demonstrates that oral pathogens V. parvula and S. mutans necessitate the existence of periodontitis to exacerbate motor dysfunction and neurodegeneration in MPTP-induced PD mice. The underlying mechanisms include alterations of oral and gut microbiota, along with immune activation in both brain and peripheral regions.
    Type of Medium: Online Resource
    ISSN: 2049-2618
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2697425-3
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  • 9
    In: The FEBS Journal, Wiley, Vol. 281, No. 15 ( 2014-08), p. 3315-3324
    Abstract: Identification of the epigenetic mechanisms involved in the transmission of Notch signaling is useful for personalized medicine. We observed that aberrantly high levels of Notch activity resulted in H4K16ac downregulation in hepatocellular carcinoma and breast cancer cell lines and tissues. This downregulated acetylation was a consequence of increased male on the first degradation following the upregulation of full‐length murine double minute 2 in different cancer types. We observed that increases in male on the first could attenuate heterogeneity induced by aberrantly high levels of Notch activity. Our results provide new insights into the analysis and treatment of Notch‐induced hepatocellular carcinoma and breast cancer.
    Type of Medium: Online Resource
    ISSN: 1742-464X , 1742-4658
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2014
    detail.hit.zdb_id: 2172518-4
    SSG: 12
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  • 10
    In: Cardiovascular Research, Oxford University Press (OUP), Vol. 119, No. 8 ( 2023-07-06), p. 1706-1717
    Abstract: Positive associations between periodontitis (PD) and atherosclerosis have been established, but the causality and mechanisms are not clear. We aimed to explore the causal roles of PD in atherosclerosis and dissect the underlying mechanisms. Methods and results A mouse model of PD was established by ligation of molars in combination with application of subgingival plaques collected from PD patients and then combined with atherosclerosis model induced by treating atheroprone mice with a high-cholesterol diet (HCD). PD significantly aggravated atherosclerosis in HCD-fed atheroprone mice, including increased en face plaque areas in whole aortas and lesion size at aortic roots. PD also increased circulating levels of triglycerides and cholesterol, hepatic levels of cholesterol, and hepatic expression of rate-limiting enzymes for lipogenesis. Using 16S ribosomal RNA (rRNA) gene sequencing, Fusobacterium nucleatum was identified as the most enriched PD-associated pathobiont that is present in both the oral cavity and livers. Co-culture experiments demonstrated that F. nucleatum directly stimulated lipid biosynthesis in primary mouse hepatocytes. Moreover, oral inoculation of F. nucleatum markedly elevated plasma levels of triglycerides and cholesterol and promoted atherogenesis in HCD-fed ApoE−/− mice. Results of RNA-seq and Seahorse assay indicated that F. nucleatum activated glycolysis, inhibition of which by 2-deoxyglucose in turn suppressed F. nucleatum-induced lipogenesis in hepatocytes. Finally, interrogation of the molecular mechanisms revealed that F. nucleatum-induced glycolysis and lipogenesis by activating PI3K/Akt/mTOR signalling pathway in hepatocytes. Conclusions PD exacerbates atherosclerosis and impairs lipid metabolism in mice, which may be mediated by F. nucleatum-promoted glycolysis and lipogenesis through PI3K/Akt/mTOR signalling in hepatocytes. Treatment of PD and specific targeting of F. nucleatum are promising strategies to improve therapeutic effectiveness of hyperlipidaemia and atherosclerosis.
    Type of Medium: Online Resource
    ISSN: 0008-6363 , 1755-3245
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 1499917-1
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