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1.
Int Immunopharmacol ; 80: 106125, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31931362

RESUMO

IgA nephropathy (IgAN) is an autoimmune kidney disease and is the most prevalent form of glomerular kidney disease in China and worldwide. IgA immune complex deposition accompanied by mesangial cell proliferation and mesangial matrix expansion is the most basic pathological feature of IgAN. Dihydroartemisinin (DHA), an antimalarial drug, was recently reported to be effective in treating autoimmune diseases. However, its potential therapeutic role in IgAN is relatively unstudied. The aim of this study was to investigate the pharmacological effects and the underlying mechanisms of DHA in the treatment of IgAN. In this study, renal biopsy specimens were collected for immunohistochemistry. In vitro, 25 µg/ml concentrations of aggregated IgA1 (aIgA1) was used to construct the IgAN mesangial cell model. Stimulated human mesangial cells (HMCs) were treated for 24 h with DHA (0-15 µM) and were collected for western blot analyses. Cell proliferation was assessed by Cell Counting Kit 8 (CCK8) and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. In vitro, our results showed that DHA could downregulate the mammalian target of rapamycin/ribosomal protein S6 kinase beta-1 (mTOR/S6K1) signaling pathway, promote cell autophagy, and ameliorate cell proliferation in aIgA1-induced HMCs. The results suggested that DHA may represent a novel class of mTOR inhibitor and promote an anti-proliferation effect in IgAN HMCs, which provides an alternative approach for IgAN treatment.

2.
Int Immunopharmacol ; 80: 106147, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31931367

RESUMO

DNA methylation, especially DNA methyltransferases (DNMTs), is involved in the pathogenesis of many autoimmune diseases through regulating immune function. This study aimed to explore the potential role of DNMTs in IgA nephropathy (IgAN). We evaluated mRNA expressions of DNMT1, DNMT3A, DNMT3B along with ß1,3-galactosyltransferase (C1GALT1) in peripheral blood mononuclear cells (PBMCs), and measured galactose-deficient IgA1 (Gd-IgA1) levels in plasma. The expression intensity of DNMT1 and DNMT3B in the renal specimen of IgAN patients were also detected. Results showed DNMT3B, not DNMT1 or DNMT3A, was notably increased in IgAN patients compared to controls and associated with pathologic types. However, DNMT1 and C1GALT1 were found positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with 24 h Urine protein in IgAN patients. No association was found between DNMT1 and Gd-IgA1. The expressions of DNMT3B and DNMT1 were barely observed in IgAN renal biopsy specimens. In conclusion, for the first time, we identified the relations of DNMTs and C1GALT1 to the clinical state and pathology of IgAN patients, which provide new clues for IgAN.

3.
BMJ Open ; 10(1): e033120, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31911518

RESUMO

INTRODUCTION: The optimal dose-fractionation schedule of palliative radiotherapy has been debated in patients with bone metastases. Our objective is to comprehensively compare multiple fraction schedules with single fraction radiotherapy in terms of efficacy and toxicities by performing a systematic review and network meta-analysis. METHODS AND ANALYSIS: Electronic searches of titles/abstracts of palliative radiotherapy for bone metastases will be performed, using PubMed, Cochrane Library, Embase, clinical trials, American Society for Therapeutic Radiology and Oncology and European Society of Radiotherapy and Oncology. The primary outcome of interest is the incidence of skeletal-related event following palliative radiotherapy for bone metastases in prospective studies. The risk of bias and quality of evidence will be evaluated based on Cochrane Collaboration's tool and Grades of Recommendation, Assessment, Development and Evaluation in the network meta-analysis. We will conduct subgroup analysis and sensitivity analysis regardless of heterogeneity estimates. ETHICS AND DISSEMINATION: This study will synthesise the evidence regarding dose-fractionation schedule of palliative radiotherapy in patients with bone metastases. We hope the findings from this study will help clinicians and patients select optimum palliative radiotherapy by identifying the optimal dose-fractionation schedule of palliative radiotherapy with the most value in terms of patient-important outcomes. The evidence obtained from network meta-analysis will help to guide head-to-head research in the future. The results will be disseminated through international conference reports and peer-reviewed manuscripts. Ethics review board is not required for this network meta-analysis. PROSPERO REGISTRATION NUMBER: CRD42019135195.

