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Signal Transduct Target Ther ; 6(1): 329, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087


It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. ( identifier: NCT01681316).

Angina Estável/tratamento farmacológico , Fármacos Cardiovasculares/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Adolescente , Adulto , Idoso , Angina Estável/genética , Angina Estável/patologia , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(6): 1771-4, 2016 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-30052389


Ethanol concentration quantitative analysis of ethanol-water solution can be realized by measuring the ratio of Raman characteristic peak heights. The content of ethanol can be determined by linear relation between relative intensity ratio and ethanol concentration. However, this analytical method only applies to the ethanol solution at low concentration. Concerning this issue, relative intensity of characteristic peak of ethanol (asymmetric stretching vibration of CH2 2 924.0 cm-1) and peak background of water (3 350 cm-1) at different ethanol concentration is experimentally measured by using a self-developed laser Raman ethanol content detection system. According to the relationship between relative ratio of characteristic peak heights and ethanol concentration, the nonlinear regression analysis methods are proposed to apply in the measurement of ethanol concentration in a wide range. Adjacent region average method is utilized to remove mutational random noise in Raman spectra of ethanol solution. Combined with multi-point interpolation processing, the baseline of Raman spectra can be calibrated. The influences of mutational random noise and the strong fluorescence background can be effectively eliminated with baseline correction and normalization methods. Polynomial and exponential mathematical models are adopted for nonlinear regression analyses by the relation between ratio of characteristic peak heights and concentration of ethanol solution. The analysis results show that the correlation coefficient of linear fitting and nonlinear fitting is about 0.991 and higher than 0.997 respectively. The linear analytical method can be effectively applied when ethanol concentration range is 15%~60%. The nonlinear analytical method has higher measurement accuracy in a wider ethanol concentration range of 3%~97%. Nonlinear mathematical model will provide theoretical basis for analysis of ethanol concentration, which can be applied in laser Raman ethanol content detection system to calculate the relatively accurate ethanol concentration of ethanol-water solution. Rapid, real-time and accurate quantitative analysis of wide concentration range ethanol solution, which has mutational random noise and strong fluorescence background interference, can be achieved by these analytical methods.

Chin J Integr Med ; 21(8): 571-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25555593


OBJECTIVE: To confirm the efficacy and safety of Wufuxinnaoqing Soft Capsule (, WSC) in the treatment of chronic stable angina (blood stasis syndrome). METHODS: A multicenter, randomized, double-blind, placebo-controlled trial with superiority test was designed. A total of 240 patients with chronic stable angina (blood stasis syndrome) from multiple centers were randomly and equally assigned to the treatment group and the control group. Based on standard treatment of Western medicine, the treatment group was given WSC, while the control group was given WSC mimetic, both for 12 weeks. Observed indicators included the efficacy in angina, the efficacy in Chinese medicine syndrome, the withdrawal or reduce rate of nitroglycerin and routine safety indices. RESULTS: After 12-week treatment, the significant effective rate and total effective rate of the treatment group were significantly better than those of the control group (23.5% vs. 9.2%, 64.7% vs. 30.8%), respectively, with statistically significant difference (P<0.01). After 12-week treatment, the decreased points and the decreased rate of angina symptom score in the treatment group were better than in the control group (5.1±4.2 points vs. 2.8±3.5 points, 44.9%±37.2% vs. 25.4%±30.7%) respectively, with significant difference (P<0.01). After 12-week treatment, the significant effective rate and total effective rate of the treatment group were better than the control group (respectively, 30.3% vs. 15.0%, 67.2% vs. 45.0%,P<0.01). After 8- or 12-week treatment, the decreased points and the decreased rate of Chinese medicine syndrome score in the treatment group were better than the control group (P<0.05 orP<0.01). After 12-week treatment, nitroglycerin withdrawal rate and the withdrawal or reduce rate in treatment group were better than the control group (P<0.01). On safety evaluation, the incidence of adverse events (7.563% vs. 7.500%) and the incidence of cardiovascular events (0.840% vs. 0.000%) in the treatment group were similar with the control group, and the difference was not statistically significant (P>0.05). CONCLUSION: In treatment of chronic stable angina (blood stasis syndrome), WSC can reduce angina attacks and consumption of nitroglycerin, decrease angina severity degree, effectively relieve the blood stasis syndromes, such as chest pain, chest tightness, palpitations, dark purple tongue and other symptoms. Besides, adverse events and cardiovascular adverse events in the treatment group and the control group showed no difference. All shows that the drug is safe and effective. [This study was registered in Chinese Clinical Trial Registry (ChiCTR), with registration number: ChiCTR-TRC-14005158.].

Angina Estável/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos