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

RESUMO

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. (ClinicalTrials.gov identifier: NCT01681316).

2.
Dalton Trans ; 50(6): 2001-2006, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33522556

RESUMO

CsMnCl3(H2O)2 (CMCH) has been widely investigated for magnetic and optical applications, including anti-Stokes photoluminescence, microwave absorption, and magnon-assisted optical transitions. Herein, CMCH crystals, which are colorless and transparent (unlike the pink crystals reported previously), were obtained through a unique approach. Consequently, a high-resolution optical absorption spectrum and distinct thermal behavior were observed. The reversible (de)hydration of CMCH being accompanied by photoluminescence switching (mainly in terms of the color temperature) was rationalized using crystal structure analysis. As a result, water-soluble CMCH could be applied as a moisture-responsive luminescent ink. Moreover, density functional theory (DFT) calculations were performed to understand the optical absorption of CMCH.

3.
Biochem Biophys Res Commun ; 518(1): 59-65, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31445702

RESUMO

Stroke is reported as a leading cause of mortality and disability in the world. Neuroinflammation is significantly induced responding to ischemic stroke, and this process is accompanied with microglial activation. However, the pathogenesis contributing to ischemic stroke remains unclear. NR4A1 (Nur77) is a nuclear receptor that is expressed in macrophages, playing a significant role in regulating inflammatory response. In the present study, we attempted to explore the effects of NR4A1 on ischemic stroke using in vivo and in vitro studies. Results suggested that NR4A1 expression in microglia was markedly increased after cerebral ischemic damage. Then, we found that NR4A1 knockout attenuated ischemia-triggered infarction volume and neuron injury. Also, cognitive impairments were improved in ischemic mice with NR4A1 deficiency, resulting in functional improvements. Moreover, M1 polarization in microglia and neutrophil recruitment was significantly alleviated by NR4A1 deletion, as evidenced by the reduced expression of M1 markers, chemokines, as well as intracellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO) levels. Importantly, we found that NR4A1 could interact with nuclear factor-κB (NF-κB)/p65 based on in vivo and in vitro results. Suppressing p65 activation by the use of its inhibitor clearly reduced the NR4A1 expression, M1 polarization and neutrophil recruitments, while rescued the expression of anti-inflammatory factors in microglia treated with oxygen-glucose deprivation (OGD). Therefore, NR4A1 suppression in microglia restrained neuroinflammation through interacting with NF-κB/p65 to attenuate ischemic stroke.


Assuntos
Lesões Encefálicas/etiologia , Lesões Encefálicas/metabolismo , Isquemia Encefálica/complicações , Encéfalo/patologia , Inflamação/patologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Fator de Transcrição RelA/metabolismo , Animais , Lesões Encefálicas/patologia , Isquemia Encefálica/patologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Deleção de Genes , Glucose/deficiência , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Inflamação/complicações , Masculino , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Oxigênio , Ligação Proteica , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia
4.
J Stroke Cerebrovasc Dis ; 27(12): 3542-3548, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30201455

RESUMO

BACKGROUND: Evidence from outside the typical clinical research setting, such as the real-world setting, complements evidence coming from randomized controlled trials. The purpose of this study was to evaluate all available evidence from the real-world observational trials about long-term outcomes of treatment with intravenous (IV) recombinant tissue-type plasminogen activator (rt-PA) compared with not treated with IV rt-PA (non-rt-PA) in patients with acute ischemic stroke. METHODS: We searched PubMed and Embase until March 1, 2018 for observational studies reporting matched or adjusted results comparing IV rt-PA versus non-rt-PA in patients with acute ischemic stroke. Outcomes assessed included all-cause mortality, hospital readmission rates, and independence rates. Hazard ratios with 95% confidence intervals were used as a measure of comparing between patients treated with IV rt-PA and non-rt-PA. RESULTS: Six observational trials with 16,399 participants were identified. The use of IV rt-PA in acute ischemic stroke patients was associated with a lower risk of mortality (hazard ratio .61; 95% confidence interval, .52-.70; P < .00001), and there was no heterogeneity across trials. There was no evidence of an effect on hospital readmission rates and independence rates. CONCLUSIONS: IV rt-PA is associated with reduced long-term mortality in acute ischemic stroke patients.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Administração Intravenosa , Humanos , Estudos Observacionais como Assunto
5.
Zhongguo Zhong Yao Za Zhi ; 43(6): 1268-1275, 2018 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-29676139

RESUMO

To evaluate the effectiveness and safety of Xinling Wan on patients with stable angina pectoris, a randomized, double-blinded, placebo parallel-controlled, multicenter clinical trial was conducted. A total of 232 subjects were enrolled and randomly divided into experiment group and placebo group. The experiment group was treated with Xinling Wan (two pills each time, three times daily) for 4 weeks, and the placebo group was treated with placebo. The effectiveness evaluation showed that Xinling Wan could significantly increase the total duration of treadmill exercise among patients with stable angina pectoris. FAS analysis showed that the difference value of the total exercise duration was between experiment group (72.11±139.32) s and placebo group (31.25±108.32) s. Xinling Wan could remarkably increase the total effective rate of angina pectoris symptom score, and the analysis showed that the total effective rate was 78.95% in experiment group and 42.61% in placebo group. The reduction of nitroglycerin dose was (2.45±2.41) tablets in experiment group and (0.50±2.24) tablets in placebo group on the basis of FAS analysis. The decrease of symptom integral was (4.68±3.49) in experiment group and (3.19±3.31) in placebo group based on FAS analysis. Besides, Xinling Wan could decrease the weekly attack time and the duration of angina pectoris. PPS analysis results were similar to those of FAS analysis. In conclusion, Xinling Wan has an obvious therapeutic effect in treating stable angina pectoris, with a good safety and a low incidence of adverse event and adverse reaction in experiment group.


