Elucidating the Synergistic Effect of Multiple Chinese Herbal Prescriptions in the Treatment of Post-stroke Neurological Damage.

Background: Traditional Chinese medicine (TCM) has been widely used in the treatment of human diseases. However, the synergistic effects of multiple TCM prescriptions in the treatment of stroke have not been thoroughly studied. Objective of the study: This study aimed to reveal the mechanisms underlying the synergistic effects of these TCM prescriptions in stroke treatment and identify the active compounds. Methods: Herbs and compounds in the Di-Tan Decoction (DTD), Xue-Fu Zhu-Yu Decoction (XFZYD), and Xiao-Xu-Ming Decoction (XXMD) were acquired from the TCMSP database. SEA, HitPick, and TargetNet web servers were used for target prediction. The compound-target (C-T) networks of three prescriptions were constructed and then filtered using the collaborative filtering algorithm. We combined KEGG enrichment analysis, molecular docking, and network analysis approaches to identify active compounds, followed by verification of these compounds with an oxygen-glucose deprivation and reoxygenation (OGD/R) model. Results: The filtered DTD network contained 39 compounds and 534 targets, the filtered XFZYD network contained 40 compounds and 508 targets, and the filtered XXMD network contained 55 compounds and 599 targets. The filtered C-T networks retained approximately 80% of the biological functions of the original networks. Based on the enriched pathways, molecular docking, and network analysis results, we constructed a complex network containing 3 prescriptions, 14 botanical drugs, 26 compounds, 13 targets, and 5 pathways. By calculating the synergy score, we identified the top 5 candidate compounds. The experimental results showed that quercetin, baicalin, and ginsenoside Rg1 independently and synergistically increased cell viability. Conclusion: By integrating pharmacological and chemoinformatic approaches, our study provides a new method for identifying the effective synergistic compounds of TCM prescriptions. The filtered compounds and their synergistic effects on stroke require further research.

The role of wall shear stress in the parent artery as an independent variable in the formation status of anterior communicating artery aneurysms.

OBJECTIVES: The study aimed to determine which hemodynamic parameters independently characterize anterior communicating artery (AcomA) aneurysm formation and explore the threshold of wall shear stress (WSS) of the parent artery to better illustrate the correlation between the magnitude of WSS and AcomA aneurysm formation. METHODS: Eighty-one patients with AcomA aneurysms and 118 patients without intracranial aneurysms (control population), as confirmed by digital subtraction angiography (DSA) from January 2014 to May 2017, were included in this cross-sectional study. Three-dimensional-DSA was performed to evaluate the morphologic characteristics of AcomA aneurysms. Local hemodynamic parameters were obtained using transcranial color-coded duplex (TCCD). Multivariate logistic regression and a two-piecewise linear regression model were used to determine which hemodynamic parameters are independent predictors of AcomA aneurysm formation and identify the threshold effect of WSS of the parent artery with respect to AcomA aneurysm formation. RESULTS: Univariate analyses showed that the WSS (p < 0.0001), angle between the A1 and A2 segments of the anterior cerebral artery (ACA) (p < 0.001), hypertension (grade II) (p = 0.007), fasting blood glucose (FBG; > 6.0 mmol/L) (p = 0.005), and dominant A1 (p < 0.001) were the significant parameters. Multivariate analyses showed a significant association between WSS of the parent artery and AcomA aneurysm formation (p = 0.0001). WSS of the parent artery (7.8-12.3 dyne/cm2) had a significant association between WSS and aneurysm formation (HR 2.0, 95% CI 1.3-2.8, p < 0.001). CONCLUSIONS: WSS ranging between 7.8 and 12.3 dyne/cm2 independently characterizes AcomA aneurysm formation. With each additional unit of WSS, there was a one-fold increase in the risk of AcomA aneurysm formation. KEY POINTS: • Multivariate analyses and a two-piecewise linear regression model were used to evaluate the risk factors for AcomA aneurysm formation and the threshold effect of WSS on AcomA aneurysm formation. • WSS ranging between 7.8 and 12.3 dyne/cm 2 was shown to be a reliable hemodynamic parameter in the formation of AcomA aneurysms. The probability of AcomA aneurysm formation increased one-fold for each additional unit of WSS. • An ultrasound-based TCCD technique is a simple and accessible noninvasive method for detecting WSS in vivo; thus, it can be applied as a screening tool for evaluating the probability of aneurysm formation in primary care facilities and community hospitals because of the relatively low resource intensity.

High wall shear stress beyond a certain range in the parent artery could predict the risk of anterior communicating artery aneurysm rupture at follow-up.

OBJECTIVE: Among clinical and morphological criteria, hemodynamics is the main predictor of aneurysm growth and rupture. This study aimed to identify which hemodynamic parameter in the parent artery could independently predict the rupture of anterior communicating artery (ACoA) aneurysms by using multivariate logistic regression and two-piecewise linear regression models. An additional objective was to look for a more simplified and convenient alternative to the widely used computational fluid dynamics (CFD) techniques to detect wall shear stress (WSS) as a screening tool for predicting the risk of aneurysm rupture during the follow-up of patients who did not undergo embolization or surgery. METHODS: One hundred sixty-two patients harboring ACoA aneurysms (130 ruptured and 32 unruptured) confirmed by 3D digital subtraction angiography at three centers were selected for this study. Morphological and hemodynamic parameters were evaluated for significance with respect to aneurysm rupture. Local hemodynamic parameters were obtained by MR angiography and transcranial color-coded duplex sonography to calculate WSS magnitude. Multivariate logistic regression and a two-piecewise linear regression analysis were performed to identify which hemodynamic parameter independently characterizes the rupture status of ACoA aneurysms. RESULTS: Univariate analysis showed that WSS (p < 0.001), circumferential wall tension (p = 0.005), age (p < 0.001), the angle between the A1 and A2 segments of the anterior cerebral artery (p < 0.001), size ratio (p = 0.023), aneurysm angle (p < 0.001), irregular shape (p = 0.005), and hypertension (grade II) (p = 0.006) were significant parameters. Multivariate analyses showed significant association between WSS in the parent artery and ACoA aneurysm rupture (p = 0.0001). WSS magnitude, evaluated by a two-piecewise linear regression model, was significantly correlated with the rupture of the ACoA aneurysm when the magnitude was higher than 12.3 dyne/cm2 (HR 7.2, 95% CI 1.5-33.6, p = 0.013). CONCLUSIONS: WSS in the parent artery may be one of the reliable hemodynamic parameters characterizing the rupture status of ACoA aneurysms when the WSS magnitude is higher than 12.3 dyne/cm2. Analysis showed that with each additional unit of WSS (even with a 1-unit increase of WSS), there was a 6.2-fold increase in the risk of rupture for ACoA aneurysms.

Cerebral Microbleeds Could Be Independently Associated with Intracranial Aneurysm Rupture: A Cross-Sectional Population-Based Study.

OBJECTIVE: To determine whether the presence of cerebral microbleeds (CMBs) is independently associated with intracranial aneurysm rupture and to identify the time interval of CMB-related intracranial aneurysm rupture. METHODS: This cross-sectional study included 1847 patients with unruptured and ruptured intracranial aneurysms from January 2010 to November 2017. Clinical records and imaging, including T2-weighted gradient-recalled echo sequence magnetic resonance imaging that identified the presence of CMBs preoperatively, were evaluated. Univariate analysis and multivariate logistic regression were done to determine which parameters were independent factors for aneurysm rupture. The time interval of CMB-related intracranial aneurysm rupture was also evaluated. RESULTS: CMBs confirmed by magnetic resonance imaging were present in 142 patients (142/1847; 7.7%). Of 142 patients with CMBs, 56 patients (including 17 ruptured aneurysms) who received endovascular treatment and another 86 consecutive patients who did not receive embolization or surgery for various reasons were followed for 3-49 months. The incidence of CMB-related intracranial aneurysm rupture was 27.9% (24/86) during the follow-up period. The time interval of CMB-related intracranial aneurysm rupture was 3-27 months (median 9.5 months). Multivariate analyses showed CMBs were significantly correlated with intracranial aneurysm rupture (odds ratio = 1.6; 95% confidence interval, 1.1-2.4; P = 0.010). CONCLUSIONS: CMBs were independently associated with intracranial aneurysm rupture. Patients with CMBs have a 60% increased risk of aneurysm rupture compared with patients without CMBs.