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  • Ovid Technologies (Wolters Kluwer Health)  (12)
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  • Ovid Technologies (Wolters Kluwer Health)  (12)
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  • 1
    Online Resource
    Online Resource
    Enhanced anticancer activity by the combination of vinpocetine and sorafenib via PI3K/AKT/GSK-3β signaling axis in hepatocellular carcinoma cells
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Anti-Cancer Drugs Vol. 32, No. 7 ( 2021-08), p. 727-733
    Details
    In: Anti-Cancer Drugs, Ovid Technologies (Wolters Kluwer Health), Vol. 32, No. 7 ( 2021-08), p. 727-733
    Abstract: Vinpocetine is widely used to treat cerebrovascular diseases. However, the effect of vinpocetine to treat hepatocellular carcinoma (HCC) has not been investigated. In this study, we revealed that vinpocetine was associated with antiproliferative activity in HCC cells, but induced cytoprotective autophagy, which restricted its antitumor activity. Autophagy inhibitors improved the antiproliferative activity of vinpocetine in HCC cells. Sorafenib is effective to treat advanced HCC, but the effect of autophagy induced by sorafenib is indistinct. We demonstrated vinpocetine plus sorafenib suppressed the cytoprotective autophagy activated by vinpocetine in HCC cells and significantly induced apoptosis and suppressed cell proliferation in HCC cells. In addition, vinpocetine plus sorafenib activates glycogen synthase kinase 3β (GSK-3β) and subsequently inhibits cytoprotective autophagy induced by vinpocetine in HCC cells. Meanwhile, overexpression of GSK-3β was efficient to increase the apoptosis induced by vinpocetine plus sorafenib in HCC cells. Our study revealed that vinpocetine plus sorafenib could suppress the cytoprotective autophagy induced by vinpocetine and subsequently show synergistically anti-HCC activity via activating GSK-3β and the combination of vinpocetine and sorafenib might reverse sorafenib resistance via the PI3K/protein kinase B/GSK-3β signaling axis. Thus, vinpocetine may be a potential candidate for sorafenib sensitization and HCC treatment, and our results may help to elucidate more effective therapeutic options for HCC patients with sorafenib resistance.
    Type of Medium: Online Resource
    ISSN: 0959-4973
    URL: Article
    DOI: 10.1097/CAD.0000000000001056
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 1065301-6
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  • 2
    Online Resource
    Online Resource
    Dual Antiplatelet Therapies and Causes in Minor Stroke or Transient Ischemic Attack: A Prespecified Analysis in the CHANCE-2 Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Stroke Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 9 ( 2023-09), p. 2241-2250
    Abstract: It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II). METHODS: This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. Patients with centralized evaluation of TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification of large-artery atherosclerosis, small-vessel occlusion, and stroke of undetermined cause were included. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. Cox proportional hazards models were used to assess the interaction of TOAST classification with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin. RESULTS: A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63–1.18]; P =0.34); 32 (3.6%) and 61 (7.0%) patients with small-vessel occlusion (hazard ratio, 0.51 [95% CI, 0.33–0.79]; P =0.002); and 68 (4.8%) and 87 (5.9%) patients with stroke of undetermined cause (hazard ratio, 0.80 [95% CI, 0.58–1.10]; P =0.17), with P =0.08 for the treatment×cause subtype interaction effect. There were no significant differences in severe or moderate bleeding events in patients with different cause and different treatment. CONCLUSIONS: In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04078737.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.122.042233
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 80381-9
    detail.hit.zdb_id: 1467823-8
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  • 3
    Online Resource
    Online Resource
    EphrinB2 Regulates Cardiac Fibrosis Through Modulating the Interaction of Stat3 and TGF-β/Smad3 Signaling
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Research Vol. 121, No. 6 ( 2017-09), p. 617-627
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 121, No. 6 ( 2017-09), p. 617-627
