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Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Subject(s)
Male , Female , Humans , Aged , Natriuretic Peptide, Brain , Simendan/therapeutic use , Non-ST Elevated Myocardial Infarction , Heart Failure/drug therapy , Peptide Fragments , Arrhythmias, Cardiac , Biomarkers , PrognosisABSTRACT
Echinacoside (ECH) is one of the active ingredients in Cistanche Herba and the principal effective component of Memoregain© as well. Moreover, a new agent namely Naoqing Zhiming tablet, derived from ECH has been licensed for clinical trials. However, the knowledge regarding the stability of is limited, till now, initiating a significant barrier for its further development along with the clinical trials. Herein, we aim to in depth characterize the transformation pattern of ECH in methanol. When ECH was stored in methanol, two primary products (P1 and P2) could be observed in HPLC chromatogram. A home-made automated fraction collector was configured via employing two 2-phase/6-port electronic valves to prepare P1 and P2. Following ¹H-NMR and LC-MS/MS assays, P1 and P2 were unambiguously identified as acteoside and cistanoside A, respectively. Moreover, the existences of cis-ECH, cis-acteoside, and cis-cistanoside A were claimed after careful analysis of the ¹H-NMR spectra of ECH, P1 and P2. Above all, the primary transformation pathways of ECH in methanol included methylation as well as hydrolysis, and mild transformation could also be initiated by cis/trans- configuration transferring for the caffeoyl group. The findings obtained in current study are envisioned to provide useful insight for the further development of ECH and the impurity detection of Naoqing Zhiming tablet. Moreover, the automated fraction collector configured in current study is able to serve as a versatile tool for the collection of signals-of-interest within phytochemical evaluations and impurity isolation.
ABSTRACT
Melicope pteleifolia belongs to the family Rutaceae, Sect. Tetradium (Lour.) Engl. plants, which is widely distributed in Guangxi, Guangdong, Hainan, Jiangxi, Fujian, Guizhu, Yunnan, and other provinces. The main components are volatile oils and alkaloids. M. pteleifolia has been reported that it has antipyretic, analgesic, anti-inflammatory effects, and so on. In this paper, the investigation of documents, chemical components, and pharmacological effects is reviewed, which can provide a theoretical basis for further research of M. pteleifolia.
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Objective: To increase the contents of Taxol and 10-deacetylbaccatin III in the callus of Taxus cuspidata through the application and combination of various plant growth regulators. Methods: Young stems of T. cuspidata were taken as expiants and then their effects of NAA, 2,4-D, and 6-BA on the accumulation of Taxol and 10-deacetylbaccatin III were examined with the method of orthogonal design. Results: NAA exhibited the largest effect on the yields of both total Taxol and 10-deacetylbaccatin III, and followed by 6-BA, 2,4-D. Conclusion: The optimal medium for production of total Taxol and total 10-deacetylbaccatin III is: B5+NAA 2.0 mg/L+2,4-D 0.5 mg/L+6-BA 0.2 mg/L.
ABSTRACT
<p><b>OBJECTIVE</b>To study on the effect and mechanism of curcumin on inhibiting injury induced by free radical in pulmonary fibrosis.</p><p><b>METHOD</b>One hundred and forty-four male SD rats were randomly divided into 6 groups (24 rats in each group). Rats in the model control group, positive medicine group, and high, moderate and low curcumin groups were injected with a single dose of bleomycin by trachea, and rats in sham-model control group with same volume normal saline. One day after the injection, curcumin solution of different dosages (200,100,50 mg x kg(-1) x d(-1)) was respectively given to rats in the high, moderate and low curcumin group by daily gastrogavage, while equal volume of normal saline was given to those in the sham-model control group and model control group, and an equal volume of prednisone (0.56 mg x kg(-1) x d(-1)) was saline was given to those in positive medicine control group. On the 7, 14, 28 days, the contents of GSH-Px, SOD, MDA and iNOS in pulmonary tissues of different groups were measured.</p><p><b>RESULT</b>Curcumin can raise the content of SOD and GSH-Px and lessen the level of MDA and iNOS.</p><p><b>CONCLUSION</b>Curcumin can regulate the level of free radical in the body of rats with pulmonary fibrosis and lessen the oxidative injury of pulmonary tissues caused by free radical, in the body of rats with pulmonary fibrosis. The mechanisms of curcumin on idiopathic pulmonary fibrosis lie in adjusting the level of free radical and inhibiting the injury of lung tissue induced by free radical.</p>