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1.
Microb Pathog ; 189: 106587, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38373644

RESUMO

BACKGROUND: The condition of COVID-19-related myocarditis has emerged as a prominent contributor to COVID-19 mortality. As the epidemic persists, its incidence continues to rise. Despite ongoing efforts, the elucidation of COVID-19-related myocarditis underlying molecular mechanisms still requires further investigation. METHODS: Hub genes for COVID-19-related myocarditis were screened by integrating gene expression profile analysis via differential expression in COVID-19 (GSE196822) and myocarditis (GSE148153 and GSE147517). After verification with independent datasets (GSE211979, GSE167028, GSE178491 and GSE215865), the hub genes were studied using a range of systems-biology approaches, such as ceRNA, TF-mRNA networks and PPI networks, as well as gene ontology, pathway enrichment, immune infiltration analysis and drug target identification. RESULTS: TBKBP1 and ERGIC1 were identified as COVID-19-related myocarditis hub genes via integrated bioinformatics analysis. In addition, receiver operating characteristic curves constructed based on the expression levels of TBKBP1 and ERGIC1 could effectively distinguish healthy control individuals from patients with COVID-19. Functional enrichment analysis suggested several enriched biological pathways related to inflammation and immune response. Immune cell changes correlated with TBKBP1 and ERGIC1 levels in patients with COVID-19 or patients with COVID-19 and myocarditis. Tamibarotene, methotrexate and theophylline were identified as a potential drug targeting TBKBP1 and ERGIC1. CONCLUSION: TBKBP1 and ERGIC1 were identified as crucial genes in the development of COVID-19-related myocarditis and have demonstrated a strong association with innate antiviral immunity. The present work may be helpful for further investigation of the molecular mechanisms and new therapeutic drug targets correlated with myocarditis in COVID-19.


Assuntos
COVID-19 , Miocardite , Humanos , Transcriptoma , Miocardite/genética , Testes Hematológicos , Perfilação da Expressão Gênica , Biologia Computacional
2.
Rev Cardiovasc Med ; 25(1): 17, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39077643

RESUMO

Background: The correlation between 5 ' -Nucleotidase ( 5 ' -NT) and the clinical outcomes in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) is not clear. This study aims to clarify this relationship. Methods: The PRACTICE study enrolled 15,250 patients between December 2016 and October 2021. After filtering out those without 5 ' -NT data, a total of 6555 patients were analyzed with a median follow-up of 24 months. Based on the receiver operating characteristic (ROC) curve analysis, a 5 ' -NT level of 5.57 U/L was selected as the optimal cutoff value. All research samples were divided into high-value ( ≥ 5.57 U/L, n = 2346) and low-value groups ( < 5.57 U/L, n = 4209). Key clinical outcomes included all-cause death (ACD), cardiovascular death (CD), major adverse cardiovascular events (MACE), and major adverse cardiovascular and cerebrovascular events (MACCE). After separating patients into high and low value groups, multivariate Cox regression analysis was used to correct for potential confounding variables. Finally, risk ratios and their 95% confidence intervals (CIs) were calculated. Results: During the follow-up period, 129 instances of ACD were recorded-49 cases (1.2%) in the low-value group and 80 cases (3.4%) in the high-value group. Similarly, 102 CDs occurred, including 42 low-value group cases (1.0%) and 60 high-value group cases (2.6%). A total of 363 MACE occurred, including 198 low-value group cases (4.7%) and 165 high-value group cases (7%). A total of 397 cases of MACCE occurred, including 227 low-value group cases (5.4%) and 170 high-value group cases (7.2%). As serum 5 ' -NT increased, the incidence of ACD, CD, MACE and MACCE increased. After multivariate Cox regression, high 5 ' -NT levels were linked with a 1.63-fold increase in ACD risk (hazard ratio [HR] = 2.630, 95% CI: [1.770-3.908], p < 0.001) when compared to low 5 ' -NT patients. Similarly, the risk of CD, MACE, and MACCE increased by 1.298-fold (HR = 2.298, 95% CI: [1.477-3.573], p < 0.001), 41% (HR = 1.410, 95% CI: [1.124-1.768], p = 0.003) and 30.5% (HR = 1.305, 95% CI: [1.049-1.623], p = 0.017), respectively. Conclusions: high serum 5 ' -NT levels were independently correlated with adverse clinical outcomes in CAD patients following PCI, affirming its potential as a prognostic indicator.