    Abstract: Cardiac fibrosis is a common feature in left ventricular remodeling that leads to heart failure, regardless of the cause. EphrinB2 (erythropoietin-producing hepatoma interactor B2), a pivotal bidirectional signaling molecule ubiquitously expressed in mammals, is crucial in angiogenesis during development and disease progression. Recently, EphrinB2 was reported to protect kidneys from injury-induced fibrogenesis. However, its role in cardiac fibrosis remains to be clarified. Objective: We sought to determine the role of EphrinB2 in cardiac fibrosis and the underlying mechanisms during the pathological remodeling process. Methods and Results: EphrinB2 was highly expressed in the myocardium of patients with advanced heart failure, as well as in mouse models of myocardial infarction and cardiac hypertrophy induced by angiotensin II infusion, which was accompanied by myofibroblast activation and collagen fiber deposition. In contrast, intramyocardial injection of lentiviruses carrying EphrinB2-shRNA ameliorated cardiac fibrosis and improved cardiac function in mouse model of myocardial infarction. Furthermore, in vitro studies in cultured cardiac fibroblasts demonstrated that EphrinB2 promoted the differentiation of cardiac fibroblasts into myofibroblasts in normoxic and hypoxic conditions. Mechanistically, the profibrotic effect of EphrinB2 on cardiac fibroblast was determined via activating the Stat3 (signal transducer and activator of transcription 3) and TGF-β (transforming growth factor-β)/Smad3 (mothers against decapentaplegic homolog 3) signaling. We further determined that EphrinB2 modulated the interaction between Stat3 and Smad3 and identified that the MAD homology 2 domain of Smad3 and the coil–coil domain and DNA-binding domain of Stat3 mediated the interaction. Conclusions: This study uncovered a previously unrecognized profibrotic role of EphrinB2 in cardiac fibrosis, which is achieved through the interaction of Stat3 with TGF-β/Smad3 signaling, implying a promising therapeutic target in fibrotic diseases and heart failure.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.117.311045
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 80100-8
    detail.hit.zdb_id: 1467838-X
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    Online Resource
  • 4
    Online Resource
    Online Resource
    Imaging Parameters Predict Recurrence After Transient Ischemic Attack or Minor Stroke Stratified by ABCD 2 Score
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Stroke Vol. 52, No. 6 ( 2021-06), p. 2007-2015
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 52, No. 6 ( 2021-06), p. 2007-2015
    Abstract: Whether imaging parameters would independently predict stroke recurrence in low-risk minor ischemic stroke (MIS) or transient ischemic attack (TIA) according to traditional score system (such as ABCD 2 score, which was termed on the basis of the initials of the five factors: age, blood pressure, clinical features, duration, diabetes) remains unclear. We sought to evaluate the association between imaging parameters and 1-year stroke recurrence in patients with TIA or MIS in different risk stratum stratified by ABCD 2 score. Methods: We included patients with TIA and MIS (National Institutes of Health Stroke Scale score ≤3) with complete baseline vessel and brain imaging data from the Third China National Stroke Registry III. Patients were categorized into different risk groups based on ABCD 2 score (low risk, 0–3; moderate risk, 4–5; and high risk, 6–7). The primary outcome was stroke recurrence within 1 year. Multivariable Cox proportional-hazards regression models were used to assess whether imaging parameters (large artery stenosis, infarction number) were independently associated with stroke recurrence. Results: Of the 7140 patients included, 584 patients experienced stroke recurrence within 1 year. According to the ABCD 2 score, large artery stenosis was associated with higher stroke recurrence in both low-risk (adjusted hazard ratio, 1.746 [95% CI, 1.200–2.540]) and moderate-risk group (adjusted hazard ratio, 1.326 [95% CI, 1.042–1.687] ) but not in the high-risk group ( P 〉 0.05). Patients with multiple acute infarctions or single acute infarction had a higher risk of recurrent stroke than those with no infarction in both low- and moderate-risk groups, but not in the high-risk group. Conclusions: Large artery stenosis and infarction number were independent predictors of 1-year stroke recurrence in low-moderate risk but not in high-risk patients with TIA or MIS stratified by ABCD 2 score. This finding emphasizes the importance of early brain and vascular imaging evaluation for risk stratification in patients with TIA or MIS.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.120.032424
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 80381-9
    detail.hit.zdb_id: 1467823-8
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    Online Resource