4.
Nutr Metab Cardiovasc Dis ; 30(2): 265-273, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31740238

RESUMO

BACKGROUND AND AIMS: The association between lipoprotein(a) [Lp(a)] levels and the risk of cardiovascular disease is of great interest but still controversial. This study sought to investigate the impact of Lp(a) on coronary severity and long-term outcomes of patients who undergo percutaneous coronary intervention (PCI). METHODS AND RESULTS: A total of 6714 consecutive patients who received PCI were enrolled to analyze the association between Lp(a) and coronary severity and major adverse cardiovascular and cerebrovascular events (MACCE). Patients were divided into tertiles according to Lp(a) levels on admission. Coronary severity was evaluated by SYNTAX scoring system. The MACCE included recurrent myocardial infarction, unplanned target vessel revascularization, stent thrombosis, ischemic stroke and all-cause mortality. Significantly, Lp(a) levels were positively associated with coronary severity (p < 0.001). Multivariate logistic regression analyses showed Lp(a) was an independent predictor of intermediate to high SYNTAX score. During an average of 874 days follow-up, 755 patients presented with MACCE (11.25%) were reported. The incidence rates of MACCE, all-cause mortality, cardiac death, target vessel revascularization, recurrent myocardial infarction, stent thrombosis, stroke and bleeding were not statistically different among the Lp(a) tertile groups. Furthermore, both Kaplan-Meier and Cox regression analyses found no relationship between Lp(a) and cardiovascular outcomes (p > 0.05). CONCLUSION: Lp(a) is an independent predictor of the prevalence of more complex coronary artery lesions (SYNTAX score ≥ 23) in patients with PCI. In addition, our study has shown that Lp(a) has no relationship with long-term cardiovascular outcomes in Chinese patients with PCI.

5.
Life Sci ; 241: 117172, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843529

RESUMO

AIMS: Allergic airway inflammation is one of the major pathological events involved in asthma, and dysregulation of regulatory T cells (Treg) plays a crucial role in the development of allergic airway inflammation. Here, we attempted to investigate the regulatory effects of B cell-activating factor (BAFF) on Tregs in allergic airway inflammation. MAIN METHODS: BAFF expression was analyzed by ELISA, quantitative reverse transcription PCR (RT-PCR) and Western blot assays. The levels of IL-4, TGF-ß, IL-2, and IL-10 were tested using ELISA kits. Flow cytometry was conducted to analyze the populations of CTLA4+ Foxp3+ Tregs. KEY FINDINGS: BAFF was found to be aberrantly expressed in sputum and lungs in patients with asthma as well as OVA sensitized mice. BAFF silencing by lentiviral BAFF shRNA reduced the number of eosinophils and levels of IL-4 in the BAL fluid, as well as the Fizz1 expression in the lungs of OVA mice. Additionally, the population of CTLA4+ Foxp3+ Tregs were significantly decreased in OVA mice and had a negative correlation to BAFF levels in asthmatic patients and OVA mice. BAFF silencing in vivo increased levels of CTLA4+ Foxp3+ Tregs and the secretion of IL-10, and improved the regulatory phenotype and suppressor function of Tregs in vitro. Furthermore, BAFF can affect Tregs generation by regulating the production of the pro-Treg cytokines IL-2 and TGF-ß. SIGNIFICANCE: BAFF has an inhibitory effect on the generation and suppressor function of Tregs by affecting pro-Tregs cytokines, thereby contributing to the development of allergic airway inflammation.


Assuntos
Asma/prevenção & controle , Fator Ativador de Células B/antagonistas & inibidores , Citocinas/metabolismo , Regulação da Expressão Gênica , Inativação Gênica , Inflamação/prevenção & controle , Linfócitos T Reguladores/imunologia , Adulto , Animais , Asma/etiologia , Asma/imunologia , Asma/patologia , Fator Ativador de Células B/genética , Estudos de Casos e Controles , Feminino , Humanos , Inflamação/etiologia , Inflamação/imunologia , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Ovalbumina/toxicidade
6.
J Cardiol ; 75(1): 60-65, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31416781

RESUMO

BACKGROUND: Inflammation plays a pivotal role in coronary artery disease (CAD). Few data from large-size studies are available on the association of high-sensitivity C-reactive protein (hs-CRP) and severity of CAD. Our aim was to investigate their relationship as well as their impact on long-term outcomes in patients undergoing percutaneous coronary intervention. METHODS: In 2013, 10,020 patients were consecutively included. Patients were divided into three groups based on hs-CRP on admission: 0-3mg/L (n=6978, 69.6%), 3.01-10mg/L (n=1997, 19.9%), >10mg/L (n=1045, 10.4%). Disease severity was determined by SYNTAX score (SS). Their differences were assessed in SS and major adverse cardiovascular events (MACEs, including all-cause death, myocardial infarction, revascularization, and in-stent thrombosis) among groups. RESULTS: The mean follow-up period was 874 days. Patients with elevated hs-CRP were older, had more risk factors such as hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, and cigarette smoking. Multivariate regression analysis showed that hs-CRP >10mg/L (OR 1.49, 95% confidence interval 1.21-1.84, p<0.001), age, previous myocardial infarction, serum creatinine, and left ventricular ejection fraction were independent predictors of intermediate-high SS (>22). Subgroup analysis indicated that the relation between hs-CRP and SS was also consistent in acute coronary syndrome and its subtypes. Although elevated hs-CRP was positively associated with increased rates of MACEs (11.0% versus 12.1% versus 14.3%, p=0.006), death (1.0% versus 1.3% versus 3.0%, p<0.001), and revascularization (8.6% versus 10.4% versus 10.0%, p=0.032), it did not show any prognostic effect for adverse outcomes in multivariate regression analyses (all adjusted p> 0.05). While SS>22 remained independently predictive of MACEs and revascularization after adjusting confounders, the risks of which were increased by 56% and 68%, respectively. CONCLUSION: Serum hs-CRP could be a useful biomarker for indicating CAD severity and could aid in risk stratification.

