OBJECTIVE: To investigate the mechanism of action of the Lingbao Huxin Dan in treating bradycardia arrhythmia with coronary heart disease (BA-CHD) by network pharmacology. METHODS: The active ingredients of the Lingbao Huxin Dan were screened on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Bioinformatics tools designed for the analysis of molecular mechanisms of Chinese medicine platform; target prediction was conducted with the SwissTargetPrediction database, and Cytoscape 3.8 was used to construct a drug ingredient-target network. The Genecards, Online Mendelian Inheritance in Man, and DrugBank databases were searched for disease targets. Venn plots were used to display the common targets of BA-CHD and active ingredients. The STRING platform was used to construct a protein-protein interaction network. The Metascape data platform was used for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to construct a signaling pathway network of the active ingredients of the Lingbao Huxin Dan. RESULTS: There were 121 active ingredients, 899 related targets, 39 targets important in BA-CHD and 14 targets which intersected between the active ingredients and BA-CHD. There were 27 core therapeutic ingredients, 153 biological processes, 18 cell ingredients and 20 molecular functions obtained by GO enrichment analysis. The KEGG pathway analysis yielded 19 signaling pathways. CONCLUSION: RBA-CHD may treat BA-CHD by regulating adrenergic receptor beta-1, alpha 1-α adrenergic receptor, calcium voltage-gated channel subunit alpha1 C, alpha-1ß-adrenergic receptor, nitric oxide synthase 2, beta-2 adrenergic receptor, voltage-dependent calcium channel subunit alpha-2/delta-1, an- giotensin-converting enzyme, Raf-1 proto-oncogene serine/threonine-protein kinase, and other targets, potentially by affecting adrenergic receptor binding and calcium channel opening, to regulate the activity of cardiomyocytes.
Bradycardia , Coronary Disease , Humans , Bradycardia/drug therapy , Network Pharmacology , Coronary Disease/complications , Coronary Disease/drug therapy , Coronary Disease/genetics , Receptors, Adrenergic
Objective To investigate the relationship among the late-life depression ( LLD ) , cognitive function and white matter lesions ( WML) , after excluding vascular risk factors and brain atrophy.Methods The depression and cognition status of 277 patients were assessed using a variety of neurological scales, and the actually enrolled patients were divided into LLD group ( 77 cases ) and the non-depressed group (103 cases).The independent samples t test and multivariate Logistic regression were used to analyze independent risk factors for depressive symptoms with the model Ⅰ of controlling age , sex, years of education and the model Ⅱof controlling age, sex, years of education, high blood pressure, diabetes and coronary heart disease.Under the premise of controlling mode Ⅱand brain atrophy , partial correlation was used to analyze the correlations of depressive symptoms and cognitive function and WML , and the correlation between depressive symptoms and cognitive items.Results The results showed that the proportion of high blood pressure (90.9%vs 74.7%, χ2 =6.342,P=0.046), cognitive scores (19.23 ±7.05 vs 22.99 ± 6.71, t=3.343,P=0.001), WML level 2 proportion (65.1% vs 34.9%, χ2 =7.373,P=0.025) and temporal lobe atrophy of hippocampal sulcus ratio (0.24 ±0.03 vs 0.22 ±0.03, t=-2.041,P=0.044) had statistically significant difference between the two groups.Multivariate Logistic regression showed that cognitive function was an independent risk factor for depression ( OR=1.63,95% CI 1.01 -2.80, P=0.030).Controlling for all risk factors , partial correlation analysis showed that depressive symptoms were correlated with cognitive function ( r=-0.239,P=0.004) and WML ( r=0.222,P=0.008) and the atrophy of temporal lobe and hippocampus ( r=0.173, P=0.040 ).Under the model Ⅱ, depressive symptoms correlated with attention (r=-0.175, P=0.040), memories (r=-0.140, P=0.050) and drawing clock test ( r=-0.186, P=0.029 ).Conclusions Excluding vascular risk factorts , brain atrophy and WML , cognitive impairment has significant correlation with depressive symptoms.Vascular risk factors are involved in the occurrence of depression , and WML may be the severity of cognitive impairment reserve marker.LLD patients showed hippocampal atrophy similar with early AD , manifesting the cognitive feature of memory and executive dysfunction and attention disorder .
Objective To investigate the independent risk factors of cerebral white matter lesions (WML) of different degrees in the elderly aged 80 years and over,and provide the evidences for forecasting the prognosis of WML.Methods Brain magnetic resonance images (MRI) findings in 151 people aged 74 to 93 years were collected and analyzed.According to the severity of WML in brain MRI using the Fazekas Scale,the persons were divided into non-WML (control) group,mildWML (grade 1 WML) group and moderate-to-severe WML (grade 2 WML) group.The cognitive score,vascular risk factors,cerebral hemodynamic and arteriosclerotic index,and radiological features were compared among the three groups.Subsequent one-way ANOVA and multivariate logistic analysis were performed to determine the statistically significant factors and the independent risk factors among groups.Results The statistically significant factors with one-way ANOVA analysis among the three groups were cognitive performance (F = 48.595,P = 0.000),hypertension (x2 =7.052,P=0.029),cigarette history (x2 = 19.476,P= 0.000),cholesterol (TC) (F= 3.086,P=0.049),Crouse score (F=3.968,P=0.021) and multiple cerebral atrophy indexes.When compared with control group,cigarette history (OR 2.031,95%CI 1.244-1.317),lacunar infarction (LI)numbers (OR 2.031,95%CI 1.316-4.015) and cholesterol (OR 1.610,95%CI 0.972-2.668) were independent risk factors in grade 1 WML group (all P＜0.05).The independent risk factors between grade 1 and 2 WML group were cognitive performance (OR 0.276,95%CI 0.143-0.532),cigarette history (OR 2.262,95% CI 1.260-4.059),and sylvian fissure ratio (SFR) (OR 1.954,95% CI 1.013-3.768) (all P＜0.05).The independent risk factors between the grade 2 WML group and control group were cognitive performance (OR 0.091,95%CI 0.030-0.273),bicoudate ratio (BCR)(OR 2.511,95%CI 1.147-5.499),Crouse score (OR 2.304,95%CI1.127-4.712)and LI numbers (OR 2.200,95%CI 1.028-4.707) (all P＜0.05).Conclusions Mild WML patients have no significant abnormalities in cognition,brain atrophy and cerebral atherosclerosis.Moderate to severe WML patients manifest remarkable cognitive disorder,cerebral atherosclerosis and brain atrophy.Compared with the controls,cognitive performance,BCR,Crouse score,LI numbers were the independent risk factors for moderate-severe WML patients.
