RESUMEN
Background: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population. Methods: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies. Results: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035). Conclusions: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.
RESUMEN
Objective To investigate the impact of fasting blood glucose on the prognosis of non-diabetic patients undergoing primary percutaneous coronary intervention (PCI) for acute ST-segment elevation myocardial infarction (STEMI). Methods We retrospectively recruited consecutive patients who underwent primary PCI in our hospital from February, 2003 to March, 2015. Patients with prior history of diabetes mellitus before the index hospitalization and those with newly diagnosed diabetes mellitus during the index hospitalization were excluded. The clinical and angiographic features, medical and interventional treatment, and 30-day outcomes were compared between patients with elevated fasting blood glucose (FBG) (>5.4 mmol/L) and those with normal FBG (≤5.4 mmol/L). Results A total of 721 patients were recruited with an age of(61.2 ± 12.8)years, of whom 601 (83.4 %) were male. As compared with patients with normal FBG,those with elevated FBG were more likely to be female(20.1 % vs.13.5 %, P=0.017),had faster heart rate on admission[(82.9 ± 17.2)bpm vs.(79.4 ± 16.7)bpm,P=0.006]and more use of intra-aortic balloon pump(3.8 % vs.1.3 %,P=0.034),and had higher rates of 30 day all-cause mortality(3.5 % vs.0.5 %,P=0.004),cardiac mortality(2.9 % vs.0.5 %,P=0.012)and heart failure(18.1 % vs. 7.4 %, P< 0.001). After adjusting baseline characteristics, FBG > 5.4 mmol/L was one of the independent predictors of 30-day all-cause mortality(HR 6.030,95 % CI 1.235-29.447,P=0.026).Other independent predictors of 30-day all-cause mortality included age(HR 1.059,95 % CI 1.002-1.120,P=0.044),heart rate on admission(HR 1.036,95 % CI 1.003-1.070,P=0.034),left descending artery as the culprit vessel(HR 6.427,95 % CI 1.389-29.728,P=0.017),and use of angiotensin converting enzyme inhibitor/angiotensin receptor blocker(HR 0.154,95 % CI 0.051-0.461,P=0.001).Conclusions In non-diabetic patients undergoing primary PCI for STEMI, elevated FBG was one of the independent predictors of 30-day all-cause mortality.
RESUMEN
Objective: To compare the efficiency of two-dimensional speckle tracking echocardiography (2D-STE) and late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) for detecting cardiac amyloidosis. Methods: Systolic longitudinal peak strain by 2D-STE and LGE by CMR were retrospectively analyzed in 10 patients with cardiac amyloidosis. Results: CMR showed 10 patients with LGE and 2D-STE showed 9 patients with ventricular systolic longitudinal peak strain decreasing, the diagnostic consistency of CMR and 2D-STE was 90%. There were 4 patients having both strain abnormality and LGE at meanwhile, 4 patients without CMR presented right ventricular involvement while with 2D-STE indicated abnormal right ventricular systolic longitudinal peak strain, 1 patient with CMR presented LGE in ventricular sepatum while 2D-STE indicated systolic longitudinal peak strain decreasing in both ventricles. Conclusion: 2D-STE and CMR had good consistency for diagnosing left ventricular involvement in patients with cardiac amyloidosis; 2D-STE may have better sensitivity for diagnosing right ventricular amyloidosis.