7.
J Interv Cardiol ; 2019: 3503876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772525

RESUMO

Objectives: This study analyzed a large sample to explain the association of baseline smoking state with long-term prognosis of coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). Background: Data is limited up to now regarding whether smoker's paradox exists in Chinese population. Methods: A total of 10724 consecutive cases were enrolled from January to December 2013. 2-year clinical outcomes were evaluated among current smokers and nonsmokers. Major adverse coronary event (MACCE) included all-cause death, revascularization, myocardial infarction (MI), and stroke. Results: Current smokers and nonsmokers accounted for 57.1% and 42.9%, respectively. Current smokers were presented with predominant male sex, lower age, and less comorbidities. The rates of 2-year all-cause death were not significantly different among two groups. But the rate of stroke and bleeding was significantly higher in nonsmokers than in current smokers (1.6% and 1.1%, P=0.031; 7.2% and 6.1%, P=0.019). The rate of revascularization was significantly higher in current smokers than in nonsmokers (9.1% and 8.0%, P=0.037). Multivariable Cox regression indicated that, compared with nonsmokers, current smokers were not independently associated with all endpoints (all P>0.05). Conclusions: 2-year all-cause death, MACCE, MI, revascularization, stroke, ST, and bleeding risk were similar between current smokers and nonsmokers in CAD patients undergoing PCI.

8.
Am J Med Sci ; 358(1): 19-25, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31228966

RESUMO

BACKGROUND: This large cohort study aimed to investigate the effect of acquired thrombocytopenia on the prognosis of patients with stable coronary artery disease undergoing percutaneous coronary intervention (PCI). MATERIALS AND METHODS: Patients with stable coronary artery disease undergoing elective PCI were prospectively enrolled during 2013. All patients were followed for a median of 30 months (the 25th and 75th percentiles for follow-up time were 27 and 32 months). After excluding patients with baseline thrombocytopenia (<150 × 109/L), in-hospital acquired thrombocytopenia was defined as lowest platelet count <150 × 109/L or a relative reduction of 50% from the preoperative baseline platelet count after PCI. RESULTS: A total of 3,614 patients were enrolled; 329 (7.8%) patients developed thrombocytopenia after PCI. Analyses showed no difference in adverse events between groups during hospitalization, while long-term all-cause mortality, minor bleeding and major bleeding were significantly higher in patients with thrombocytopenia than in the control group. After multivariable adjustment, thrombocytopenia remained an independent risk factor for long-term all-cause mortality (HR 2.782, 95% CI 1.182-6.552, P = 0.019), minor bleeding (HR 2.198, 95% CI 1.217-3.972, P = 0.009) and major bleeding (HR 5.409, 95% CI 1.541-8.999, P = 0.008). Predictors of acquired thrombocytopenia were age, body mass index, baseline platelet count and left ventricular ejection fraction. CONCLUSIONS: Acquired thrombocytopenia may predict long-term all-cause mortality and bleeding events in patients with stable coronary artery disease who receive elective PCI.


Assuntos
Doença da Artéria Coronariana/terapia , Intervenção Coronária Percutânea/efeitos adversos , Trombocitopenia/etiologia , Causas de Morte , Estudos de Coortes , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Feminino , Fibrinolíticos/efeitos adversos , Fibrinolíticos/uso terapêutico , Seguimentos , Hemorragia/etiologia , Hemorragia/mortalidade , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Contagem de Plaquetas , Prognóstico , Estudos Prospectivos , Fatores de Risco , Trombocitopenia/mortalidade , Resultado do Tratamento
9.
Clin Appl Thromb Hemost ; 25: 1076029619853638, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31215225