3.
Rev Cardiovasc Med ; 25(4): 111, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-39076545

RESUMO

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel inflammatory biomarker, and its association with the prognosis of coronary artery disease (CAD) after percutaneous coronary intervention (PCI) has not previously been studied. Therefore, this study aimed to investigate the effect of using the CALLY index on adverse outcomes in CAD patients undergoing PCI. Methods: From December 2016 to October 2021, we consecutively enrolled 15,250 CAD patients and performed follow-ups for primary endpoints consisting of all-cause mortality (ACM) and cardiac mortality (CM). The CALLY index was computed using the following formula: (albumin × lymphocyte)/(C-reactive protein (CRP) × 10 4 ). The average duration of the follow-up was 24 months. Results: A total of 3799 CAD patients who had undergone PCI were ultimately enrolled in the present study. The patients were divided into four groups according to the CALLY index quartiles: Q1 ( ≤ 0.69, n = 950), Q2 (0.69-2.44, n = 950), Q3 (2.44-9.52, n = 950), and Q4 ( > 9.52, n = 949). The low-Q1 group had a significantly higher prevalence of ACM (p < 0.001), CM (p < 0.001), major adverse cardiac events (MACEs) (p = 0.002), and major adverse cardiac and cerebrovascular events (MACCEs) (p = 0.002). Kaplan-Meier analysis revealed that a low CALLY index was significantly linked with adverse outcomes. After univariate and multivariate Cox regression analysis, the risk of ACM, CM, MACEs, and MACCEs decreased by 73.7% (adjust hazard risk [HR] = 0.263, 95% CI: 0.147-0.468, p < 0.001), 70.6% (adjust HR = 0.294, 95% CI: 0.150-0.579, p < 0. 001), 37.4% (adjust HR = 0.626, 95% CI: 0.422-0.929, p = 0.010), and 41.5% (adjust HR = 0.585, 95% CI: 0.401-0.856, p = 0.006), respectively, in the Q4 quartiles compared with the Q1 quartiles. Conclusions: This study revealed that a decreased CALLY index was associated with worse prognoses for CAD patients after PCI. The categorization of patients with a decreased CALLY index could provide valuable evidence for the risk stratification of adverse outcomes in CAD patients after PCI. Clinical Trial Registration: The details are available at http://www.chictr.org.cn (Identifier: NCT05174143).

4.
Cell Commun Signal ; 22(1): 54, 2024 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243314

RESUMO

BACKGROUND: The gut microbiota plays a crucial role in coronary artery disease (CAD) development, but limited attention has been given to the role of the microbiota in preventing this disease. This study aimed to identify key biomarkers using metagenomics and untargeted metabolomics and verify their associations with atherosclerosis. METHODS: A total of 371 participants, including individuals with various CAD types and CAD-free controls, were enrolled. Subsequently, significant markers were identified in the stool samples through gut metagenomic sequencing and untargeted metabolomics. In vivo and in vitro experiments were performed to investigate the mechanisms underlying the association between these markers and atherosclerosis. RESULTS: Faecal omics sequencing revealed that individuals with a substantial presence of Faecalibacterium prausnitzii had the lowest incidence of CAD across diverse CAD groups and control subjects. A random forest model confirmed the significant relationship between F. prausnitzii and CAD incidence. Notably, F. prausnitzii emerged as a robust, independent CAD predictor. Furthermore, our findings indicated the potential of the gut microbiota and gut metabolites to predict CAD occurrence and progression, potentially impacting amino acid and vitamin metabolism. F. prausnitzii mitigated inflammation and exhibited an antiatherosclerotic effect on ApoE-/- mice after gavage. This effect was attributed to reduced intestinal LPS synthesis and reinforced mechanical and mucosal barriers, leading to decreased plasma LPS levels and an antiatherosclerotic outcome. CONCLUSIONS: Sequencing of the samples revealed a previously unknown link between specific gut microbiota and atherosclerosis. Treatment with F. prausnitzii may help prevent CAD by inhibiting atherosclerosis.


Assuntos
Aterosclerose , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Faecalibacterium prausnitzii/metabolismo , Lipopolissacarídeos
5.
Rev Cardiovasc Med ; 24(6): 161, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39077519

RESUMO

Background: To establish a modified Global Registry of Acute Coronary Events (GRACE) scoring system with an improved predictive performance compared with the traditional GRACE scoring system. Methods: We identified 5512 patients who were hospitalized with a definite diagnosis of acute myocardial infarction (AMI) from January 1, 2015, to December 31, 2020, at the Heart Center of the First Affiliated Hospital of Xinjiang Medical University through the hospital's electronic medical record system. A total of 4561 patients were enrolled after the inclusion and exclusion criteria were applied. The mean follow-up was 51.8 ± 23.4 months. The patients were divided into dead and alive groups by endpoint events. The differences between the two groups were compared using the two-sample t test and chi-square test. Adjusted traditional risk factors as well as LogBNP (B-type natriuretic peptide precursor, BNP) and the modified GRACE scoring system were included in a multifactorial COX regression model. The predictive performance of the traditional and modified GRACE scoring systems was compared by (Receiver Operating Characteristic) ROC curves. Results: Significant differences in age, heart rate, creatinine, uric acid, LogBNP, traditional GRACE score, and modified GRACE score were found between the dead and alive groups by the two-sample t test. Comparison of the two groups by the chi-square test revealed that the dead group had a higher incidence of males; higher cardiac function class; a previous history of hypertension, diabetes, coronary artery disease (CAD), or cerebrovascular disease; a history of smoking; the need for intra-aortic balloon pump (IABP) support; and more patients taking aspirin, clopidogrel, ticagrelor, and ß -blockers. The results were analyzed by a multifactorial COX regression model, and after adjusting for confounders, age, cardiac function class, history of CAD, use of aspirin and ß -blockers, and the modified GRACE scoring system were found to be associated with all-cause mortality (ACM) in patients with AMI. The ROC curve was used to compare the predictive performance of the conventional GRACE scoring system with that of the modified GRACE scoring system, and it was found that the modified GRACE scoring system (Area Under Curve (AUC) = 0.809, p < 0.001, 95% (Confidence Interval) CI (0.789-0.829)) was significantly better than the traditional GRACE scoring system (AUC = 0.786, p < 0.001, 95% CI (0.764-0.808)), the comparison between the two scores was statistically significant (p < 0.001). The change in the C statistic after 10-fold crossover internal validation of the modified GRACE score was not significant, and the integrated discrimination improvement (IDI) between the old and new models was calculated with IDI = 0.019 > 0, suggesting that the modified GRACE score has a positive improvement on the traditional GRACE score. Conclusions: The modified GRACE scoring system, established by combining B-type natriuretic peptide precursor (BNP) and the traditional GRACE scoring system, was independently associated with ACM in patients with AMI, with a larger AUC and higher predictive value than the traditional GRACE scoring system. Clinical Trial Registration: NCT02737956.