RESUMEN
<p><b>OBJECTIVE</b>To investgate the effects of rapamycin(RPM)and RPM-loaded poly(lactic-co-glycolic)acid(PLGA)nanoparticles(NPs)on the apoptosis of human umbilical arterial vascular smooth muscle cells(HUASMCs)in vitro and expression of bcl-2 and p27(kip1) protein.</p><p><b>METHODS</b>HUASMCs were cultured in vitro and divided to RPM and RPM-PLGA-NPs groups treated at 3 different concentration by 12 and 24 hours,with M231-smooth muscle growth supplements medium and null-PLGA-NPs treated groups as controlled. The apoptosis of HUASMCs was determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and flow cytometry. The expressions of bcl-2 and p27(kip1) were detected by streptacidin/peroxidase immunohistochemical method. The effect on cellular proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromidecolorimetry.</p><p><b>RESULTS</b>The proliferation of HUASMCs was inhibited by RPM and RPM-PLGA-NPs in a dose-dependent manner. DNA electrophoresis showed DNA ladder in RPM and RPM-PLGA-NPs groups and classical scalar strips in control groups. The apoptotic indexes of RPM 100 ng/ml group and RPM-PLGA-NPs 500 ng/ml group detected by flow cytometry were(45.45<2.36)% and(35.04<5.64)%,respectively,which were significantly higher than that of M231-smooth muscle growth supplements control group [(2.60<0.95)%,all P<0.01]. The apoptotic indexes of groups incubated with RPM and RPM-PLGA-NPs for 24 hours were significantly higher than those of groups which incubated for 12 hours(P<0.05,P<0.01). The positive expression indexes(PEI)of p27(kip1) and bcl-2 protein were higher in RPM and RPM-PLGA-NPs groups than that of control groups. The Spearman's rank correlation coefficient test showed that there was no significant correlation between the PEI of p27(kip1) and the apoptotic indexes in the RPM group and RPM-PLGA-NPs group(P>0.05).</p><p><b>CONCLUSIONS</b>Rapamycin-loaded PLGA nanoparticles and rapamycin have similar effects in inhibiting proliferation and inducing apoptosis;meanwhile,they upregulate the expression of p27(kip1) protein without downregulating the expression of bcl-2 protein in HUASMCs in vitro. RPM-PLGA-NPs has more potent pro-apoptotic effect than equivalent dose of RPM but is not linearly correlated with the p27(kip1) expression level.</p>
Asunto(s)
Humanos , Apoptosis , Proliferación Celular , Células Cultivadas , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Etiquetado Corte-Fin in Situ , Ácido Láctico , Músculo Liso Vascular , Miocitos del Músculo Liso , Nanopartículas , Ácido Poliglicólico , Sirolimus , Arterias UmbilicalesRESUMEN
<p><b>OBJECTIVE</b>To summarize the clinical and echocardiographic features of cardiac myxomas.</p><p><b>METHODS</b>The medical records of patients with diagnosis of cardiac myxomas who hospitalized in our department from October 1985 to February 2011 were analyzed.</p><p><b>RESULTS</b>A total of 64 patients were enrolled [40 female, the mean age was 2 - 77 (47 ± 17) years]. The main complaints were palpitation (n = 24, 38%), short breath (n = 23, 36%), fever (n = 13, 20%), chest tightness (n = 11, 17%), dizziness (n = 10, 16%), fatigue (n = 10, 16%), weight loss (n = 10, 16%), syncope (n = 9, 14%), edema (n = 8, 13%); and thrombus embolisms (n = 13, 20%), including stroke (n = 7, 11%) and periphery artery embolism (n = 6, 9%). The interval from symptoms onset to diagnosis (surgical removal) ranged from 1 day to 9 years (median: 3 months). Single myxoma was detected in 62 (97%) patients (58 in left atria, 2 in right atria and 2 in right ventricle) and multiple myxomas were found in 2 (3%) patients and one patient was diagnosed as Carney syndrome. The mean size of tumor assessed by echocardiography was (5.0 ± 1.8) cm × (2.9 ± 1.0) cm. All myxomas were surgically removed (54 patients received operation in our hospital and 10 patients were operated in other hospitals) and diagnosis was confirmed during operation and the mean myxoma size obtained from operation was (5.4 ± 1.6) cm × (3.6 ± 1.3) cm × (2.6 ± 1.2) cm (P > 0.05 vs. tumor size assessed by echocardiography). The locations of tumor stalks found by echocardiography were confirmed during surgery in most cases (97%). Incidence of NYHA class III diagnosis was more often in patients with right heart myxomas [3 cases (3/4)] than in patients with left atrium myxomas [17% (10/58), P < 0.05].</p><p><b>CONCLUSIONS</b>Clinical manifestations of cardiac myxomas were various and non-specific. Echocardiography remains the most valuable diagnosis tool for patients with cardiac myxomas.</p>
Asunto(s)
Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Ecocardiografía , Neoplasias Cardíacas , Diagnóstico , Diagnóstico por Imagen , Mixoma , Diagnóstico , Diagnóstico por Imagen , Estudios RetrospectivosRESUMEN