RESUMO

The Patterns of non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) thrombotic risk score is a novel score for predicting the risk of coronary thrombotic events after percutaneous coronary intervention (PCI). We assessed the prognostic value of this score for mortality in patients with PCI. In this prospective, observational study, we enrolled 10 724 consecutive patients underwent PCI. The primary end point was all-cause death and the secondary end point was major adverse cardiovascular and cerebrovascular events (MACCE) as a composite of all-cause death, myocardial infarction, revascularization, stent thrombosis, or stroke. Among 9782 patients without in-hospital events, a total of 97 deaths and 1002 MACCE occurred during the 2-year follow-up. The mortality risk of patients in the high-risk group was 2.31 times higher than that in the low-risk group (hazard ratio, 2.31; P = .001). This risk score showed prognostic value in evaluating mortality (area under the receiver operating characteristic curve [AUROC], 0.607; 95% confidence interval [CI], 0.551-0.663) and MACCE (AUROC, 0.544; 95% CI, 0.526-0.563; both P < .001). The prognostic value of mortality was higher than that of MACCE (Z = 2.09, P = .04). The PARIS thrombotic risk score shows modest prognostic value for mortality and MACCE, and the prognostic value of mortality is better than that of MACCE.


Assuntos
Transtornos Cerebrovasculares/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Medição de Risco/métodos , Trombose/diagnóstico , Idoso , Transtornos Cerebrovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade , Intervenção Coronária Percutânea/mortalidade , Prognóstico , Estudos Prospectivos , Curva ROC
10.
J Chin Med Assoc ; 82(8): 616-622, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31135575

RESUMO

BACKGROUND: A novel risk model to predict long-term mortality in patients with acute coronary syndrome (ACS), derived from the EPICOR (long-term follow-up of antithrombotic management patterns in acute coronary syndrome patients) registry, has been released recently and its performance remains to be assessed. The objective is to evaluate the EPICOR score for 2-year mortality risk in ACS patients after percutaneous coronary intervention (PCI). METHODS: From January to December in 2013, a total of 6087 consecutive patients presenting with ACS who were scheduled for PCI were enrolled. Use online simplified EPICOR calculator to assess the expected risk of death. RESULTS: Sixty-eight patients (1.1%) died during 2-year follow-up. The areas under the receiver operating characteristics curve for mortality in the overall population, ST-segment elevation myocardial infarction (STEMI), and non-ST-segment elevation ACS were 0.712 (95% CI, 0.650-0.772; p < 0.001), 0.790 (95% CI, 0.676-0.903; p < 0.001), and 0.683 (95% CI, 0.615-0.751; p < 0.001), respectively. Moreover, it was noninferior to the updated Global Registry of Acute Coronary Events (GRACE) risk score. Patients were stratified into three categories: low-risk (n = 3382), medium-risk (n = 2547), and high-risk (n = 158). Kaplan-Meier curve demonstrated significant ongoing divergence in both mortality (0.6% vs 1.3% vs 9.5%; p < 0.001) and major adverse cardiovascular and cerebrovascular events (MACCEs) (11.8% vs 12.3% vs 19.6%; p = 0.014) among them. Multivariate Cox analysis revealed that medium- and high-risk groups predicted 2- and 12-fold hazards of death comparing to the lowest. Yet, it was not a significant predictor for MACCEs after adjusting confounding factors. CONCLUSION: The simplified EPICOR score showed fair discriminatory power of 2-year mortality in patients with ACS and an improved performance in the STEMI subgroup. It could aid in risk stratification of ACS patients as an independent predictor.

11.
Kidney Blood Press Res ; 44(2): 245-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31071709

RESUMO

BACKGROUND/AIMS: Diabetic nephropathy (DN) is a leading cause of end-stage renal disease. Microalbuminuria (MA) is widely used to predict early progressive renal function decline (ERFD) of DN in type 2 diabetes mellitus (T2D) patients, but the sensitivity and specificity of MA have been questioned. Here, we determined the urine metabolites differences between T2D patients with MA who maintained stable renal function and those who progressed to ERFD in order to identify specific biomarkers of the progression of renal dysfunction. METHODS: A total of 102 T2D patients with MA and normal renal function at baseline were followed up for 5-6 years. Of these, 52 patients were selected and classified into two groups according to the later renal function; 25 patients who experienced ERFD were regarded as the progressive group, while 27 patients who maintained stable renal function were considered as the stable group. In the pilot study, untargeted, broad-spectrum urine metabolomics was performed on the urine of 12 subjects from the progressive group (5 patients as "progressors") and stable group (7 patients as "non-progressors") to discover candidate markers. We then used a targeted metabolomics analysis to identify the selected markers in the urine of an additional 40 patients (20 from the progressive group as cases, and 20 from the stable group as controls) in the validation study. RESULTS: A total of 318 known metabolites were detected in the pilot study and 6 metabolites with significant difference between progressors and non-progressors were identified. The levels of 4 metabolites, including azelaic acid, adipic acid, 5-hydroxyhexanoic acid, and L-tryptophan decreased significantly, while levels of L-pyroglutamic acid and D-norvaline increased observably in the progressors compared with non-progressors. Furthermore, in the validation study, 6 metabolites were confirmed by quantitative measurements and their concentrations were consistent with the changes in the pilot study. Concentrations of L-pyroglutamic acid and D-norvaline still increased in the cases, but were not statistically significant. Of the 4 metabolites with decreased concentrations among the cases, only 5-hydroxyhexanoic acid remained statistically significant while the other 3 metabolites did not differ between cases and controls. CONCLUSION: We have identified urine metabolites and shown that 5-hydroxyhexanoic acid can be used as a predictor of progression of ERFD in T2D patients with MA. This finding provides the new perspective that 5-hydroxyhexanoic acid may be useful to identify T2D patients with MA who are at risk of ERFD.


