Association of frailty with in-hospital outcomes in elderly patients with heart failure.

BACKGROUND: Frailty is prevalent in elderly patients with cardiovascular diseases. However, the association between frailty and in-hospital outcomes for elderly patients with heart failure and reduced ejection (HFrEF) remains unknown. AIM: To evaluate the predictive efficacy of frailty, compared with pre-frailty, for adverse events in these patients. METHODS: Elderly patients (≥ 60 years) with HFrEF were assessed. Frailty was evaluated with the Fried phenotype criteria, and physical performance was evaluated based on handgrip strength and the short physical performance battery (SPPB). The composite incidence of adverse events, including all-cause death, multiple organ failure, cardiac shock, and malignant arrhythmia, during hospitalization was recorded. RESULTS: Overall, 252 elderly individuals with HFrEF [mean age: 69.4 ± 6.7 years, male: 169 (67.0%)] were included. One hundred and thirty-five (53.6%) patients were frail and 93 (36.9%) were pre-frail. Frail patients were older, more likely to be female, to have a lower blood pressure, and to present with left ventricular thrombosis (P all < 0.05). Frail patients with HFrEF had a higher incidence of in-hospital mortality (11.9% vs 4.3%, P = 0.048). Multivariate analyses showed that female gender (OR = 0.422), aging (OR = 1.090), poor cardiac functional class (OR = 2.167), frailty (OR = 2.379), and lower handgrip strength (OR = 1.106) were independent predictors of in-hospital adverse events (P all < 0.05). CONCLUSION: Frailty may be associated with poor in-hospital outcomes for elderly patients with HFrEF. The influence of frailty on long-term prognosis in these patients deserves further investigation.

Effect of continuous use of metformin on kidney function in diabetes patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Diabetes patients presenting with ST-segment elevation myocardial infarction (STEMI) scheduled for primary percutaneous coronary intervention (PCI) have an increased risk of contrast induced-acute kidney injury (CI-AKI). The effects of continuous use of metformin on kidney function are still controversial in patients submitted to primary PCI. This study aimed to assess continuous metformin therapy on kidney function in diabetic patients undergoing coronary intervention. METHODS: Two hundred eighty-four patients with metformin-treated diabetes, who underwent coronary intervention within 24 h for STEMI, were enrolled in the retrospective study. All the patients had estimated glomerular filtration rate (eGFR) of > 30 mL/min/1.73 m2. According to the physicians' decisions after admission, 119 patients continued metformin treatment after primary PCI, while 165 patients discontinued it > 48 h after the procedure. Serum creatinine was collected at admission and within 48 h post primary PCI to evaluate the incidence of CI-AKI. We performed a multiple logistic regression analysis to examine the determinants of CI-AKI. RESULTS: No statistical difference in CI-AKI incidence between the continuous and the discontinuous metformin group (12.6%vs10.3%, p = 0.545). Multivariable logistic regression analysis indicated eGFR ≤60 ml/min/1.73 m2[p = 0.025, OR: 3.131; 95% CI (1.156-8.482)] and contrast volume [p = 0.002, OR: 1.010; 95% CI (1.004-1.016)] were predictive factors of CI-AKI. Metformin therapy was irrelevant to CI-AKI [p = 0.365, OR: 0.698; 95% CI (0.320-1.521)]. No case of lactic acidosis was found in this study. Besides, the study supported discontinuation of metformin was not beneficial for patients' blood glucose control after admission. CONCLUSIONS: The study indicated that the metformin continuation after primary PCI for STEMI in diabetic patients with eGFR > 30 ml/min / 1.73 m2 did not increase the risk of CI-AKI.

Risk factors for adverse cardiac events in adults with fulminant myocarditis during hospitalization.