6.
Rev Cardiovasc Med ; 24(10): 278, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39077558

RESUMO

Background: Coronary heart disease is one of the main causes of Mortality. Many biological indicators have been used to predict the prognosis of patients with coronary heart disease. The ratio of serum globulin to albumin (GAR) has been used to predict the prognosis of patients with various cancers. It has been proven that GAR is related to the prognosis of patients with stroke. However, GAR's role in cardiovascular disease remains unclear. Our purpose was to investigate the predictive value of GAR on clinical outcomes in post-percutaneous coronary intervention (PCI) patients with coronary artery disease (CAD). Methods: From Dec. 2016 to Oct. 2021, a total of 14,994 patients undergoing PCI patients admitted to the First Affiliated Hospital of Xinjiang Medical University were divided into high GAR group (GAR ≥ 0.76, n = 4087) and low GAR group (GAR < 0.76, n = 10,907). The incidence of adverse outcomes including all-cause mortality (ACM), cardiovascular mortality (CM), major adverse cardiovascular events (MACE) and major adverse cardiovascular and cerebrovascular events (MACCE) was compared between the two groups. Multivariate Cox regression was used to adjust for the effects of confounding factors, while hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated. Median follow-up time was 24 months. Results: Compared with the low GAR group, the high GAR group had significantly higher incidence of ACM (6.5% vs. 1.7%, p < 0.001); CM (4.9% vs. 1.2%, p < 0.001), MACE (10.5% vs. 6.7%, p < 0.001), and MACCE (11.3% vs. 7.5%, p < 0.001). Cox regression analysis showed the patients in the high GAR group had a 1.62-fold increased risk for ACM (HR = 2.622, 95% CI: 2.130-3.228, p < 0.01), a 1.782-fold increased risk for CM (HR = 2.782, 95% CI: 2.180-3.550, p < 0.01). There was a 37.2% increased risk for MACE (HR = 1.372, 95% CI: 1.204-1.564, p < 0.01), and 32.4% increased risk for MACCE (HR = 1.324, 95% CI: 1.169-1.500, p < 0.01), compared to the patients in the low GAR group. Conclusions: The present study suggested that post-PCI CAD patients with higher GAR presented significantly increased mortality and adverse events GAR level at admission may 296 be considered as part of risk stratification when PCI is possible in patients with coronary heart disease. Clinical Trial Registration: The detailed information of the PRACTICE study has been registered on http://Clinicaltrials.gov (Identifier: NCT05174143).

7.
Rev Cardiovasc Med ; 24(12): 369, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39077103

RESUMO

Background: The ratio of fibrinogen to γ -glutamine transferase (FGR) was used to predict long-term prognosis in patients with coronary heart disease (CHD). Methods: A total of 5638 patients with CHD who were hospitalized from January 2008 to December 2016 were retrospectively enrolled in the study. The mean follow-up time was 35.9 ± 22.5 months. The follow-up endpoints were major cardiac and cerebrovascular adverse events (MACCE). The optimal FGR cut-off value was determined and divided into high- and low-FGR groups according to the receiver operating characteristic (ROC) curve. Statistical methods were used to compare the differences between the two groups and their prognoses to determine whether FGR can predict prognosis in patients with CHD. The traditional predictors were incorporated into the logistic regression model to observe the correlation between these indicators and all-cause mortality (ACM) events. We compared the prediction performance of FGR and traditional predictors on the occurrence of ACM events by ROC curves. Results: The optimal cut-off value was determined via a ROC analysis (FGR = 1.22, p = 0.002), and subjects were classified into high and low FGR groups. The follow-up found that the incidence of MACCE in the high FGR group was higher than that in the low FGR group. The COX multivariate regression model showed that high FGR was independently correlated with the occurrence of MACCE. In addition, the Kaplan-Meier survival curve showed that the risk of events was significantly increased in the group with high FGR. With increases in the FGR ratio, the risk of MACCE was increased. The ROC curve revealed that the risk of ACM was statistically different between the FGR and the traditional risk factor model (p = 0.002), (Fibrinogen (p = 0.008), γ -glutamine transferase (GGT) (p = 0.004), and N-terminal pro brain natriuretic peptide (NT-ProBNP) (p = 0.024)). The comparison between other different models were not statistically significant (p > 0.05). The area under the FGR model curve was larger than that of the traditional risk factors, fibrinogen, GGT and NT-ProBNP models. Conclusions: High FGR can increase the risk of MACCE in patients with CHD; additionally, it can be used as a new biomarker for long-term prognosis in CHD patients. Clinical Trial Registration: All details of this study are registered on the website (http://www.chictr.org.cn), registration number: ChiCTR-ORC-16010153.

8.
Cell Commun Signal ; 21(1): 155, 2023 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370070

RESUMO

BACKGROUND: Coronary artery disease (CAD) is a multi-factor complex trait and is heritable, especially in early-onset families. However, the genetic factors affecting the susceptibility of early-onset CAD are not fully characterized. METHODS: In the present study, we identified a rare nonsense variant in the CYP17A1 gene from a Chinese Han family with CAD. To validate the effect of this variation on atherosclerosis and early-onset coronary artery disease, we conducted studies on population, cells, and mice. RESULTS: The mutation precisely congregated with the clinical syndrome in all the affected family members and was absent in unaffected family members and unrelated controls. Similar to the human phenotype, the CYP17A1-deficient mice present the phenotype of metabolic syndrome with hypertension, increased serum glucose concentration, and presentation of central obesity and fatty liver. Furthermore, CYP17A1 knockout mice or CYP17A1 + ApoE double knockout mice developed more atherosclerotic lesions than wild type (WT) with high fat diary. In cell models, CYP17A1 was found to be involved in glucose metabolism by increasing glucose intake and utilization, through activating IGF1/mTOR/HIF1-α signaling way, which was consistent in CYP17A1 knockout mice with impaired glucose tolerance and insulin resistance. CONCLUSIONS: Through our study of cells, mice and humans, we identified CYP17A1 as a key protein participating in the pathophysiology of the atherosclerotic process and the possible mechanism of CYP17A1 C987X mutation induced atherosclerosis and early-onset CAD involving glucose homeostasis regulation was revealed. Video Abstract.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Animais , Humanos , Camundongos , Aterosclerose/genética , Doença da Artéria Coronariana/genética , Camundongos Knockout , Camundongos Knockout para ApoE , Transdução de Sinais , Esteroide 17-alfa-Hidroxilase/genética
9.
J Org Chem ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37976373

RESUMO

(±)-Salvicatone A (1), a C27-meroterpenoid featuring a unique 6/6/6/6/6-pentacyclic carbon skeleton with a 7,8,8a,9,10,10a-hexahydropyren-1 (6H)-one motif, was isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Its structure was characterized by comprehensive spectroscopic analyses along with computer-assisted structure elucidation, including ACD/structure elucidator and quantum chemical calculations with 1H/13C NMR and electronic circular dichroism. Biogenetically, compound 1 was constructed from decarboxylation following [4 + 2] Diels-Alder cycloaddition reaction between caffeic acid and miltirone analogue. Bioassays showed that (-)-1 and (+)-1 inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophage cells with an IC50 value of 6.48 ± 1.25 and 15.76 ± 5.55 µM, respectively. The structure-based virtual screening based on the pharmacophores in ePharmaLib, as well as the molecular docking and molecular dynamics simulations study, implied that (-)-1 and (+)-1 may potentially bind to retinoic acid receptor-related orphan receptor C to exert anti-inflammatory activities.

10.
Platelets ; 34(1): 2206915, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37154019

RESUMO

It is particularly important to establish more effective and safer antiplatelet treatment strategies according to age. The present subanalysis of the PATH-PCI trial was to determine the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy in different age groups. We randomized 2285 chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) into a standard group or a personalized group from December 2016 to February 2018. The personalized group received personalized antiplatelet therapy (PAT) based on a novel platelet function test (PFT). The standard group received standard antiplatelet therapy (SAT). Then, all patients were divided according to age (under the age of 65 years and aged 65 years or over) to investigate the association and interaction of age on clinical outcomes at 180 days. In the patients under the age of 65 years, the incidence of NACEs was decreased in the personalized group compared to the standard group (5.1% vs. 8.8%, HR: 0.603, 95% CI: 0.409-0.888, P = .010). The rates of MACCEs (3.3% vs. 7.7%, HR: 0.450, 95% CI: 0.285-0.712, P = .001), MACEs (2.2% vs. 5.4%, HR: 0.423, 95% CI: 0.243-0.738, P = .002) also decreased. We did not find a significant difference in bleeding between the groups. In the patients aged 65 years or over, no difference in the primary endpoint was found (4.9% vs. 4.2%, P = .702), and comparable rates of survival were observed with the two strategies (all Ps > 0.05). The present study shows that PAT according to PFT was comparable to SAT at the 180-day follow-up for both ischemic and bleeding endpoints in CCS patients aged 65 years or over who underwent PCI. In patients under the age of 65 years, PAT can reduce ischemic events but does not increase bleeding, and it is an effective and safe treatment strategy. It may be necessary for young CCS patients after PCI to undergo PAT early after PCI.


What is the context? The PATH-PCI trial reported that personalized antiplatelet therapy (PAT) based on a novel platelet function test (PFT) can greatly reduce the incidence of ischemic events.Antiplatelet strategies may have very different effects on clinical outcomes in patients in China who are undergoing PCI at different ages.What is new? PL-12 is a new point-of-care platelet function analyzer that is used to test the platelet maximum aggregation rate (MAR).We explored the efficacy and safety of different antiplatelet strategies in chronic coronary syndrome (CCS) patients in different age groups.What is the impact? PAT according to PFT was comparable to standard antiplatelet therapy (SAT) at the 180-day follow-up for both ischemic and bleeding endpoints in CCS patients aged 65 years or over who underwent PCI.In patients under the age of 65 years, PAT can reduce ischemic events but not increase bleeding.PAT may be an effective and safe treatment strategy in CCS patients under the age of 65 years who underwent PCI.Abbreviation: PCI: percutaneous coronary intervention; CCS: chronic coronary syndrome; DAPT: dual antiplatelet therapy; PAT: personalized antiplatelet therapy; SAT: standard antiplatelet therapy; PFT: platelet function test; NACEs: net adverse clinical events; MACCEs: major adverse cardiac and cerebrovascular events; MACEs: major adverse cardiovascular events.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/terapia , Quimioterapia Combinada , Terapia Antiplaquetária Dupla , Hemorragia/tratamento farmacológico , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Resultado do Tratamento
11.
Lipids Health Dis ; 22(1): 108, 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516842

RESUMO

BACKGROUND: There is an urgent need to learn more about the epidemiological features of dyslipidemia in youth to address the high burden of cardiovascular disease. METHODS: This experiment was an observational, cross-sectional study. The samples were collected from 22,379 college students at Xinjiang Medical University. RESULT: The overall prevalence of dyslipidemia was 13.17%, which was significantly higher in men (23%) than in women (7.2%), p < 0.01. Similarly, the prevalence rate of obesity in men (11.4%) was significantly higher than that in women (3.4%). The composition of blood lipids, such as triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), began to increase gradually from the age of 22 and showed a sharp increase after the age of 30; however, a reverse trend was present in high density lipoprotein cholesterol (HDL-C). In terms of the proportion of dyslipidemia in both men and women, low HDL-C accounted for the largest proportion (74%), followed by elevated TGs (14.5%). The overall distribution of rates of dyslipidemia and excess weight showed a U-shaped trend with increasing age, with the lowest rates seen in the 20-24 age group. CONCLUSION: Our study sheds light on the epidemiological features of dyslipidemia in young adults and enriches the limited data available on dyslipidemia, providing a reference for the close monitoring and control of risk factors to reduce the occurrence and progression of atherosclerotic cardiovascular disease events.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Dislipidemias , Masculino , Adolescente , Humanos , Feminino , Adulto Jovem , Estudos Transversais , Dislipidemias/epidemiologia , HDL-Colesterol
12.
J Enzyme Inhib Med Chem ; 37(1): 451-461, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35012401

RESUMO

Different oleanolic acid (OA) oxime ester derivatives (3a-3t) were designed and synthesised to develop inhibitors against α-glucosidase and α-amylase. All the synthesised OA derivatives were evaluated against α-glucosidase and α-amylase in vitro. Among them, compound 3a showed the highest α-glucosidase inhibition with an IC50 of 0.35 µM, which was ∼1900 times stronger than that of acarbose, meanwhile compound 3f exhibited the highest α-amylase inhibitory with an IC50 of 3.80 µM that was ∼26 times higher than that of acarbose. The inhibition kinetic studies showed that the inhibitory mechanism of compounds 3a and 3f were reversible and mixed types towards α-glucosidase and α-amylase, respectively. Molecular docking studies analysed the interaction between compound and two enzymes, respectively. Furthermore, cytotoxicity evaluation assay demonstrated a high level of safety profile of compounds 3a and 3f against 3T3-L1 and HepG2 cells.HighlightsOleanolic acid oxime ester derivatives (3a-3t) were synthesised and screened against α-glucosidase and α-amylase.Compound 3a showed the highest α-glucosidase inhibitory with IC50 of 0.35 µM.Compound 3f presented the highest α-amylase inhibitory with IC50 of 3.80 µM.Kinetic studies and in silico studies analysed the binding between compounds and α-glucosidase or α-amylase.


Assuntos
Inibidores Enzimáticos/farmacologia , Ésteres/farmacologia , Ácido Oleanólico/farmacologia , Oximas/farmacologia , alfa-Amilases/antagonistas & inibidores , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Ésteres/síntese química , Ésteres/química , Humanos , Estrutura Molecular , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Oximas/síntese química , Oximas/química , Relação Estrutura-Atividade , alfa-Amilases/metabolismo
13.
BMC Womens Health ; 21(1): 276, 2021 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325677

RESUMO

BACKGROUND: Gynecologic cancers are among the most prevalent malignancies in China. Cervical and uterine cancer respectively account for the sixth and eighth highest incidence of cancer among Chinese women. Abdominal surgery is one of the important treatment methods for gynecological tumors. However, the tumor- and surgery-related symptom burden are not well studied owing to a lack of a standardized and validated assessment tool in the Chinese population. The study aimed to translate and validate the MD Anderson Symptom Inventory for measuring perioperative symptom burden in gynecologic cancer patients (MDASI-PeriOp-GYN) and examine the utility of the Chinese version of MDASI-PeriOp-GYN. METHODS: The MDASI-PeriOp-GYN was translated in a stepwise manner. First, two native speakers independently translated the 9 PeriOp-GYN symptom items. Then the nine items were translated back into English by two different bilingual translators. After discussion and revision, the four translators reached an agreement. Finally, the finalized Chinese version was administered to women with three common gynecologic cancer types (cervical, ovarian, and endometrial cancers) recruited from the gynecological oncology department of Sichuan Cancer Hospital & Institute between July and October 2019. The reliability and validity of the translated version were assessed. RESULTS: Overall, 324 women with gynecologic cancers were enrolled. Cronbach's α values were 0.826 and 0.735 for the symptom severity and interference scales, respectively. Test-retest reliability values were 0.885, 0.873, and 0.914 for symptom severity, PeriOp-GYN, and interference scales. Significant correlations were found between the MDASI-PeriOp-GYN-C and EORTC QLQ-C30 along with the QLQ-OV28 module (- 0.608-0.871, P < 0.001). Known-group validity was supported by significant differences in the scores of the four scales grouped by time intervals, surgery type, and functional status (all P < 0.01). CONCLUSIONS: The MDASI-PeriOp-GYN-C is a valid and reliable tool for measuring symptoms in Chinese patients undergoing surgery for gynecologic cancers. The tool could be used in clinical practice and clinical trials to instantly gather patients' health and quality of life data.


Assuntos
Neoplasias dos Genitais Femininos , Qualidade de Vida , China , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/cirurgia , Humanos , Psicometria , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Inquéritos e Questionários
14.
Catheter Cardiovasc Interv ; 95 Suppl 1: 572-578, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31912975

RESUMO

OBJECTIVES: To determine whether gamma-glutamyl transferase (GGT) to albumin ratio (GAR) independently predicts mortality and bleeding events in coronary artery disease (CAD) patients who undergo percutaneous coronary intervention (PCI). BACKGROUND: Serum GGT and albumin levels have been associated with CAD risk and mortality. However, more analysis is needed to determine their predictive relationship with adverse outcomes. METHODS: In total, 5,638 patients from a large retrospective cohort study were enrolled from January 2008 to December 2016 and divided into two groups (GAR <0.62, n = 2,712 and GAR ≥0.62, n = 2,926). The average follow-up time was 35.9 ± 22.6 months. Multivariate Cox regression analyses were performed to determine the risk of all-cause mortality and bleeding events associated with GAR. RESULTS: The low-GAR group had a significantly higher number of all-cause mortality (p = .016) and bleeding events (p = .010) than the high-GAR group. Multivariate Cox regression analyses showed that the risk of all-cause death and bleeding events decreased by 23.8% (hazard risk [HR] = 0.762 95% confidence interval [CI]: 0.601-0.966, p = .025) and 39.4% (HR = 00.616, 95% CI: 0.446-0.852, p = .003), respectively, in the high-GAR group. In patients with acute coronary syndrome, the risk of bleeding events decreased by 57.3% in the high-GAR group (HR = 0.427, 95% CI: 0.234-0.781, p = .006). In patients with stable coronary heart disease, the risk of all-cause death decreased 28.6% (HR = 0.714, 95% CI: 0.540-0.944, p = .018) in the high-GAR group. CONCLUSION: GAR was an independent and novel predictor of mortality and bleeding events in CAD patients who underwent PCI.


Assuntos
Doença da Artéria Coronariana/terapia , Hemorragia/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Albumina Sérica Humana/análise , gama-Glutamiltransferase/sangue , Idoso , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Feminino , Hemorragia/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/mortalidade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
J Interv Cardiol ; 2020: 4713591, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32372887

RESUMO

BACKGROUND: Alanine aminotransferase (ALT) is referred as liver transaminase and predominantly expressed by hepatocytes. Previous evidences showed that high levels of ALT were reversely associated with short- and long-term outcomes in patients with myocardial infarction. Besides, low lymphocyte has been demonstrated to be significantly correlated with adverse clinical outcomes in coronary artery disease (CAD). However, evidences about the relationship between ALT-to-lymphocyte ratio (ALR) and outcomes in CAD patients with normal liver function are limited. The aim of this study was to assess the relationship between ALR and clinical outcomes in patients with CAD. METHODS: This is a retrospective cohort study, and a total of 3561 patients were enrolled in Clinical Outcomes and Risk Factors of Patients with CAD after percutaneous coronary intervention (PCI), from January 2013 to December 2017. After excluding patients with liver dysfunction, we finally enrolled 2714 patients. These patients were divided into two groups according to ALR value: the lower group (ALR < 14.06, n = 1804) and the higher group (ALR ≥ 14.06, n = 910). The average follow-up time was 37.59 ± 22.24 months. RESULTS: We found that there were significant differences between the two groups in the incidence of all-cause mortality (ACM) (P < 0.001) and cardiac mortality (CM) (P=0.010). Kaplan-Meier survival analysis suggested that CAD patients with higher ALR tended to have an increased accumulated risk of ACM and CM (log rank P < 0.001 and P=0.006, respectively). Multivariate Cox regression analysis showed that ALR was an independent predictor of ACM (hazard ratio (HR) = 2.017 (95% confidence interval (CI): 1.289-3.158), P=0.002) and CM (HR = 1.862 (95% CI: 1.047-3.313), P=0.034). We did not find significant difference in the incidence of major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs) between the two groups after adjustments of confounders. CONCLUSION: Our results indicate that ALR is an independent predictor of long-term adverse outcomes in CAD patients who underwent PCI.