Assuntos
Albuminúria/urina , Caproatos/urina , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Progressão da Doença , Hidroxiácidos/urina , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Feminino , Seguimentos , Humanos , Nefropatias/urina , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade
12.
Cell Cycle ; 18(13): 1498-1512, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31145019

RESUMO

Geminin is a master regulator of cell-cycle progression that ensures the timely onset of DNA replication and prevents re-replication in vertebrates and invertebrates. Previously, we identified two Geminin genes, BmGeminin1 and BmGeminn2, in the silkworm Bombyx mori, and we found that RNA interference of BmGeminin1 led to re-replication. However, the function of BmGeminin2 remains poorly understood. In this study, we found that knockdown of BmGeminin2 can improve cell proliferation, and upregulated G2/M-associated gene-cyclinB/CDK1 expression. Then, we performed yeast two-hybrid screening to identify interacting proteins. Our results yielded 23 interacting proteins, which are involved in DNA replication, chromosome stabilization, embryonic development, energy, defense, protein processing, or structural protein. Here, we focused on BmRRS1, a chromosome congression-related protein that is closely related to cell cycle G2/M progression. The interaction between BmGeminin2 and BmRRS1 was confirmed by immunofluorescence and immunoprecipitation. Analysis of its expression profile showed that BmRRS1 was related to BmGeminin2. In addition, BmGeminin2 overexpression downregulated the BmRRS1 transcript. Knockdown of BmGeminin2 led to upregulation of the BmRRS1 transcript. Furthermore, overexpression of BmRRS1 can upregulate G2/M-associated gene-cyclinB/CDK1 expression, and improved cell proliferation, consistent with the effects of BmGeminin2 knockout. In addition, BmRRS1 RNA interference can eliminate the impact of BmGem2 knockout on cell proliferation, the ratio of cell cycle stage and the expression of cyclinB/CDK1. These data suggested that the cell proliferation advantage of BmGeminin2 knockout was closely related to BmRRS1. Our findings provide insight into the functions of Geminin and the mechanisms underlying the regulation of the cell cycle in the silkworm.

13.
Chin Med J (Engl) ; 132(8): 914-921, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30958432

RESUMO

BACKGROUND: It is currently unclear if fibrinogen is a risk factor for adverse events in patients receiving percutaneous coronary intervention (PCI) or merely serves as a marker of pre-existing comorbidities and other causal factors. We therefore investigated the association between fibrinogen levels and 2-year all-cause mortality, and compared the additional predictive value of adding fibrinogen to a basic model including traditional risk factors in patients receiving contemporary PCI. METHODS: A total of 6293 patients undergoing PCI with measured baseline fibrinogen levels were enrolled from January to December 2013 in Fuwai Hospital. Patients were divided into three groups according to tertiles of baseline fibrinogen levels: low fibrinogen, <2.98 g/L; medium fibrinogen, 2.98 to 3.58 g/L; and high fibrinogen, ≥3.58 g/L. Independent predictors of 2-year clinical outcomes were determined by multivariate Cox proportional hazards regression modeling. The increased discriminative value of fibrinogen for predicting all-cause mortality was assessed using the C-statistic and integrated discrimination improvement (IDI). RESULTS: The 2-year all-cause mortality rate was 1.2%. It was significantly higher in the high fibrinogen compared with the low and medium fibrinogen groups according to Kaplan-Meier analyses (1.7% vs. 0.9% and 1.7% vs. 1.0%, respectively; log-rank, P = 0.022). Fibrinogen was significantly associated with all-cause mortality according to multivariate Cox regression (hazard ratio 1.339, 95% confidence interval: 1.109-1.763, P = 0.005), together with traditional risk factors including age, sex, diabetes mellitus, left ventricular ejection fraction, creatinine clearance, and low-density lipoprotein cholesterol. The area under the curve for all-cause mortality in the basic model including traditional risk factors was 0.776, and this value increased to 0.787 when fibrinogen was added to the model (IDI = 0.003, Z = 0.140, P = 0.889). CONCLUSIONS: Fibrinogen is associated with 2-year all-cause mortality in patients receiving PCI, but provides no additional information over a model including traditional risk factors.