<p><b>BACKGROUND</b>There have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose losartan on clinical outcomes in Chinese subjects with heart failure.</p><p><b>METHODS</b>This study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin II Antagonist losartan (HEAAL) trial (n = 545). Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) II-IV) intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily. The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure. Safety and tolerability were assessed.</p><p><b>RESULTS</b>Median follow-up was 4.8 years. Baseline characteristics were generally similar to the overall HEAAL cohort. Overall, 120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807, 95%CI 0.631 - 1.031). There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.</p><p><b>CONCLUSION</b>The results of this post hoc analysis in Chinese subjects, although not powered to show significance, were generally consistent with the main study results, which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs. losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors, supporting the use of the higher dose for optimum clinical benefit.</p>
Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Bloqueadores del Receptor Tipo 1 de Angiotensina II , Usos Terapéuticos , Inhibidores de la Enzima Convertidora de Angiotensina , Usos Terapéuticos , Método Doble Ciego , Insuficiencia Cardíaca , Quimioterapia , Losartán , Usos TerapéuticosRESUMEN
<p><b>OBJECTIVE</b>To analyze the clinical characteristics of infective endocarditis in patients with hypertrophic obstructive cardiomyopathy.</p><p><b>METHODS</b>Clinical characteristics from 5 patients with infective endocarditis and hypertrophic obstructive cardiomyopathy hospitalized from January 2000 to December 2010 in our hospital were analyzed.</p><p><b>RESULTS</b>Four patients were diagnosed with left ventricular outflow tract obstructive cardiomyopathy with outflow pressure gradient from 36 to 140 mm Hg (1 mm Hg = 0.133 kPa) and left atrial size 44 - 68 mm. Another patient was diagnosed as ventricular hypertrophic cardiomyopathy with significant right-ventricular outflow tract hypertrophy (30 mm), high pressure gradient (164 mm Hg) and enlarged right atrial (56 mm × 53 mm), there was a 17 mm × 8 mm vegetation on right-ventricular outflow tract in this patient. Blood cultures were positive for streptococcus viridans in all five patients, and enterococcus faecium was revealed in one aortic valve vegetation culture. Transthoracic echocardiogram was performed 2 - 4 times for each patient, the vegetations of two patients was detected only by transesophageal echocardiography. The mitral valve vegetation was detected in two patients, the aortic and mitral valve vegetations were detected in one patients, mitral and tricuspid vegetations in one patient and right ventricular outflow tract vegetation in one patient. The four hemodynamically stable patients were successfully treated with antibiotic therapy, one patient received urgent surgery (replacement of the aortic and mitral valve as well as septal myectomy). All patients recovered and follow-up (1 - 6 years) was available in 4 patients and no complication was observed.</p><p><b>CONCLUSION</b>The risk of infective endocarditis complicating hypertrophic obstructive cardiomyopathy is the highest in patients with both outflow obstruction and marked valve insufficiency, these patients should receive prophylactic antibiotic therapy during procedures that predispose to infective endocarditis.</p>
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cardiomiopatía Hipertrófica , Microbiología , Patología , Endocarditis Bacteriana , PatologíaRESUMEN
<p><b>OBJECTIVE</b>To investigate the cardiovascular risk profile in patients with glycogen storage disease (GSD) type I.</p><p><b>METHOD</b>The clinical information of 62 patients with GSD type I who admitted to Peking Union Medical Hospital were reviewed and the cardiovascular risk profile was analyzed.</p><p><b>RESULTS</b>The age of the patient cohort was (8.4 ± 6.9) years and the ratio of male vs. female was 36:26. The median disease duration was (6.7 ± 6.2) years and treatment duration was (38.3 ± 35.2) months. The rate of abnormal change in electrocardiogram and echocardiography was 17.7% and 24.2%, respectively. The serum concentration of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and uric acid in patient before and after treatment were (6.18 ± 2.47) mmol/L vs. (5.61 ± 1.84) mmol/L (P = 0.020), (11.17 ± 9.85) mmol/L vs. (6.81 ± 5.97) mmol/L (P = 0.010), (2.55 ± 1.27) mmol/L vs. (2.78 ± 1.07) mmol/L (P = 0.617), (0.98 ± 0.37) mmol/L vs. (0.96 ± 0.23) mmol/L (P = 0.005), (526.53 ± 127.09) µmol/L vs. (490.78 ± 129.79) µmol/L (P = 0.977), respectively. The high-sensitivity C-reactive protein levels tended to be higher after therapy compared before treatment (2.33 ± 3.30) mg/L vs. (3.35 ± 3.39) mg/L, P = 0.431.</p><p><b>CONCLUSION</b>Patients with GSD I are associated with an increased risk for cardiovascular disease.</p>
Asunto(s)
Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Proteína C-Reactiva , Metabolismo , Enfermedades Cardiovasculares , HDL-Colesterol , Sangre , LDL-Colesterol , Sangre , Enfermedad del Almacenamiento de Glucógeno Tipo I , Sangre , Diagnóstico por Imagen , Lipoproteínas LDL , Sangre , Factores de Riesgo , Triglicéridos , Sangre , UltrasonografíaRESUMEN
<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of tolvaptan on treating congestive heart failure patients with hyponatremia.</p><p><b>METHODS</b>This randomized double-blind placebo-controlled multicenter trial enrolled 65 patients with congestive heart failure and hyponatremia. On top of standard therapy, patients were randomized to receive either tolvaptan 15 - 60 mg daily or placebo according to the serum sodium concentration. The primary end points were the change of average daily serum sodium concentration from baseline to day 4 and to day 7 respectively. Patients' weight, urine volume, sign of heart failure, heart function, blood pressure, heart rate, and all adverse events were observed.</p><p><b>RESULTS</b>The daily serum sodium concentration increase was significantly higher in tolvaptan group than in placebo group during the first 4 days [(5.6 ± 3.5) mmol/L vs. (2.5 ± 3.4) mmol/L, P < 0.05] and 7 days [(5.9 ± 3.5) mmol/L vs. (2.8 ± 3.3) mmol/L, P < 0.05]. Moreover, urine volume increase and body weight decrease were more significant in tolvaptan group than in placebo group (all P < 0.05). The change of sign of heart failure, heart function, blood pressure and heart rate was similar between two groups (P > 0.05). There were more drug related adverse events of thirst (11.4%) and hypernatremia (5.7%) in Tolvaptan group. One patient in tolvaptan group developed agranulocytosis during therapy period and recovered post therapy.</p><p><b>CONCLUSIONS</b>Tolvaptan could effectively increase serum sodium concentration, urine volume, and improve liquid balance in heart failure patients with hyponatremia. Tolvaptan related serious adverse event was low and could be well tolerated by patients tested in this cohort.</p>
Asunto(s)
Anciano , Humanos , Antagonistas de los Receptores de Hormonas Antidiuréticas , Usos Terapéuticos , Benzazepinas , Usos Terapéuticos , Presión Sanguínea , Peso Corporal , Método Doble Ciego , Insuficiencia Cardíaca , Quimioterapia , Hiponatremia , Sodio , SangreRESUMEN
<p><b>BACKGROUND</b>Multiple neonatal characteristics and adult cardiovascular risk factors are associated with the development of atherosclerosis, however little conclusive evidence exists characterizing the relative strength of these factors. In a large retrospective study, we investigated the association between both objective neonatal measurements and comprehensive adult cardiovascular risk factors with the development of atherosclerosis, quantified by carotid intima-media thickness (CIMT). Further, we assessed the impact of gender on the relative impact of these risk factors.</p><p><b>METHODS</b>CIMT, a measure of atherosclerosis, was determined by carotid ultrasound on 1568 participants (age 50-85) whose birth records were obtained from Peking Union Medical College Hospital. In addition, each participant was given a physical examination, and completed a medical questionnaire to identify a panel of cardiovascular risk factors. Multiple regression analysis was performed on the population and on the male and female cohorts individually, to identify the relative contribution of these risk factors to increased CIMT.</p><p><b>RESULTS</b>For the total population the Framingham score, renal function, adult abdominal circumference and mother's gestational age were associated with CIMT, accounting for 14.7%, 1.4%, 0.9%, and 0.2% of total variance, respectively. In the male population the Framingham score, renal function, abdominal circumference and hemoglobin were the most significant risk factors for CIMT. Risk in the female population was associated with Framingham score, renal function, insulin resistance and gestational age. No relationship between birth weight or head circumference and CIMT were observed.</p><p><b>CONCLUSIONS</b>Adult cardiovascular risk factors were the most significantly associated with the development of atherosclerosis; however mother's age at birth was associated with CIMT, particularly in the female cohort. The relative contribution of the risk factors analyzed varied between the male and female populations.</p>
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Recién Nacido , Masculino , Persona de Mediana Edad , Embarazo , Aterosclerosis , Peso al Nacer , Enfermedades Cardiovasculares , Arterias Carótidas , Patología , China , Estudios de Cohortes , Edad Gestacional , Edad Materna , Factores de Riesgo , Caracteres Sexuales , Túnica Íntima , Patología , Túnica Media , PatologíaRESUMEN
<p><b>OBJECTIVE</b>To evaluate Candesartan therapeutic effect against atherosclerotic plaque rupture and to explore the related mechanisms.</p><p><b>METHODS</b>Thirty-four New Zealand White male rabbits were randomly divided into three groups: the control group, the model control group and the Candesartan intervention group. The control group rabbits were fed with a normal diet. Rabbits of the latter two groups were fed with a 1% high-cholesterol diet and received a balloon catheter injury respectively one week after the cholesterol feeding. Candesartan (0.5 mgⁱkg⁻¹ⁱd⁻¹) was given to the Candesartan group rabbits 2 days before the performance of the balloon catheter injury. By the end of 12(th) week of the experiment, Russell's viper venom was used for rabbits of both the model control and the Candesartan groups in order to induce rupture of the plaques developed and followed by sacrifice of all the rabbits of the 3 groups. The aortas were removed and fixed for histological evaluation. Immunohistochemistry of MMP-9, macrophage markers and collagen were performed. The protein expression of MMP-9 was determined using Western blot analysis.</p><p><b>RESULTS</b>In the model control group, 7 of 9 rabbits with a total of 12 plaques developed rupture and thrombosis of the plaques after the induction. In contrast, only 2 of 10 rabbits with a total of 3 plaques demonstrated rupture and thrombosis in the Candesartan group (P < 0.05). The control group rabbits did not have plaque rupture and thrombosis. Compared with the model group, both the percentage area of MMP-9 and macrophages in the plaques were significantly decreased in the Candesartan group (12.35% ± 4.28% vs 32.58% ± 9.16%, P < 0.05; 13.87% ± 4.91% vs 23.8% ± 7.45%, P < 0.05). There was an increased percentage of collagen content in total plaques of the Candesartan group (30.27% ± 11.36% vs 4.18% ± 1.28%, P < 0.01). Compared with the model group, the protein expression of MMP-9 was significantly decreased in the Candesartan group (P < 0.01).</p><p><b>CONCLUSION</b>Candesartan has a preventive value against atherosclerotic plaque rupture in hypercholesterolemic rabbits, likely through its reduction of MMP-9 expression, inhibition of macrophage accumulation and increase of collagen content within the plaques.</p>
Asunto(s)
Animales , Masculino , Conejos , Bloqueadores del Receptor Tipo 1 de Angiotensina II , Usos Terapéuticos , Antihipertensivos , Usos Terapéuticos , Aorta Abdominal , Heridas y Lesiones , Bencimidazoles , Usos Terapéuticos , Colágeno , Metabolismo , Macrófagos , Patología , Metaloproteinasa 9 de la Matriz , Metabolismo , Placa Aterosclerótica , Metabolismo , Patología , Distribución Aleatoria , Rotura Espontánea , Tetrazoles , Usos Terapéuticos , Trombosis , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To evaluate the effects of rapamycin (RPM)-loaded poly (lactic-co- glycolic) acid (PLGA) nanoparticles (NPs) on the proliferation, distribution of cell cycle, and expression of p27 protein in human umbilical arterial vascular smooth muscle cell (HUASMC) in vitro.</p><p><b>METHODS</b>The primarily culture model of HUASMC was successfully established by explant-attached method in vitro. The cells were administrated with different doses of RPM, and RPM-PLGA NPs were observed as treat groups compared with PLGA NPs and M231-SMGs medium cultured group. The effect of RPM-PLGA NPs on proliferation of HUASMC was assessed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) colorimetry method. The influences of RPM-PLGA NPs on the cell cycle and cellular growth kinetics of HUASMCs were tested by flow cytometry. The effect of RPM-PLGA NPs on the expression of p27 protein of HUASMCs was assessed through an immunohistochemical method.</p><p><b>RESULTS</b>Compared with the control group, the proliferation of HUASMCs was inhibited by 50 microg/L and higher concentration of RPM-PLGA NPs in a dose-dependent manner (P < 0.05). The numbers of cells entering cell cycle of S/G2/M phases were significantly lower in RPM-PLGA NPs and RPM treated groups. Histologically, the expression of p27 were up-regulated in 500 microg/L RPM-PLGA NPs and 100 microg/L RPM treated group (all P < 0.01 ) when compared with the control group.</p><p><b>CONCLUSIONS</b>RPM-PLGA NPs has a similar effects as RPM in inhibiting the growth of in vitro cultured HUASMC. It can remarkably suppress the expression of in vitro cultured HUASMC p27 protein, arrest its cell cycle at G1/S phase, and inhibit its proliferation.</p>
Asunto(s)
Humanos , Ciclo Celular , Proliferación Celular , Células Cultivadas , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Metabolismo , Portadores de Fármacos , Ácido Láctico , Músculo Liso Vascular , Biología Celular , Miocitos del Músculo Liso , Biología Celular , Metabolismo , Nanopartículas , Ácido Poliglicólico , Sirolimus , Farmacología , Arterias Umbilicales , Biología CelularRESUMEN
<p><b>OBJECTIVE</b>To evaluate the value of low-dose adenosine echocardiography (LDAE) for detection of myocardial viability in patients with acute myocardial infarction (MI).</p><p><b>METHODS</b>Thirty-six patients underwent LDAE within 3 - 10 days after onset of first acute MI before (n = 4) or after (n = 32) percutaneous coronary intervention. A 17-segment semi-quantitative scoring model was adopted. Wall motion improvement derived from two dimensional images at follow-up (2 - 3 months after acute MI) comparing baseline before adenosine infusion was used as gold criteria for myocardial viability.</p><p><b>RESULTS</b>Low-dose adenosine slightly increased heart rates [(70.7 +/- 10.8) beats/min vs. (78.1 +/- 10.9) beats /min, P < 0.01] and also significantly reduced left ventricular endsystolic volume [(30.4 +/- 1.9) ml vs. (20.1 +/- 9.3) ml, P < 0.01] and increased ejection fraction (62.6% +/- 10.4% vs. 74.7% +/- 9.8%, P < 0.01). The sensitivity, specificity, diagnostic accuracy, positive and negative prective values of LDAE for identification of viable myocardium were 90.3%, 80.8%, 86.0%, 84.8% and 87.5%, respectively. Incidence of mild adverse reaction during LDAE was 38.9% (14/36). LDAE at dose of 100 microgxkg(-1)xmin(-1) was ideal in terms of balanced sensitivity and specificity for detecting viable myocardium without increasing the adverse effects compared to lower doses.</p><p><b>CONCLUSIONS</b>LDAE (100 microgxkg(-1)xmin(-1)) has excellent sensitivity and specificity for detecting viable myocardium in acute MI with only minimal adverse effects.</p>
Asunto(s)
Humanos , Adenosina , Dobutamina , Ecocardiografía , Infarto del Miocardio , MiocardioRESUMEN
<p><b>OBJECTIVE</b>To compare clinical characteristics among premenopausal women with coronary arterial disease (CAD) with or without atherosclerosis (AS) and postmenopausal women with CAD.</p><p><b>METHODS</b>The clinical and coronary angiographic data, traditional risk factors (age, smoking, blood pressure, lipid profile, blood glucose, BMI, family history) were compared among premenopause (Pre-M, n=42) and post-menopause (Post-M, n=172) women with CAD as well as Pre-M patients with non-AS CAD (non-AS CAD, n=8).</p><p><b>RESULTS</b>Compared with the Post-M patients with CAD, Pre-M CAD patients had significantly fewer traditional risk factors, such as hypertension, diabetes and hypercholesterolemia, significantly more acute coronary syndrome and fewer previous history of chest pain, significantly more single vessel lesion and lower Gessini score (all P < 0. 01). The logistic regression results showed that obesity is an independent risk factor for the development of CAD in premenopausal women (OR = 3. 655, 95% CI: 1. 5-11.59, P = 0.028). Hypertension (OR = 4.73, 95% CI: 0.991-22.589, P = 0.051) and hypercholesterolemia (OR = 4.68, 95% CI: 0.971-22.564, P = 0.055) might also contribute to the development of CAD in these patients. Clinical characteristics were similar between Pre-M and non-AS CAD patients (P > 0.05).</p><p><b>CONCLUSIONS</b>Pre-M CAD patients had less traditional risk factors and lower coronary lesion score compared to post-M CAD patients. Obesity is an independent risk factor for Pre-M CAD. Non-AS coronary artery disease is also an important reason for the development of coronary arterial events in premenopausal women.</p>
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Aterosclerosis , Estudios de Cohortes , Enfermedad de la Arteria Coronaria , Premenopausia , Factores de RiesgoRESUMEN
<p><b>OBJECTIVE</b>To sought to engineer and characterize a biodegradable nanoparticles (NPs) containing rapamycin which use poly (lactic-co-glycolic) acid (PLGA) as the carrier matrix and to assess its in vivo release characteristics by local drug delivery system intravascularly.</p><p><b>METHODS</b>Rapamycin-loaded PLGA NPs were prepared by an emulsification/solvent evaporation technique, and NPs size distribution was assessed by submicro laser defractometer. The particle morphology was observed by scanning electron microscopy. In vitro release from the NPs was performed in TE buffer at 37 degrees C under rotation utilizing double-chamber diffusion cells on a shake stander. In vivo NPs intravascular local delivery were performed by DISPATCH catheter in New Zealand rabbit abdominal aorta and Chinese experimental mini-pigs coronary artery models.</p><p><b>RESULTS</b>Biodegradable rapamycin loaded PLGA NPs were constructed successfully by emulsification solvent-evaporation technique. The diameter of rapamycin-PLGA NPs was around 246.8 nm with very narrow size distribution, and rapamycin-NPs showed good spherical shape with smooth uniform surface. Rapamycin loaded in NPs were around was 19.42%. Encapsulation efficiency of drug was over 77.53%. The in vitro release of rapamycin from NPs showed that 75% of the drug was sustained released over 2 weeks and controlled release in a linear pattern. After a single 10 minutes infusion of rapamycin-PLGA NPs suspension (5 mg/ml) under 20.27 kPa through DISPATCH catherter in vivo, the mean rapamycin levels at 7 day and 14 day were (2.438 +/- 0.439) and (0.529 +/- 0.144) microg/mg of the dry-weight of the artery segments (2 cm) which local delivery were administrated.</p><p><b>CONCLUSIONS</b>PLGA NPs controlled drug delivery system for intraarterial local anti-proliferative drug delivery can potentially improve local drug concentration and prolong drug residence time in animal model in vivo. It should be appropriate for further study of its therapy efficiency in human.</p>