Assuntos
Angina Pectoris/tratamento farmacológico , Angina Estável/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Método Duplo-Cego , Teste de Esforço , Humanos , Nitroglicerina
6.
Neuropsychiatr Dis Treat ; 14: 273-284, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29391800

RESUMO

Aim: This meta-analysis aimed to assess the effect of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) for the treatment of depression in patients with Parkinson's disease (PD). Methods: The design was a meta-analysis of randomized controlled trials (RCTs). The participants were patients with PD who suffered from depression. The interventions were HF-rTMS alone or in combination with other treatments compared with sham-rTMS, placebo, and anti-depressant treatments. The primary outcome measure was changes in depressive symptoms, defined as the mean change in the total depression score. The secondary outcome was changes in motor symptoms, defined by Unified Parkinson's Disease Rating Scale part III scores, and the acceptability, defined as the risk of all-cause discontinuation. These were expressed as mean differences (MDs), standardized mean differences (SMDs), or risk ratios (RRs) with 95% confidence intervals (CIs). Results: We identified nine suitable trials, with data from 332 participants. For the patients with depression in PD, HF-rTMS was not better than sham-rTMS (SMD =-0.33, 95% CI -0.83 to 0.17) or selective serotonin re-uptake inhibitors (SSRIs) (SMD =0.07, 95% CI -0.52 to 0.18) for the treatment of depressive symptoms. However, the motor benefits after treatment with HF-rTMS might be better than sham-rTMS (MD =-2.80, 95% CI -5.45 to -0.15) and SSRIs (MD =-2.70, 95% CI -4.51 to -0.90). Conclusion: This meta-analysis provides some evidence that in patients with PD with depression, HF-rTMS may lead to improvement in motor function but not in depression compared with sham-rTMS or SSRIs.

7.
J Clin Psychopharmacol ; 38(1): 55-59, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29257786

RESUMO

PURPOSE: The purpose of this study was to assess the efficacy and acceptability of cariprazine treatment in acute exacerbation of schizophrenia. METHODS: This review included randomized controlled trials of patients with acute exacerbation of schizophrenia in relation to efficacy and acceptability. The efficacy outcomes were assessed by pooling standardized mean differences (SMDs) calculated from the difference in the reduction in the mean of the Positive and Negative Syndrome Scale (PANSS) total score, PANSS positive and negative scores, and response rate. The primary acceptability outcomes were determined by pooling the risk ratios (RRs) of discontinuation for any reason, the incidence of serious adverse events, and treatment emergent events. FINDINGS: Four randomized controlled trials consisting of 1843 patients met all inclusion and exclusion criteria. Efficacy analysis showed significant positive effects in relation to cariprazine therapy (SMD: -0.37, P < 0.00001 for PANSS total score change; SMD: -0.32, P < 0.00001 for PANSS positive score change; SMD: -0.32, P < 0.0001 for PANSS negative score change; RR, 1.41; 95% confidence interval [CI], 1.19-1.67; P < 0.0001 for response rate). For primary acceptability outcomes, less patients taking cariprazine discontinued treatment for any reason compared with patients receiving placebo (RR, 0.90; 95% CI, 0.78-1.04; P = 0.16). Significantly less patients on cariprazine had serious adverse events during the double-blind treatment period compared with patients taking placebo (RR, 0.55; 95% CI, 0.34-0.89; P = 0.01). Significantly more patients on cariprazine had treatment emergent events compared with those receiving placebo (RR, 1.10; 95% CI, 1.03-1.18; P = 0.006). IMPLICATIONS: Results suggest that cariprazine may be an effective and acceptable treatment for schizophrenia and future research is warranted.


Assuntos
Antipsicóticos/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde , Piperazinas/uso terapêutico , Esquizofrenia/tratamento farmacológico , Doença Aguda , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Esquizofrenia/diagnóstico , Resultado do Tratamento
8.
Chin J Integr Med ; 21(8): 571-8, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25555593

RESUMO

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.].


Assuntos
Angina Estável/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Placebos
9.
Zhonghua Nan Ke Xue ; 8(1): 25-7, 2002.
Artigo em Chinês | MEDLINE | ID: mdl-12479042

RESUMO

OBJECTIVES: To evaluate the relationship between sperm apoptosis and male infertility. METHODS: Percentage of apoptotic sperm (PAS) in spermatozoa of fertile and infertile men were tested by flow cytometry (FCM). RESULTS: Sperm apoptosis had happened in all different people. PAS in fertile and infertile group was (4.28 +/- 1.66)% and (18.67 +/- 8.55)% respectively, and difference was significant between two groups (P < 0.01). There was negative correlation between PAS and semen volume, sperm density, percentage of forward motility, percentage of normal morphology (P < 0.01). CONCLUSIONS: There was very close relationship between sperm apoptosis and male infertility. FCM used to test sperm apoptosis is rapid, accurate, objective and reliable to analyse sperm functions and male fertility.


Assuntos
Apoptose , Infertilidade Masculina/patologia , Espermatozoides/patologia , Citometria de Fluxo , Humanos , Masculino
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