Study on the Composition and Mechanism of Santiao Decoction in Treating Insomnia Based on UPLC and Network Pharmacology and Molecular Docking Technology.

OBJECTIVE: To identify the chemical components of Santiao Decoction (STD) using Ultra Performance Liquid Chromatography (UPLC) and to conduct a network pharmacological study of STD for the treatment of insomnia based on this technique. METHODS: An ACQUITY UPLC BEH C18 column (2.1 mm×100 mm, 1.7 µm) was used to identify the chemical components of STD by relative molecular weight, mass spectrometry information, and comparison with the control. The active ingredients of the formula and their corresponding gene targets and targets for insomnia were retrieved from several databases, and a visual network diagram of "drug-active ingredient-target-disease" was constructed using Cytoscape 3.8.2 software, and GO functional annotation and KEGG pathway enrichment analysis were performed using various databases such as DAVID. RESULTS: Five active ingredients were identified from STD by UPLC technique, 268 active ingredients of STD were screened from the TCMSP database, and 109 genes related to STD for insomnia were screened by network pharmacology, among which IL6, MMP9, VEGFA, IL10, CCL2 may be the key targets of STD for insomnia. KEGG pathway analysis showed that STD acts on membrane rafts, plasma membrane micro-regions, and other related pathways, such as Toll-like receptor signaling pathway, prolactin signaling pathway, dopaminergic synapse, relaxin signaling pathway, ErbB signaling pathway, steroid hormone biosynthesis and NF-kappa B signaling pathway for regulation. CONCLUSION: The active ingredients in STD, such as (+)-catechin, Swertisin, quercetin, baicalein, and wogonin, may act on IL6, CCL2, VEGFA, MMP9, and other targets to regulate Toll-like receptor signaling pathway, ErbB signaling pathway, NF-kappa B and other signaling pathways, and exert certain therapeutic effects on insomnia, which provide a reference and basis for further research on the mechanism of action of STD.

[The comorbid mechanism of vestibular migraine and persistent postural-perceptual dizziness].

Vestibular migraine and persistent postural-perceptual dizziness both involve the vestibular system and are similar in clinical manifestations. After acute attack of vestibular migraine, it can gradually evolve into persistent posture-perceptual dizziness; persistent posture-perceptual dizziness caused by various factors can be combined with symptoms similar to vestibular migraine. Studies have shown that abnormal multi-sensory signal integration, abnormal neurotransmitters and genetic factors may be the co-disease mechanism of the two.

[Research progress on the mechanism of comorbidities of vestibular migraine and sleep disorders].

Vestibular migraine （VM） is one of the common vestibular diseases characterized by recurrent vertigo and migraine. Studies have shown that the sleep structure of VM patients is similar to that of migraine patients, and they have a common pathophysiological pathogenesis. There is a strong correlation between VM and the clinical symptoms of sleep disorders. Sleep disorders can trigger VM. On the contrary, VM can affect sleep regulatory centers and lead to structural sleep disorders. In addition, there is a common relationship between VM and sleep disorders in neuroanatomy, neurotransmitters and neural pathways. A correct understanding of the relationship between vestibular migraine and sleep disorders can provide some help for clinical diagnosis and treatment. This article reviews the relationship between vestibular migraine and the pathogenesis of sleep disorders.

Study on Mechanism of Jiawei Chaiqin Wendan Decoction in Treatment of Vestibular Migraine Based on Network Pharmacology and Molecular Docking Technology.

