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1.
J Geriatr Cardiol ; 18(4): 261-270, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33995505

RESUMO

BACKGROUND: The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD). METHODS: This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE. RESULTS: In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group ( P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49-12.97, P = 0.250). CONCLUSIONS: In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

2.
Biomarkers ; 18(7): 601-6, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24033083

RESUMO

OBJECTIVE: To evaluate whether urinary phospholipids could be regarded as biomarkers of chronic kidney disease. MATERIALS AND METHODS: Thirteen healthy volunteers and 26 consecutive chronic kidney disease patients were included. Urinary phospholipids were quantified by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. RESULTS: Urinary phosphatidylcholines concentrations (PC 16:0/16:0, 16:0/22:3, 16:0/18:1 and 16:0/18:2) were significantly higher both in glomerulonephritis group (all p < 0.001) and in tubulointerstitial injury group (all p < 0.05) than in healthy control group. Meanwhile, sphingomyelin concentrations (SM 18:1/16:0 and 18:1/18:0) in glomerulonephritis group were significantly higher than those in healthy control group (all p < 0.001). Urinary PCs and SMs were positively correlated with proteinuria but negatively correlated with serum albumin. Meanwhile, PCs were positively correlated with serum creatinine. CONCLUSION: Our work first demonstrated that urinary phospholipids might be biomarkers for the chronic kidney disease patients. Increased urinary phospholipids in chronic kidney disease patients might result from proteinuria, damaged kidney function or proteinuria induced hypoalbuminemia or lipotoxicity.


Assuntos
Glomerulonefrite/urina , Fosfolipídeos/urina , Insuficiência Renal Crônica/urina , Adulto , Estudos de Casos e Controles , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
Mol Biol Rep ; 38(6): 4007-13, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21127995

RESUMO

The majority of experimental and clinical studies indicates that the hypertrophied and failing myocardium are characterized by changes in energy and substrate metabolism that attributed to failing heart changes at the genomic level, in fact, heart failure is caused by various diseases, their energy metabolism and substrate are in different genetic variations, then the potential significance of the molecular mechanisms for the aetiology of heart failure is necessary to be evaluated. Persistent viral infection (especially coxsackievirus group B3) of the myocardium in viral myocarditis and viral dilated cardiomyopathy has never been neglected by experts. This study aimed to explore the role and regulatory mechanism of the altered gene expression for energy metabolism involved in mitochondrial oxidative phosphorylation, fatty acid metabolism in viral dilated cardiomyopathy. cDNA Microarray technology was used to evaluate the expression of >35,852 genes in a mice model of viral dilated cardiomyopathy. In total 1385 highly different genes expression, we analyzed 33 altered genes expression for energy metabolism involved in mitochondrial oxidative phosphorylation, fatty acid metabolism and further selected real-time-PCR for quantity one of regulatory mechanisms for energy including fatty acid metabolism-the UCP2 and assayed cytochrome C oxidase activity by Spectrophotometer to explore mitochondrial oxidative phosphorylation function. We found obviously different expression of 33 energy metabolism genes associated with mitochondria oxidative phosphorylation, fatty acid metabolism in cardiomyopathy mouse heart, the regulatory gene for energy metabolism: UCP2 was down-regulated and cytochrome C oxidase activity was decreased. Genes involved in both fatty acid metabolism and mitochondrial oxidative phosphorylation were down-regulated, mitochondrial uncoupling proteins (UCP2) expression did not increase but decrease which might be a kind of adaptive protection response to regulate energy metabolism for ATP produce.


Assuntos
Cardiomiopatias/genética , Cardiomiopatias/virologia , Regulação para Baixo/genética , Metabolismo Energético/genética , Ácidos Graxos/metabolismo , Mitocôndrias Cardíacas/genética , Fosforilação Oxidativa , Animais , Peso Corporal/genética , Cardiomiopatias/patologia , Cardiomiopatias/fisiopatologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Fibrose , Perfilação da Expressão Gênica , Testes de Função Cardíaca , Canais Iônicos/genética , Canais Iônicos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias Cardíacas/patologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Tamanho do Órgão/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Desacopladora 1
4.
Zhonghua Xin Xue Guan Bing Za Zhi ; 37(2): 169-73, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19719999

RESUMO

OBJECTIVE: To investigate the in vivo gene expression of adenovirus-mediated human tissue factor pathway inhibitor (hTFPI) and its inhibition effects on intimal proliferation in rabbit carotid arteries after balloon injury. METHODS: Rabbits underwent carotid artery balloon injuries were treated with Ad-TFPI (n = 25), Ad-LacZ (n = 25) or PBS (n = 10), respectively. Sham operated rabbits (n = 10) serve as normal controls. The expressions of human TFPI at mRNA and protein levels were detected by RT-PCR and ELISA respectively on the 3rd, 7th, 10th, 14th, 28th day after operation. Intimal proliferation was detected by angiograms and morphometric analysis. RESULTS: TFPI mRNA and protein expressions were detected at 3 days and peaked at the 10th and 14th day after TFPI gene transfer. The expressions were still detectable on the 28th day. There was no TFPI expression in Ad-LacZ group. The carotid angiogram results indicated that the minimal lumen diameter in TFPI group was significantly larger and the lumina stenosis percentage was significantly lower in TFPI group compared those in Ad-LacZ and PBS groups (all P < 0.05). The morphometric analysis showed that the intimal area, the ratio of the intimal/media area, the lumina stenosis percentage in TFPI group were all significantly reduced compared with those in Ad-LacZ and PBS groups (all P < 0.01). CONCLUSIONS: The TFPI gene could be effectively transferred by adenovirus vector to injured carotid arteries and transferred Ad-TFPI could significantly attenuate intimal proliferation in balloon injured carotid arteries in rabbits.


Assuntos
Artérias Carótidas/metabolismo , Lesões das Artérias Carótidas/metabolismo , Lipoproteínas/genética , Adenoviridae/genética , Animais , Lesões das Artérias Carótidas/patologia , Feminino , Técnicas de Transferência de Genes , Vetores Genéticos , Humanos , Masculino , Coelhos , Transfecção , Túnica Íntima/patologia
5.
Am J Nephrol ; 28(6): 1007-13, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18648191

RESUMO

BACKGROUND: High peritoneal transport status in end-stage renal disease patients receiving peritoneal dialysis was shown to be associated with increased morbidity and mortality. Although the pathogenesis of increased peritoneal transport is still not clear, previous studies have demonstrated that phospholipids (PLs) are present on the peritoneal mesothelium and when added to dialysate can decrease the peritoneal fluid absorption rate and increase peritoneal fluid removal. In the present report, we explored the relationship between peritoneal transport and dialysate loss of endogenous PLs. METHODS: We evaluated 48 prevalent continuous ambulatory peritoneal dialysis patients with high or low peritoneal transport in a cross-sectional study. The 4-hour dwell dialysate PL profile was analyzed by high-performance liquid chromatography coupled with electrospray ionization ion trap mass spectrometry. The patients' peritoneal small solute transport rate was assessed by D/P(Cr) at 4 h and their fluid transport by kinetic modeling. RESULTS: While there were no significant differences between the 2 groups in age, sex, diabetic status and time on dialysis, high transporters had a significantly higher D/P(Cr) and peritoneal fluid absorption rate (K(e)) than low transporters. The PLs in dialysate effluents mainly consisted of PLs containing unsaturated fatty acid, and the concentrations, as well as the amount, of PLs were significantly elevated in the dialysate of high transporters as compared to low transporters. CONCLUSION: Our results showed that dialysate from high transporters exhibited elevated levels of PLs, especially PLs containing unsaturated fatty acid, suggesting a possible loss of peritoneal surface-active PLs in peritoneal dialysis, and this loss may contribute to the alteration in peritoneal transport.


Assuntos
Soluções para Diálise/metabolismo , Ácidos Graxos Insaturados/metabolismo , Fosfolipídeos/metabolismo , Idoso , Transporte Biológico , Cromatografia/métodos , Diabetes Mellitus/metabolismo , Ácidos Graxos/metabolismo , Feminino , Glucose/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Peritônio/patologia , Espectrometria de Massas por Ionização por Electrospray
6.
Zhongguo Zhong Yao Za Zhi ; 31(6): 494-7, 2006 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16722383

RESUMO

OBJECTIVE: To test the effect of asarinin, the extract of Herba Asari, on the acute heart transplantation rejection and the expression of adhesion molecule. METHOD: Asarinin was extracted from herba asari. 64 SD rats undergone heart transplantation were divided into four groups: group A (control group), group B (Cyclosporine A treated), group C (Asarinin treated), and group D (1/2 CsA and 1/2 Asarinin). Some rats were used to examine survival time (n = 8) and the others were used to observe the pathological injury and the expression level of interrellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-I (VCAM-1) by using immunohistochemistry. RESULT: Asarinin could prolong the survival time of allografts, which was similar to CsA group (P > 0.05). Asarinin could relieve the damage of cardiomyocytes of the transplanted. Asarinin could also decrease the level of ICAM-1 and VCAM-1 in the allografts. CONCLUSION: Asarinin may play important roles in suppressing the immune rejection, prolong the allografts survival time and protect the donor organ, which was similar to CsA. The expression level of ICAM-1 and VCAM-1 is increased in suppressing the course of acute rejection and asarinin can inhibit their expression level. Asarinin can decrease the dosage of CsA.


Assuntos
Asarum , Dioxóis/farmacologia , Rejeição de Enxerto/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Lignanas/farmacologia , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Asarum/química , Dioxóis/isolamento & purificação , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração , Lignanas/isolamento & purificação , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Plantas Medicinais/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos Wistar
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