  • 5
    Online Resource
    Online Resource
    Correction to: Cap-Assisted Endoscopic Sclerotherapy vs Ligation in the Long-Term Management of Medium Esophageal Varices: A Randomized Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Clinical and Translational Gastroenterology Vol. 12, No. 2 ( 2021-2-15), p. e00318-
    Details
    In: Clinical and Translational Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 2 ( 2021-2-15), p. e00318-
    Type of Medium: Online Resource
    ISSN: 2155-384X
    URL: Article
    DOI: 10.14309/ctg.0000000000000318
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2581516-7
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  • 6
    Online Resource
    Online Resource
    Genome-Wide Analysis of DNA Methylation and Acute Coronary Syndrome
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Research Vol. 120, No. 11 ( 2017-05-26), p. 1754-1767
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 120, No. 11 ( 2017-05-26), p. 1754-1767
    Abstract: Acute coronary syndrome (ACS) is a leading cause of death worldwide. Immune functions play a vital role in ACS development; however, whether epigenetic modulation contributes to the regulation of blood immune cells in this disease has not been investigated. Objective: We conducted an epigenome-wide analysis with circulating immune cells to identify differentially methylated genes in ACS. Methods and Results: We examined genome-wide methylation of whole blood in 102 ACS patients and 101 controls using HumanMethylation450 array, and externally replicated significant discoveries in 100 patients and 102 controls. For the replicated loci, we further analyzed their association with ACS in 6 purified leukocyte subsets, their correlation with the expressions of annotated genes, and their association with cardiovascular traits/risk factors. We found novel and reproducible association of ACS with blood methylation at 47 cytosine-phosphoguanine sites (discovery: false discovery rate 〈 0.005; replication: Bonferroni corrected P 〈 0.05). The association of methylation levels at these cytosine-phosphoguanine sites with ACS was further validated in at least 1 of the 6 leukocyte subsets, with predominant contributions from CD8 + T cells, CD4 + T cells, and B cells. Blood methylation of 26 replicated cytosine-phosphoguanine sites showed significant correlation with expressions of annotated genes (including IL6R , FASLG , and CCL18 ; P 〈 5.9×10 −4 ), and differential gene expression in case versus controls corroborated the observed differential methylation. The replicated loci suggested a role in ACS-relevant functions including chemotaxis, coronary thrombosis, and T-cell–mediated cytotoxicity. Functional analysis using the top ACS-associated methylation loci in purified T and B cells revealed vital pathways related to atherogenic signaling and adaptive immune response. Furthermore, we observed a significant enrichment of the replicated cytosine-phosphoguanine sites associated with smoking and low-density lipoprotein cholesterol ( P enrichment ≤1×10 −5 ). Conclusions: Our study identified novel blood methylation alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets. Our results may suggest that immune signaling and cellular functions might be regulated at an epigenetic level in ACS.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.116.310324
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 80100-8
    detail.hit.zdb_id: 1467838-X
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    Online Resource
  • 7
    Online Resource
    Online Resource
    Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients : A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Chinese Medical Journal Vol. 129, No. 22 ( 2016-11-20), p. 2659-2665
    Details
    In: Chinese Medical Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 129, No. 22 ( 2016-11-20), p. 2659-2665
    Type of Medium: Online Resource
    ISSN: 0366-6999
    URL: Article
    DOI: 10.4103/0366-6999.193443
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 127089-8
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  • 8
    Online Resource
    Online Resource
    Cap-Assisted Endoscopic Sclerotherapy vs Ligation in the Long-Term Management of Medium Esophageal Varices: A Randomized Trial
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Clinical and Translational Gastroenterology Vol. 11, No. 12 ( 2020-12-15), p. e00285-
    Details
    In: Clinical and Translational Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 12 ( 2020-12-15), p. e00285-