OBJECTIVE: To predict the main active ingredients, potential targets, and key pathways of Jiawei Chaiqin Wendan decoction treatment in vestibular migraine and explore possible mechanisms by network pharmacology and molecular docking technology. METHODS: The active ingredients and related targets of Jiawei Chaiqin Wendan decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The corresponding genes of the target were queried by UniProt database, and the "drug-compound-target-disease" network was constructed by Cytoscape 3.7.2 software. GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by R software and Bioconductor, and column chart and bubble chart were drawn by Prism software and OmicShare database for visualization. Finally, the mechanism and potential targets of Jiawei Chaiqin Wendan decoction in the treatment of vestibular migraine were predicted. RESULTS: The "drug-compound-target-disease" network contains 154 active ingredients and 85 intersection targets. The key targets include AKT1, IL6, MAPK3, VEGFA, EGFR, CASP3, EGF, MAPK1, PTGS2, and ESR1. A total of 1939 items were obtained by GO functional enrichment analysis (P < 0.05). KEGG pathway enrichment analysis screened 156 signal pathways (P < 0.05), involving PI3K-Akt signal pathway, AGE-RAGE signal pathway in diabetes complications, MAPK signal pathway, HIF-1 signal pathway, IL-17 signal pathway, etc. Molecular docking results showed that quercetin, luteolin, kaempferol, tanshinone IIa, wogonin, naringenin, nobiletin, dihydrotanshinlactone, beta-sitosterol, and salviolone have good affinity with core target proteins IL6, PTGS2, MAPK1, MAPK3, and CGRP1. CONCLUSION: The active ingredients in Jiawei Chaiqin Wendan decoction may regulate the levels of inflammatory factors and neurotransmitters by acting on multiple targets such as IL6, MAPK3, MAPK1, and PTGS2, so as to play a therapeutic role in vestibular migraine.

A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental Parkinson's Disease.

To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson's disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P < 0.01), two studies for improving the swim-score values (P < 0.01), six studies for improving the level of TH protein expression (P < 0.01), and two studies for increasing the expression of TH mRNA in the substantia nigra of mice (P < 0.01). The studies reported that G-Rg1 exerted potential neuroprotective effects on PD model through different mechanisms as antineuroinflammatory activities (n = 10), antioxidant stress (n = 3), and antiapoptosis (n = 11). In conclusion, G-Rg1 exerted potential neuroprotective functions against PD largely by antineuroinflammatory, antioxidative, and antiapoptotic effects. G-Rg1 as a promising neuroprotectant for PD needs further confirmation by clinical trials.

[Effect of different blood pressure control targets within 48 h after hypertensive cerebral hemorrhage on hematoma enlargement and prognosis].

OBJECTIVE: To study the effect of different blood pressure control targets on hematoma enlargement and prognosis in patients within 48 h after hypertensive cerebral hemorrhage (HCH). METHODS: Between January, 2013 and July, 2016, 102 patients with HCH were randomized into group A (51 cases) and group B (51 cases) with different systolic blood pressure (SBP) control targets within 48 h. The patients in group A were given early active antihypertensive treatment with SBP control target of 130-140 mm Hg; those in group B received standard antihypertensive treatment with SBP control target of 170-180 mm Hg. The changes in the volume of hematomas and the patients' prognosis were compared between the two groups. RESULTS: After 48 h of treatment, SBP, hematoma volume and the National Institutes of Health Stroke Scale (NIHSS) score were significantly lower and Glasgou Coma Scale (GCS) score was significantly higher in group A than in group B (P<0.01 or 0.05). After 30 days of treatment, the patients in group A showed significantly better indicators of treatment efficacy than those in group B (Z=2.331, P=0.020). The mortality rate was lower in group A than in group B, but the difference was not statistically significant (Χ2=2.772, P=0.096). CONCLUSION: Early active antihypertensive treatment is safe and feasible in patients with HCH and can reduce the enlargement of the hematomas, alleviate deterioration of neurological function, and improve the prognosis of the patients.

Basilar artery bending length, vascular risk factors, and pontine infarction.

BACKGROUND: Patients exhibiting basilar artery (BA) curvature (not dolichoectasia) are at an increased risk of posterior circulation ischemic stroke. In this study, pontine infarction patients were analyzed to assess the effect of BA bending length (BL) together with other vascular factors on pontine stroke risk. METHODS: Acute pontine infarction patients were divided into BA bending and non-BA bending groups by magnetic resonance angiography (MRA). Patients with BA bending who reported symptoms of dizziness or vertigo but who had not suffered brain infarction constituted the control group. The diameter of the vertebral artery (VA) and BL were measured using MRA. Based on the bilateral VA diameter data in vertebral artery-dominant (VAD) patients, the study participants were divided into three classes for VA diameter: class one, 0.30-0.80 mm (20 cases); class two, 0.81-1.37 mm (20 cases); and class three, 1.38-3.24 mm (20 cases). The measured BL in VAD cases allowed division of patients into three levels for BL: level one, 1.02-2.68 mm (21 cases); level two, 2.69-3.76 mm (20 cases); and level three, 3.77-7.25 mm (19 cases). Vascular risk factors were compared among the three groups. Correlations of BL and VA diameter differences were studied, and multivariate analysis was applied to search for predictors of ischemic stroke in BA bending patients. RESULTS: Among BA bending, non-BA bending, and control groups, VA dominance (VAD) proved to be a significant differentiator. For all three groups, a patient age of ≥ 65 years, the occurrence of hypertension, smoking, high homocysteine levels, high cholesterol, and a history of type 2 diabetes, were all statistically significant factors (P<0.05). After adjusting for other relevant factors, multivariate analysis shows that BL of level 3 was an independent risk factor for pontine infarction (OR=2.74; 95% CI, 1.27 to 4.48). Both BL and diameter differences between the VAs were positively correlated with risk with statistical significance (r=0.769, P<0.001). CONCLUSIONS: Both BL and diameter differences between the VAs are positively correlated with the risk of pontine infarction. When BA bending was coupled with other vascular risk factors, the probability of pontine infarction increased. BA bending with a BL greater than 3.77 mm was an independent predictor of pontine infarction.

