Objective: This paper aims to investigate the effect of applying recombinant human brain natriuretic peptide in patients with heart failure combined with hypotension. Recombinant human brain natriuretic peptide is a s...Objective: This paper aims to investigate the effect of applying recombinant human brain natriuretic peptide in patients with heart failure combined with hypotension. Recombinant human brain natriuretic peptide is a synthetic polypeptide drug that is primarily used to treat acute heart failure. Its mechanism of action closely mimics that of human endogenous brain natriuretic peptide. By binding to receptors on cardiomyocytes, it exerts its pharmacological effects. Methods: For the study, 76 heart failure patients with hypotension were selected from our hospital between May 2022 and June 2023. These patients were divided into two groups: a control group and an observation group, each comprising 38 patients. The control group received dopamine treatment, while the observation group was treated with recombinant brain natriuretic peptide. The objective was to compare the effects of the treatments in both groups by analyzing cardiac function indices and levels of vasoactive substances to identify any significant differences in outcomes. Results: The overall response rate of the patients in the observation group and the control group was 94.74% and 73.68%, significantly higher as compared with the observation group (P 0.05). After the following treatment, BNP, ANNP and urine output in the observation group were significantly different compared with the control group, of the statistical significance (P Conclusion: For the treatment of heart failure patients with hypotension, the clinical application of recombinant human brain natriuretic peptide is the most ideal, and significantly improves the cardiac function of patients, which is worth popularizing.展开更多
BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative t...BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative treatments.Recombinant human brain natriuretic peptide(BNP)has emerged as a potential therapy,with evidence suggesting that it can improve cardiac function and reduce inflammation in patients with CHF.However,further research is required to determine the efficacy and safety of lyophilized recombinant human BNP in CHF patients and its impact on microinflammatory status.This study aimed to investigate the effects of lyophilized recombinant human BNP therapy on CHF patients’cardiac function and microinflammatory status.AIM To investigate the effects of freeze-dried recombinant human BNP therapy on cardiac function and microinflammatory status in patients with CHF.METHODS In total,102 CHF patients admitted to our hospital from January 2021 to January 2022 were randomly assigned to control and observation groups(n=51 patients/group).The control patients were treated with standard HF therapy for 3 d,whereas the observational patients were injected with the recombinant human BNP for 3 d.Clinical efficacy,inflammatory factor levels,myocardial damage,cardiac function before and after the treatment,and adverse reactions during treatment were compared between the two groups.RESULTS The overall clinical efficacy was higher in the observation group than in the control group.Compared with baseline,serum hypersensitive C-reactive protein,N-terminal proBNP,and troponin I level,and physical,emotional,social,and economic scores were lower in both groups after treatment,with greater reductions in levels and scores noted in the observation group than in the control group.The overall incidence of adverse reactions in the observation group was not significantly different compared with that in the control group(P>0.05).CONCLUSION Freeze-dried recombinant human BNP therapy can improve heart function and enhance microinflammatory status,thereby improving overall quality of life without any obvious side effects.This therapy is safe and reliable.展开更多
Lyophilized recombinant brain natriuretic peptide(BNP)is an exogenous peptide synthesized by artificial recombination technology,with a similar structure and similar physiological effects with the endogenous natriuret...Lyophilized recombinant brain natriuretic peptide(BNP)is an exogenous peptide synthesized by artificial recombination technology,with a similar structure and similar physiological effects with the endogenous natriuretic peptide secreted by the human body.It’s main mechanism of action is to increase cyclic guanosine monophosphate by binding with its corresponding receptor in the body,regulating,thus,the imbalance of the vascular system and cardiac hemodynamics,improving the heart’s pumping capacity,and inhibiting sympathetic excitability and myocardial remodeling.Moreover,it can promote mitochondrial metabolism and enhance the use of adenosine triphosphate in cardiomyocytes.In the present study,102 chronic heart failure(HF)patients were randomly assigned to a control and an observation group consisting of 51 patients each.Patients of the control group were treated with standard HF therapy for 3 d including oral metoprolol tartrate tablets,spironolactone,and olmesartanate while patients of the observation group were administered the recombinant human BNP injection for the same time-period,plus the standard HF therapy.The recombinant human BNP group(observation group)demonstrated better physical,emotional,social,and economic scores,as well as cardiac and inflammatory biomarkers such as serum hypersensitive C-reactive protein,N-terminal pro BNP and troponin I levels,compared to the control group.Moreover,cardiac function was also improved,as left ventricular ejection fraction and stroke volume were significantly higher in the observation group than in the control group.Interestingly,adverse reactions were not different between the 2 groups.However,these results are not generalizable and the need of large multicenter randomized controlled trials examining the safety and efficacy of recombinant human BNP in HF patients is of major importance.展开更多
Objectives To observe the efficacy and safety of recombinant human brain natriuretic peptide(rh-BNP) on patients with acute myocardial infarction complicating congestive heart failure.Methods 40 patients with acute my...Objectives To observe the efficacy and safety of recombinant human brain natriuretic peptide(rh-BNP) on patients with acute myocardial infarction complicating congestive heart failure.Methods 40 patients with acute myocardial infarction complicated by congestive heart failure were randomly divided into control group and treatment group of 20 cases.The control group,15 cases of acute anterior myocardial infarction,5 cases of acute inferior wall myocardial infarction, 15 males and 5 females,aged 55-70 years,mean age 58±12 years;treated 16 cases of acute anterior myocardial infarction,4 cases of acute myocardial infarction,16 males and 4 females,aged 56-70 years,mean age 59±11 years;two groups of age,gender,severity of disease and vascular lesions no significant difference and comparable(P】0.05).Conventional group were given aspirin,clopidogrel, statins,Inotropic,diuretic and vasodilator therapy.In the con- ventional treatment group based on the use of recombinant human brain natriuretic peptide(new bios,Tibet Pharmaceutical Co.,Ltd.Chengdu Nuodikang biopharmaceutical production, usage:1.5μg/Kg intravenous injection(impact), then 0.0075μg-0.01μg/(kg·min)infusion rate).Continuous medication 72 h.The clinical symptoms observed for 3 days in patients before treatment and after treatment,heart rate,blood pressure and left ventricular ejection fraction (LVEF) and tumor necrosis factor(TNF-α),brain natriuretic peptide(BNP) levels were measured.Results In control group,8 cases markedly effect,5 cases effect and 7 cases no effect,the total effective rate was 65%;In treatment group,13 cases markedly effect,6 cases effect and 1 cases no effect,the total effective rate was 95%,compared with two groups P New bios treatment group significantly increased cardiac index(CI) in patients with heart failure and left ventricular ejection fraction(LVEF) than the control group(all P【0.05),further reduce the levels of tumor necrosis (TNF-α) and brain natriuretic peptide(BNP).Conclusions rh-BNP can improve symptoms and heart function,reduced plasma tumor necrosis factor(TNF-α) and BNP levels of acute myocardial infarction patients with congestive heart failure,the treatment safe and reliable.As small sample size observed,larger sample to be accumulated to further evaluate its efficacy and safety.展开更多
Heart failure (HF) is a common disease associated with increasing age. B-type natriuretic peptide (BNP), is a cardiac neurohormone, and is released as prepro BNP and then enzyrnatically cleaved to the Ntenninal-proBNP...Heart failure (HF) is a common disease associated with increasing age. B-type natriuretic peptide (BNP), is a cardiac neurohormone, and is released as prepro BNP and then enzyrnatically cleaved to the Ntenninal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP have been used to identify patients with I-IF. The BNP assay is currently used as a diagnostic and prognostic aid in HF. In general, a BNP level below 100 pg/mL excludes acutely decompensated HF and levels ＞ 500 pg/ml indicate decompensation. Recombinant human BNP (hBNP, nesiritide) is an approved intravenous treatment for acute,decompensated -HF. Nesiritide given in supraphysiologic doses causes vasodilation, natriuresis, diuresis, and improved symptoms over the course of a 48-hour infusion. This paper will sort out the literature concerning the use of this peptide both as a diagnostic test and as an intravenous therapy.展开更多
Objective:To investigate the effect of recombinant human brain natriuretic peptide (BNP) on inflammatory factors, neuroendocrine hormones and cardiac function indexes in patients with acute myocardial infarction compl...Objective:To investigate the effect of recombinant human brain natriuretic peptide (BNP) on inflammatory factors, neuroendocrine hormones and cardiac function indexes in patients with acute myocardial infarction complicated with heart failure.Methods:A total of91 cases of acute myocardial infarction with heart failure patients were divided into the control group (n=44) and observation group (n=47) according to the random data table, two groups of patients were given conventional treatment, based on this, the control group was given intravenous infusion of Nitroglycerin Injection treatment, the observation group received intravenous injection of recombinant human brain natriuretic peptide treatment, compared serum inflammatory factors, neuroendocrine hormone and cardiac function and other indexes of two groups before and after treatment.Results: there was no significant difference between the two groups before treatment. After treatment, the levels of TNF-α, hs-CRP, IL-6, MCP-1, LVESD and LVEDD in the two groups were significantly lower than those within the group before treatment, and the observation group was significantly lower than the control group;The two groups after treatment LVEF levels were significantly higher than those in the group before treatment, and the observation group was significantly higher than that of control group;the observation group after treatment PRA, Ang II and ALD and NE levels were significantly lower than those before treatment, and was significantly lower than the control group after treatment, the difference was significant, PRA, Ang, ALD and NE levels of control group before and after the treatment was no significant difference.Conclusion:recombinant human brain natriuretic peptide in the treatment of acute myocardial infarction with heart failure can effectively reduce the serum inflammatory factors and neuroendocrine hormone levels, improve heart function, and have a certain clinical value.展开更多
To investigate the changes of plasma brain natriuretic peptide （BNF） levels inpatients with chronic heart failure （CHF）. Methods Plasma BNP concentrations in patients with CHF （n=56） and in normal controls （n...To investigate the changes of plasma brain natriuretic peptide （BNF） levels inpatients with chronic heart failure （CHF）. Methods Plasma BNP concentrations in patients with CHF （n=56） and in normal controls （n=60） were measured with specific radioimmunoassay. Left ventricular ejection fraction in patients with chronic heart failure was measured with 99mTc gated cardiac blood pool scintigraphy. Results The results showed that Plasma BNP concentrations in patients with CHF were significantly higher than normal controls （223±79 ng/L vs 40±15 ng/L, P 〈 0.01）. Plasma BNP concentrations had a significant negative correlation with left ventricular ejection fractions（r=-0.68, P 〈 0.01 ）. Conclusions These results indicates that Plasma BNP levels are increased in patients with CHF, and they markedly increased according to the severity of heart failure classified by NYHA classifi- cation. The plasma BNP levels may be a biochemical parameter for evaluating the left ventricular function.展开更多
Objective:To observe the influence of tirofiban on the troponin, brain natriuretic peptide, heart function in patients with Acute Myocardial Infarction after PCI and provide scientific basis for treatment of acute myo...Objective:To observe the influence of tirofiban on the troponin, brain natriuretic peptide, heart function in patients with Acute Myocardial Infarction after PCI and provide scientific basis for treatment of acute myocardial infarction.Methods:A total of 100 cases of hypertensive cerebral hemorrhage patients in our hospital were selected and randomly divided into 2 groups: the control group (50 cases) and the observation group (50 cases). The conventional treatment of PCI was performed on both groups. Tirofiban injection was given to the observation group on the basis of conventional treatment. cTnI, BNP and echocardiography parameters (LVEF, LVEDD, LVESD) were detected before and after treatment.Results:The comparison of cTnI in the two groups before operation was not statistically significant. cTnI in the 2 groups increased 12 h and 24 h after operation. But the cTnI in observation group (0.10±0.23) ng/mL decreased