Assuntos
Alanina Transaminase/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Contagem de Linfócitos , Intervenção Coronária Percutânea , Idoso , Doença da Artéria Coronariana/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Fígado , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
16.
Lipids Health Dis ; 19(1): 43, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32178685

RESUMO

BACKGROUND: Previous studies suggested that baseline white blood cell count and apolipoprotein A1 levels were associated with clinical outcomes in patients with coronary heart disease (CAD) who underwent percutaneous coronary intervention (PCI). However, the ratio of baseline white blood cell count-to-apolipoprotein A1 level (WAR) and CAD after PCI have not been investigated. The present study investigated the effects of baseline WAR on long-term outcomes after PCI in patients with CAD. METHODS: A total of 6050 patients with CAD who underwent PCI were included in the study. Of these, 372 patients were excluded because no baseline white blood cell counts or apolipoprotein A1 (ApoA1) data was available or because of malignancies or other diseases. Finally, 5678 patients were enrolled in the present study and were divided into 3 groups according to WAR value: lower group - WAR< 5.25 (n = 1889); median group - 5.25 ≤ WAR≤7.15 (n = 1892); and higher group - WAR≥7.15 (n = 1897). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM), after PCI. The average follow-up time was 35.9 ± 22.6 months. RESULTS: A total of 293 patients developed ACM, including 85 (4.5%) patients in the lower group, 90 (4.8%) patients in the median group, and 118 (6.2%) patients in the higher group. The risk of ACM, cardiac mortality (CM), major adverse cardiovascular and cerebrovascular events (MACCEs), and major adverse cardiovascular events (MACEs) increased 62.6% (hazard risk [HR] =1.626, 95%CI: 1.214-2.179, P = 0.001), 45.5% (HR = 1.455, 95%CI: 1.051-2.014, P = 0.024), 21.2% (HR = 1.212, 95%CI: 1.011-1.454, P = 0.038), and 23.8% (HR = 1.238, 95%CI: 1.025-1.495, P = 0.027), respectively, as determined by multivariate Cox regression analyses comparing the patients in the higher group to patients in the lower group. Patients with a WAR≥4.635 had 92.3, 81.3, 58.1 and 58.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, compared to the patients with WAR< 4.635. Every 1 unit increase in WAR was associated with 3.4, 3.2, 2.0 and 2.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, at the 10-year follow-up. CONCLUSION: The present study indicated that baseline WAR is a novel and an independent predictor of adverse long-term outcomes in CAD patients who underwent PCI.


Assuntos
Apolipoproteína A-I/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Contagem de Leucócitos , Idoso , Análise de Variância , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Estudos Retrospectivos
17.
J Interv Cardiol ; 2019: 2387929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772517

RESUMO

BACKGROUND: Primary percutaneous coronary intervention (PPCI) plays a pivotal role in the treatment of ST-segment elevation myocardial infarction (STEMI). However, it remains controversial whether PCI delayed beyond the recommended time window of 12 h after the onset of symptoms is applicable to STEMI. OBJECTIVE: The acute myocardial infarction (AMI) registration study in Xinjiang, China, is a real-world clinical trial (retrospective cohort study) that includes hospitalized patients. The purpose of this study was to compare delayed PCI and medication therapy beyond the recommended time window of 12 h after the onset of symptoms on the outcomes of STEMI patients. METHODS AND RESULTS: From May 2012 to December 2015, a total of 1072 STEMI patients received delayed PCI (n=594) or standard medication therapy (MT) (n=478) more than 12 h after the onset of symptoms. The number of all-cause deaths in the delayed PCI group and that in the MT group were 55 (9.3%) and 138 (28.9%), respectively, and a significant difference between the groups was indicated for this variable (P<0.001). The number of cardiac deaths in the delayed PCI group and that in the medication therapy group were 47 (7.9%) and 120 (25.1%), respectively, and a significant difference between the groups was indicated for this variable (P<0.001). We also found that the MACE incidence in the delayed PCI group was significantly higher than it was in the MT group (32.2% versus 43.5%, P<0.001). Propensity score matching (PSM) analyses remained significant differences between the delayed PCI group and the MT group, respectively, in all-cause deaths (9.3% versus 25.8%, P<0.001) and cardiac death (8.7% versus 21.6%, P<0.001). CONCLUSION: Compared to medication therapy, PCI for STEMI delayed beyond 12 h after the onset of symptoms can better reduce mortality and the incidence of MACEs. TRIAL REGISTRATION: This study is registered with the following: Trial Registration: clinicaltrials.gov; Identifier: NCT02737956.


Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Aspirina/uso terapêutico , China/epidemiologia , Clopidogrel/uso terapêutico , Feminino , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/antagonistas & inibidores , Adulto Jovem
18.
Clin Exp Pharmacol Physiol ; 46(11): 984-994, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31347187

RESUMO

The clinical significance of dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) in coronary heart disease (CHD) has not been thoroughly elucidated to date. We performed a meta-analysis to clarify the correlations between endogenous DHEA(S) and CHD. We performed a literature search without language restriction up to August 10, 2017, and retrieved records from EMBase, PubMed, Web of Science, CNKI and WanFang databases to identify eligible cohort studies focused on the relation between DHEA(S) and CHD. A total of 26 studies were included in the systematic review and 14 case-control studies were included in the meta-analysis,which was performed using RevMan 5.1 and STATA 12. Subgroup analyses were used to discover possible sources of heterogeneity. Quality assessment was carried out using the Newcastle-Ottawa Scale. Odds ratios with 95% confidence intervals were calculated. Heterogeneity analyses were performed using meta-regression and tests for publication bias were performed. The overall average DHEAS diffusivity of CHD cases was significantly lower than that of controls with a summarized standard (std) mean difference of -0.23(95% CI, -0.45 to -0.01, P = .04). There was no association between DHEA concentration and CHD with a summarized mean difference of -0.07 (95% CI, -0.32 to 0.18, P = .59). No association was found between DHEAS concentration and arteriosclerosis patients with a summarized standard (std) mean difference of -0.46(95% CI, -0.96 to 0.04, P = .07). All of the results had a high degree of heterogeneity. The present study suggested that decreased DHEAS may be associated with coronary heart disease risk but not with arteriosclerosis. We did not find a significant association between DHEA and CHD risk.


Assuntos
Doença das Coronárias/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Desidroepiandrosterona/metabolismo , Doença das Coronárias/mortalidade , Humanos
19.
Lipids Health Dis ; 18(1): 140, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31186012

RESUMO

BACKGROUND: The aim of this study was to assess the prognostic value of red blood cell distribution width (RDW) in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS: A retrospective cohort study (CORFCHD-PCI, [Identifier: ChiCTR-INR-16010153]) of 6050 patients who were hospitalized with a diagnosis of coronary artery disease (CAD) and treated with PCI from January 2008 to December 2016 were enrolled in the study. The primary outcome was long-term mortality after PCI. Clinical follow-up data of participating patients were obtained during an outpatient examination 35.9 ± 22.6 months after PCI. Demographic and clinical data and admission laboratory parameters were recorded, and patients were categorized into two groups according to RDW level (high group ≥13.1%; low group < 13.1%). RESULTS: Multivariate Cox regression analysis revealed RDW as an independent prognosis factor for cardiac death. The incidence of cardiac death increased 1.33 times in patients in the high RDW group (HR, 1.331; 95% CI, 1.009-1.755, P = 0.043). Kaplan-Meier survival analysis suggested that patients with high RDW tended to have an increased accumulated risk of cardiac death. However, we did not found significant differences in the incidence of long-term mortality (adjusted HR = 1.203[0.941-1.537], P = 0.140), MACCE (adjusted HR = 1.128[0.979-1.301], P = 0.096), MACE (adjusted HR = 1.155[0.994-1.341], P = 0.059), stroke, bleeding events or readmission between the two groups. CONCLUSION: The baseline level of RDW is an independent predictor for cardiac death in post-PCI CAD patients.


Assuntos
Doença da Artéria Coronariana/patologia , Eritrócitos/metabolismo , Idoso , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/terapia , Índices de Eritrócitos/fisiologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Prognóstico , Estudos Retrospectivos , Fatores de Risco
20.
Lipids Health Dis ; 18(1): 180, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640740

RESUMO

BACKGROUND: The relation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains controversial. The present study aims to assess the prognostic value of MHR in patients with CAD who underwent PCI. METHODS: A total of 673 CAD patients were retrospectively enrolled and divided into four groups according to MHR values. Multivariate Cox regression analysis was performed to study the effects of different variables to clinical outcomes reported as major adverse cardiac events (MACE) and all-cause mortality (ACM). RESULTS: In a multivariate Cox analysis, after adjustment of other confounders, MHR was found to be an independent predictor of ACM (HR: 3.655; 95% CI: 1.170-11.419, P = 0.026) and MACE (HR =2.390, 95% CI 1.379-4.143, p < 0.002). Having a MHR in the third and fourth quartile were associated with a 2.83-fold and 3.26 -flod increased risk of MACE. CONCLUSIONS: MHR is an independent predictor of ACM and MACE in CAD patients undergoing PCI.


Assuntos
Colesterol/sangue , Doença da Artéria Coronariana/diagnóstico , Lipoproteínas HDL/sangue , Monócitos/patologia , Intervenção Coronária Percutânea , Idoso , Consumo de Bebidas Alcoólicas/fisiopatologia , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/mortalidade , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Análise Multivariada , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fumar/fisiopatologia , Análise de Sobrevida
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