Assuntos
Fibrinogênio/análise , Intervenção Coronária Percutânea , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/terapia , Idoso , Jejum/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Fatores de Risco
14.
Coron Artery Dis ; 30(4): 249-254, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30762624

RESUMO

BACKGROUND: With the advancements of percutaneous coronary interventions (PCI), it is not clear whether unprotected left main (ULM) coronary artery disease (CAD) remains an independent predictor of adverse outcomes after PCI therapy. We have therefore carried out a large cohort study to investigate the impact of ULM disease on 2-year clinical outcomes in Chinese patients undergoing contemporary PCI treatment. METHODS AND RESULTS: From January 2013 to December 2013, 10 724 consecutive patients undergoing PCI were prospectively collected. Two-year clinical outcomes were compared for patients undergoing ULM PCI and non-ULM PCI. Among the 10 724 patients, 272 (2.5%) patients underwent ULM PCI. Overall, these patients had higher baseline clinical risks of CAD and more extensive CAD compared with non-ULM PCI patients. During the 2-year follow-up, patients who underwent ULM PCI experienced higher incidence of cardiac death (2.2 vs. 0.7%; log-rank P=0.002), myocardial infarction (7.0 vs. 1.9%; log-rank P<0.001), stroke (2.9 vs. 1.3%; log-rank P=0.02), and definite and probable stent thrombosis (3.3 vs. 0.5%; log-rank P<0.001), than patients who underwent non-ULM PCI. However, the rates of revascularization (7.4 vs. 8.7%; log-rank P=0.48), target vessel revascularization (5.5 vs. 5.0%; log-rank P=0.66), and major adverse cardiac and cerebrovascular events (15.1 vs. 12.0%; log-rank P=0.11) were not significantly different between the groups. When performing adjusted Cox regression after propensity score matching, ULM PCI was not an independent risk factor of any clinical events (all P>0.05). CONCLUSION: In this large cohort of patients who underwent modern PCI, ULM PCI patients had higher baseline clinical risks and poorer prognosis during 2-year follow-up. However, after multivariate analysis, ULM PCI was not an independent risk factor of any clinical adverse events.

15.
Platelets ; 30(7): 901-907, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30518271

RESUMO

This study aimed to evaluate the platelet reactivity in real-world patients with different chronic kidney disease (CKD) stages after percutaneous coronary intervention (PCI), and to examine whether high residual platelet reactivity (HRPR) is associated with higher incidence of adverse cardiovascular events in a 2-year follow up. A total of 10 724 consecutive patients receiving DAPT with aspirin and clopidogrel after PCI throughout 2013 were enrolled. We applied modified thromboelastography (mTEG) in 6745 patients. Kaplan-Meier analysis and Cox proportional regression analysis were applied to illustrate end points for patients. The prevalence of HRPR for adenosine diphosphate (ADP) was higher in patients with CKD3-5 than patients with CKD1-2 (47.0% vs. 37.3%, p = 0.002), but not for arachidonic acid (AA). No significant difference was observed for MACCE between patients with or without HRPR for ADP (HR 1.004, 95%CI: 0.864-1.167, p = 0.954). Patients with HRPR for ADP was associated with less bleeding events than patients without HRPR for ADP (HR 0.795, 95%CI: 0.643-0.982, p = 0.034). In this large cohort of real-world patients after PCI, the deterioration of renal function was linked to HRPR for ADP. HRPR was not associated with MACCE in patients with CKD in a 2-year follow up. Bleeding risks were significantly lower in PCI patients with versus without HRPR for ADP.


Assuntos
Plaquetas/metabolismo , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/uso terapêutico , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Feminino , Humanos , Masculino , Inibidores da Agregação de Plaquetas/farmacologia
16.
Glia ; 67(2): 246-262, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30565755