BACKGROUND: Fulminant myocarditis is the critical form of myocarditis that is often associated with heart failure, malignant arrhythmia, and circulatory failure. Patients with fulminant myocarditis who end up with severe multiple organic failure and death are not rare. AIM: To analyze the predictors of in-hospital major adverse cardiovascular events (MACE) in patients diagnosed with fulminant myocarditis. METHODS: We included a cohort of adult patients diagnosed with fulminant myocarditis who were admitted to Beijing Anzhen Hospital from January 2007 to December 2017. The primary endpoint was defined as in-hospital MACE, including death, cardiac arrest, cardiac shock, and ventricular fibrillation. Baseline demographics, clinical history, characteristics of electrocardiograph and ultrasonic cardiogram, laboratory examination, and treatment were recorded. Multivariable logistic regression was used to examine risk factors for in-hospital MACE, and the variables were subsequently assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: The rate of in-hospital MACE was 40%. Multivariable logistic regression analysis revealed that baseline QRS duration > 120 ms was the independent risk factor for in-hospital MACE (odds ratio = 4.57, 95%CI: 1.23-16.94, P = 0.023). The AUC of QRS duration > 120 ms for predicting in-hospital MACE was 0.683 (95%CI: 0.532-0.833, P = 0.03). CONCLUSION: Patients with fulminant myocarditis has a poor outcome. Baseline QRS duration is the independent risk factor for poor outcome in those patients.

Predictive Value of Electromechanical Activation Time for In-Hospital Major Cardiac Adverse Events in Heart Failure Patients.

OBJECTIVE: This prospective study aimed to evaluate the value of the cardiac cycle time-corrected electromechanical activation time (EMATc) measured at admission for predicting major cardiac adverse events (MACEs) in hospitalized patients with chronic heart failure (CHF). METHODS: CHF patients with a left ventricular ejection fraction (LVEF) lower than 50% (N = 145) were enrolled in this study. Documented clinical end-points (MACEs) included cardiogenic death, onset of acute HF as assessed with invasive and noninvasive mechanical ventilation, and cardiogenic shock. According to the different clinical end-points, patients were divided into two groups: a MACE group (n = 22) and a nonMACE group (n = 123). EMATc, LVEF, and circulating levels of B type natriuretic peptide (BNP) and Troponin I (TnI) were measured. Multivariate logistic regression analysis was used to examine the association between EMATc and MACEs. The parameters adjusted in the multivariable model included EMATc, BNP, and heart rate. The predictive value of EMATc was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: Elevated EMATc was an independent risk factor for MACEs (odds ratio [OR] 1.1443, 95% confidence interval [CI] 1.016-1.286, P = 0.027). The area under the ROC curve for EMATc was 0.799 (95% CI 0.702-0.896, P < 0.001). The optimal cutoff EMATc value was >13.8% with a sensitivity of 81.8% and a specificity of 65.9%. CONCLUSIONS: We demonstrated that an elevated EMATc measured at admission is an independent risk factor for MACEs among hospitalized CHF patients. Acoustic cardiography measured at admission may provide a simple, noninvasive method for risk stratification of CHF patients. This trial is registered with ChiCTR1900021470.

Clinical Characteristics and Adverse Events in Acute Coronary Syndrome Patients with a History of Peripheral Arterial Disease.

BACKGROUND: In clinical observation, patients with acute coronary syndrome complicated with peripheral artery disease have poor prognosis, so the relationship between the diseases and clinical characteristics need to be further explored. OBJECTIVE: This study aims to investigate clinical characteristics and independent risk factors for in-hospital adverse events in acute coronary syndrome patients with a history of peripheral arterial disease (PAD). METHODS: A total of 5,682 patients with acute coronary syndrome were included into this study. These patients were divided into two groups according to the presence or absence of a history of PAD: PAD group (n = 188), and non-PAD (control) group (n = 5,494). Then, the clinical characteristics and incidence of in-hospital adverse events were analyzed; p < 0.05 was considered statistically significant. RESULTS: The age of PAD patients was higher than that in the control group (65.5 ± 10.3 years vs. 58.6 ± 11 years, p < 0.001), and the proportion of PAD patients with diabetes history and stroke history was higher than that in the control group (73 [39%] vs. 1472 [26.8%], p = 0.018; 36 [19.3%] vs. 396 [7.2%], p < 0.001). The multivariate logistic regression analysis between groups based on in-hospital adverse events revealed that a history of PAD (OR = 1.791, p = 0.01), a history of diabetes (OR = 1.223, p = 0.001), and age of > 65 years old (OR = 4.670, p < 0.001) were independent risk factors for in-hospital adverse events. CONCLUSION: A history of PAD, advanced age, and a history of diabetes are independent risk factors for in-hospital adverse events in patients with acute coronary syndrome.

Clinical Characteristics and Adverse Events in Acute Coronary Syndrome Patients with a History of Peripheral Arterial Disease / Características Clínicas e Eventos Adversos em Pacientes com Síndrome Coronariana Aguda e História de Doença Arterial Periférica

Abstract Background: In clinical observation, patients with acute coronary syndrome complicated with peripheral artery disease have poor prognosis, so the relationship between the diseases and clinical characteristics need to be further explored. Objective: This study aims to investigate clinical characteristics and independent risk factors for in-hospital adverse events in acute coronary syndrome patients with a history of peripheral arterial disease (PAD). Methods: A total of 5,682 patients with acute coronary syndrome were included into this study. These patients were divided into two groups according to the presence or absence of a history of PAD: PAD group (n = 188), and non-PAD (control) group (n = 5,494). Then, the clinical characteristics and incidence of in-hospital adverse events were analyzed; p < 0.05 was considered statistically significant. Results: The age of PAD patients was higher than that in the control group (65.5 ± 10.3 years vs. 58.6 ± 11 years, p < 0.001), and the proportion of PAD patients with diabetes history and stroke history was higher than that in the control group (73 [39%] vs. 1472 [26.8%], p = 0.018; 36 [19.3%] vs. 396 [7.2%], p < 0.001). The multivariate logistic regression analysis between groups based on in-hospital adverse events revealed that a history of PAD (OR = 1.791, p = 0.01), a history of diabetes (OR = 1.223, p = 0.001), and age of > 65 years old (OR = 4.670, p < 0.001) were independent risk factors for in-hospital adverse events. Conclusion: A history of PAD, advanced age, and a history of diabetes are independent risk factors for in-hospital adverse events in patients with acute coronary syndrome.

Resumo Fundamento: Na observação clínica, os pacientes com síndrome coronariana aguda com doença arterial periférica têm prognóstico ruim, portanto, a relação entre as doenças e as características clínicas precisa ser mais explorada. Objetivos: Este estudo tem o objetivo de investigar características clínicas e fatores de risco independentes para eventos adversos hospitalares em pacientes com síndrome coronariana aguda e história de doença arterial periférica (DAP). Métodos: Foram incluídos no estudo 5682 pacientes com síndrome coronariana aguda. Os pacientes foram divididos em dois grupos de acordo com a presença ou ausência de DAP prévia: grupo DAP (n = 188) e grupo sem DAP (n = 5494, grupo controle). Em seguida, foram analisadas características clínicas e a incidência de eventos adversos hospitalares nesses grupos; um p < 0,05 foi considerado estatisticamente significativo. Resultados: A idade dos pacientes com DAP foi maior que a idade do grupo controle (65,5 ± 10,3 anos vs. 58,6 ± 11 anos, p < 0,001), e a proporção de pacientes com história de diabetes ou acidente vascular cerebral foi maior no grupo DAP que no grupo controle [73 (39%) vs. 1472 (26,8%), p = 0,018; 36 (19,3%) vs. 396 (7,2%), p < 0,001). A análise de regressão logística multivariada para eventos adversos hospitalares mostrou que história de DAP (OR = 1,791, p = 0,01), história de diabetes (OR = 1,223, p = 0,001), e idade >65 anos de idade (OR = 4,670, p < 0,001) foram fatores de risco independentes para eventos adversos hospitalares. Conclusão: DAP prévia, idade avançada, e história de diabetes são fatores de risco independentes para eventos adversos hospitalares em pacientes com síndrome coronariana aguda.

Circulating microRNA signature for the diagnosis of childhood dilated cardiomyopathy.

Circulating miRNAs are proposed as a biomarker of heart disease. This study evaluated whether circulating miRNAs could be used as a biomarker for childhood dilated cardiomyopathy (CDCM). A total of 28 participants were enrolled in a discovery set, including patients with CDCM (n = 16) and healthy children (n = 12). The cardiac function of patients with CDCM was characterized by echocardiography and serum miRNA profiles of all participants were assessed by miRNA sequencing. After miRNA profiling, we quantitatively confirmed 148 regulated miRNAs in patients with CDCM compared with healthy subjects, and none were downregulated. Validation of candidate miRNAs was assessed by quantitative real-time polymerase chain reaction in other patients with CDCM (n = 30) and healthy controls (n = 16). A unique signature comprising mir-142-5p, mir-143-3p, mir-27b-3p, and mir-126-3p differentiated patients with CDCM from healthy subjects. Importantly, we observed an increase in mir-126-3p or let-7g in parallel with a robust decrease in the ejection fraction in patients with CDCM, which could differentiate heart failure patients from non-heart failure patients with CDCM. Moreover, mir-126-3p and let-7g were significantly negatively associated with the left ventricular ejection fraction. This study shows that a signature of four serum miRNAs may be a potential biomarker for diagnosing CDCM and assessing heart failure.

Resveratrol prevents hepatic steatosis and endoplasmic reticulum stress and regulates the expression of genes involved in lipid metabolism, insulin resistance, and inflammation in rats.

Previous research demonstrated that resveratrol possesses promising properties for preventing obesity. Endoplasmic reticulum (ER) stress was proposed to be involved in the pathophysiology of both obesity and hepatic steatosis. In the current study, we hypothesized that resveratrol could protect against high-fat diet (HFD)-induced hepatic steatosis and ER stress and regulate the expression of genes related to hepatic steatosis. Rats were fed either a control diet or a HFD for 12 weeks. After 4 weeks, HFD-fed rats were treated with either resveratrol or vehicle for 8 weeks. Body weight, serum metabolic parameters, hepatic histopathology, and hepatic ER stress markers were evaluated. Moreover, an RT2 Profiler Fatty Liver PCR Array was performed to investigate the mRNA expressions of 84 genes related to hepatic steatosis. Our work showed that resveratrol prevented dyslipidemia and hepatic steatosis induced by HFD. Resveratrol significantly decreased activating transcription factor 4, C/EBP-homologous protein and immunoglobulin binding protein levels, which were elevated by the HFD. Resveratrol also decreased PKR-like ER kinase phosphorylation, although it was not affected by the HFD. Furthermore, resveratrol increased the expression of peroxisome proliferator-activated receptor δ, while decreasing the expression of ATP citrate lyase, suppressor of cytokine signaling-3, and interleukin-1ß. Our data suggest that resveratrol can prevent hepatic ER stress and regulate the expression of peroxisome proliferator-activated receptor δ, ATP citrate lyase, suppressor of cytokine signaling-3, tumor necrosis factor α, and interleukin-1ß in diet-induced obese rats, and these effects likely contribute to resveratrol's protective function against excessive accumulation of fat in the liver.

Clinical characteristics of abnormal savda syndrome type in human immunodeficiency virus infection and acquired immune deficiency syndrome patients: A cross-sectional investigation in Xinjiang, China.

OBJECTIVE: To investigate the distribution of abnormal hilit syndromes in traditional Uighur medicine (TUM) among human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) patients, and to find out the clinical characteristics of abnormal savda syndrome type HIV/AIDS patients. METHODS: Between June and July in 2012, 307 eligible HIV/AIDS patients from in-patient department and out-patient clinics of Xinjiang Uighur Autonomous Region the Sixth People's Hospital in Urumqi were investigated. TUM syndrome differentiation was performed by a senior TUM physician. Each participant completed a Sign and Symptom Check-List for Persons Living with HIV/AIDS (SSC-HIV) questionnaire. Depression was evaluated by using Hamilton Rating Scale for Depression Questionnaire. Blood specimen was collected from each participant to test the levels of blood chemicals. RESULTS: Of 307 HIV/AIDS patients, 189 (61.6%) were abnormal savda syndrome type, 118 (38.4%) were non-abnormal-savda syndrome type. Mean CD4 counts of abnormal savda syndrome type patients was (227.61±192.93) cells/µL, and the prevalence of anemia, thrombocytopenia, and elevated cystatin C were 49.7%, 28.6%, and 44.7%, which were significantly higher than those in the non-abnormal-savda syndrome type patients (26.3%, 16.0% and 25.0%,P<0.05). In addition, depression (79.9%) and HIV/AIDS-related symptoms such as fatigue (42.3%), back aches (40.7%), lack of appetite (33.9%), night sweats (31.7%) were more common among abnormal savda syndrome patients (P<0.05). CONCLUSION: Abnormal savda syndrome is the dominant syndrome among HIV/AIDS patients, and they present a more sever clinical manifestation.

Resveratrol increases nephrin and podocin expression and alleviates renal damage in rats fed a high-fat diet.

Resveratrol is well known for its anti-inflammation and anti-oxidant properties, and has been shown to be effective in alleviating the development of obesity. The purpose of this investigation was to analyze the effect of resveratrol on renal damage in obese rats induced by a high-fat diet (HFD) and its possible mechanisms. Male Sprague-Dawley rats were divided into three groups: control, HFD, and HFD plus resveratrol (treated with 100 mg/kg/day resveratrol). Body weight, serum and urine metabolic parameters, and kidney histology were measured. Meanwhile, the activities of nuclear factor-κB (NF-κB) and superoxide dismutase (SOD), the content of malondialdehyde (MDA), and the protein levels of tumor necrosis factor (TNF-α), monocyte chemotactic protein-1 (MCP-1), nephrin and podocin in kidney were detected. Our work showed that resveratrol alleviated dyslipidemia and renal damage induced by HFD, decreased MDA level and increased SOD activity. Furthermore, the elevated NF-κB activity, increased TNF-α and MCP-1 levels, and reduced expressions of nephrin and podocin induced by HFD were significantly reversed by resveratrol. These results suggest resveratrol could ameliorate renal injury in rats fed a HFD, and the mechanisms are associated with suppressing oxidative stress and NF-κB signaling pathway that in turn up-regulate nephrin and podocin protein expression.

Embryo-specific expression of soybean oleosin altered oil body morphogenesis and increased lipid content in transgenic rice seeds.

Oleosin is the most abundant protein in the oil bodies of plant seeds, playing an important role in regulating oil body formation and lipid accumulation. To investigate whether lipid accumulation in transgenic rice seeds depends on the expression level of oleosin, we introduced two soybean oleosin genes encoding 24 kDa proteins into rice under the control of an embryo-specific rice promoter REG-2. Overexpression of soybean oleosin in transgenic rice leads to an increase of seed lipid content up to 36.93 and 46.06 % higher than that of the non-transgenic control, respectively, while the overall fatty acid profiles of triacylglycerols remained unchanged. The overexpression of soybean oleosin in transgenic rice seeds resulted in more numerous and smaller oil bodies compared with wild type, suggesting that an inverse relationship exists between oil body size and the total oleosin level. The increase in lipid content is accompanied by a reduction in the accumulation of total seed protein. Our results suggest that it is possible to increase rice seed oil content for food use and for use as a low-cost feedstock for biodiesel by overexpressing oleosin in rice seeds.

[Relationship between plasma N-terminal pro-brain natriuretic peptide and GRACE risk stratification in non-ST-segment elevation acute coronary syndrome].

OBJECTIVE: To explore the relationship between plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level obtained on admission and global registry of acute coronary events (GRACE) scores and the value for risk stratification in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: A total of 231 NSTE-ACS patients admitted in our hospital between June 2009 and September 2010 were included [161 patients with unstable angina (UA) and 70 patients with non-ST-segment elevation myocardial infarction (NSTEMI)]. On admission plasma NT-proBNP was measured in all patients. The GRACE risk score were used for risk assessment. Patients were followed up for 6 months and incidence of new or recurrent myocardial infarction, target vessel revascularization, cardiac death, heart failure (MACE) was recorded. RESULTS: According to GRACE risk stratification, there were 62 low-risk patients, 78 middle-risk patients and 91 high-risk patients. lgNT-proBNP level on admission increased in proportion to increasing risk defined by GRACE risk stratification and lgNT-proBNP positively correlated with GRACE risk score (r = 0.59, P < 0.001). The GRACE risk score was the highest in the fourth NT-proBNP quartile (P < 0.001 vs. lowest, second and third quartiles). GRACE score was significantly higher in patients with NT-proBNP level above the 75 percentile compared patients with NT-proBNP under the 75 percentile (P < 0.001). MACE occurred in 9 [3.9% (9/231)] patients during follow up. ROC analysis showed AUC of on admission NT-proBNP was 0.831 (SE = 0.062, P = 0.001, 95%CI 0.711 - 0.952) and AUC of GRACE risk score was 0.799 (SE = 0.079, P = 0.002, 95%CI 0.644 - 0.954) for predicting the short-term risk of MACE (P = 0.75). CONCLUSION: On admission plasma NT-proBNP level parallels GRACE risk score in NSTE-ACS patients, both on admission plasma NT-proBNP level and GRACE risk score are valuable parameters for risk stratification in patients with NSTE-ACS and increased NT-proBNP level and GRACE values are predictors for increased short-term risk of MACE.

[Comparison on efficacy and safety between domestic levosimendan versus dobutamine for patients with acute decompensated heart failure].

OBJECTIVE: To compare the efficacy and safety of domestic levosimendan versus dobutamine for patients with acute decompensated heart failure (ADHF). METHODS: ADHF patients from 8 medical centers were recruited in this multicenter, blind, positive-controlled, randomized study and received 24 h intravenous levosimendan (n = 114) or dobutamine (n = 114) therapy. SWAN-GANZ catheter was performed in patients with pulmonary capillary wedge pressure (PCWP) ≥ 15 mm Hg (1 mm Hg = 0.133 kPa) and cardiac index (CI) ≤ 2.5 L·min(-1)×m(-2) (n = 39 each). RESULTS: Compared with baseline level, LVEF increased [(31.56 ± 9.69)% vs. (28.44 ± 7.08)%, P < 0.01] at 24 h in both groups. LVEF increase at 24 h was similar between two groups [(3.11 ± 6.90)% vs. (3.00 ± 6.63)%, P > 0.05]. The PCWP decrease at 24 h was significantly greater in levosimendan group than in dobutamine group [(-8.90 ± 7.14) mm Hg vs. (-5.64 ± 6.83) mm Hg, P = 0.04]. Decrease in NT-proBNP at 3 days was also more significant in levosimendan group than in dobutamine group [the percentage change compared to baseline: (-22.36 ± 38.98)% vs. (-8.56 ± 42.42)%, P < 0.01]. Dyspnea improvement at 24 h was more significant in levosimendan group than in dobutamine group. The incidences of adverse reactions and events were similar between two groups. CONCLUSION: LVEF improvement is similar between dobutamine and domestic levosimendan while greater decreases in PCWP and NT-proBNP are achieved with domestic levosimendan in patients with ADHF.

Proliferation, migration and apoptosis activities of endothelial progenitor cells in acute coronary syndrome.

BACKGROUND: There are numerous articles on the endothelial progenitor cells (EPCs) in different disease conditions. However, the functional properties of EPCs in acute coronary syndrome (ACS) are still uncertain. Here we aimed to study the number and functions of EPCs in ACS patients. METHODS: Patients were enrolled with admitted ACS (n = 25) and another 25 gender-, age-, atherosclerotic risk factors-matched stable coronary artery disease (CAD) controls. EPCs were defined as CD34(+)/CD133(+)/VEGFR-2(+) and quantified by flow cytometry. Moreover, functional properties of EPCs including colony-forming unit (CFU), proliferation, migration as well as apoptosis were evaluated and compared between the two groups. Plasma matrix metalloproteinase-9 (MMP-9) was detected in all patients as well. RESULTS: The two groups had similar medication and clinical characteristics on admission. The EPCs in ACS patients were more than 2.6 times that in stable CAD subjects (15.6 ± 2.7 vs. 6.0 ± 0.8/100 000 events, P < 0.01). CFU was not statistically different between the two groups (10.8 ± 2.9 vs. 8.2 ± 1.8, number/well, P > 0.05). Furthermore, EPCs isolated from ACS patients were significantly impaired in their proliferation (0.498 ± 0.035 vs. 0.895 ± 0.067, OD value, P < 0.01) and migration capacity (20.5 ± 3.4 vs. 30.7 ± 4.3, number/well, P < 0.01) compared with controls. Moreover, the apoptosis cell in cultured EPCs was drastically increased in ACS group ((18.3 ± 2.1)% vs. (7.8 ± 0.4)%, P < 0.01). CONCLUSIONS: Patients with ACS exhibited apparently increased circulating EPCs as well as cultured apoptosis percentage together with a remarkable impairment of proliferation and migration activities compared with stable CAD subjects.