more significantly than that in control group (0.24±0.31) ng/mL, the difference was considered to be statistically significant. The comparison of BNP in the two groups before operation was not statistically significant. BNP in the 2 groups decreased obviously 7 d and 30 d after operation. BNP in observation group decreased more significantly than that in control group and the difference was considered to be statistically significant LVEF in the observation group increased significantly compared with that in control group 7 d after operation. The comparison of LVEDD, LVESD were not considered to be statistically significant. LVEDD and LVESD in the observation group were lower than that in control group obviously 30 d after operation. While the LVEF in the observation group was still higher than that in the control group. The comparsion was considered to be statistically significant.Conclusion:Tirofiban can improve the troponin, brain natriuretic peptide, heart function in patients with Acute Myocardial Infarction after PCI. It can also decrease the heart injury as well as helping the recovery of heart function.展开更多
BACKGROUND Chronic obstructive pulmonary disease(COPD)is a chronic respiratory disease with worldwide occurrence and high disability and mortality rate.It occurs mostly in the elderly population with pulmonary heart d...BACKGROUND Chronic obstructive pulmonary disease(COPD)is a chronic respiratory disease with worldwide occurrence and high disability and mortality rate.It occurs mostly in the elderly population with pulmonary heart disease,type II respiratory failure,and other serious complications.AIM To investigate the correlation of plasma brain natriuretic peptide(BNP)and platelet parameters with cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease.METHODS From June 2016 to June 2019,52 patients with COPD-pulmonary heart disease(pulmonary heart disease group),30 patients with COPD(COPD group),and 30 healthy individuals(control group)in our hospital were enrolled in the study.The pulmonary heart disease group was further divided into subgroups according to cardiac function classification and pulmonary artery pressure.Plasma BNP and platelet parameters were estimated and compared among each group and subgroup.The correlation of plasma BNP and platelet parameters with cardiac function classification and pulmonary artery pressure was then analyzed.RESULTS In the pulmonary heart disease group,the COPD group,and the control group,the levels of plasma BNP,platelet distribution width(PDW),and mean platelet volume(MPV)showed a decreasing trend(P<0.05),while an increasing trend was found in platelet count(PLT)and plateletcrit(PCT)levels among the three groups(P<0.05).In the pulmonary hypertension mild,moderate,and severe subgroups,the levels of plasma BNP,PDW,and MPV showed an increasing trend(P<0.05),while a decreasing trend was observed in PLT levels(P<0.05);however,PCT levels showed no significant difference among the three subgroups(P>0.05).In the cardiac function grade I,II,III,and IV subgroups,the levels of plasma BNP,PDW,and MPV showed an increasing trend(P<0.05),while a decreasing trend was noted in PLT and PCT levels among the four subgroups(P<0.05).Correlation analysis showed that the levels of plasma BNP,PDW,and MPV in patients with pulmonary heart disease were positively correlated with their pulmonary artery pressure(P<0.05),while PLT was negatively correlated with their pulmonary artery pressure(P<0.05).Moreover,plasma BNP,PDW,and MPV levels were positively correlated with cardiac function grade(P<0.05)of these patients,while PLT and PCT levels were negatively correlated with their cardiac function grade(P<0.05).CONCLUSION Plasma BNP and PLT parameters are significantly correlated with the cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease,indicating that these parameters have high clinical relevance in reflecting the health condition of these patients and for guiding their treatment.展开更多
BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(...BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)are associated with a worsening of heart failure and a poor prognosis.AIM To test whether a high concentration of BNP would inhibit relaxation to ANP.METHODS Pulmonary arteries were dissected from disease-free areas of lung resection,as well as pulmonary artery rings of internal diameter 2.5–3.5 mm and 2 mm long,were prepared.Pulmonary artery rings were mounted in a multiwire myograph,and a basal tension of 1.61gf was applied.After equilibration for 60 min,rings were pre-constricted with 11.21μmol/L PGF2α(EC80),and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.RESULTS Although both ANP and BNP were found to vasodilate the pulmonary vessels,ANP is more potent than BNP.pEC50 of ANP and BNP were 8.96±0.21 and 7.54±0.18,respectively,and the maximum efficacy(Emax)for ANP and BNP was-2.03 gf and-0.24 gf,respectively.After addition of BNP,the Emax of ANP reduced from-0.96gf to-0.675gf(P=0.28).CONCLUSION BNP could be acting as a partial agonist in small human pulmonary arteries,and inhibits relaxation to ANP.Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure.This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.展开更多
BACKGROUND Heart failure(HF),a common cardiovascular condition,is characterized by significant morbidity and mortality.While traditional Chinese medicine(TCM)is often used as a complementary approach in HF management,...BACKGROUND Heart failure(HF),a common cardiovascular condition,is characterized by significant morbidity and mortality.While traditional Chinese medicine(TCM)is often used as a complementary approach in HF management,systematic evalua-tions of its impact on clinical outcomes,TCM syndrome scores,and B-type natriuretic peptide(BNP)levels are lacking.This study fills this gap through a comprehensive analysis of randomized controlled trials(RCTs)focusing on TCM for HF treatment.It encompasses an assessment of methodological quality,a meta-analysis,and an evaluation of evidence quality based on established standards.The results offer crucial insights into the potential advantages and constraints of TCM in HF management.RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases,including China National Knowledge Infrastructure,Wanfang,VIP Information Chinese Science and Technology Journal,and PubMed.Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool,and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software.Finally,the quality of evidence was rated according to the GRADE criteria.RESULTS A total of 1098 RCTs were initially retrieved.After screening,16 RCTs were finally included in our study,which were published between 2020 and 2023.These RCTs involved 1660 HF patients,including 832 in the TCM group[TCM combined with conventional Western medicine(CMW)treatment]and 828 in the CWM group(CWM treatment).The course of treatments varied from 1 wk to 3 months.TCM syndrome differentiation was analyzed in 11 of the included RCTs.In all included RCTs,outcome indicators included comprehensive clinical outcomes,TCM syndrome scores,and BNP levels.The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes[risk ratio=-0.54;95%confidence interval(CI)=-0.61,-0.47;P<0.00001],TCM syndrome scores[weighted mean difference(WMD)=-142.07;95%CI=-147.56,-136.57;P<0.00001],and BNP levels(WMD=-142.07;95%CI=-147.56,-136.57;P<0.00001).According to the GRADE criteria,RCTs where"TCM improves clinical comprehensive outcomes"were rated as low-quality evidence,and RCTs where"TCM reduces TCM syndrome scores"or"TCM decreases BNP levels"were rated as medium-quality evidence.CONCLUSION TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients.Given the low and medium quality of the included RCTs,the application of these results should be cautious.展开更多
Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is diffi...Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The author assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with chronic heart failure. Methods: The author evaluated plasma brain natriuretic peptide (BNP) levels in 98 hemodialysis patients in a clinic. A total of nine patients whose BNP levels were more than 500 pg/mL agreed to be enrolled in this study and received thermal therapy using hot water bottles. Results: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 pg/mL to 680 ± 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44℃± 0.45℃ to 37.04℃ ± 0.48℃ (+0.597℃, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. Conclusion: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF.展开更多
Mechanical ventilation provide important support organ function in critical ill patients. However, mechanical ventilation can produce many complications. Patients should be weaned from mechanical ventilation promptly....Mechanical ventilation provide important support organ function in critical ill patients. However, mechanical ventilation can produce many complications. Patients should be weaned from mechanical ventilation promptly. It is difficult to identify which patients are suitable for weaning, and studies show that 4%-23% of patients who have passed SBT can not be successfully weaning. There is many reasons for weaning failure. Cardiac function may play a key role. Brain natriuretic peptide(BNP) is a powerful biomarker for the diagnosis of heart failure. BNP has been shown to help determine whether weaning failure is caused by cardiovascular dysfunction.展开更多
Plasma concentration of Natriuretic Peptide (NP) is a valuable diagnostic tool for heart failure (HF). It can help rule out or confirm a diagnosis of HF based on symptoms, but its use is not clearly defined. NPs shoul...Plasma concentration of Natriuretic Peptide (NP) is a valuable diagnostic tool for heart failure (HF). It can help rule out or confirm a diagnosis of HF based on symptoms, but its use is not clearly defined. NPs should be used in conjunction with physical examination and other diagnostic tests. However, it is important to note that several conditions besides the diagnosis of HF may cause NPs levels to be elevated. Additionally, there are situations when NP concentrations may be below diagnostic thresholds in [1]. This consensus statement aims to provide a straightforward diagnostic flowchart for clinicians in both the emergency department and outpatient settings to aid in diagnosing both acute and chronic HF. The diagnosis of acute HF can be ruled out with a BNP level of 100 pg/mL or NTproBNP level of 300 pg/mL, regardless of the patient’s age. To identify HF, a 3-level cut-off point based on the patient’s age is recommended. Chronic heart failure can be ruled out with a BNP level of 35 pg/mL or NTproBNP level of 125 pg/mL, regardless of thepatient’s age [1].展开更多
Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients wit...Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.展开更多
Background:Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers.The objective of this study was to investigate the prognostic predictive value of growth differentiation facto...Background:Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers.The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15(GDF-15)and N-terminal prohormone of brain natriuretic peptide(NT-proBNP)in assessing hospitalized patients with acute heart failure(AHF).Methods:In total,260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016.Medical history and blood samples were collected within 24 h after the admission.The primary endpoint was the all-cause mortality within 1 year.The patients were divided into survival group and death group based on the endpoint.With established mortality risk factors and serum GDF-15 level,receiver-operator characteristic(ROC)analyses were performed.Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.Results:Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors(P<0.001).In ROC analyses,area under curve(AUC)for GDF-15 to predict 1-year mortality was 0.707(95%confidence interval[CI]:0.648–0.762,P<0.001),and for NT-proBNP was 0.682(95%CI:0.622–0.738,P<0.001).No statistically significant difference was found between the two markers(P=0.650).Based on the optimal cut-offs(GDF-15:4526.0 ng/L;NT-proBNP:1978.0 ng/L),the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction(AUC=0.743,95%CI:0.685–0.795,P<0.001).Conclusions:GDF-15,as a prognostic marker in patients with AHF,is not inferior to NT-proBNP.Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.Clinical trial registration:ChiCTR-ONC-12001944,http://www.chictr.org.cn.展开更多
文摘Objective: This paper aims to investigate the effect of applying recombinant human brain natriuretic peptide in patients with heart failure combined with hypotension. Recombinant human brain natriuretic peptide is a synthetic polypeptide drug that is primarily used to treat acute heart failure. Its mechanism of action closely mimics that of human endogenous brain natriuretic peptide. By binding to receptors on cardiomyocytes, it exerts its pharmacological effects. Methods: For the study, 76 heart failure patients with hypotension were selected from our hospital between May 2022 and June 2023. These patients were divided into two groups: a control group and an observation group, each comprising 38 patients. The control group received dopamine treatment, while the observation group was treated with recombinant brain natriuretic peptide. The objective was to compare the effects of the treatments in both groups by analyzing cardiac function indices and levels of vasoactive substances to identify any significant differences in outcomes. Results: The overall response rate of the patients in the observation group and the control group was 94.74% and 73.68%, significantly higher as compared with the observation group (P 0.05). After the following treatment, BNP, ANNP and urine output in the observation group were significantly different compared with the control group, of the statistical significance (P Conclusion: For the treatment of heart failure patients with hypotension, the clinical application of recombinant human brain natriuretic peptide is the most ideal, and significantly improves the cardiac function of patients, which is worth popularizing.
文摘BACKGROUND Chronic heart failure(CHF)is a serious and prevalent condition characterized by impaired cardiac function and inflammation.Standard therapy for CHF has limitations,prompting the exploration of alternative treatments.Recombinant human brain natriuretic peptide(BNP)has emerged as a potential therapy,with evidence suggesting that it can improve cardiac function and reduce inflammation in patients with CHF.However,further research is required to determine the efficacy and safety of lyophilized recombinant human BNP in CHF patients and its impact on microinflammatory status.This study aimed to investigate the effects of lyophilized recombinant human BNP therapy on CHF patients’cardiac function and microinflammatory status.AIM To investigate the effects of freeze-dried recombinant human BNP therapy on cardiac function and microinflammatory status in patients with CHF.METHODS In total,102 CHF patients admitted to our hospital from January 2021 to January 2022 were randomly assigned to control and observation groups(n=51 patients/group).The control patients were treated with standard HF therapy for 3 d,whereas the observational patients were injected with the recombinant human BNP for 3 d.Clinical efficacy,inflammatory factor levels,myocardial damage,cardiac function before and after the treatment,and adverse reactions during treatment were compared between the two groups.RESULTS The overall clinical efficacy was higher in the observation group than in the control group.Compared with baseline,serum hypersensitive C-reactive protein,N-terminal proBNP,and troponin I level,and physical,emotional,social,and economic scores were lower in both groups after treatment,with greater reductions in levels and scores noted in the observation group than in the control group.The overall incidence of adverse reactions in the observation group was not significantly different compared with that in the control group(P>0.05).CONCLUSION Freeze-dried recombinant human BNP therapy can improve heart function and enhance microinflammatory status,thereby improving overall quality of life without any obvious side effects.This therapy is safe and reliable.
文摘Lyophilized recombinant brain natriuretic peptide(BNP)is an exogenous peptide synthesized by artificial recombination technology,with a similar structure and similar physiological effects with the endogenous natriuretic peptide secreted by the human body.It’s main mechanism of action is to increase cyclic guanosine monophosphate by binding with its corresponding receptor in the body,regulating,thus,the imbalance of the vascular system and cardiac hemodynamics,improving the heart’s pumping capacity,and inhibiting sympathetic excitability and myocardial remodeling.Moreover,it can promote mitochondrial metabolism and enhance the use of adenosine triphosphate in cardiomyocytes.In the present study,102 chronic heart failure(HF)patients were randomly assigned to a control and an observation group consisting of 51 patients each.Patients of the control group were treated with standard HF therapy for 3 d including oral metoprolol tartrate tablets,spironolactone,and olmesartanate while patients of the observation group were administered the recombinant human BNP injection for the same time-period,plus the standard HF therapy.The recombinant human BNP group(observation group)demonstrated better physical,emotional,social,and economic scores,as well as cardiac and inflammatory biomarkers such as serum hypersensitive C-reactive protein,N-terminal pro BNP and troponin I levels,compared to the control group.Moreover,cardiac function was also improved,as left ventricular ejection fraction and stroke volume were significantly higher in the observation group than in the control group.Interestingly,adverse reactions were not different between the 2 groups.However,these results are not generalizable and the need of large multicenter randomized controlled trials examining the safety and efficacy of recombinant human BNP in HF patients is of major importance.
文摘Objectives To observe the efficacy and safety of recombinant human brain natriuretic peptide(rh-BNP) on patients with acute myocardial infarction complicating congestive heart failure.Methods 40 patients with acute myocardial infarction complicated by congestive heart failure were randomly divided into control group and treatment group of 20 cases.The control group,15 cases of acute anterior myocardial infarction,5 cases of acute inferior wall myocardial infarction, 15 males and 5 females,aged 55-70 years,mean age 58±12 years;treated 16 cases of acute anterior myocardial infarction,4 cases of acute myocardial infarction,16 males and 4 females,aged 56-70 years,mean age 59±11 years;two groups of age,gender,severity of disease and vascular lesions no significant difference and comparable(P】0.05).Conventional group were given aspirin,clopidogrel, statins,Inotropic,diuretic and vasodilator therapy.In the con- ventional treatment group based on the use of recombinant human brain natriuretic peptide(new bios,Tibet Pharmaceutical Co.,Ltd.Chengdu Nuodikang biopharmaceutical production, usage:1.5μg/Kg intravenous injection(impact), then 0.0075μg-0.01μg/(kg·min)infusion rate).Continuous medication 72 h.The clinical symptoms observed for 3 days in patients before treatment and after treatment,heart rate,blood pressure and left ventricular ejection fraction (LVEF) and tumor necrosis factor(TNF-α),brain natriuretic peptide(BNP) levels were measured.Results In control group,8 cases markedly effect,5 cases effect and 7 cases no effect,the total effective rate was 65%;In treatment group,13 cases markedly effect,6 cases effect and 1 cases no effect,the total effective rate was 95%,compared with two groups P New bios treatment group significantly increased cardiac index(CI) in patients with heart failure and left ventricular ejection fraction(LVEF) than the control group(all P【0.05),further reduce the levels of tumor necrosis (TNF-α) and brain natriuretic peptide(BNP).Conclusions rh-BNP can improve symptoms and heart function,reduced plasma tumor necrosis factor(TNF-α) and BNP levels of acute myocardial infarction patients with congestive heart failure,the treatment safe and reliable.As small sample size observed,larger sample to be accumulated to further evaluate its efficacy and safety.
文摘Heart failure (HF) is a common disease associated with increasing age. B-type natriuretic peptide (BNP), is a cardiac neurohormone, and is released as prepro BNP and then enzyrnatically cleaved to the Ntenninal-proBNP (NT-proBNP) and BNP upon ventricular myocyte stretch. Blood measurements of BNP have been used to identify patients with I-IF. The BNP assay is currently used as a diagnostic and prognostic aid in HF. In general, a BNP level below 100 pg/mL excludes acutely decompensated HF and levels ＞ 500 pg/ml indicate decompensation. Recombinant human BNP (hBNP, nesiritide) is an approved intravenous treatment for acute,decompensated -HF. Nesiritide given in supraphysiologic doses causes vasodilation, natriuresis, diuresis, and improved symptoms over the course of a 48-hour infusion. This paper will sort out the literature concerning the use of this peptide both as a diagnostic test and as an intravenous therapy.
基金Basic Research Program of Jiangsu Province(Natural Science Foundation of China)(BK2015125).
文摘Objective:To investigate the effect of recombinant human brain natriuretic peptide (BNP) on inflammatory factors, neuroendocrine hormones and cardiac function indexes in patients with acute myocardial infarction complicated with heart failure.Methods:A total of91 cases of acute myocardial infarction with heart failure patients were divided into the control group (n=44) and observation group (n=47) according to the random data table, two groups of patients were given conventional treatment, based on this, the control group was given intravenous infusion of Nitroglycerin Injection treatment, the observation group received intravenous injection of recombinant human brain natriuretic peptide treatment, compared serum inflammatory factors, neuroendocrine hormone and cardiac function and other indexes of two groups before and after treatment.Results: there was no significant difference between the two groups before treatment. After treatment, the levels of TNF-α, hs-CRP, IL-6, MCP-1, LVESD and LVEDD in the two groups were significantly lower than those within the group before treatment, and the observation group was significantly lower than the control group;The two groups after treatment LVEF levels were significantly higher than those in the group before treatment, and the observation group was significantly higher than that of control group;the observation group after treatment PRA, Ang II and ALD and NE levels were significantly lower than those before treatment, and was significantly lower than the control group after treatment, the difference was significant, PRA, Ang, ALD and NE levels of control group before and after the treatment was no significant difference.Conclusion:recombinant human brain natriuretic peptide in the treatment of acute myocardial infarction with heart failure can effectively reduce the serum inflammatory factors and neuroendocrine hormone levels, improve heart function, and have a certain clinical value.
文摘To investigate the changes of plasma brain natriuretic peptide （BNF） levels inpatients with chronic heart failure （CHF）. Methods Plasma BNP concentrations in patients with CHF （n=56） and in normal controls （n=60） were measured with specific radioimmunoassay. Left ventricular ejection fraction in patients with chronic heart failure was measured with 99mTc gated cardiac blood pool scintigraphy. Results The results showed that Plasma BNP concentrations in patients with CHF were significantly higher than normal controls （223±79 ng/L vs 40±15 ng/L, P 〈 0.01）. Plasma BNP concentrations had a significant negative correlation with left ventricular ejection fractions（r=-0.68, P 〈 0.01 ）. Conclusions These results indicates that Plasma BNP levels are increased in patients with CHF, and they markedly increased according to the severity of heart failure classified by NYHA classifi- cation. The plasma BNP levels may be a biochemical parameter for evaluating the left ventricular function.
文摘Objective:To observe the influence of tirofiban on the troponin, brain natriuretic peptide, heart function in patients with Acute Myocardial Infarction after PCI and provide scientific basis for treatment of acute myocardial infarction.Methods:A total of 100 cases of hypertensive cerebral hemorrhage patients in our hospital were selected and randomly divided into 2 groups: the control group (50 cases) and the observation group (50 cases). The conventional treatment of PCI was performed on both groups. Tirofiban injection was given to the observation group on the basis of conventional treatment. cTnI, BNP and echocardiography parameters (LVEF, LVEDD, LVESD) were detected before and after treatment.Results:The comparison of cTnI in the two groups before operation was not statistically significant. cTnI in the 2 groups increased 12 h and 24 h after operation. But the cTnI in observation group (0.10±0.23) ng/mL decreased more significantly than that in control group (0.24±0.31) ng/mL, the difference was considered to be statistically significant. The comparison of BNP in the two groups before operation was not statistically significant. BNP in the 2 groups decreased obviously 7 d and 30 d after operation. BNP in observation group decreased more significantly than that in control group and the difference was considered to be statistically significant LVEF in the observation group increased significantly compared with that in control group 7 d after operation. The comparison of LVEDD, LVESD were not considered to be statistically significant. LVEDD and LVESD in the observation group were lower than that in control group obviously 30 d after operation. While the LVEF in the observation group was still higher than that in the control group. The comparsion was considered to be statistically significant.Conclusion:Tirofiban can improve the troponin, brain natriuretic peptide, heart function in patients with Acute Myocardial Infarction after PCI. It can also decrease the heart injury as well as helping the recovery of heart function.
文摘BACKGROUND Chronic obstructive pulmonary disease(COPD)is a chronic respiratory disease with worldwide occurrence and high disability and mortality rate.It occurs mostly in the elderly population with pulmonary heart disease,type II respiratory failure,and other serious complications.AIM To investigate the correlation of plasma brain natriuretic peptide(BNP)and platelet parameters with cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease.METHODS From June 2016 to June 2019,52 patients with COPD-pulmonary heart disease(pulmonary heart disease group),30 patients with COPD(COPD group),and 30 healthy individuals(control group)in our hospital were enrolled in the study.The pulmonary heart disease group was further divided into subgroups according to cardiac function classification and pulmonary artery pressure.Plasma BNP and platelet parameters were estimated and compared among each group and subgroup.The correlation of plasma BNP and platelet parameters with cardiac function classification and pulmonary artery pressure was then analyzed.RESULTS In the pulmonary heart disease group,the COPD group,and the control group,the levels of plasma BNP,platelet distribution width(PDW),and mean platelet volume(MPV)showed a decreasing trend(P<0.05),while an increasing trend was found in platelet count(PLT)and plateletcrit(PCT)levels among the three groups(P<0.05).In the pulmonary hypertension mild,moderate,and severe subgroups,the levels of plasma BNP,PDW,and MPV showed an increasing trend(P<0.05),while a decreasing trend was observed in PLT levels(P<0.05);however,PCT levels showed no significant difference among the three subgroups(P>0.05).In the cardiac function grade I,II,III,and IV subgroups,the levels of plasma BNP,PDW,and MPV showed an increasing trend(P<0.05),while a decreasing trend was noted in PLT and PCT levels among the four subgroups(P<0.05).Correlation analysis showed that the levels of plasma BNP,PDW,and MPV in patients with pulmonary heart disease were positively correlated with their pulmonary artery pressure(P<0.05),while PLT was negatively correlated with their pulmonary artery pressure(P<0.05).Moreover,plasma BNP,PDW,and MPV levels were positively correlated with cardiac function grade(P<0.05)of these patients,while PLT and PCT levels were negatively correlated with their cardiac function grade(P<0.05).CONCLUSION Plasma BNP and PLT parameters are significantly correlated with the cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease,indicating that these parameters have high clinical relevance in reflecting the health condition of these patients and for guiding their treatment.
文摘BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)are associated with a worsening of heart failure and a poor prognosis.AIM To test whether a high concentration of BNP would inhibit relaxation to ANP.METHODS Pulmonary arteries were dissected from disease-free areas of lung resection,as well as pulmonary artery rings of internal diameter 2.5–3.5 mm and 2 mm long,were prepared.Pulmonary artery rings were mounted in a multiwire myograph,and a basal tension of 1.61gf was applied.After equilibration for 60 min,rings were pre-constricted with 11.21μmol/L PGF2α(EC80),and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.RESULTS Although both ANP and BNP were found to vasodilate the pulmonary vessels,ANP is more potent than BNP.pEC50 of ANP and BNP were 8.96±0.21 and 7.54±0.18,respectively,and the maximum efficacy(Emax)for ANP and BNP was-2.03 gf and-0.24 gf,respectively.After addition of BNP,the Emax of ANP reduced from-0.96gf to-0.675gf(P=0.28).CONCLUSION BNP could be acting as a partial agonist in small human pulmonary arteries,and inhibits relaxation to ANP.Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure.This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.
文摘BACKGROUND Heart failure(HF),a common cardiovascular condition,is characterized by significant morbidity and mortality.While traditional Chinese medicine(TCM)is often used as a complementary approach in HF management,systematic evalua-tions of its impact on clinical outcomes,TCM syndrome scores,and B-type natriuretic peptide(BNP)levels are lacking.This study fills this gap through a comprehensive analysis of randomized controlled trials(RCTs)focusing on TCM for HF treatment.It encompasses an assessment of methodological quality,a meta-analysis,and an evaluation of evidence quality based on established standards.The results offer crucial insights into the potential advantages and constraints of TCM in HF management.RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases,including China National Knowledge Infrastructure,Wanfang,VIP Information Chinese Science and Technology Journal,and PubMed.Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool,and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software.Finally,the quality of evidence was rated according to the GRADE criteria.RESULTS A total of 1098 RCTs were initially retrieved.After screening,16 RCTs were finally included in our study,which were published between 2020 and 2023.These RCTs involved 1660 HF patients,including 832 in the TCM group[TCM combined with conventional Western medicine(CMW)treatment]and 828 in the CWM group(CWM treatment).The course of treatments varied from 1 wk to 3 months.TCM syndrome differentiation was analyzed in 11 of the included RCTs.In all included RCTs,outcome indicators included comprehensive clinical outcomes,TCM syndrome scores,and BNP levels.The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes[risk ratio=-0.54;95%confidence interval(CI)=-0.61,-0.47;P<0.00001],TCM syndrome scores[weighted mean difference(WMD)=-142.07;95%CI=-147.56,-136.57;P<0.00001],and BNP levels(WMD=-142.07;95%CI=-147.56,-136.57;P<0.00001).According to the GRADE criteria,RCTs where"TCM improves clinical comprehensive outcomes"were rated as low-quality evidence,and RCTs where"TCM reduces TCM syndrome scores"or"TCM decreases BNP levels"were rated as medium-quality evidence.CONCLUSION TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients.Given the low and medium quality of the included RCTs,the application of these results should be cautious.
文摘Introduction: The use of repeated thermal therapy for improving the symptoms of chronic heart failure (CHF) has been recently demonstrated. Usually, thermal therapy requires an infrared dry sauna. However, it is difficult for small clinics to acquire such an expensive and extensive system. The author assessed the efficacy of its substitution with hot water bottles. Moreover, there are no prior studies demonstrating the efficacy of thermal therapy in hemodialysis patients with chronic heart failure. Methods: The author evaluated plasma brain natriuretic peptide (BNP) levels in 98 hemodialysis patients in a clinic. A total of nine patients whose BNP levels were more than 500 pg/mL agreed to be enrolled in this study and received thermal therapy using hot water bottles. Results: Plasma BNP levels, a potential marker for CHF, tended to decrease (891 ± 448 pg/mL to 680 ± 339 pg/mL), but the difference was not significant (P = 0.0845). The oral temperature changed from 36.44℃± 0.45℃ to 37.04℃ ± 0.48℃ (+0.597℃, P < 0.0001). No side effects were experienced during the therapy. Moreover, most patients had an improvement in their symptoms and the ability to perform activities of daily living. Conclusion: Thermal therapy using hot water bottles is very safe and tends to reduce plasma BNP levels in hemodialysis patients with CHF.
基金the National Natural Science Foundation of China(81570069).
文摘Mechanical ventilation provide important support organ function in critical ill patients. However, mechanical ventilation can produce many complications. Patients should be weaned from mechanical ventilation promptly. It is difficult to identify which patients are suitable for weaning, and studies show that 4%-23% of patients who have passed SBT can not be successfully weaning. There is many reasons for weaning failure. Cardiac function may play a key role. Brain natriuretic peptide(BNP) is a powerful biomarker for the diagnosis of heart failure. BNP has been shown to help determine whether weaning failure is caused by cardiovascular dysfunction.
文摘Plasma concentration of Natriuretic Peptide (NP) is a valuable diagnostic tool for heart failure (HF). It can help rule out or confirm a diagnosis of HF based on symptoms, but its use is not clearly defined. NPs should be used in conjunction with physical examination and other diagnostic tests. However, it is important to note that several conditions besides the diagnosis of HF may cause NPs levels to be elevated. Additionally, there are situations when NP concentrations may be below diagnostic thresholds in [1]. This consensus statement aims to provide a straightforward diagnostic flowchart for clinicians in both the emergency department and outpatient settings to aid in diagnosing both acute and chronic HF. The diagnosis of acute HF can be ruled out with a BNP level of 100 pg/mL or NTproBNP level of 300 pg/mL, regardless of the patient’s age. To identify HF, a 3-level cut-off point based on the patient’s age is recommended. Chronic heart failure can be ruled out with a BNP level of 35 pg/mL or NTproBNP level of 125 pg/mL, regardless of thepatient’s age [1].
基金supported by the Project of Baoding Science and Technology Bureau(Project number:2241ZF343).
文摘Objective:To investigate the value of N-terminal pro B-type natriuretic peptide(NT-proBNP),high-sensitivity C-reactive protein(hs-CRP),and homocysteine(Hcy)levels in predicting cardiovascular events(CV)in patients with chronic heart failure(CHF).Methods:A total of 63 patients with CHF admitted to our hospital between June 2019 and July 2021 were selected.Their NT-proBNP,hs-CRP,and Hcy levels were detected at discharge,and a 12-month follow-up was done after their discharge to collect clinical data.The collected data were inclusive of data from 21 CHF patients with cardiovascular disease and 42 CHF patients without cardiovascular disease.The effect of NT-proBNP,hs-CRP,and Hcy levels on the occurrence of CV was analyzed.Results:The levels of NT-proBNP,hs-CRP,and Hcy in the group with cardiovascular disease were significantly higher than those in the group without cardiovascular disease(P<0.05);the levels of serum NT-proBNP,hs-CRP,and Hcy at discharge had certain value in predicting short-term CV in CHF patients(P<0.05).Conclusion:NT-proBNP,hs-CRP,and Hcy levels can be used to predict CV in CHF patients,thus having clinical application value.
文摘Background:Clinical assessment and treatment guidance for heart failure depends on a variety of biomarkers.The objective of this study was to investigate the prognostic predictive value of growth differentiation factor-15(GDF-15)and N-terminal prohormone of brain natriuretic peptide(NT-proBNP)in assessing hospitalized patients with acute heart failure(AHF).Methods:In total,260 patients who were admitted for AHF in the First Affiliated Hospital of Nanjing Medical University were enrolled from April 2012 to May 2016.Medical history and blood samples were collected within 24 h after the admission.The primary endpoint was the all-cause mortality within 1 year.The patients were divided into survival group and death group based on the endpoint.With established mortality risk factors and serum GDF-15 level,receiver-operator characteristic(ROC)analyses were performed.Cox regression analyses were used to further analyze the combination values of NT-proBNP and GDF-15.Results:Baseline GDF-15 and NT-proBNP were significantly higher amongst deceased than those in survivors(P<0.001).In ROC analyses,area under curve(AUC)for GDF-15 to predict 1-year mortality was 0.707(95%confidence interval[CI]:0.648–0.762,P<0.001),and for NT-proBNP was 0.682(95%CI:0.622–0.738,P<0.001).No statistically significant difference was found between the two markers(P=0.650).Based on the optimal cut-offs(GDF-15:4526.0 ng/L;NT-proBNP:1978.0 ng/L),the combination of GDF-15 and NT-proBNP increased AUC for 1-year mortality prediction(AUC=0.743,95%CI:0.685–0.795,P<0.001).Conclusions:GDF-15,as a prognostic marker in patients with AHF,is not inferior to NT-proBNP.Combining the two markers could provide an early recognition of high-risk patients and improve the prediction values of AHF long-term prognosis.Clinical trial registration:ChiCTR-ONC-12001944,http://www.chictr.org.cn.