RESUMO

Astrocytes express a complex repertoire of intracellular Ca2+ transients (events) that represent a major form of signaling within individual cells and in astrocytic syncytium. These events have different spatiotemporal profiles, which are modulated by neuronal activity. Spontaneous Ca2+ events appear more frequently in distal astrocytic processes and independently from each other. However, little is known about the mechanisms underlying such subcellular distribution of the Ca2+ events. Here, we identify the initiation points of the Ca2+ events within the territory of single astrocytes expressing genetically encoded Ca2+ indicator GCaMP2 in culture or in hippocampal slices. We found that most of the Ca2+ events start in an optimal range of thin distal processes. Our mathematical model demonstrated that a high surface-to-volume of the thin processes leads to increased amplitude of baseline Ca2+ fluctuations caused by a stochastic opening of Ca2+ channels in the plasma membrane. Suprathreshold fluctuations trigger Ca2+ -induced Ca2+ release from the Ca2+ stores by activating inositol 1,4,5-trisphosphate (IP3 ) receptors. In agreement with the model prediction, the spontaneous Ca2+ events frequency depended on the extracellular Ca2+ concentration. Astrocytic depolarization by high extracellular K+ increased the frequency of the Ca2+ events through activation of voltage-gated Ca2+ channels in cultured astrocytes. Our results suggest that the morphological profile of the astrocytic processes is responsible for tuning of the Ca2+ events frequency. Therefore, structural plasticity of astrocytic processes can be directly translated into changes in astrocytic Ca2+ signaling. This may be important for both physiological and pathological astrocyte remodeling.


Assuntos
Astrócitos/metabolismo , Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/ultraestrutura , Benzilaminas/farmacologia , Sinalização do Cálcio/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Técnicas de Cocultura , Embrião de Mamíferos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas GABAérgicos/farmacologia , Hipocampo/citologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Ácidos Fosfínicos/farmacologia , Ratos , Ratos Wistar , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologia , Transfecção
17.
Int Immunopharmacol ; 66: 13-18, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30415190

RESUMO

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) is a common primary glomerular disease that potentially leads to renal failure, risk prediction of declining kidney function is crucial for early clinical management. Immunoglobulin G (IgG) is an important constituent of the immune system and serves as the preferred therapeutic target in human autoimmune diseases. However, its role in the progression of IgAN is unclear. METHODS: From May 2009 to April 2014, 455 patients diagnosed with IgAN at the Second Xiangya Hospital were enrolled in this study; the median follow-up was 42.2 months. All subjects were divided into four groups according to IgG level quartiles. The study endpoint was end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Clinical data and pathological features of renal biopsy specimens were collected. RESULTS: Among IgAN patients, serum IgG levels were directly correlated with the levels of serum albumin and serum IgA but reversely correlated with body weight, systolic blood pressure, and serum creatinine and cholesterol levels. According to stratified analysis of serum IgG, the proportions of composite renal endpoints among the enrolled IgAN patients in the serum IgG concentration subgroups 1 (<7.86), 2 (7.86-10.30), 3 (10.31-12.70), and 4 (>12.71 g/l) were 9.6%, 9.2%, 3.7%, and 3.7% respectively. Importantly, cumulative renal survival rates were significantly higher in the patients with increased serum IgG (p = 0.0114). Serum IgG was also predictive of renal survival, with an HR of 0.745 (95% CI, 0.614 to 0.905, p = 0.003) after adjusting for significant factors in the univariate Cox regression and an HR of 0.871 (95% CI, 0.780 to 0.973, p = 0.014) adjusting for traditional risk factors of IgAN. CONCLUSION: These findings demonstrate that a decreased serum IgG level at the time of renal biopsy is independently associated with a poor renal outcome in IgAN patients.


Assuntos
Biomarcadores/sangue , Glomerulonefrite por IGA/diagnóstico , Imunoglobulina G/sangue , Falência Renal Crônica/diagnóstico , Rim/patologia , Adulto , Estudos de Coortes , Creatinina/sangue , Progressão da Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/mortalidade , Humanos , Falência Renal Crônica/mortalidade , Masculino , Prognóstico , Risco , Análise de Sobrevida , Adulto Jovem
18.
Artigo em Inglês | MEDLINE | ID: mdl-32143897

RESUMO

BACKGROUND AND AIM: To explore the prevalence of unknown diabetes (DM) or prediabetes (pre-DM) in "nondiabetic" patients and its association with 2-year clinical outcomes after primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: 5202 consecutive "nondiabetic" patients who underwent primary PCI at Fuwai Hospital from January to December 2013 were prospectively enrolled. The patients were grouped according to their glycemia status: unknown DM (HbA1c ≥ 47 mmol/L; FPG≥ 7.0 mmol/L), pre-DM (HbA1c 39-47 mmol/L; FPG: 5.6-6.9 mmol/L) and normoglycemia (NG, HbA1c < 39 mmol/L; FPG < 5.6 mmol/L). The main endpoint was 2-year major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, and target vessel revascularization. A total of 905 patients had unknown DM, and 3407 patients had pre-DM. Unknown DM and pre-DM were associated with aging (p < 0.001); a greater proportion of hypertension (p < 0.001), previous myocardial infarction (p < 0.001), and chronic kidney disease (p = 0.004). During the 2-year follow-up, the rate of MACE was significantly higher in the unknown DM and pre-DM groups than in the NG group (8.1% vs. 5.8% vs. 4.1%, respectively, p = 0.001). Multivariate analyses demonstrated that unknown DM was associated with a 1.9-fold higher event risk compared to NG (95% CI: 1.2-2.8). CONCLUSIONS: The prevalence of abnormal glucose metabolism was high in "nondiabetic" Chinese PCI patients. Patients with unknown DM and pre-DM had higher event risks than those with NG. In "nondiabetes" patients requiring PCI, routine assessment of HbA1c and FPG appears to be of value to identify patients with an increased event risk.