    Abstract: Compared with endoscopic variceal ligation (EVL), cap-assisted endoscopic sclerotherapy (CAES) improves efficacy in the treatment of small esophageal varices (EVs) but has not been evaluated in the management of medium EVs. The aim of this study was to compare CAES with EVL in the long-term management of patients exhibiting cirrhosis with medium EVs and a history of esophageal variceal bleeding (EVB), with respect to variceal eradication and recurrence, adverse events, rebleeding, and survival. METHODS: Cirrhotic patients with medium EVs and a history of EVB were divided randomly into EVL and CAES groups. EVL or CAES was repeated each month until variceal eradication. Lauromacrogol was used as a sclerosant. Patients were followed up until 1 year after eradication. RESULTS: In total, 240 patients (age: 51.1 ± 10.0 years; men: 70.8%) were included and randomized to the EVL and CAES groups. The recurrence rate of EVs was much lower in the CAES group than in the EVL group (13.0% vs 30.7%, P = 0.001). The predictors for variceal recurrence were eradication by EVL (hazard ratio [HR]: 2.37, P = 0.04), achievement of complete eradication (HR: 0.27, P 〈 0.001), and nonselective β-blocker response (HR: 0.32, P = 0.003). There was no significant difference in the rates of eradication, rebleeding, requirement for alternative therapy, and mortality or the incidence of complications between groups. DISCUSSION: CAES reduces the recurrence rate of EVs with comparable safety to that of EVL in the long-term management of patients presenting cirrhosis with medium EVs and a history of EVB.
    Type of Medium: Online Resource
    ISSN: 2155-384X
    URL: Article
    DOI: 10.14309/ctg.0000000000000285
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2581516-7
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  • 9
    Online Resource
    Online Resource
    SPINK1 , PRSS1 , CTRC , and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Clinical and Translational Gastroenterology Vol. 9, No. 11 ( 2018-11), p. e204-
    Details
    In: Clinical and Translational Gastroenterology, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 11 ( 2018-11), p. e204-
    Type of Medium: Online Resource
    ISSN: 2155-384X
    URL: Article
    DOI: 10.1038/s41424-018-0069-5
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2581516-7
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  • 10
    Online Resource
    Online Resource
    Estimation of Mycophenolic Acid Exposure in Chinese Renal Transplant Patients by a Joint Deep Learning Model
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Therapeutic Drug Monitoring Vol. 44, No. 6 ( 2022-12), p. 738-746
    Details
    In: Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 6 ( 2022-12), p. 738-746
    Abstract: To predict mycophenolic acid (MPA) exposure in renal transplant recipients using a deep learning model based on a convolutional neural network with bilateral long short-term memory and attention methods. Methods: A total of 172 Chinese renal transplant patients were enrolled in this study. The patients were divided into a training group (n = 138, Ruijin Hospital) and a validation group (n = 34, Zhongshan Hospital). Fourteen days after renal transplantation, rich blood samples were collected 0–12 hours after MPA administration. The plasma concentration of total MPA was measured using an enzyme-multiplied immunoassay technique. A limited sampling strategy based on a convolutional neural network–long short-term memory with attention (CALS) model for the prediction of the area under the concentration curve (AUC) of MPA was established. The established model was verified using the data from the validation group. The model performance was compared with that obtained from multiple linear regression (MLR) and maximum a posteriori (MAP) methods. Results: The MPA AUC 0–12 of the training and validation groups was 54.28 ± 18.42 and 41.25 ± 14.53 µg·ml −1 ·h, respectively. MPA plasma concentration after 2 (C 2 ), 6 (C 6 ), and 8 (C 8 ) hours of administration was the most significant factor for MPA AUC 0–12 . The predictive performance of AUC 0–12 estimated using the CALS model of the validation group was better than the MLR and MAP methods in previous studies (r 2 = 0.71, mean prediction error = 4.79, and mean absolute prediction error = 14.60). Conclusions: The CALS model established in this study was reliable for predicting MPA AUC 0–12 in Chinese renal transplant patients administered mycophenolate mofetil and enteric-coated mycophenolic acid sodium and may have good generalization ability for application in other data sets.
    Type of Medium: Online Resource
    ISSN: 0163-4356
    URL: Article
    DOI: 10.1097/FTD.0000000000001020
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
    detail.hit.zdb_id: 424443-6
    SSG: 15,3
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