Evaluation of vertebrobasilar artery changes in patients with benign paroxysmal positional vertigo.

The aim of this study was to investigate vertebrobasilar artery (VBA) lesions in elderly patients with benign paroxysmal positional vertigo (BPPV) by magnetic resonance angiography. VBA lesions in patients older than 65 years of age with BPPV were prospectively investigated by magnetic resonance angiography. Vascular risk factors, blood vessel changes, and vertigo severity were recorded. Age-matched individuals without BPPV were included in the control group. Of 126 patients screened for this study, 104 were included. Relevant comorbidities included diabetes (12 patients), hypertension (23 patients), and dyslipidemia (20 patients). Findings included left or right vertebral artery (VA) stenosis or occlusion (22 patients, 21.2%), VA tortuosity (25 patients, 24.0%), VA dominance (20 patients, 19.2%), basilar artery (BA) stenosis or occlusion (nine patients, 8.6%), and BA tortuosity (12 patients, 11.5%). These abnormal vessels differed between BPPV patients and the control group (all P<0.05). The severity of Vertigo did not differ between the abnormal VA and abnormal BA groups (P>0.05), but did differ between the normal group and the abnormal VA or BA group (P<0.05). Vertigo severity correlated with VA stenosis or occlusion, VA dominance, and unilateral or bilateral VA tortuosity. VBA tortuosity and VA dominance were common in BPPV patients and may contribute toward BPPV.

Aldosterone synthase gene (CYP11B2) -344C/T polymorphism contributes to the risk of recurrent cerebral ischemia.

BACKGROUND: Accumulating evidence suggests that CYP11B2 rs1799998 (-344C/T) polymorphism is independently associated with an increased risk of stroke. Our aim was to determine whether -344C/T also predisposes to recurrent cerebral ischemia following in patients with symptomatic intracranial atherosclerosis disease (ICAD). METHODS: Genotypes of the CYP11B2 -344C/T polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphism. A total of 208 ICAD patients were enrolled and underwent a long-term clinical follow-up to detect the recurrent cerebral ischemia. RESULTS: During a median follow-up time of 35 months, 40 recurrent strokes (19.2%) were documented. Kaplan-Meier and multivariable Cox regression analyses adjusted for age, gender, and other cardiovascular risk factors identified that the presence of the TT genotype within the CYP11B2 -344C/T polymorphism was associated with an increased risk of 1.98-fold for recurrent cerebral ischemia (the hazard ratio 1.98, 95% confidence interval 1.16-3.41; p=0.01). CONCLUSIONS: Our findings suggest that the -344C/T polymorphism of the CYP11B2 gene confers an increased risk of recurrent cerebral ischemia.

Vertebral artery dominance, brainstem auditory evoked potential, and vertigo of vascular origin.