Evaluation of seed storage-protein gene 5' untranslated regions in enhancing gene expression in transgenic rice seed.

5' untranslated regions (UTRs) are important sequence elements that modulate the expression of genes. Using the ß-glucuronidase (GUS) reporter gene driven by the GluC promoter for the rice-seed storage-protein glutelin, we evaluated the potential of the 5'-UTRs of six seed storage-protein genes in enhancing the expression levels of the foreign gene in stable transgenic rice lines. All of the 5'-UTRs significantly enhanced the expression level of the GluC promoter without altering its expression pattern. The 5'-UTRs of Glb-1 and GluA-1 increased the expression of GUS by about 3.36- and 3.11-fold, respectively. The two 5'-UTRs downstream of the Glb-1, OsAct2 and CMV35S promoters also increased GUS expression level in stable transgenic rice lines or in transient expression protoplasts. Therefore, the enhancements were independent of the promoter sequence. Real-time quantitative RT-PCR analysis showed that the increase in protein production was not accompanied by alteration in mRNA levels, which suggests that the enhancements were due to increasing the translational efficiencies of the mRNA. The 5'-UTRs of Glb-1 and GluA-1, when combined with strong promoters, might be ideal candidates for high production of recombinant proteins in rice seeds.

Expression pattern and activity of six glutelin gene promoters in transgenic rice.

The shortage of strong endosperm-specific expression promoters for driving the expression of recombinant protein genes in cereal endosperm is a major limitation in obtaining the required level and pattern of expression. Six promoters of seed storage glutelin genes (GluA-1, GluA-2, GluA-3, GluB-3, GluB-5, and GluC) were isolated from rice (Oryza sativa L.) genomic DNA by PCR. Their spatial and temporal expression patterns and expression potential in stable transgenic rice plants were examined with beta-glucuronidase (GUS) used as a reporter gene. All the promoters showed the expected spatial expression within the endosperm. The GluA-1, GluA-2, and GluA-3 promoters directed GUS expression mainly in the outer portion (peripheral region) of the endosperm. The GluB-5 and GluC promoters directed GUS expression in the whole endosperm, with the latter expressed almost evenly throughout the whole endosperm, a feature different from that of other rice glutelin gene promoters. The GluB-3 promoter directed GUS expression solely in aleurone and subaleurone layers. Promoter activities examined during seed maturation showed that the GluC promoter had much higher activity than the other promoters. These promoters are ideal candidates for achieving gene expression for multiple purposes in monocot endosperm but avoid promoter homology-based gene silencing. The GluC promoter did not contain the endosperm specificity-determining motifs GCN4, AACA, and the prolamin-box, which suggests the existence of additional regulatory mechanism in determining endosperm specificity.

[Pharmacokinetics of paroxetine tablet in healthy Chinese volunteers].

OBJECTIVE: To study the pharmacokinetics of paroxetine tablet in Chinese healthy volunteers. METHODS: Twenty healthy subjects received a single oral dose of 40 mg paroxetine tablet. The plasma concentrations of paroxetine were determined using high-performance liquid chromatography (HPLC) and the measurements were analyzed with 3P97 program. RESULTS: The plasma concentration curve of paroxetine following a single oral dose administration conformed to the two-compartment open model. The main pharmacokinetics parameters of paroxetine were: C(max)64.74-/+18.43 ng/ml, T(max)5.64-/+1.84 h, t(1/2) 20.03-/+5.33 h, AUC(0-120) 976.47-/+309.49 ng.h/ml, and AUC(0-inf) 1086.75-/+376.54 ng.h/ml. CONCLUSION: The pharmacokinetics of paroxetine in human body conforms to the two-compartment open model.