ABSTRACT
Objective:To explore the mechanism of the prescription consisting Aconiti Lateralis Radix Praeparata and Epimedii Folium in the treatment of chronic heart failure （CHF） based on network pharmacology，followed by verification in H9c2 myocardial cells with hypoxia-reoxygenation injury <italic>in vitro</italic> and in zebrafish with vascular endothelial growth factor receptor （VEGFR） tyrosine kinase inhibitor Ⅱ （VRI） -induced vascular insufficiency. Method:The active ingredients in Aconiti Lateralis Radix Praeparata and Epimedii Folium were searched from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），the corresponding target genes from the Universal Protein Resource （UniProt）， and the CHF-related targets from Online Mendelian Inheritance in Man （OMIM） and GeneCards. Both the active ingredient-potential target network and the active ingredient-CHF-related target network were generated using Cytoscape 3.6.1， followed by the protein-protein interaction （PPI） network construction and Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genome （KEGG） enrichment analysis based on MetaScape. H9c2 myocardial cells exposed to hypoxia-reoxygenation were selected for determining the proliferation-promoting effect by methyl thiazolyl tetrazolium （MTT） assay. The protein expression of B-cell lymphoma-2（Bcl-2）， Bcl-2-associated X protein（Bax），cysteinyl aspartate-specific protease-3（Caspase-3）， protein kinase B（PKB/Akt），phosphorylated protein kinase B（p-Akt），phosphorylated extracellular signal-regulated kinases 1/2 （p-ERK1/2），extracellular signal-regulated kinase 1/2 （ERK1/2）， and poly adenosine diphosphate ribose polymerase（PARP）was detected by Western blotting. The efficacy of the prescription in promoting angiogenesis was verified in a zebrafish model of VRI-induced vascular injury. Result:There were 28 active ingredients for the prescription， 209 corresponding targets， 1 296 CHF-related targets， and 94 common gene targets shared by the prescription and CHF. PPI network clustering suggested that Aconiti Lateralis Radix Praeparata and Epimedii Folium alleviated CHF by interfering with cell differentiation and metabolism and angiogenesis. GO analysis revealed that CHF relief was achieved via the intervention in such biological processes as cell migration，vascular development， and angiogenesis. Pharmacodynamic experiments verified that Epimedii Folium （10 mg·L<sup>-1</sup>） alone and the prescription （10 mg·L<sup>-1</sup>）both enhanced the proliferation of H9c2 myocardial cells under the hypoxia-reoxygenation condition （<italic>P</italic><0.05），while the latter also increased the expression of Bcl-2，Bcl-2/Bax， and PARP （<italic>P</italic><0.05） and reduced the expression of Caspase-3， Akt， and ERK （<italic>P</italic><0.05）. The prescription at the concentrations of 0.3 and 0.1 g·L<sup>-1</sup> promoted angiogenesis （<italic>P</italic><0.05）. Conclusion:Aconiti Lateralis Radix Praeparata and Epimedii Folium exert the therapeutic effect against CHF via multiple ingredients，multiple targets， and multiple channels. Such combination promotes the proliferation of H9c2 myocardial cells under hypoxic condition and protects zebrafish from vascular injury by up-regulating the expression of Bcl-2 and PARP，increasing Bcl-2/Bax ratio，and down-regulating the expression of Caspase-3，Akt， and ERK.
ABSTRACT
Objective:To investigate the changes of gray matter volume in patients with chronic nonfluent aphasia after cortical cerebral infarction and the relationship between gray matter volume and language function. Methods:From June, 2016 to June, 2019, 19 patients with chronic nonfluent aphasia after cortical cerebral infarction from the First Affiliated Hospital of Ji'nan University and 28 healthy subjects (controls) were scanned with structural magnetic resonance imaging. The data were analyzed using voxel-based morphological measurement to measure the gray matter volumes of the brain regions, and the differences between patients and controls were compared. The correlation between volumes of brain regions with difference and scores of items of Aphasia Battery of Chinese (ABC) was analyzed. Results:The gray matter volumes increased in the brain regions of right inferior frontal gyrus triangle, right inferior frontal gyrus island cover, right angular gyrus, the right medial frontal gyrus, left insula, left medial frontal gyrus in the patients; while decreased in right globus pallidus. The volumes of left insular lobe correlated with the scores of repeating (r = 0.665, P = 0.001) and naming (r = 0.638, P = 0.003); and the volumes of right inferior frontal gyrus triangle correlated with the scores of hearing comprehension (r = 0.493, P = 0.031), repeating (r = 0.576, P = 0.009) and naming (r = 0.674, P = 0.001) in the patients. Conclusion:The cortex volumes of left insula and right inferior frontal gyrus triangle increase in patients with chronic nonfluent aphasia after cerebral infarction, which may play a role in the language dysfunction.
ABSTRACT
Objective To investigate the awareness rate,treatment rate and control rate of mineral and bone disorder in patients with moderate or advanced stage chronic kidney disease (CKD). Methods The awareness rate,treatment rate and control rate of mineral and bone disorder were evaluated based on a questionnaire and related laboratory examinations in 503 CKD stage 3 to 5 patients. Results The awareness rate of mineral and bone disorder in patients with moderate or advanced stage CKD was highest in hemodialysis patients,moderate in peritoneal dialysis patients and lowest in non-dialyzed patients (all P ＜0.01).The total scores of the questionnaire were lowest in non-dialyzed patients [6 (5,8)] and were significantly higher in peritoneal dialysis [11 (9,12)] and hemodialysis patients [13 (11,15)] (P＜0.01).The extent of awareness was negatively correlated with age (r=-0.11,P＜0.05),and positively correlated with educational background (r=0.226,P＜0.01),duration of CKD (r=0.597,P＜0.01) and duration of dialysis (r=0.366,P＜0.01).The source of knowledge was mainly from publicity and education made by medical staff,which accounted for 94.0％,79.5％ and 69.4％ respectively in nondialyzed,peritoneal dialysis and hemodialysis patients.The treatment rate was significantly higher in peritoneal dialysis (88.6％) and hemodialysis patients (96.9％) than that in non-dialyzed patients (58.2％) (all P＜0.01).According to K/DOQI guideline,the control rate of serum calcium,phosphorus,calcium and phosphorus product and parathyroid hormone (PTH) were much better in non-dialyzed patients as compared to dialyzed ones.The percentage of number of lab indicators meeting the standard was significantly higher in non-dialyzed patients as compared to dialyzed ones (P＜0.01).According to KDIGO guideline,the control rate of serum phosphorus was significantly lower in hemodialysis patients (23.6％) than that in peritoneal dialysis (36.9％) and non-dialyzed patients (46.7％) (P＜0.01). Conclusions In non-dialyzed patients with moderate or advanced stage CKD,the awareness rate and treatment rate of mineral and bone disorder are relatively low,and the control rate is relatively high.Whereas in dialyzed patients,the awareness rate and treatment rate are relatively high,and the control rate is relatively low.