OBJECTIVE: Vertebral artery dominance (VAD) is defined when there is a significant difference between the diameters of the vertebral arteries (VAs). VAD may be a risk factor for vertigo of vascular origin. The objectives of this study were: (1) to investigate changes of brainstem auditory evoked potential (BAEP) in patients with vertigo caused by VAD through magnetic resonance; and (2) to understand the possible mechanism(s) by which VAD triggers vertigo of vascular origin. METHODS: This prospective study involved 64 patients with vertigo, including 35 patients with VAD (VAD group) and 29 without VAD (non-VAD group) as detected by head magnetic resonance angiography. Age, sex, and other clinical histories were comparable in both groups. The degree of vertigo was graded and BAEP examination was performed in each patient. BAEP changes as well as their correlations of BAEP with the dominant VA and basilar artery (BA) were analyzed in both groups. RESULTS: The rate of abnormal BA shapes was 60% in the VAD group compared with 34.5% in the non-VAD group (Chi-square = 4.135, P<0.05). The median BA curvature was higher in the VAD group than that in the non-VAD group, 3.67 and 1.73 mm, respectively (P<0.01). Peak latencies (I, III, and V) in the VAD group were longer than those in the non-VAD group (P<0.01), but the difference in the III did not reach statistical significance (t = 1.916, P>0.05). Interpeak latencies (III-V and I-V) were longer in the VAD group than those in the non-VAD group (P<0.05); there was no significant difference in the interpeak latencies of I-III (P>0.05). The III-V/I-III ratios were higher in the VAD group than those in the non-VAD group. The vertigo severity level was significantly higher in the VAD group than that in the non-VAD group (3.2 ± 1.0 versus 2.2 ± 0.7). The vertigo severity level correlated with VAD and every major anomaly index of BAEP; its correlations with III-V/I-III were remarkably significant (r = 0.617, P = 0.013). CONCLUSION: The incidence of abnormal BA shapes and abnormal BAEP, and the vertigo severity level were higher in VAD patients. Moreover, VAD was found to correlate with abnormal BAEP, suggesting that VAD contributed to vertigo of vascular origin.

Characteristics of vascular lesions in patients with posterior circulation infarction according to age and region of infarct.

Patients with posterior circulation infarction underwent CT angiography and magnetic resonance angiography. Intracranial and extracranial vasculopathy was evaluated according to age group and location of stroke. Patients aged > 60 years and < 60 years had similar rates of vertebral artery dominance and vertebrobasilar artery developmental or origin anomalies. Vertebrobasilar artery stenosis or occlusion and tortuosity occurred more frequently in patients aged > 60 years than < 60 years. The rates of vertebrobasilar artery anomalies and tortuosity were high in patients with posterior circulation infarction. Vertebrobasilar artery tortuosity occurred more frequently in patients aged > 60 years, whereas vertebrobasilar artery developmental anomalies occurred with similar frequency in patients aged < 60 years and > 60 years. Patients with infarction of the brainstem or cerebellum were more likely to have vertebral artery stenosis or occlusion, basilar artery stenosis or occlusion, vertebral artery dominance or tortuosity, and basilar artery tortuosity, and patients with infarction of the thalamus, medial temporal, or occipital lobes were more likely to have stenosis or occlusion of the vertebral or basilar arteries. Vertebrobasilar artery tortuosity, vertebral artery dominance (hypoplasia), and congenital variations of the vertebrobasilar system may lead to posterior circulation infarction at different locations in different age groups.

Risk factors for fever in critically ill patients with acute new-onset stroke.

OBJECTIVE: The purpose of this project was to identify risk factors for fever among critically ill patients with acute new-onset stroke, treated in a neurological intensive care unit (NICU). The frequency and risk factors for fever in the stroke patients during the first 7 days after admission were retrospectively studied. METHODS: Fever was defined as a patient's axillary temperature >37.5 degrees C in two separate measurements or >37.8 degrees C in one single measurement. Multivariable logistic regressions were applied to analyse the risk factors for any fever, explained infectious fever and unexplained fever. One hundred and thirty-seven patients were included in the final analysis. RESULTS: Febrile episodes occurred in 65% (89/137) of the patients; 48.9% of the fever were explained by infection (predominantly pneumonia or bronchitis), and 15.3% were unexplained despite a complete diagnostic evaluation. Significant risk factors for any fever included age 65 years or older, impaired consciousness, extremity paralysis (muscle force < or = grade 3), center venous catheterization and tracheal intubation. In addition to those risk factors, the length of the stay at NICU before the fever was also a significant risk factor for explained infectious fever. Brain midline shift and initial serum leucocyte count more than 12.0 x 10(9)/l were significant risk factors for unexplained fever. CONCLUSION: These results suggest that critically ill and new-onset stroke patients treated in NICU often have fever. The risk factors for different types of fever vary considerably.