Asunto(s)
Animales , Conejos , Aorta Abdominal , Vasos Coronarios , Portadores de Fármacos , Química , Sistemas de Liberación de Medicamentos , Métodos , Infusiones Intraarteriales , Ácido Láctico , Química , Nanopartículas , Química , Tamaño de la Partícula , Ácido Poliglicólico , Química , Sirolimus , Farmacocinética , Porcinos , Porcinos EnanosRESUMEN
<p><b>OBJECTIVE</b>To analyze clinical characteristics in young and aged patients with coronary artery disease (CAD).</p><p><b>METHODS</b>The clinical and coronary angiographic data were compared between young (PCAD, male < 55 years old, n = 74, female < 65 years old, n = 71) and aged (CAD, male > 55 years old, n = 106, female > 65 years old, n = 111) patients. Seventy-one patients excluded with CAD by angiography served as controls (non-CAD). The traditional risk factors (including age, smoking, blood pressure, lipid profile, blood glucose, BMI, family history), coronary angiographic changes were analyzed and compared among various groups.</p><p><b>RESULTS</b>(1) Compared with CAD group, PCAD patients had significantly higher rate of smoking (50.3% vs. 38.0%, P < 0.05), significantly higher positive CAD family history rate (29.7% vs. 19.9%, P < 0.05) and significantly higher TG level [(2.13 +/- 1.89) mmol/L vs. (1.78 +/- 1.14) mmol/L, P < 0.05], while had significantly fewer traditional risk factors (2.50 +/- 1.28 vs. 2.76 +/- 1.43, P < 0.05) and lower hypertension rate (59.3% vs. 73.3%, P < 0.05). There were significantly more PCAD patients with acute coronary syndrome (66.2% vs. 42.6%, P < 0.05), more PCAD patients had single vessel lesion (51.0% vs. 30.4%, P < 0.05), lower average lesion score (4.86 +/- 2.30 vs. 5.92 +/- 2.66, P < 0.05). (2) The logistic regression results showed that positive CAD family history (P = 0.029, OR = 1.766, 95% CI 1.060 - 2.940) and smoking (P = 0.066, OR = 1.561, 95% CI 0.971 - 2.510) are important independent risk factors for the development of PCAD.</p><p><b>CONCLUSIONS</b>Smoking, positive family history and the increased TG might contribute to the pathogenesis of PCAD.</p>
Asunto(s)
Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria , Diagnóstico , Epidemiología , Factores de Riesgo , Fumar , Triglicéridos , SangreRESUMEN
<p><b>OBJECTIVE</b>To analyze factors associated with reduced renal function post primary percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients with normal baseline serum creatinine level.</p><p><b>METHOD</b>The clinical and angiographic data of 216 consecutive AMI patients undergoing primary PCI with normal baseline serum creatinine level (< 1.5 mg/dl) were obtained and compared between patients with (n = 32) and without (n = 184) renal function deterioration (increase in serum creatinine > or = 25% from baseline level within 72 hours of primary PCI) post PCI.</p><p><b>RESULTS</b>The incidence of renal function deterioration was 14.8% (32/216). Patients with age > 75 years (28.1% vs. 14.1%, P = 0.047), congestive heart failure (25.0% vs. 9.2%, P = 0.017), less use of low-molecular weight heparins (84.4% vs. 95.1%, P = 0.039) and beta-blockers (75.0% vs. 95.6%, P = 0.001) as well as angiotensin converting enzyme inhibitors/angiotensin receptor blockers (81.3% vs. 93.5%, P = 0.025) and statins (84.4% vs. 97.3%, P = 0.008) were risk factors for developing renal dysfunction post PCI. Renal function deterioration post PCI was also associated with increased in-hospital mortality (25.0% vs. 2.2%, P < 0.001). Multivariate analysis showed that congestive heart failure was the single independent predictor of renal function deterioration (odds ratio = 3.275, 95% confidence interval 1.275 - 8.408, P = 0.014), while renal function deterioration was the strongest independent predictor of in-hospital death (odds ratio = 10.313, 95% confidence interval 2.569 - 41.402, P = 0.001).</p><p><b>CONCLUSION</b>Renal function deterioration is a common complication post primary PCI and is associated with higher risk of in-hospital death in AMI patients with normal baseline serum creatinine level.</p>
Asunto(s)
Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lesión Renal Aguda , Angioplastia Coronaria con Balón , Creatinina , Sangre , Pruebas de Función Renal , Infarto del Miocardio , Sangre , Terapéutica , PronósticoRESUMEN
<p><b>OBJECTIVE</b>To analyze the cardiac manifestations of patients with primary and secondary Sjogren syndrome.</p><p><b>METHODS</b>Clinical data (clinical manifestations, serologic measurements, echocardiogram) of 396 patients with Sjogren syndrome who admitted to our hospital from 2004--2007 were retrospectively analyzed. Patients with congenital, rheumatic and coronary heart diseases, hypertension and diabetes (n = 221) and patients with incomplete clinic data (n = 51) were excluded.</p><p><b>RESULTS</b>A total of 124 cases were included in this analysis (mean age 47.4 years old; 5 males; average disease duration 85.5 months). Cardiac involvement in Sjogren syndrome is usually asymptomatic. Pericardial effusion (PE) were evidenced in 20.2%, left ventricular diastolic dysfunction (LVDD) in 13.7%, pulmonary artery hypertension (PAH) in 12.9%, left atrium enlargement/in 7.3%, mitral insufficiency in 4.8%, aortic dilation in 5.6%, tricuspid insufficiency in 3.2%, left ventricular enlargement in 2.4% and left ventricular systolic dysfunction in 0.8% patients by echocardiography examinations. Patients with PE had significantly lower CH50, C3, C4 levels and significantly higher C reactive protein level (CRP) and SSA positive rate than patients without PE (all P < 0.05). The serum level of CRP was significantly associated with PE (OR 0.976, 95% CI 0.956 - 0.997, P < 0.05). Age is positively correlated to LVDD (OR 0.884, 95% CI 0.811 - 0.964, P < 0.005). The gammaglobulin level is significantly higher in the PAH group than that in the non-PAH group (P < 0.05).</p><p><b>CONCLUSIONS</b>Cardiac involvement is not rare in patients with Sjogren syndrome. PE, LVDD and PAH are usual cardiac manifestations in these patients. The serum level of CRP is positively related to PE in these patients with Sjogren syndrome.</p>
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ecocardiografía Doppler en Color , Hipertensión Pulmonar , Diagnóstico por Imagen , Derrame Pericárdico , Diagnóstico por Imagen , Estudios Retrospectivos , Síndrome de Sjögren , Diagnóstico por Imagen , Disfunción Ventricular Izquierda , Diagnóstico por ImagenRESUMEN
<p><b>OBJECTIVE</b>To observe the urokinase receptor (uPAR) expression in atherosclerotic plaques of human femoral arteries.</p><p><b>METHODS</b>Human femoral artery samples were collected from patients underwent femoral endarterectomy. Normal internal mammary artery samples were taken from bypass surgery served as control. uPAR protein distribution at shoulders, lipid pool and rupture sites of a plaque and the association with macrophages and smooth muscle cells (SMCs) were detected by immunohistochemistry methods.</p><p><b>RESULTS</b>There was no uPAR expression in intima or tunica media of normal internal mammary arteries. In atherosclerotic lesions of femoral artery, the mean optical density (A) of uPAR was 92 +/- 37 in intima and 46 +/- 28 in tunica media (P < 0.05). The intimal uPAR was coexisted with macrophages and SMCs. uPAR expression was observed at plaque shoulders and lipid pool, while the maximal expression was found at rupture sites.</p><p><b>CONCLUSION</b>The increased expression of uPAR in atherosclerotic lesion and uPAR distribution at shoulders, lipid pool, as well as rupture sites of plaques suggest a role of uPAR in plaque rupture process.</p>
Asunto(s)
Humanos , Aterosclerosis , Metabolismo , Patología , Endarterectomía , Arteria Femoral , Patología , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Metabolismo , Activador de Plasminógeno de Tipo Uroquinasa , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To compare the value of low-dose dobutamine echocardiography (LDDE) and dual-isotope emission simultaneous myocardial perfusion acquisition (technetium-99-m-tetrofosmin/fluorine 18-fluorodeoxy-glucose) single-photon emission computed tomography (DISA-SPECT) for myocardial viability assessment in patients with acute myocardial infarction (MI).</p><p><b>METHODS</b>LDDE and DISA-SPECT were performed in 44 patients within 5-10 days after onset of first acute MI and percutaneous coronary intervention was made thereafter. A 16-segment semi-quantitative scoring model was adopted for both techniques. Wall motion improvement at follow-up (3 months after acute MI) compared with baseline before dobutamine infusion derived from two dimensional images was used as golden criteria for myocardial viability.</p><p><b>RESULTS</b>The sensitivity, specificity, diagnostic accuracy, positive and predictive values for identification of viable myocardium were 77%, 82%, 79%, 82% and 77%, respectively by LDDE and 85%, 62%, 74%, 71% and 79%, respectively by DISA. No difference was found between LDDE and DISA for identifying viable myocardium in hypokinetic segments (74.1% vs. 77.6%, P > 0.05) but less viable myocardium was detected by LDDE than DISA in akinetic segments (29% vs. 53%, P < 0.01).</p><p><b>CONCLUSIONS</b>Sensitivity was higher while specificity was lower on detecting viable myocardium by DISA compared to LDDE. Combined use of the two techniques could improve viable myocardium detection in patients with acute MI.</p>