19.
Kidney Blood Press Res ; 43(6): 1852-1864, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30537719

RESUMO

BACKGROUND/AIMS: There is an increasing risk of end-stage renal disease (ESRD) among Asian people with immunoglobulin A nephropathy (IgAN). A computer-aided system for ESRD prediction in Asian IgAN patients has not been well studied. METHODS: We retrospectively reviewed biopsy-proven IgAN patients treated at the Department of Nephrology of the Second Xiangya Hospital from January 2009 to November 2013. Demographic and clinicopathological data were obtained within 1 month of renal biopsy. A random forest (RF) model was employed to predict the ESRD status in IgAN patients. All cases were initially trained and validated, taking advantage of the out-of-bagging(OOB) error. Predictors used in the model were selected according to the Gini impurity index in the RF model and verified by logistic regression analysis. The area under the receiver operating characteristic(ROC) curve (AUC) and F-measure were used to evaluate the RF model. RESULTS: A total of 262 IgAN patients were enrolled in this study with a median follow-up time of 4.66 years. The importance rankings of predictors of ESRD in the RF model were first obtained, indicating some of the most important predictors. Logistic regression also showed that these factors were statistically associated with ESRD status. We first trained an initial RF model using gender, age, hypertension, serum creatinine, 24-hour proteinuria and histological grading suggested by the Clinical Decision Support System for IgAN (CDSS, www.IgAN.net). This 6-predictor model achieved a F-measure of 0.8 and an AUC of 92.57%. By adding Oxford-MEST scores, this model outperformed the initial model with an improved AUC (96.1%) and F-measure (0.823). When C3 staining was incorporated, the AUC was 97.29% and F-measure increased to 0.83. Adding the estimated glomerular filtration rate (eGFR) improved the AUC to 95.45%. We also observed improved performance of the model with additional inputs of blood urea nitrogen (BUN), uric acid, hemoglobin and albumin. CONCLUSION: In addition to the predictors in the CDSS, Oxford-MEST scores, C3 staining and eGFR conveyed additional information for ESRD prediction in Chinese IgAN patients using a RF model.


Assuntos
Árvores de Decisões , Glomerulonefrite por IGA/complicações , Falência Renal Crônica/etiologia , Adulto , Área Sob a Curva , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Aprendizado de Máquina Supervisionado , Adulto Jovem
20.
Am J Cardiol ; 122(12): 2043-2048, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30477725

RESUMO

We aimed to determine the association of plasma lipoprotein(a) (Lp[a]) with long-term clinical outcomes in patients with chronic kidney disease (CKD) after percutaneous coronary intervention (PCI) in an observational cohort study. Four hundred and twenty-seven consecutive patients with CKD who underwent PCI from January 2013 to December 2013 were included in this study. Patients were divided into 2 groups according to median levels of Lp(a). Outcomes included 2-year risk of major adverse cardiovascular and cerebrovascular events (MACCEs) and bleeding according to Bleeding Academic Research Consortium definitions. Overall, median of Lp(a) in all the patients was 217.8 mg/L. The 2-year MACCE rate across the high Lp(a) and low Lp(a) group was 23.0% versus 15.4% (p = 0.047) and bleeding event rate of the two groups 8.9% versus 4.2% (p = 0.049). The Lp(a) was significantly and positively correlated with high-sensitivity C-reactive protein levels (r2 = 0.03, p < 0.001). Kaplan-Meier curves revealed that high Lp(a) had higher incidence of bleeding than low Lp(a) (p = 0.043) and had higher risk of MACCE (p = 0.049). Multivariable Cox regression analysis indicated that high Lp(a) was an independent predictor of Bleeding Academic Research Consortium bleeding compared with low Lp(a) (hazard ratios 2.29, 95% confidence intervals 1.01 to 5.15, p = 0.046). In conclusion, a high Lp(a) value may be associated with a poor prognosis after PCI for patients with CKD.


Assuntos
Doença da Artéria Coronariana/sangue , Lipoproteína(a)/sangue , Intervenção Coronária Percutânea/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Insuficiência Renal Crônica/sangue , Idoso , Biomarcadores/sangue , China/epidemiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Hemorragia Pós-Operatória/sangue , Prognóstico , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Fatores de Risco , Fatores de Tempo
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